TY  - RPRT
T1  - Assessment of osteoporosis at the primary health-care level.
A1  - Kanis JA on behalf of the World Health Organization Scientific Group
Y1  - 2007///
JF  - Technical Report. World Health Organization Collaborating Centre for Metabolic Bone Diseases.
UR  - http://www.sheffield.ac.uk/FRAX/pdfs/WHO_Technical_Report.pdf
N2  - Assessment of osteoporosis at the primary health-care level. Technical Report. World Health Organization Collaborating Centre for Metabolic Bone Diseases, University of Sheffield, UK. 2007: Printed by the University of Sheffield.
ER  - 
TY  - JOUR
T1  - Book Review: Guidelines for Preclinical Evaluation and Clinical Trials in Osteoporosis <b>Guidelines for Preclinical Evaluation and Clinical Trials in Osteoporosis</b> Published by the World Health Organization, Geneva, Switzerland, 1998. ISBN 92-4-154522
A1  - Raman-Wilms, Lalitha
Y1  - 1999///
JF  - Annals of Pharmacotherapy
VL  - 33
IS  - 12
SP  - 1377
EP  - 1378
DO  - 10.1177/106002809903301207
UR  - http://journals.sagepub.com/doi/10.1177/106002809903301207
ER  - 
TY  - UNPB
T1  - Orthopaedic Care of Patients with Fragility Fractures
A1  - Statement, Position
Y1  - 2011///
ER  - 
TY  - JOUR
T1  - Osteoporosis: from a rare symptom of endocrine diseases to the tacit epidemic of XX-XXI centuries
A1  - Dedov, I I
A1  - Mel'nichenko, G A
A1  - Belaia, Zh E
A1  - Rozhinskaia, L Ia
Y1  - 2011///
JF  - Problems of Endocrinology
VL  - 57
IS  - 1
SP  - 35
EP  - 35
DO  - 10.14341/probl201157135-45
UR  - http://endojournals.ru/index.php/probl/article/view/4580
ER  - 
TY  - JOUR
T1  - American Association of Clinical Endocrinologists and American College of Endocrinology Clinical Practice Guidelines for the Diagnosis and Treatment of Postmenopausal Osteoporosis — 2016
A1  - Camacho, Pauline M.
A1  - Petak, Steven M.
A1  - Binkley, Neil
A1  - Clarke, Bart L.
A1  - Harris, Steven T.
A1  - Hurley, Daniel L.
A1  - Kleerekoper, Michael
A1  - Lewiecki, E. Michael
A1  - Miller, Paul D.
A1  - Narula, Harmeet S.
A1  - Pessah-Pollack, Rachel
A1  - Tangpricha, Vin
A1  - Wimalawansa, Sunil J.
A1  - Watts, Nelson B.
Y1  - 2016///
JF  - Endocrine Practice
VL  - 22
IS  - Supplement 4
SP  - 1
EP  - 42
DO  - 10.4158/EP161435.GL
UR  - http://journals.aace.com/doi/10.4158/EP161435.GL
N2  - Abbreviations: AACE = American Association of Clinical Endocrinologists AFF = atypical femur fracture ASBMR = American Society for Bone and Mineral Research BEL = best evidence level BMD = bone mineral density BTM = bone turnover marker CBC = complete blood count CI = confidence interval DXA = dual-energy X-ray absorptiometry EL = evidence level FDA = U.S. Food and Drug Administration FLEX = Fracture Intervention Trial (FIT) Long-term Extension FRAX® = Fracture Risk Assessment Tool GFR = glomerular filtration rate GI = gastrointestinal HORIZON = Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly IOF = International Osteoporosis Foundation ISCD = International Society for Clinical Densitometry IU = international units IV = intravenous LSC = least significant change NBHA = National Bone Health Alliance NOF = National Osteoporosis Foundation 25(OH)D = 25-hydroxy vitamin D ONJ = osteonecrosis of the jaw PINP = serum carboxy-terminal propeptide of type I collagen PTH = parathyroid hormone R...
ER  - 
TY  - BOOK
T1  - Остеопороз. Диагностика, профилактика и лечение. Клинические рекомендации
A1  - Евстигнеева Л.П., Солодовников А.Г., Ершова О.Б., и др
Y1  - 2010///
PB  - Геотар-Медиа
CY  - Москва
ER  - 
TY  - JOUR
T1  - European guidance for the diagnosis and management of osteoporosis in postmenopausal women
A1  - Kanis, J. A.
A1  - McCloskey, E. V.
A1  - Johansson, H.
A1  - Cooper, C.
A1  - Rizzoli, R.
A1  - Reginster, J. Y.
Y1  - 2013///
KW  - Bone mineral density
KW  - Diagnosis of osteoporosis
KW  - FRAX
KW  - Fracture risk assessment
KW  - Health economics
KW  - Treatment of osteoporosis
JF  - Osteoporosis International
VL  - 24
IS  - 1
SP  - 23
EP  - 57
SN  - 0937-941X\n1433-2965
DO  - 10.1007/s00198-012-2074-y
N2  - UNLABELLED Guidance is provided in a European setting on the assessment and treatment of postmenopausal women at risk of fractures due to osteoporosis. INTRODUCTION The International Osteoporosis Foundation and European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis published guidance for the diagnosis and management of osteoporosis in 2008. This manuscript updates these in a European setting. METHODS Systematic literature reviews. RESULTS The following areas are reviewed: the role of bone mineral density measurement for the diagnosis of osteoporosis and assessment of fracture risk, general and pharmacological management of osteoporosis, monitoring of treatment, assessment of fracture risk, case finding strategies, investigation of patients and health economics of treatment. CONCLUSIONS A platform is provided on which specific guidelines can be developed for national use.
ER  - 
TY  - RPRT
T1  - Аудит состояния проблемы остеопороза в странах Восточной Европы и Центральной Азии 2010
A1  - Лесняк О.М., Ершова, О.Б.
Y1  - 2011///
ER  - 
TY  - CONF
T1  - Сравнительная оценка социальных последствий перелома проксимального отдела бедра и инфаркта миокарда у пациентов старшего возраста
A1  - Бахтиярова С.А., Бортник С.Б., Лесняк О.М., и др.
Y1  - 2003///
JF  - Остеопороз и остеопатии. Приложение. Научная программа и тезисы Росс. Конгресса по остеопорозу, 20-22 октября 2003 г.
SP  - 45
EP  - 45
CY  - Москва
ER  - 
TY  - JOUR
T1  - Ближайшие и отдаленные исходы переломов проксимального отдела бедра у лиц пожилого возраста и их медико-социальные последствия (по данным многоцентрового исследования)
A1  - Меньшикова Л.В., Храмцова Н.А., Ершова, О.Б.
Y1  - 2002///
JF  - Остеопороз и остеопатии
VL  - 1
SP  - 8
EP  - 11
ER  - 
TY  - THES
T1  - Осложненный остеопороз: минеральная плотность костной ткани различных отделов скелета, качество жизни, приверженность терапии и затраты на лечение: Автореферат дис. … канд. мед. наук. – Москва
A1  - Добровольская, О.В.
Y1  - 2016///
ER  - 
TY  - BOOK
T1  - Руководство по остеопорозу
A1  - Михайлов Е.Е., Беневоленская, Л.И.
Y1  - 2003///
PB  - Бином. Лаборатория знаний
CY  - Москва
ER  - 
TY  - CONF
T1  - Эпидемиология переломов проксимального отдела бедренной кости у городского населения Российской Федерации: результаты многоцентрового исследования
A1  - Ершова О.Б., Белова К.Ю., Белов М.В., и др.
Y1  - 2012///
JF  - Материалы научно-практической конференции «Остеопороз – важнейшая мультидисциплинарная проблема здравоохранения XXI века»
SP  - 23
EP  - 27
CY  - Санкт-Петербург
ER  - 
TY  - JOUR
T1  - Pre-existing fractures and bone mass predict vertebral fracture incidence in women
A1  - Ross, Philip D.
A1  - Davis, James W.
A1  - Epstein, Robert S.
A1  - Wasnich, Richard D.
Y1  - 1991///
JF  - Annals of Internal Medicine
VL  - 114
IS  - 11
SP  - 919
EP  - 923
SN  - 0003-4819 (Print)
DO  - 10.7326/0003-4819-114-11-919
N2  - OBJECTIVE: To determine the independent contributions of bone mass and existing fractures as predictors of the risk for new vertebral fractures. SUBJECTS: Postmenopausal Japanese-American women. MEASUREMENTS: Baseline measurements of the distal radius, the proximal radius, and the calcaneus were obtained in 1981 using single-photon absorptiometry. Measurements of the lumbar spine were obtained in 1984 using dual-photon absorptiometry. Prevalent vertebral fractures were identified using dimensions measured on lateral radiographs; vertebral height values more than 3 SD below vertebra-specific means were considered to indicate fracture. Statistical models were used to evaluate the utility of bone mass and existing (prevalent) fractures to predict the risk for new fractures during an average follow-up of 4.7 years. MAIN RESULTS: Differences of 2 SD in bone mass were associated with fourfold to sixfold increases in the risk for new vertebral fractures. A single fracture at the baseline examination increased the risk for new vertebral fractures fivefold. Presence of two or more fractures at baseline increased the risk 12-fold. A combination of low bone mass (below the 33d percentile) and the presence of two or more prevalent fractures increased the risk 75-fold, relative to women with the highest bone mass (above the 67th percentile) and no prevalent fractures. Stature, body mass index, arm span, and spinal conditions such as scoliosis, osteoarthritis, and sacroiliitis did not predict fracture incidence (P greater than 0.05). Weight was marginally predictive (P = 0.04) of fracture incidence but became nonpredictive after adjusting for bone mass (P greater than or equal to 0.05). CONCLUSIONS: Both bone mass and prevalent vertebral fractures are powerful predictors of the risk for new vertebral fractures. Combining information about bone mass and prevalent fracture appears to be better for predicting new fractures than either variable alone. Physicians can use these risk factors to identify patients at greatest risk for new fractures.
ER  - 
TY  - JOUR
T1  - FRAX??? and the assessment of fracture probability in men and women from the UK
A1  - Kanis, J. A.
A1  - Johnell, O.
A1  - Oden, A.
A1  - Johansson, H.
A1  - McCloskey, E.
Y1  - 2008///
KW  - Clinical risk factors
KW  - Fracture probability
KW  - Frax???
KW  - Osteoporotic fracture
JF  - Osteoporosis International
VL  - 19
IS  - 4
SP  - 385
EP  - 397
SN  - 0937-941X
DO  - 10.1007/s00198-007-0543-5
N2  - Summary: A fracture risk assessment tool (FRAX registered ) is developed based on the use of clinical risk factors with or without bone mineral density tests applied to the UK. Introduction: The aim of this study was to apply an assessment tool for the prediction of fracture in men and women with the use of clinical risk factors (CRFs) for fracture with and without the use of femoral neck bone mineral density (BMD). The clinical risk factors, identified from previous meta-analyses, comprised body mass index (BMI, as a continuous variable), a prior history of fracture, a parental history of hip fracture, use of oral glucocorticoids, rheumatoid arthritis and other secondary causes of osteoporosis, current smoking, and alcohol intake 3 or more units daily. Methods: Four models were constructed to compute fracture probabilities based on the epidemiology of fracture in the UK. The models comprised the ten-year probability of hip fracture, with and without femoral neck BMD, and the ten-year probability of a major osteoporotic fracture, with and without BMD. For each model fracture and death hazards were computed as continuous functions. Results: Each clinical risk factor contributed to fracture probability. In the absence of BMD, hip fracture probability in women with a fixed BMI (25 kg/m super(2)) ranged from 0.2% at the age of 50 years for women without CRF's to 22% at the age of 80 years with a parental history of hip fracture (approximately 100-fold range). In men, the probabilities were lower, as was the range (0.1 to 11% in the examples above). For a major osteoporotic fracture the probabilities ranged from 3.5% to 31% in women, and from 2.8% to 15% in men in the example above. The presence of one or more risk factors increased probabilities in an incremental manner. The differences in probabilities between men and women were comparable at any given T-score and age, except in the elderly where probabilities were higher in women than in men due to the higher mortality of the latter. Conclusion: The models provide a framework which enhances the assessment of fracture risk in both men and women by the integration of clinical risk factors alone and/or in combination with BMD.
ER  - 
TY  - JOUR
T1  - Clinician???s Guide to Prevention and Treatment of Osteoporosis
A1  - Cosman, F.
A1  - de Beur, S. J.
A1  - LeBoff, M. S.
A1  - Lewiecki, E. M.
A1  - Tanner, B.
A1  - Randall, S.
A1  - Lindsay, R.
Y1  - 2014///
KW  - Diagnosis
KW  - Guide
KW  - Osteoporosis
KW  - Prevention
KW  - Treatment
JF  - Osteoporosis International
VL  - 25
IS  - 10
SP  - 2359
EP  - 2381
SN  - 978-0-9798989-9-0
DO  - 10.1007/s00198-014-2794-2
N2  - The Clinician’s Guide to Prevention and Treatment of Osteoporosis was developed by an expert committee of the National Osteoporosis Foundation (NOF) in collaboration with a multispecialty council of medical experts in the field of bone health convened by NOF. Readers are urged to consult current prescribing information on any drug, device, or procedure discussed in this publication.
ER  - 
TY  - JOUR
T1  - Epidemiology of fracture in the Russian Federation and the development of a FRAX model
A1  - Lesnyak, Olga
A1  - Ershova, Olga
A1  - Belova, Ksenia
A1  - Gladkova, Elena
A1  - Sinitsina, Olga
A1  - Ganert, Olga
A1  - Romanova, Marina
A1  - Khodirev, Vitalij
A1  - Johansson, Helena
A1  - McCloskey, Eugene
A1  - Kanis, John A.
Y1  - 2012///
KW  - Burden of fractures
KW  - FRAX
KW  - Forearm fracture
KW  - Fracture probability
KW  - Hip fracture
KW  - Humerus fracture
JF  - Archives of Osteoporosis
VL  - 7
IS  - 1-2
SP  - 67
EP  - 73
SN  - 1165701200
DO  - 10.1007/s11657-012-0082-3
N2  - UNLABELLED: The incidence of hip, forearm and humeral fractures was studied in two cities from the Russian Federation. Fracture rates were used to create a FRAX model for Russia and to estimate the current and future burden of fracture.\n\nPURPOSE: There is scant information on the epidemiology of fracture in Russia. The aim of the study was to determine the incidence of major fractures in order to populate a new FRAX model and to characterise the burden and future burden of fractures.\n\nMETHODS: The number of hip, forearm and humeral fractures was determined in two Russian cities with a well-defined catchment population over a 2-3-year period. Incidence rates for the two cities were merged and used to populate a FRAX model for Russia. Incidence rates were also applied to the general population in 2010 and 25 years later in 2035.\n\nRESULTS: A total of 6,012 fractures were documented. For hip fracture, 27 % of cases in Pervouralsk and 1.8 % in Yaroslavl were not registered in the hospital data base. The incidence of index fractures increased with age and was higher in women than in men. The lifetime probability of hip fracture at the age of 50 years was 4 % in men and 7 % in women. The total number of hip fractures estimated in 2010 (112,000) is expected to rise to 159,000 in 2035. The estimated number of major fractures will rise from 590,000 to 730,000 over the same time interval.\n\nCONCLUSIONS: Fragility fractures pose a serious health care problem in Russia. Urgent steps are needed to improve the acute management of hip fracture and long-term care of other osteoporotic fractures.
ER  - 
TY  - JOUR
T1  - The diagnosis of osteoporosis
A1  - Kanis, John A.
A1  - Melton, L. Joseph
A1  - Christiansen, Claus
A1  - Johnston, Conrad C.
A1  - Khaltaev, Nikolai
Y1  - 2009/12//
PB  - John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)
JF  - Journal of Bone and Mineral Research
VL  - 9
IS  - 8
SP  - 1137
EP  - 1141
DO  - 10.1002/jbmr.5650090802
UR  - http://doi.wiley.com/10.1002/jbmr.5650090802
ER  - 
TY  - JOUR
T1  - Potential cost-effective use of spine radiographs to detect vertebral deformity and select osteopenic post-menopausal women for amino-bisphosphonate therapy
A1  - Schousboe, John T.
A1  - Ensrud, Kristine E.
A1  - Nyman, John A.
A1  - Kane, Robert L.
A1  - Melton, L. Joseph
Y1  - 2005///
KW  - Amino-bisphosphonate therapy
KW  - Cost-effectiveness
KW  - Fracture
KW  - Spine radiography
JF  - Osteoporosis International
VL  - 16
IS  - 12
SP  - 1883
EP  - 1893
SN  - 0937-941X (Print)
DO  - 10.1007/s00198-005-1956-7
N2  - Prevalent vertebral deformities are predictive of future clinical fractures independent of bone density. We used a Markov model with eight health states to estimate from the societal perspective the cost-effectiveness of using spine radiographs to identify postmenopausal women age 60 or older with one or more vertebral deformities and then treat them with anti-resorptive drug therapy to prevent fractures. We compared three strategies: 5 years of amino-bisphosphonate (alendronate) therapy for all, 5 years of alendronate therapy for only those with prevalent a radiographic vertebral deformity or no initial alendronate treatment. Lifetime direct medical and indirect costs, quality adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were tracked. For women with one or more prevalent vertebral deformities, the costs per QALY gained ranged from 5,084 dollars (for an 80 year old with a T-score of -2.4) to 61,192 dollars (for a 60 year old with a T-score of -1.0). For women without prevalent vertebral deformity, the costs per QALY gained ranged from 41,897 dollars (for a 60 year old with a T-score of -2.4) to 166,219 dollars (for an 80 year old with a T-score of -1.0). These results were modestly sensitive to reasonable changes in fracture rates, disutility, discount rates and assumptions about the accuracy of spinal radiographs for detecting vertebral deformity. Assuming a societal willingness to pay per QALY gained of 50,000 dollars, the strategy of performing spine radiographs in post-menopausal osteopenic women with T-scores at or below -1.5 and treating those with 1 or more prevalent vertebral deformities is likely to be cost-effective. However, further research on the accuracy of vertebral deformity ascertainment from routine clinical radiographs and on the efficacy of amino-bisphosphonate drugs for reducing the risk of non-vertebral fractures in osteopenic women is needed to define more precisely the subset of osteopenic post-menopausal women in whom use of spinal radiographs is most cost-effective.
ER  - 
TY  - JOUR
T1  - Type 2 diabetes mellitus and fracture risk
A1  - Dede, Anastasia D.
A1  - Tournis, Symeon
A1  - Dontas, Ismene
A1  - Trovas, George
Y1  - 2014///
KW  - Advanced glycation end-products
KW  - Bone fragility
KW  - Collagen cross-linking
KW  - Diabetes
KW  - Fracture healing
JF  - Metabolism: Clinical and Experimental
VL  - 63
IS  - 12
SP  - 1480
EP  - 1490
SN  - 0026-0495
DO  - 10.1016/j.metabol.2014.09.002
N2  - Increased fracture risk, traditionally associated with type 1 diabetes, has lately been of great concern in patients with type 2 diabetes. A variable increase in fracture risk has been reported, ranging from 20% to 3-fold, depending on skeletal site, diabetes duration and study design. Longer disease duration, the presence of diabetic complications, inadequate glycemic control, insulin use and increased risk for falls are all reported to increase fracture risk. Patients with type 2 diabetes display a unique skeletal phenotype with either normal or more frequently increased, bone mineral density and impaired structural and geometric properties. Recently, alterations in bone material properties seem to be the predominant defect leading to increased bone fragility. Accumulation of advanced glycation end-products and changes in collagen cross-linking along with suppression of bone turnover seem to be significant factors impairing bone strength. FRAX score has been reported to underestimate fracture risk and lumbar spine BMD is inadequate in predicting vertebral fractures. Anti-diabetic medications, apart from thiazolidinediones, appear to be safe for the skeleton, although more data are needed. Optimal strategies to reduce skeletal fragility in type 2 diabetic patients are yet to be determined.
ER  - 
TY  - JOUR
T1  - Towards a diagnostic and therapeutic consensus in male osteoporosis
A1  - Kanis, J. A.
A1  - Bianchi, G.
A1  - Bilezikian, J. P.
A1  - Kaufman, J. M.
A1  - Khosla, S.
A1  - Orwoll, E.
A1  - Seeman, E.
Y1  - 2011///
KW  - Bone mineral density
KW  - Bone quality
KW  - Fracture risk
KW  - Gonadal hormone status
KW  - Obesity
KW  - T-score
KW  - Testosterone
KW  - Treatment
JF  - Osteoporosis International
VL  - 22
IS  - 11
SP  - 2789
EP  - 2798
SN  - 0937-941X
DO  - 10.1007/s00198-011-1632-z
N2  - UNLABELLED: The consensus views on osteoporosis in men are reported.\n\nINTRODUCTION: A workshop was convened within a meeting on osteoporosis in men to identify areas of consensus amongst the panel (the authors) and the participants of the meeting.\n\nMETHODS: A public debate with an expert panel on preselected topics was conducted.\n\nRESULTS AND CONCLUSIONS: Consensus views were reached on diagnostic criteria and several aspects on the pathophysiology and treatment of osteoporosis in men.
ER  - 
TY  - JOUR
T1  - Diabetic Patients Have an Increased Risk of Vertebral Fractures Independent of BMD or Diabetic Complications
A1  - Yamamoto, Masahiro
A1  - Yamaguchi, Toru
A1  - Yamauchi, Mika
A1  - Kaji, Hiroshi
A1  - Sugimoto, Toshitsugu
Y1  - 2009///
JF  - Journal of Bone and Mineral Research
VL  - 24
IS  - 4
SP  - 702
EP  - 709
SN  - 1523-4681 (Electronic)
DO  - 10.1359/jbmr.081207
UR  - http://doi.wiley.com/10.1359/jbmr.081207
N2  - Although patients with type 2 diabetes (T2DM) have an increased risk of hip fracture, risk of vertebral fracture (VF) and its association with BMD are still unclear. We examined Japanese T2DM patients (161 men >50 yr and 137 postmenopausal women) and non-DM controls (76 and 622, respectively) by lateral spine radiography and DXA at the lumbar spine (L), femoral neck (FN), and radius (R). Logistic regression analysis adjusted for age, body mass index, and L-BMD showed that the presence of T2DM was an independent risk factor for prevalent VFs in women (OR = 1.86, p = 0.019) and men (OR = 4.73, p < 0.001). BMD at any site, however, was not significantly associated with the presence of prevalent VFs in T2DM patients, in contrast to the significant association in controls (at least p = 0.010). Comparison of T2DM patients with and without VFs showed no significant differences in BMD values, bone markers, or diabetes status. Receiver operating characteristic analysis showed that the absolute L-, FN-, and R-BMD values for detecting prevalent VFs were higher in T2DM patients than controls, whereas their sensitivity and specificity were lower. T2DM patients may have an increased risk of VFs independent of BMD or diabetic complication status, suggesting that bone quality may define bone fragility in T2DM.
ER  - 
TY  - JOUR
T1  - Recognizing and reporting osteoporotic vertebral fractures
A1  - Grigoryan, Mikayel
A1  - Guermazi, Ali
A1  - Roemer, Frank W.
A1  - Delmas, Pierre D.
A1  - Genant, Harry K.
Y1  - 2003///
KW  - Bone mineral density
KW  - Osteoporosis
KW  - Quantitative morphometry
KW  - Semiquantitative assessment
KW  - Vertebral fractures
JF  - European Spine Journal
VL  - 12
IS  - SUPPL. 2
SN  - 0940-6719
DO  - 10.1007/s00586-003-0613-0
N2  - Vertebral fractures are the hallmark of osteoporosis, and occur with a higher incidence earlier in life than any other type of osteoporotic fractures. It has been shown that both symptomatic and asymptomatic vertebral fractures are associated with increased morbidity and mortality. Morbidity associated with these fractures includes decreased physical function and social isolation, which have a significant impact on the patient's overall quality of life. Since the majority of vertebral fractures do not come to clinical attention, radiographic diagnosis is considered to be the best way to identify and confirm the presence of osteoporotic vertebral fractures in clinical practice. Traditionally, conventional lateral radiographs of the thoracolumbar spine have been visually evaluated by radiologists or clinicians to identify vertebral fractures. The two most widely used methods to determine the severity of such fractures in clinical research are the semiquantitative assessment of vertebral deformities, which is based on visual evaluation, and the quantitative approach, which is based on different morphometric criteria. In our practice for osteoporosis evaluation we use the Genant semiquantitative approach: an accurate and reproducible method tested and applied in many clinical studies. The newest generation of fan-beam DXA systems delivering "high-resolution" lateral spine images offers a potential practical alternative to radiographs for clinical vertebral fracture analysis. The advantages of using DXA over conventional radiographic devices are its minimal radiation exposure and high-speed image acquisition. It also allows combined evaluation of vertebral fracture status and bone mass density, which could become a standard for patient evaluation in osteoporosis. The disadvantage of DXA use is that upper thoracic vertebrae cannot be evaluated in a substantial number of patients due to poor imaging quality. We truly believe that the that there is a major role for radiologists and clinicians alike to carefully assess and diagnose vertebral fractures using standardized grading schemes such as the one outlined in this review. Quantitative morphometry is useful in the context of epidemiological studies and clinical drug trials; however, the studies would be flawed if quantitative morphometry were to be performed in isolation without additional adjudication by a trained and highly experienced radiologist or clinician.
ER  - 
TY  - JOUR
T1  - International variations in hip fracture probabilities: implications for risk assessment.
A1  - Kanis, John A.
A1  - Johnell, Olof
A1  - De Laet, Chris
A1  - Jonsson, Bengt
A1  - Oden, Anders
A1  - Ogelsby, Alan K.
Y1  - 2002///
KW  - 10-year probability
KW  - hip fracture risk
KW  - intervention threshold
KW  - lifetime risk
JF  - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
VL  - 17
IS  - 7
SP  - 1237
EP  - 1244
SN  - 0884-0431 (Print)\r0884-0431 (Linking)
DO  - 10.1359/jbmr.2002.17.7.1237
UR  - http://doi.wiley.com/10.1359/jbmr.2002.17.7.1237
N2  - It is recommended that intervention thresholds should be based on absolute fracture risk, but there is a large variation in hip fracture incidence from different regions of the world. The aim of this study was to examine heterogeneity of hip fracture probability in different regions from recent estimates of hip fracture incidence and mortality to adjust intervention thresholds. Ten-year probabilities of hip fracture were computed in men and women at 10-year intervals from the age of 50 years and lifetime risks at the age of 50 years from the hazard functions of hip fracture and death. Lifetime risk at the age of 50 years varied from 1% in women from Turkey to 28.5% in women from Sweden. High lifetime risks in women were associated with high lifetime risks in men (r = 0.83). There also were significant correlations of 10-year risk at any age between men and women. Ten-year probability was standardized to that of men and women from Sweden (set at 1.0). There was a 15-fold range in 10-year probability from 1.24 in Norway to 0.08 in Chile. Countries were categorized by 10-year probabilities comprising very high risk (Norway, Iceland, Sweden, Denmark, and the United States), high risk (China [Taiwan [TW]], Germany, Switzerland, Finland, Greece, Canada, The Netherlands, Hungary, Singapore, Italy, United Kingdom, Kuwait, Australia, and Portugal), medium risk (China [Hong Kong [HK]], France, Japan, Spain, Argentina, and China), and low risk (Turkey, Korea, Venezuela, and Chile). The categorization of hip fracture probabilities can be used to adjust intervention thresholds based on age, sex, and relative risk from a reference population such as Sweden.
ER  - 
TY  - JOUR
T1  - Hip Fracture Prediction in Elderly Men and Women: Validation in the Rotterdam Study
A1  - De Laet, Chris E. D. H.
A1  - Van Hout, Ben A.
A1  - Burger, Huibert
A1  - Weel, Angelique E. A. M.
A1  - Hofman, Albert
A1  - Pols, Huibert A. P.
Y1  - 2009///
JF  - Journal of Bone and Mineral Research
VL  - 13
IS  - 10
SP  - 1587
EP  - 1593
DO  - 10.1359/jbmr.1998.13.10.1587
UR  - http://doi.wiley.com/10.1359/jbmr.1998.13.10.1587
ER  - 
TY  - JOUR
T1  - Assessment of prevalent and incident vertebral fractures in osteoporosis research.
A1  - Genant, H K
A1  - Jergas, M
Y1  - 2003///
JF  - Osteoporosis International
VL  - 14 Suppl 3
SP  - S43
EP  - 55
DO  - 10.1007/s00198-002-1348-1
UR  - http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=12730798&retmode=ref&cmd=prlinks%5Cnpapers3://publication/doi/10.1007/s00198-002-1348-1
N2  - Vertebral fractures are the hallmark of osteoporosis, and it has been shown that the presence of vertebral fractures adds to the risk of future osteoporotic fractures. Thus, the evaluation of spinal radiographs for prevalent or incident vertebral fractures is important in the clinical evaluation of patients with osteoporosis, in clinical drug trials for osteoporosis treatment and in the epidemiologic evaluation of populations at risk for osteoporosis. Traditionally, conventional lateral radiographs of the thoracolumbar spine have been analyzed visually by radiologists or experienced clinicians to identify vertebral fractures in patients with clinical indications. Epidemiologic studies or clinical drug trials in osteoporosis research have considerably different requirements and expectations. To reduce potential subjectivity in qualitative readings and to provide definable, reproducible and objective methods to detect vertebral fracture, and to accommodate the assessment of large numbers of radiographs, various morphometric approaches have been explored and employed. However, potential deficiencies in morphometry have led to a renewed interest in standardized qualitative visual approaches for defining vertebral fractures and visual criteria. Numerous studies have shown that semiquantitative interpretation, after careful centralized training and standardization, can produce results with excellent intra- and interobserver reproducibility. We firmly believe that the experience from several studies has shown that there is a major role for radiologists and clinicians alike to carefully assess and diagnose vertebral fractures using standardized grading schemes such as the one proposed in this review. In the context of epidemiologic studies and clinical drug trials, quantitative morphometry may be used; however, the studies would be flawed if quantitative morphometry were to be performed in isolation without additional adjudication by a trained and highly experienced radiologist or clinician.
ER  - 
TY  - JOUR
T1  - Diagnosis of osteoporotic vertebral fractures: Importance of recognition and description by radiologists
A1  - Lenchik, Leon
A1  - Rogers, Lee F.
A1  - Delmas, Pierre D.
A1  - Genant, Harry K.
Y1  - 2004///
JF  - American Journal of Roentgenology
VL  - 183
IS  - 4
SP  - 949
EP  - 958
DO  - 10.2214/ajr.183.4.1830949
N2  - PDF Densitometry, X-Ray; Diagnostic Imaging; Humans; Magnetic Resonance Imaging; Osteoporosis/complications/diagnosis; Radiography, Thoracic; Spinal Fractures/diagnosis/etiology;
ER  - 
TY  - JOUR
T1  - Radiation exposure in X-ray-based imaging techniques used in osteoporosis
A1  - Damilakis, John
A1  - Adams, Judith E.
A1  - Guglielmi, Giuseppe
A1  - Link, Thomas M.
Y1  - 2010///
KW  - Bone densitometry
KW  - Bone structure
KW  - DXA
KW  - Osteoporosis
KW  - QCT
JF  - European Radiology
VL  - 20
IS  - 11
SP  - 2707
EP  - 2714
SN  - 1432-1084 (Electronic)\r0938-7994 (Linking)
DO  - 10.1007/s00330-010-1845-0
N2  - Recent advances in medical X-ray imaging have enabled the development of new techniques capable of assessing not only bone quantity but also structure. This article provides (a) a brief review of the current X-ray methods used for quantitative assessment of the skeleton, (b) data on the levels of radiation exposure associated with these methods and (c) information about radiation safety issues. Radiation doses associated with dual-energy X-ray absorptiometry are very low. However, as with any X-ray imaging technique, each particular examination must always be clinically justified. When an examination is justified, the emphasis must be on dose optimisation of imaging protocols. Dose optimisation is more important for paediatric examinations because children are more vulnerable to radiation than adults. Methods based on multi-detector CT (MDCT) are associated with higher radiation doses. New 3D volumetric hip and spine quantitative computed tomography (QCT) techniques and high-resolution MDCT for evaluation of bone structure deliver doses to patients from 1 to 3 mSv. Low-dose protocols are needed to reduce radiation exposure from these methods and minimise associated health risks.
ER  - 
TY  - JOUR
T1  - Osteoporosis imaging: effects of bone preservation on MDCT-based trabecular bone microstructure parameters and finite element models
A1  - Baum, Thomas
A1  - Grande Garcia, Eduardo
A1  - Burgkart, Rainer
A1  - Gordijenko, Olga
A1  - Liebl, Hans
A1  - Jungmann, Pia M.
A1  - Gruber, Michael
A1  - Zahel, Tina
A1  - Rummeny, Ernst J.
A1  - Waldt, Simone
A1  - Bauer, Jan S.
Y1  - 2015///
JF  - BMC Medical Imaging
VL  - 15
IS  - 1
SP  - 22
EP  - 22
SN  - 0001-4575
DO  - 10.1186/s12880-015-0066-z
UR  - http://bmcmedimaging.biomedcentral.com/articles/10.1186/s12880-015-0066-z
N2  - BACKGROUND: Osteoporosis is defined as a skeletal disorder characterized by compromised bone strength due to a reduction of bone mass and deterioration of bone microstructure predisposing an individual to an increased risk of fracture. Trabecular bone microstructure analysis and finite element models (FEM) have shown to improve the prediction of bone strength beyond bone mineral density (BMD) measurements. These computational methods have been developed and validated in specimens preserved in formalin solution or by freezing. However, little is known about the effects of preservation on trabecular bone microstructure and FEM. The purpose of this observational study was to investigate the effects of preservation on trabecular bone microstructure and FEM in human vertebrae.\n\nMETHODS: Four thoracic vertebrae were harvested from each of three fresh human cadavers (n=12). Multi-detector computed tomography (MDCT) images were obtained at baseline, 3 and 6 month follow-up. In the intervals between MDCT imaging, two vertebrae from each donor were formalin-fixed and frozen, respectively. BMD, trabecular bone microstructure parameters (histomorphometry and fractal dimension), and FEM-based apparent compressive modulus (ACM) were determined in the MDCT images and validated by mechanical testing to failure of the vertebrae after 6 months.\n\nRESULTS: Changes of BMD, trabecular bone microstructure parameters, and FEM-based ACM in formalin-fixed and frozen vertebrae over 6 months ranged between 1.0-5.6% and 1.3-6.1%, respectively, and were not statistically significant (p>0.05). BMD, trabecular bone microstructure parameters, and FEM-based ACM as assessed at baseline, 3 and 6 month follow-up correlated significantly with mechanically determined failure load (r=0.89-0.99; p<0.05). The correlation coefficients r were not significantly different for the two preservation methods (p>0.05).\n\nCONCLUSIONS: Formalin fixation and freezing up to six months showed no significant effects on trabecular bone microstructure and FEM-based ACM in human vertebrae and may both be used in corresponding in-vitro experiments in the context of osteoporosis.
ER  - 
TY  - JOUR
T1  - Assessment of the morpho-densitometric parameters of the lumbar pedicles in osteoporotic and control women undergoing routine abdominal MDCT examinations
A1  - Papadakis, Antonios E.
A1  - Karantanas, Apostolos H.
A1  - Papadokostakis, Giorgos
A1  - Damilakis, John
Y1  - 2011///
KW  - Multidetector CT
KW  - Osteoporosis
KW  - Pedicle isthmus
KW  - QCT/spine
KW  - Transpedicular fixation
JF  - Journal of Bone and Mineral Metabolism
VL  - 29
IS  - 3
SP  - 352
EP  - 358
DO  - 10.1007/s00774-010-0227-7
N2  - In transpedicular surgical operations, the pedicle should be safely penetrated. In this study, we hypothesize that morpho-densitometric data describing the physical status of the pedicle isthmus in osteoporotic versus control postmenopausal women may be generated using high-resolution three-dimensional images obtained from routine abdominal multidetector computed tomography (MDCT) scans. Thus, 32 osteoporotic and 38 postmenopausal control women had a routine abdominal scan using a 16-row CT scanner. Images of the pedicle isthmus of the L2-L4 vertebrae were generated at the plane that was vertical to the pedicle axis. Several indices were calculated based on the measurements of outer and inner dimension of the pedicle isthmus, pedicle isthmus area, and pedicle isthmus endosteal area. The mean Hounsfield unit number within the isthmus endosteal area (HU(IEA)) and the trabecular portion of the vertebral body (HU(VERT)) were measured. All subjects had a dual X-ray absorptiometry scan (DXA) in the lumbar spine. Most of the indices calculated showed statistically significant differences between osteoporotic and control women. HU(IEA) was significantly correlated to T-score (r = 0.580, P < 0.0001). HU(IEA) showed the best discriminatory ability between the two groups (area under ROC curve, 0.840). Routine abdominal MDCT can be used to assess the morpho-densitometric characteristics of the lumbar pedicle isthmus and differentiate osteoporotic from control postmenopausal women.
ER  - 
TY  - JOUR
T1  - Vertebral fracture assessment using a semiquantitative technique
A1  - Genant, Harry K.
A1  - Wu, Chun Y.
A1  - van Kuijk, Cornelis
A1  - Nevitt, Michael C.
Y1  - 1993///
JF  - Journal of Bone and Mineral Research
VL  - 8
IS  - 9
SP  - 1137
EP  - 1148
SN  - 0884-0431 (Print)
DO  - 10.1002/jbmr.5650080915
N2  - Abstract The assessment of vertebral fracture by conventional radiography has been refined and improved using either semiquantitative or quantitative criteria. The inter-and intraobserver variability was determined for a semiquantitative visual approach that we ... \n
ER  - 
TY  - JOUR
T1  - Can abdominal multi-detector CT diagnose spinal osteoporosis?
A1  - Papadakis, Antonios E.
A1  - Karantanas, Apostolos H.
A1  - Papadokostakis, Giorgos
A1  - Petinellis, Effie
A1  - Damilakis, John
Y1  - 2009///
KW  - Abdominal imaging
KW  - CT densitometry
KW  - Image analysis
KW  - Multi-detector CT
KW  - Osteoporosis
JF  - European Radiology
VL  - 19
IS  - 1
SP  - 172
EP  - 176
SN  - 0938-7994
DO  - 10.1007/s00330-008-1099-2
N2  - The aim of this study was to (1) generate quantitative CT (QCT) densitometric data based on routine abdominal multi-detector (MDCT) examinations and (2) investigate whether these data can be used to differentiate osteoporotic from healthy females. Twenty-five female patients (group A) with a history of radiotherapy were examined both with routine abdominal MDCT and standard QCT to generate a MDCT-to-QCT conversion equation. Twenty-one osteoporotic (group B) and 23 healthy female patients (group C) were also recruited in the study. Patients of groups B and C underwent routine abdominal MDCT examination for various clinical indications. Mean bone mineral density (BMD) in patients of group A was 103.4 mg/ml +/- 32.8 with routine abdominal MDCT and 91.0 mg/ml +/- 28.5 with QCT. Quantitative CT BMD(QCT) values for patients in groups B and C were calculated utilizing the BMD(MDCT) values derived from routine abdominal MDCT data sets and the MDCT to QCT conversion equation: BMD(QCT)=0:78 x BMD(MDCT) + 10:13. The calculated QCT densitometric data adequately differentiated osteoporotic from healthy females (area under ROC curve 0.828, p = 0.05). In conclusion, this study showed that in a group of female patients, QCT data derived from routine abdominal MDCT examinations discriminated osteoporotic from healthy subjects.
ER  - 
TY  - JOUR
T1  - Effects of exercise programmes on quality of life in osteoporotic and osteopenic postmenopausal women: a systematic review and meta-analysis.
A1  - Li, Wei-Chun
A1  - Chen, Yi-Chan
A1  - Yang, Rong-Sen
A1  - Tsauo, Jau-Yih
Y1  - 2009///
JF  - Clinical rehabilitation
VL  - 23
IS  - 10
SP  - 888
EP  - 96
SN  - 02692155
DO  - 10.1177/0269215509339002
UR  - http://www.ncbi.nlm.nih.gov/pubmed/19717503
N2  - OBJECTIVE To examine the effect of exercise therapy on quality of life in postmenopausal women with osteoporosis or osteopenia. METHODS We searched MEDLINE, CINAHL, PEDro, EMBASE and the Cochrane library from January 1966 to March 2007. Two reviewers independently selected all studies that met predetermined inclusion criteria. Randomized controlled trials that used the Short Form 36 of the Medical Outcome Study (SF-36) questionnaire or the Quality of Life Questionnaire of the European Foundation for Osteoporosis (QUALEFFO) as outcome measures were selected. The PEDro Scale was applied to rate the quality of each article. All studies had a quality score above 5/10. Meta-analysis was facilitated by RevMan 4.1. RESULTS Four randomized controlled trials met the inclusion criteria, involving a total of 256 participants. Results revealed that the exercise groups showed significant improvements in the domains of physical function, pain, role physical and vitality (P<0.05). Furthermore, intervention with combined exercise programmes had better effects on physical function, pain and vitality domains than controls. Group exercise programmes also produced better results in these three domains. A short-duration exercise programme produced more improvement in physical function, role physical and vitality, whereas a long-duration exercise programme resulted in more improvement in physical function and pain domains. CONCLUSIONS This meta-analysis revealed better improvement in physical function, pain, role physical and vitality in the exercise groups. Combined exercise and group exercise programmes showed better outcomes in the physical function, pain and vitality domains, but different durations of exercise programme showed improvement in different domains.
ER  - 
TY  - JOUR
T1  - Exercise for improving balance in older people
A1  - Howe, Tracey E.
A1  - Rochester, L.
A1  - Jackson, A.
A1  - Banks, P. M H
A1  - Blair, V. A.
Y1  - 2007///
KW  - Aged
KW  - Breathing exercises
KW  - Dancing
KW  - Exercise [*physiology]
KW  - Female
KW  - Gait [physiology]
KW  - Humans
KW  - Male
KW  - Middle aged
KW  - Muscle strength [physiology]
KW  - Musculoskeletal equilibrium [*physiology]
KW  - Randomized controlled trials as topic
KW  - Tai Ji
KW  - Yoga
JF  - Cochrane Database of Systematic Reviews
IS  - 4
SN  - 1469-493X (Electronic)\r1361-6137 (Linking)
DO  - 10.1002/14651858.CD004963.pub2
N2  - BACKGROUND In older adults, diminished balance is associated with reduced physical functioning and an increased risk of falling. This is an update of a Cochrane review first published in 2007. OBJECTIVES To examine the effects of exercise interventions on balance in older people, aged 60 and over, living in the community or in institutional care. SEARCH METHODS We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, CENTRAL (The Cochrane Library 2011, Issue 1), MEDLINE and EMBASE (to February 2011). SELECTION CRITERIA Randomised controlled studies testing the effects of exercise interventions on balance in older people. The primary outcomes of the review were clinical measures of balance. DATA COLLECTION AND ANALYSIS Pairs of review authors independently assessed risk of bias and extracted data from studies. Data were pooled where appropriate. MAIN RESULTS This update included 94 studies (62 new) with 9,917 participants. Most participants were women living in their own home.Most trials were judged at unclear risk of selection bias, generally reflecting inadequate reporting of the randomisation methods, but at high risk of performance bias relating to lack of participant blinding, which is largely unavoidable for these trials. Most studies only reported outcome up to the end of the exercise programme.There were eight categories of exercise programmes. These are listed below together with primary measures of balance for which there was some evidence of a statistically significant effect at the end of the exercise programme. Some trials tested more than one type of exercise. Crucially, the evidence for each outcome was generally from only a few of the trials for each exercise category. 1. Gait, balance, co-ordination and functional tasks (19 studies of which 10 provided primary outcome data): Timed Up & Go test (mean difference (MD) -0.82 s; 95% CI -1.56 to -0.08 s, 114 participants, 4 studies); walking speed (standardised mean difference (SMD) 0.43; 95% CI 0.11 to 0.75, 156 participants, 4 studies), and the Berg Balance Scale (MD 3.48 points; 95% CI 2.01 to 4.95 points, 145 participants, 4 studies).2. Strengthening exercise (including resistance or power training) (21 studies of which 11 provided primary outcome data): Timed Up & Go Test (MD -4.30 s; 95% CI -7.60 to -1.00 s, 71 participants, 3 studies); standing on one leg for as long as possible with eyes closed (MD 1.64 s; 95% CI 0.97 to 2.31 s, 120 participants, 3 studies); and walking speed (SMD 0.25; 95% CI 0.05 to 0.46, 375 participants, 8 studies).3. 3D (3 dimensional) exercise (including Tai Chi, qi gong, dance, yoga) (15 studies of which seven provided primary outcome data): Timed Up & Go Test (MD -1.30 s; 95% CI -2.40 to -0.20 s, 44 participants, 1 study); standing on one leg for as long as possible with eyes open (MD 9.60 s; 95% CI 6.64 to 12.56 s, 47 participants, 1 study), and with eyes closed (MD 2.21 s; 95% CI 0.69 to 3.73 s, 48 participants, 1 study); and the Berg Balance Scale (MD 1.06 points; 95% CI 0.37 to 1.76 points, 150 participants, 2 studies).4. General physical activity (walking) (seven studies of which five provided primary outcome data). 5. General physical activity (cycling) (one study which provided data for walking speed). 6. Computerised balance training using visual feedback (two studies, neither of which provided primary outcome data). 7. Vibration platform used as intervention (three studies of which one provided primary outcome data).8. Multiple exercise types (combinations of the above) (43 studies of which 29 provided data for one or more primary outcomes): Timed Up & Go Test (MD -1.63 s; 95% CI -2.28 to -0.98 s, 635 participants, 12 studies); standing on one leg for as long as possible with eyes open (MD 5.03 s; 95% CI 1.19 to 8.87 s, 545 participants, 9 studies), and with eyes closed ((MD 1.60 s; 95% CI -0.01 to 3.20 s, 176 participants, 2 studies); walking speed (SMD 0.04; 95% CI -0.10 to 0.17, 818 participants, 15 studies); and the Berg Balance Scale ((MD 1.84 points; 95% CI 0.71 to 2.97 points, 80 participants, 2 studies).Few adverse events were reported but most studies did not monitor or report adverse events.In general, the more effective programmes ran three times a week for three months and involved dynamic exercise in standing. AUTHORS' CONCLUSIONS There is weak evidence that some types of exercise (gait, balance, co-ordination and functional tasks; strengthening exercise; 3D exercise and multiple exercise types) are moderately effective, immediately post intervention, in improving clinical balance outcomes in older people. Such interventions are probably safe. There is either no or insufficient evidence to draw any conclusions for general physical activity (walking or cycling) and exercise involving computerised balance programmes or vibration plates. Further high methodological quality research using core outcome measures and adequate surveillance is required.
ER  - 
TY  - JOUR
T1  - Exercise for preventing and treating osteoporosis in postmenopausal women
A1  - Howe, Tracey E.
A1  - Shea, Beverley
A1  - Dawson, Lesley J.
A1  - Downie, Fiona
A1  - Murray, Ann
A1  - Ross, Craig
A1  - Harbour, Robin T.
A1  - Caldwell, Lynn M.
A1  - Creed, Gisela
Y1  - 2011///
JF  - Cochrane Database of Systematic Reviews
VL  - 2011
IS  - 7
SP  - 1
EP  - 167
SN  - 1469-493X (Electronic)\n1361-6137 (Linking)
DO  - 10.1002/14651858.CD000333.pub2.
N2  - Osteoporosis is a condition resulting in an increased risk of skeletal fractures due to a reduction in the density of bone tissue. Treatment of osteoporosis typically involves the use of pharmacological agents. In general it is thought that disuse (prolonged periods of inactivity) and unloading of the skeleton promotes reduced bone mass, whereas mechanical loading through exercise increases bone mass.
ER  - 
TY  - JOUR
T1  - Bone Mineral Density in Adults Disabled Through Acquired Neurological Conditions: A Review
A1  - Smith, Éimear
A1  - Carroll, Áine
Y1  - 2011///
KW  - Dual-energy X-ray absorptiometry
KW  - Fracture risk
KW  - Low bone mineral density
KW  - Neurological disability
KW  - Osteoporosis
JF  - Journal of Clinical Densitometry
VL  - 14
IS  - 2
SP  - 85
EP  - 94
SN  - 1094-6950 (Print)\r1094-6950 (Linking)
DO  - 10.1016/j.jocd.2010.12.002
N2  - This article is a review of the changes in bone mineral density (BMD), which occur in a number of acquired neurological conditions resulting in disability. For each of spinal cord injury, stroke, multiple sclerosis, Parkinson's disease, and traumatic brain injury, the following aspects are discussed, where information is available: prevalence of low BMD according to World Health Organization diagnostic categories and recommended diagnostic method, prevalence based on other diagnostic tools, comparison of BMD with a control population, rate of decline of BMD following onset of the neurological condition, factors influencing decline; mechanism of bone loss, and fracture rates. The common risk factors of immobilization and vitamin D deficiency would appear to cross all disability groups, with the most rapid phase of bone loss occurring in the acute and subacute phases of each condition. ?? 2011 The International Society for Clinical Densitometry.
ER  - 
TY  - JOUR
T1  - Sustained efficacy and safety of bazedoxifene in preventing fractures in postmenopausal women with osteoporosis: Results of a 5-year, randomized, placebo-controlled study
A1  - Silverman, S. L.
A1  - Chines, A. A.
A1  - Kendler, D. L.
A1  - Kung, A. W C
A1  - Teglbj??rg, C. S.
A1  - Felsenberg, D.
A1  - Mairon, N.
A1  - Constantine, G. D.
A1  - Adachi, J. D.
Y1  - 2012///
KW  - Bazedoxifene
KW  - Fracture
KW  - Osteoporosis
KW  - Postmenopausal
KW  - SERMs
JF  - Osteoporosis International
VL  - 23
IS  - 1
SP  - 351
EP  - 363
SN  - 0937-941X 1433-2965
DO  - 10.1007/s00198-011-1691-1
N2  - In this 2-year extension of a 3-year study, bazedoxifene showed sustained efficacy in preventing new vertebral fractures in postmenopausal women with osteoporosis and in preventing non-vertebral fractures in higher-risk women. Bazedoxifene significantly increased bone mineral density and reduced bone turnover versus placebo and was generally safe and well tolerated.
ER  - 
TY  - JOUR
T1  - Russian Association of Endocrinologists recommendations for diagnosis, treatment and prevention of vitamin D deficiency in adults
A1  - Pigarova, Ekaterina A.
A1  - Rozhinskaya, Ludmila Ya.
A1  - Belaya, Janna E.
A1  - Dzeranova, Larisa K.
A1  - Karonova, Tatiana L.
A1  - Ilyin, Alexanrd V.
A1  - Melnichenko, Galina A.
A1  - Dedov, Ivan I.
Y1  - 2016///
JF  - Problems of Endocrinology
VL  - 62
IS  - 4
SP  - 60
EP  - 60
DO  - 10.14341/probl201662460-84
UR  - http://endojournals.ru/index.php/probl/article/view/7987
ER  - 
TY  - JOUR
T1  - A 7-year randomized, placebo-controlled trial assessing the long-term efficacy and safety of bazedoxifene in postmenopausal women with osteoporosis
A1  - Palacios, Santiago
A1  - Silverman, Stuart L.
A1  - de Villiers, Tobie J.
A1  - Levine, Amy B.
A1  - Goemaere, Stefan
A1  - Brown, Jacques P.
A1  - De Cicco Nardone, Fiorenzo
A1  - Williams, Robert
A1  - Hines, Teresa L.
A1  - Mirkin, Sebastian
A1  - Chines, Arkadi A.
Y1  - 2015///
JF  - Menopause
VL  - 22
IS  - 8
SP  - 806
EP  - 813
SN  - 0000000000000
DO  - 10.1097/GME.0000000000000419
UR  - http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00042192-201508000-00004
N2  - OBJECTIVE: In a 3-year randomized, double-blind, osteoporosis treatment study (N = 7,492), bazedoxifene 20 mg and bazedoxifene 40 mg significantly (P < 0.05) reduced the risk of new vertebral fractures by 42% and 37%, respectively, compared with placebo in postmenopausal women with osteoporosis. This study evaluated the long-term (7-y) efficacy and safety of bazedoxifene in generally healthy postmenopausal women with osteoporosis. METHODS: This was a second 2-year extension of the 3-year multicenter outpatient core study. During extension I (years 4-5), women receiving bazedoxifene 40 mg transitioned to bazedoxifene 20 mg. In extension II (years 6-7; N = 1,530), all bazedoxifene-treated women continued bazedoxifene 20 mg. Main outcome measures included year 7 endpoints: incidences of new vertebral and nonvertebral fractures, bone mineral density changes, and safety assessments. RESULTS: At 7 years, the cumulative incidences of new vertebral fractures were significantly lower in the bazedoxifene (6.4%) and bazedoxifene 20 mg (7.6%) groups than in the placebo group (9.9%); the relative risk reductions were 36.5% and 30.4%, respectively (both P < 0.001). Bazedoxifene had no effect on the overall incidence of nonvertebral fractures (bazedoxifene, 11.2%; bazedoxifene 20 mg, 12.0%; placebo, 10.8%). The mean changes from baseline in lumbar spine bone mineral density were 2.95%, 2.73%, and 2.19%, respectively. Seven-year decreases in total hip bone mineral density were significantly smaller in the bazedoxifene (-1.15%) and bazedoxifene 20 mg (-1.19%) groups than in the placebo group (-2.53%; P </= 0.002). Bazedoxifene showed a favorable safety/tolerability profile across 7 years, with similar adverse events, serious adverse events, and study discontinuations in all groups. CONCLUSIONS: Efficacy and safety of bazedoxifene are sustained across 7 years in postmenopausal women with osteoporosis.
ER  - 
TY  - JOUR
T1  - Efficacy of Bazedoxifene in Reducing New Vertebral Fracture Risk in Postmenopausal Women With Osteoporosis: Results From a 3-Year, Randomized, Placebo-, and Active-Controlled Clinical Trial*
A1  - Silverman, Stuart L
A1  - Christiansen, Claus
A1  - Genant, Harry K
A1  - Vukicevic, Slobodan
A1  - Zanchetta, José R
A1  - de Villiers, Tobie J
A1  - Constantine, Ginger D
A1  - Chines, Arkadi A
Y1  - 2008///
JF  - Journal of Bone and Mineral Research
VL  - 23
IS  - 12
SP  - 1923
EP  - 1934
SN  - 0884-0431
DO  - 10.1359/jbmr.080710
UR  - http://doi.wiley.com/10.1359/jbmr.080710
N2  - In this 3-yr, randomized, double-blind, placebo- and active-controlled study, healthy postmenopausal women with osteoporosis (55-85 yr of age) were treated with bazedoxifene 20 or 40 mg/d, raloxifene 60 mg/d, or placebo. The primary endpoint was incidence of new vertebral fractures after 36 mo; secondary endpoints included nonvertebral fractures, BMD, and bone turnover markers. Among 6847 subjects in the intent-to-treat population, the incidence of new vertebral fractures was significantly lower (p < 0.05) with bazedoxifene 20 mg (2.3%), bazedoxifene 40 mg (2.5%), and raloxifene 60 mg (2.3%) compared with placebo (4.1%), with relative risk reductions of 42%, 37%, and 42%, respectively. The treatment effect was similar among subjects with or without prevalent vertebral fracture (p = 0.89 for treatment by baseline fracture status interaction). The incidence of nonvertebral fractures with bazedoxifene or raloxifene was not significantly different from placebo. In a posthoc analysis of a subgroup of women at higher fracture risk (femoral neck T-score <or= -3.0 and/or >or=1 moderate or severe vertebral fracture or multiple mild vertebral fractures; n = 1772), bazedoxifene 20 mg showed a 50% and 44% reduction in nonvertebral fracture risk relative to placebo (p = 0.02) and raloxifene 60 mg (p = 0.05), respectively. Bazedoxifene significantly improved BMD and reduced bone marker levels (p < 0.001 versus placebo). The incidence of vasodilatation, leg cramps, and venous thromboembolic events was higher with bazedoxifene and raloxifene compared with placebo. In conclusion, bazedoxifene significantly reduced the risk of new vertebral fracture in postmenopausal women with osteoporosis and decreased the risk of nonvertebral fracture in subjects at higher fracture risk.
ER  - 
TY  - JOUR
T1  - Effects of Bazedoxifene on BMD and Bone Turnover in Postmenopausal Women: 2-Yr Results of a Randomized, Double-Blind, Placebo-, and Active-Controlled Study
A1  - Miller, Paul D
A1  - Chines, Arkadi A
A1  - Christiansen, Claus
A1  - Hoeck, Hans C
A1  - Kendler, David L
A1  - Lewiecki, E Michael
A1  - Woodson, Grattan
A1  - Levine, Amy B
A1  - Constantine, Ginger
A1  - Delmas, Pierre D
Y1  - 2007///
JF  - Journal of Bone and Mineral Research
VL  - 23
IS  - 4
SP  - 525
EP  - 535
SN  - 1523-4681 (Electronic)\r0884-0431 (Linking)
DO  - 10.1359/jbmr.071206
UR  - http://doi.wiley.com/10.1359/jbmr.071206
N2  - UNLABELLED: Osteoporosis is an increasingly common health concern in postmenopausal women. In a 2-yr phase III study, bazedoxifene prevented bone loss, reduced bone turnover, and was well tolerated in early postmenopausal women with normal or low BMD.\n\nINTRODUCTION: Bazedoxifene is a novel selective estrogen receptor modulator that has increased BMD and bone strength in experimental models, without stimulating breast or uterus. This 24-mo, randomized, double-blind study assessed the efficacy and safety of three doses of bazedoxifene compared with placebo and raloxifene in the prevention of postmenopausal osteoporosis.\n\nMATERIALS AND METHODS: Healthy postmenopausal women with a BMD T-score at the lumbar spine or femoral neck between -1.0 and -2.5 or clinical risk factors for osteoporosis were randomly assigned to one of five groups: bazedoxifene 10, 20, or 40 mg/d, placebo, or raloxifene 60 mg/d. All women received elemental calcium. Efficacy outcomes included changes from baseline through 24 mo in BMD of the lumbar spine, hip, femoral neck, and femoral trochanter and biomarkers of bone metabolism.\n\nRESULTS: The intent-to-treat population included 1434 women (mean age, 58 yr; mean time from last menstrual period, 11 yr). All doses of bazedoxifene and raloxifene prevented bone loss, whereas in the placebo group, there was significant loss of BMD at all skeletal sites. Mean differences in percent change in lumbar spine BMD from baseline to 24 mo relative to placebo were 1.08 +/- 0.28%, 1.41 +/- 0.28%, 1.49 +/- 0.28%, and 1.49 +/- 0.28% for 10, 20, and 40 mg bazedoxifene and 60 mg raloxifene, respectively (p < 0.001 for all comparisons). Comparable BMD responses were observed at other body sites. Significant and comparable decreases in serum osteocalcin and C-telopeptide levels from baseline and relative to placebo with active treatment were observed as early as 3 mo and were sustained through study conclusion (p < 0.001). Overall incidences of adverse events, serious adverse events, and discontinuations caused by adverse events were similar between groups. The most common adverse events included headache, infection, arthralgia, pain, hot flush, and back pain.\n\nCONCLUSIONS: Treatment with bazedoxifene prevented bone loss and reduced bone turnover equally as well as raloxifene and was generally well tolerated in postmenopausal women with normal/low BMD.
ER  - 
TY  - JOUR
T1  - Safety of bazedoxifene in a randomized, double-blind, placebo- and active-controlled phase 3 study of postmenopausal women with osteoporosis
A1  - Christiansen, Claus
A1  - Chesnut, Charles H
A1  - Adachi, Jonathan D
A1  - Brown, Jacques P
A1  - Fernandes, César E
A1  - Kung, Annie WC
A1  - Palacios, Santiago
A1  - Levine, Amy B
A1  - Chines, Arkadi A
A1  - Constantine, Ginger D
Y1  - 2010///
JF  - BMC Musculoskeletal Disorders
VL  - 11
IS  - 1
SP  - 130
EP  - 130
SN  - 1471247411130
DO  - 10.1186/1471-2474-11-130
UR  - http://bmcmusculoskeletdisord.biomedcentral.com/articles/10.1186/1471-2474-11-130
N2  - BACKGROUND: We report the safety findings from a 3-year phase 3 study (NCT00205777) of bazedoxifene, a novel selective estrogen receptor modulator under development for the prevention and treatment of postmenopausal osteoporosis. METHODS: Healthy postmenopausal osteoporotic women (N = 7,492; mean age, 66.4 years) were randomized to daily doses of bazedoxifene 20 or 40 mg, raloxifene 60 mg, or placebo for 3 years. Safety and tolerability were assessed by adverse event (AE) reporting and routine physical, gynecologic, and breast examination. RESULTS: Overall, the incidence of AEs, serious AEs, and discontinuations due to AEs in the bazedoxifene groups was not different from that seen in the placebo group. The incidence of hot flushes and leg cramps was higher with bazedoxifene or raloxifene compared with placebo. The rates of cardiac disorders and cerebrovascular events were low and evenly distributed among groups. Venous thromboembolic events, primarily deep vein thromboses, were more frequently reported in the active treatment groups compared with the placebo group; rates were similar with bazedoxifene and raloxifene. Bazedoxifene showed a neutral effect on the breast and an excellent endometrial safety profile. The incidence of fibrocystic breast disease was lower with bazedoxifene 20 and 40 mg versus raloxifene or placebo. Reductions in total and low-density lipoprotein levels and increases in high-density lipoprotein levels were seen with bazedoxifene versus placebo; similar results were seen with raloxifene. Triglyceride levels were similar among groups. CONCLUSION: Bazedoxifene showed a favorable safety and tolerability profile in women with postmenopausal osteoporosis. TRIAL REGISTRATION: TRIAL REGISTRATION NUMBER: NCT00205777; Trial registration date: September 16, 2005.
ER  - 
TY  - JOUR
T1  - Safety and tolerability of bazedoxifene in postmenopausal women with osteoporosis: Results of a 5-year, randomized, placebo-controlled phase 3 trial
A1  - De Villiers, T. J.
A1  - Chines, A. A.
A1  - Palacios, S.
A1  - Lips, P.
A1  - Sawicki, A. Z.
A1  - Levine, A. B.
A1  - Codreanu, C.
A1  - Kelepouris, N.
A1  - Brown, J. P.
Y1  - 2011///
KW  - Bazedoxifene
KW  - Osteoporosis
KW  - Postmenopausal
KW  - SERMs
KW  - Safety
KW  - Tolerability
JF  - Osteoporosis International
VL  - 22
IS  - 2
SP  - 567
EP  - 576
SN  - 0937-941X 1433-2965
DO  - 10.1007/s00198-010-1302-6
N2  - Summary: Findings from this 5-year phase 3 study of postmenopausal women with osteoporosis showed that bazedoxifene was associated with an overall favorable safety and tolerability profile, with no evidence of endometrial or breast stimulation. Overall, the results at 5 years were consistent with those seen at 3 years. Introduction: We report safety and tolerability findings from a 5-year randomized, double-blind, phase 3 study of bazedoxifene in postmenopausal women with osteoporosis. Methods: In the core study, healthy postmenopausal women with osteoporosis (N=7,492; mean age, 66.4 years) were randomized to daily doses of bazedoxifene 20 or 40 mg, raloxifene 60 mg, or placebo for 3 years. During the 2-year study extension, the raloxifene 60-mg treatment arm was discontinued after the 3-year database was finalized, and subjects receiving bazedoxifene 40 mg were transitioned in a blinded manner to bazedoxifene 20 mg (bazedoxifene 40-/20-mg group) after 4 years. Safety and tolerability data are reported for subjects in the bazedoxifene 20- and 40-/20-mg and placebo groups; efficacy findings are reported elsewhere. Results: A total of 3,146 subjects in the bazedoxifene 20- and 40-mg and placebo groups were enrolled in the extension study (years 4 and 5). Overall, the 5-year incidence of adverse events (AEs), serious AEs, and discontinuations due to AEs were similar among groups. The incidence of hot flushes and leg cramps was higher with bazedoxifene compared with placebo. Venous thromboembolic events, primarily deep vein thrombosis, were more frequently reported in the bazedoxifene groups compared with the placebo group. Reports of cardiac disorders and cerebrovascular events were few and evenly distributed among groups. Bazedoxifene showed a neutral effect on the breast and endometrium. Conclusion: Bazedoxifene was associated with an overall favorable safety and tolerability profile in postmenopausal women with osteoporosis over 5 years of therapy, consistent with findings at 3 years. (copyright) 2010 International Osteoporosis Foundation and National Osteoporosis Foundation.
ER  - 
TY  - JOUR
T1  - Ten Years' Experience with Alendronate for Osteoporosis in Postmenopausal Women
A1  - Bone, Henry G.
A1  - Hosking, David
A1  - Devogelaer, Jean-Pierre
A1  - Tucci, Joseph R.
A1  - Emkey, Ronald D.
A1  - Tonino, Richard P.
A1  - Rodriguez-Portales, Jose Adolfo
A1  - Downs, Robert W.
A1  - Gupta, Jayanti
A1  - Santora, Arthur C.
A1  - Liberman, Uri A.
Y1  - 2004///
JF  - New England Journal of Medicine
VL  - 350
IS  - 12
SP  - 1189
EP  - 1199
DO  - 10.1056/NEJMoa030897
UR  - http://www.nejm.org/doi/abs/10.1056/NEJMoa030897
N2  - BACKGROUND: Antiresorptive agents are widely used to treat osteoporosis. We report the results of a multinational randomized, double-blind study, in which postmenopausal women with osteoporosis were treated with alendronate for up to 10 years.\n\nMETHODS: The initial three-year phase of the study compared three daily doses of alendronate with placebo. Women in the original placebo group received alendronate in years 4 and 5 and then were discharged. Women in the original active-treatment groups continued to receive alendronate during the initial extension (years 4 and 5). In two further extensions (years 6 and 7, and 8 through 10), women who had received 5 mg or 10 mg of alendronate daily continued on the same treatment. Women in the discontinuation group received 20 mg of alendronate daily for two years and 5 mg daily in years 3, 4, and 5, followed by five years of placebo. Randomized group assignments and blinding were maintained throughout the 10 years. We report results for the 247 women who participated in all four phases of the study.\n\nRESULTS: Treatment with 10 mg of alendronate daily for 10 years produced mean increases in bone mineral density of 13.7 percent at the lumbar spine (95 percent confidence interval, 12.0 to 15.5 percent), 10.3 percent at the trochanter (95 percent confidence interval, 8.1 to 12.4 percent), 5.4 percent at the femoral neck (95 percent confidence interval, 3.5 to 7.4 percent), and 6.7 percent at the total proximal femur (95 percent confidence interval, 4.4 to 9.1 percent) as compared with base-line values; smaller gains occurred in the group given 5 mg daily. The discontinuation of alendronate resulted in a gradual loss of effect, as measured by bone density and biochemical markers of bone remodeling. Safety data, including fractures and stature, did not suggest that prolonged treatment resulted in any loss of benefit.\n\nCONCLUSIONS: The therapeutic effects of alendronate were sustained, and the drug was well tolerated over a 10-year period. The discontinuation of alendronate resulted in the gradual loss of its effects.
ER  - 
TY  - JOUR
T1  - Drug rash with eosinophilia and systemic symptoms (DRESS) in patients receiving strontium ranelate
A1  - Cacoub, P.
A1  - Descamps, V.
A1  - Meyer, O.
A1  - Speirs, C.
A1  - Belissa-Mathiot, P.
A1  - Musette, P.
Y1  - 2013///
KW  - DRESS
KW  - Drug hypersensitivity
KW  - Drug rash
KW  - Eosinophilia
KW  - Strontium ranelate
JF  - Osteoporosis International
VL  - 24
IS  - 5
SP  - 1751
EP  - 1757
SN  - 0937-941X
DO  - 10.1007/s00198-013-2265-1
N2  - We have reviewed 47 drug rash with eosinophilia and systemic symptoms (DRESS) cases associated to stron-tium ranelate reported up to March 2011 to the Marketing Holder. The main signs were skin rash, fever, face oedema hypereosinophilia and liver involvement. For ten patients, persistence of DRESS symptoms was reported at the latest news obtained, and DRESS was identified as the direct cause of death in one case. The maximum incidence of DRESS associated with strontium ranelate was 1/24,112 [95 % CI (1/14,859; 1/42,194)] newly treated patients in France. Because DRESS is a severe drug reaction, the occurrence of a rash in a patient treated with strontium ranelate should lead to prompt and permanent treatment discontinuation. Introduction This study aims to describe cases of DRESS reported to the Marketing Authorisation Holder worldwide for patients receiving strontium ranelate by practitioner or by regulatory authorities. Methods Spontaneously reported hypersensitivity events from the strontium ranelate pharmacovigilance database since marketing authorisation (2004) to March 2011 were reviewed by an expert committee. Cases of DRESS were classified as established, probable, possible or no DRESS according to expert judgement. National incidences of DRESS were estimated in relation to the number of newly treated patients. Results Up to March 2011, 325 cases of strontium ranelate-induced hypersensitivity events were assessed from which 47 DRESS cases were confirmed. Mean age was 68.7 years and besides skin rash, the main signs and symptoms were hypereosinophilia, liver involvement, fever and face oede-ma. Median time to skin reaction was 33.5 days after treat-ment start. Most patients (62 %) recovered at the time of reporting or were recovering. For ten patients, persistence of DRESS symptoms was reported at the latest news obtained. Relapses were observed in a single case. The mortality rate was 8.5 %. The maximum incidence of DRESS associated with strontium ranelate was 1/24,112 [95 % CI (1/14,859; 1/42,194)] newly treated patients in France. Conclusion DRESS is a well-identified and characterised adverse reaction to strontium ranelate. This risk should be integrated in the risk-benefit balance evaluation of patient treatment, and the occurrence of a rash should lead to prompt and permanent treatment discontinuation with care-ful follow-up.
ER  - 
TY  - JOUR
T1  - Managing Osteoporosis in Patients on Long-Term Bisphosphonate Treatment: Report of a Task Force of the American Society for Bone and Mineral Research
A1  - Adler, Robert A.
A1  - El-Hajj Fuleihan, Ghada
A1  - Bauer, Douglas C.
A1  - Camacho, Pauline M.
A1  - Clarke, Bart L.
A1  - Clines, Gregory A.
A1  - Compston, Juliet E.
A1  - Drake, Matthew T.
A1  - Edwards, Beatrice J.
A1  - Favus, Murray J.
A1  - Greenspan, Susan L.
A1  - McKinney, Ross
A1  - Pignolo, Robert J.
A1  - Sellmeyer, Deborah E.
Y1  - 2016///
KW  - BISPHOSPHONATES
KW  - DRUG HOLIDAY
KW  - LONG TERM-BISPHOSPHONATE USE
KW  - OTHER OSTEOPOROSIS THERAPIES
KW  - RISK BENEFIT
JF  - Journal of Bone and Mineral Research
VL  - 31
IS  - 1
SP  - 16
EP  - 35
SN  - 1523-4681\r0884-0431
DO  - 10.1002/jbmr.2708
N2  - Best review ever on long term benefit and safety of BP use
ER  - 
TY  - JOUR
T1  - Stevens-Johnson Syndrome Due to Strontium Ranelate
A1  - Tan K-W, Wang Y-S, Tay, Y-K
Y1  - 2011///
JF  - Ann Acad Med Singapore
IS  - 40
SP  - 10
EP  - 11
ER  - 
TY  - CONF
T1  - Ten Years of Denosumab Treatment in Postmenopausal Women With Osteoporosis: Results From the FREEDOM Extension Trial
A1  - Bone, HG
ED  - Compston, JE
Y1  - 2015///
KW  - icle
PB  - ASBMR
JF  - Asbmr 2015
VL  - 1
SP  - 1689
EP  - 1699
CY  - Seattle
SN  - 9788578110796
DO  - 10.1017/CBO9781107415324.004
N2  - Predicting the binding mode of flexible polypeptides to proteins is an important task that falls outside the domain of applicability of most small molecule and protein−protein docking tools. Here, we test the small molecule flexible ligand docking program Glide on a set of 19 non-α-helical peptides and systematically improve pose prediction accuracy by enhancing Glide sampling for flexible polypeptides. In addition, scoring of the poses was improved by post-processing with physics-based implicit solvent MM- GBSA calculations. Using the best RMSD among the top 10 scoring poses as a metric, the success rate (RMSD ≤ 2.0 Å for the interface backbone atoms) increased from 21% with default Glide SP settings to 58% with the enhanced peptide sampling and scoring protocol in the case of redocking to the native protein structure. This approaches the accuracy of the recently developed Rosetta FlexPepDock method (63% success for these 19 peptides) while being over 100 times faster. Cross-docking was performed for a subset of cases where an unbound receptor structure was available, and in that case, 40% of peptides were docked successfully. We analyze the results and find that the optimized polypeptide protocol is most accurate for extended peptides of limited size and number of formal charges, defining a domain of applicability for this approach.
ER  - 
TY  - JOUR
T1  - Discontinuation of denosumab and associated fracture incidence: Analysis from the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) Trial
A1  - Brown, Jacques P.
A1  - Roux, Christian
A1  - Törring, Ove
A1  - Ho, Pei Ran
A1  - Beck Jensen, Jens Erik
A1  - Gilchrist, Nigel
A1  - Recknor, Christopher
A1  - Austin, Matt
A1  - Wang, Andrea
A1  - Grauer, Andreas
A1  - Wagman, Rachel B.
Y1  - 2013///
KW  - Denosumab
KW  - discontinuation
KW  - fracture
KW  - off-treatment
KW  - postmenopausal osteoporosis
JF  - Journal of Bone and Mineral Research
VL  - 28
IS  - 4
SP  - 746
EP  - 752
SN  - 0884-0431
DO  - 10.1002/jbmr.1808
N2  - Osteoporosis is a chronic disease and requires long-term treatment with pharmacologic therapy to ensure sustained antifracture benefit. Denosumab reduced the risk for new vertebral, nonvertebral, and hip fractures over 36 months in the Fracture Reduction Evaluation of Denosumab in Osteoporosis Every 6 Months (FREEDOM) trial. Whereas discontinuation of denosumab has been associated with transient increases in bone remodeling and declines in bone mineral density (BMD), the effect on fracture risk during treatment cessation is not as well characterized. To understand the fracture incidence between treatment groups after cessation of investigational product, we evaluated subjects in FREEDOM who discontinued treatment after receiving two to five doses of denosumab or placebo, and continued study participation for ≥7 months. The off-treatment observation period for each individual subject began 7 months after the last dose and lasted until the end of the study. This subgroup of 797 subjects (470 placebo, 327 denosumab), who were evaluable during the off-treatment period, showed similar baseline characteristics for age, prevalent fracture, and lumbar spine and total hip BMD T-scores. During treatment, more placebo-treated subjects as compared with denosumab-treated subjects sustained a fracture and had significant decreases in BMD. During the off-treatment period (median 0.8 years per subject), 42% versus 28% of placebo- and denosumab-treated subjects, respectively, initiated other therapy. Following discontinuation, similar percentages of subjects in both groups sustained a new fracture (9% placebo, 7% denosumab), resulting in a fracture rate per 100 subject-years of 13.5 for placebo and 9.7 for denosumab (hazard ratio [HR] 0.82; 95% confidence interval [CI], 0.49-1.38), adjusted for age and total hip BMD T-score at baseline. There was no apparent difference in fracture occurrence pattern between the groups during the off-treatment period. In summary, there does not appear to be an excess in fracture risk after treatment cessation with denosumab compared with placebo during the off-treatment period for up to 24 months.
ER  - 
TY  - JOUR
T1  - Rebound-associated vertebral fractures after discontinuation of denosumab—from clinic and biomechanics
A1  - Popp, A. W.
A1  - Zysset, P. K.
A1  - Lippuner, K.
Y1  - 2016///
KW  - Bone antiresorptives
KW  - Bone turnover
KW  - Denosumab
KW  - Microdamage repair
KW  - Rebound-associated vertebral fractures
JF  - Osteoporosis International
VL  - 27
IS  - 5
SP  - 1917
EP  - 1921
DO  - 10.1007/s00198-015-3458-6
N2  - Rebound-associated vertebral fractures may follow treatment discontinuation of highly potent reversible bone antiresorptives, resulting from the synergy of rapid bone resorption and accelerated microdamage accumulation in trabecular bone.\n\nINTRODUCTION: The purposes of this study are to characterize rebound-associated vertebral fractures following the discontinuation of a highly potent reversible antiresorptive therapy based on clinical observation and propose a pathophysiological rationale.\n\nMETHODS: This study is a case report of multiple vertebral fractures early after discontinuation of denosumab therapy in a patient with hormone receptor-positive non-metastatic breast cancer treated with an aromatase inhibitor.\n\nRESULTS: Discontinuation of highly potent reversible bone antiresorptives such as denosumab may expose patients to an increased fracture risk due to the joined effects of absent microdamage repair during therapy followed by synchronous excess activation of multiple bone remodelling units at the time of loss-of-effect. We suggest the term rebound-associated vertebral fractures (RVF) for this phenomenon characterized by the presence of multiple new clinical vertebral fractures, associated with either no or low trauma, in a context consistent with the presence of high bone turnover and rapid loss of lumbar spine bone mineral density (BMD) occurring within 3 to 12 months after discontinuation (loss-of-effect) of a reversible antiresorptive therapy in the absence of secondary causes of bone loss or fractures. Unlike atypical femoral fractures that emerge from failure of microdamage repair in cortical bone with long-term antiresorptive treatment, RVF originate from the synergy of rapid bone resorption and accelerated microdamage accumulation in trabecular bone triggered by the discontinuation of highly potent reversible antiresorptives.\n\nCONCLUSIONS: Studies are urgently needed to i) prove the underlying pathophysiological processes suggested above, ii) establish the predictive criteria exposing patients to an increased risk of RVF, and iii) determine appropriate treatment regimens to be applied in such patients.
ER  - 
TY  - JOUR
T1  - Teriparatide in postmenopausal women with osteoporosis and mild or moderate renal impairment
A1  - Miller, P. D.
A1  - Schwartz, E. N.
A1  - Chen, P.
A1  - Misurski, D. A.
A1  - Krege, J. H.
Y1  - 2007///
KW  - Adverse events
KW  - Bone mineral density
KW  - Fragility fracture
KW  - Osteoporosis
KW  - Renal impairment
KW  - Teriparatide
JF  - Osteoporosis International
VL  - 18
IS  - 1
SP  - 59
EP  - 68
SN  - 0019800601898
DO  - 10.1007/s00198-006-0189-8
N2  - INTRODUCTION: The prevalence of both osteoporosis and renal impairment increases with age.METHODS: Using data from the Fracture Prevention Trial, the safety and efficacy of teriparatide [rhPTH(1-34)] in postmenopausal women with osteoporosis and renal impairment were explored. Patients were required to have serum creatinine concentrations < or =2.0 mg/dl and normal serum parathyroid hormone (PTH) concentrations and were randomized to receive daily subcutaneous injections of placebo or teriparatide 20 or 40 mcg/day. Glomerular filtration rate (GFR) was estimated using the Cockcroft-Gault equation. Patients were defined from baseline assessments to have normal (GFR > or =80 ml/min), mildly impaired (GFR 50-79 ml/min), or moderately impaired (GFR 30-49 ml/min) renal function for bone mineral density (BMD) and amino-terminal extension peptide of procollagen type 1 (PINP) analyses, and normal (GFR > or =80 ml/min) or impaired (GFR <80 ml/min) renal function for fracture analyses.RESULTS AND CONCLUSIONS: Compared with patients with normal renal function, patients with renal impairment were older, shorter, weighed less, had been postmenopausal longer, and had lower baseline lumbar spine and femoral neck BMD. Compared with placebo, teriparatide significantly increased PINP and lumbar spine and femoral neck BMD within each renal function subgroup, and there was no evidence that these increases were altered by renal insufficiency (each treatment-by-subgroup interaction p>0.05). Similarly, teriparatide-mediated vertebral and nonvertebral fracture risk reductions were similar and did not differ significantly between patients with normal or impaired renal function (treatment-by-subgroup interactions p>0.05). The incidences of treatment-emergent and renal-related adverse events were consistent across treatment assignment in the normal, mildly impaired, and moderately impaired renal function subgroups. Teriparatide induced changes in mean GFR were unaffected by baseline renal function (treatment-by-renal function interaction p>0.05 for normal, mildly impaired, or moderately impaired subgroups). Patients in all renal function categories treated with teriparatide 20 or 40 mcg had an increased incidence of 4-6-h postdose serum calcium >10.6 mg/dl (the upper limit of normal) versus placebo; however, teriparatide 20 mcg/day was not associated with significantly increased incidence of 4-6-h postdose serum calcium >11 mg/dl in any renal function category. Teriparatide therapy was associated with increased incidence of elevated uric acid, with the incidences being highest in patients with moderately impaired renal function and in those receiving teriparatide 40 mcg/day. Even so, adverse event data did not suggest an increased incidence of gout or arthralgia or of nephrolithiasis events in teriparatide-treated patients with normal, mild, or moderate renal impairment.
ER  - 
TY  - JOUR
T1  - Hypercalcemia after discontinuation of long-term denosumab treatment
A1  - Koldkjær Sølling, A. S.
A1  - Harsløf, T.
A1  - Kaal, A.
A1  - Rejnmark, L.
A1  - Langdahl, B.
Y1  - 2016///
KW  - Bone turnover markers
KW  - Case report
KW  - Denosumab
KW  - Hypercalcemia
KW  - Osteoporosis
JF  - Osteoporosis International
VL  - 27
IS  - 7
SP  - 2383
EP  - 2386
DO  - 10.1007/s00198-016-3535-5
N2  - Denosumab is used for treatment of osteoporosis. We present a case report of hypoparathyroid hypercalcemia and increased bone turnover associated with discontinuation of treatment for 10 years with denosumab. There is a need for evidence-based guidelines on discontinuation of long-term denosumab treatment to avoid side effects and preserving anti-fracture efficacy. PURPOSE: Denosumab is commonly used as an anti-resorptive agent for the treatment of osteoporosis. After discontinuation of denosumab, however, bone resorption increases again, and the bone mass gained during therapy is rapidly declining. Thus, treatment with denosumab is considered to be reversible. METHODS: We present a case report of asymptomatic hypoparathyroid hypercalcemia in a patient who discontinued long-term treatment with denosumab. RESULTS: A 67-year-old woman with osteoporosis was treated with denosumab 60 mg subcutaneously every 6 months from 2004 to 2014. She received the last injection in May 2014. Routine biochemistry in November 2014 showed increased s-ionized calcium (I-Ca) 1.64 mmol/L (1.18-1.32 mmol/L) and suppressed p-parathyroid hormone (PTH) 1.6 pmol/L (1.6-6.9 pmol/L). The patient was extensively examined, but no underlying disease was found. In January 2015, the patient began treatment with alendronat 70 mg weekly. In April 2015, serum levels of type 1 collagen C-terminal cross-linked telopeptide, procollagen type 1 N-terminal propeptide and bone-specific alkaline phosphatase were still markedly elevated. From then on, I-Ca and PTH normalized and the bone turnover markers (BTM) decreased. CONCLUSION: In this case report, we describe increased BTMs and hypercalcemia associated with discontinuation of 10 years treatment with denosumab. The increase in BTMs is assumed to be temporary and normalization is expected. Since denosumab is commonly used, there is an urgent need for evidence-based guidelines on discontinuation of long-term treatment, avoiding side effects and preserving anti-fracture efficacy.
ER  - 
TY  - JOUR
T1  - Comparative Effects of Teriparatide and Strontium Ranelate on Bone Biopsies and Biochemical Markers of Bone Turnover in Postmenopausal Women With Osteoporosis*
A1  - Recker, Robert R
A1  - Marin, Fernando
A1  - Ish-Shalom, Sophia
A1  - Möricke, Rüdiger
A1  - Hawkins, Federico
A1  - Kapetanos, Georgios
A1  - de la Peña, María P
A1  - Kekow, Jörn
A1  - Farrerons, Jordi
A1  - Sanz, Beatriz
A1  - Oertel, Heide
A1  - Stepan, Jan
Y1  - 2009///
JF  - Journal of Bone and Mineral Research
VL  - 24
IS  - 8
SP  - 1358
EP  - 1368
SN  - 1523-4681 (Electronic)\r0884-0431 (Linking)
DO  - 10.1359/jbmr.090315
UR  - http://doi.wiley.com/10.1359/jbmr.090315
N2  - We assessed the effects on bone remodeling and histomorphometry after daily subcutaneous injections of teriparatide (n = 39, 20 microg/d) or oral strontium ranelate (SrR, n = 40, 2 g/d) in postmenopausal women with osteoporosis. Evaluable biopsies were obtained from 29 patients in the teriparatide group and 22 in the SrR group after 6 mo of treatment. The mean +/- SD mineralization surfaces as a percent of bone surfaces (MS/BS, %) at the trabecular level were 7.73 +/- 1.48% for teriparatide and 5.25 +/- 1.15% for SrR (p = 0.219) and at the endocortical level were 17.22 +/- 3.06% and 9.70 +/- 2.07%, respectively (p = 0.052). Cortical porosity was 5.40 +/- 0.41% in the teriparatide and 4.14 +/- 0.40% in the SrR group (p = 0.037). Teriparatide induced significant increases from baseline in bone formation and resorption markers, reaching statistical significance for amino-terminal propeptide of type I collagen (PINP) after 1 mo (+57%, p < 0.001). SrR induced small, but statistically significant, reductions from baseline in PINP at 3 (-14%, p = 0.005) and 6 mo (-19%, p < 0.001) and in serum beta-C-terminal telopeptide of type I collagen (beta-CTX) at 1 and 3 mo (-11%, for both, p < 0.05). There were more patients with adverse events after SrR (70%) than teriparatide (41%) treatment (p = 0.013). In conclusion, the changes in biochemical markers of bone formation confirmed bone-forming activity of teriparatide but not of SrR treatment. The effects of SrR on bone remodeling and cell activity were modest, indicating that its effects on fracture reduction may be predominantly mediated through a different mechanism than that observed with anabolic or more potent antiresorptive agents.
ER  - 
TY  - JOUR
T1  - Influence of Strontium on Bone Mineral Density and Bone Mineral Content Measurements by Dual X-Ray Absorptiometry
A1  - Nielsen, Stig Pors
A1  - Slosman, Daniel
A1  - Sbren~en, Ole Helmer
A1  - Basse-Cathalinat, Bernard
A1  - De, Patrice
A1  - O U X, Christian R
A1  - Meunier7, Pierre J
Y1  - 1999///
KW  - absorptiometry Strontium
KW  - adjustment factor
KW  - bone mineral content
KW  - bone mineral density
KW  - dual X-ray
JF  - Journal of Clinical Densirometry
VL  - 2
IS  - 4
SP  - 371
EP  - 379
SN  - 1094-6950 (Print)\r1094-6950 (Linking)
DO  - JCD:2:4:371 [pii]
N2  - The presence of Sr in bone influences bone mineral density (BMD) and bone mineral content (BMC) mea-surements by dual X-ray absorptiometry (DXA). This interaction is of interest, since strontium ranelate (S12911) demonstrated positive effects on bone metabolism in various animal models of osteoporosis, and is currently being evaluated for treatment of postmenopausal osteoporosis. The present in vitro study aimed to determine adjustment factors for DXA measurements of BMC and BMD at different Sr concentrations in order to estimate the corresponding values that would have been measured without Sr. A series of mixtures of Ca and Sr hydroxyapatites were prepared, with biologically relevant Sr/Ca ratios ranging from 0 to 3.5 mol/mol%, and a constant total concentration of divalent cations (145 mmol). The mixtures were conditioned in plastic dishes 4.5 cm in diameter, to obtain an areal density close to the human vertebral mineral density of 0.7-1.1 g/cm2. DXA measurements of the mixtures were made with a wide range of different instruments and various acqui-sition modes. A direct linear relationship (r2 > 0.99) was found between Sr content and overestimation of BMD and BMC. There were no significant differences in adjustment factors for BMC or BMD between the different machines or acquisition modes, and the presence of Sr in the water bath used to mimic soft tissues did not affect the accuracy and precision of the method. This demonstrates that reliable DXA determinations of BMD may be carried out in the presence of Sr, and may be interpreted in terms of calcium hydroxyapatite equivalent if the bone Sr content of the measured bone is known. The same adjustment factor (10% overestimation for 1 mol/mol% Sr) can be used for all presently available types of instrument and acquisition modes.
ER  - 
TY  - JOUR
T1  - Could Strontium Ranelate Have a Synergistic Role in the Treatment of Osteoporosis?
A1  - Blake, Glen M
A1  - Compston, Juliet E
A1  - Fogelman, Ignac
Y1  - 2009///
JF  - Journal of Bone and Mineral Research
VL  - 24
IS  - 8
SP  - 1354
EP  - 1357
DO  - 10.1359/jbmr.090601
UR  - http://doi.wiley.com/10.1359/jbmr.090601
ER  - 
TY  - UNPB
T1  - EMEA recommends changes in the product information for Protelos/Osseor due to the risk of severe hypersensitivity reactions
A1  - Agency, European Medicines
Y1  - 2007///
UR  - http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2009/11/WC500015592.pdf
ER  - 
TY  - JOUR
T1  - Prevention of venous thromboembolism in surgical patients
A1  - Agnelli, Giancarlo
Y1  - 2004///
KW  - Deep vein thrombosis
KW  - Heparin
KW  - Low-molecular-weight heparin
KW  - Pulmonary embolism
KW  - Venous thromboembolism
KW  - Vitamin K antagonists
JF  - Circulation
VL  - 110
IS  - 24 SUPPL.
SN  - 0009-7322
DO  - 10.1161/01.CIR.0000150639.98514.6c
N2  - Venous thromboembolism (VTE) is a common complication of surgical procedures. The risk for VTE in surgical patients is determined by the combination of individual predisposing factors and the specific type of surgery. Prophylaxis with mechanical and pharmacological methods has been shown to be effective and safe in most types of surgery and should be routinely implemented. For patients undergoing general, gynecologic, vascular, and major urologic surgery, low-dose unfractionated heparin or low-molecular-weight heparin (LMWH) are the options of choice. For low-risk urologic surgery, early postoperative mobilization of patients is the only intervention warranted. For higher-risk patients, including those undergoing elective hip or knee replacement and surgery for hip fracture, vitamin K antagonists, LMWH, or fondaparinux are recommended. For patients undergoing neurosurgery, graduated elastic stockings are effective and safe and may be combined with LMWH to further reduce the risk of VTE. The role of prophylaxis is less defined in patients undergoing elective spine surgery, as well as laparoscopic and arthroscopic surgery. A number of issues related to prophylaxis of VTE after surgery deserve further clarification, including the role of screening for asymptomatic deep vein thrombosis, the best timing for initiation of pharmacological prophylaxis, and the optimal duration of prophylaxis in high-risk patients.
ER  - 
TY  - JOUR
T1  - Strontium ranelate-induced toxic epidermal necrolysis in a patient with post-menopausal osteoporosis
A1  - Lee, H. Y.
A1  - Lie, D.
A1  - Lim, K. S.
A1  - Thirumoorthy, T.
A1  - Pang, S. M.
Y1  - 2009///
JF  - Osteoporosis International
VL  - 20
IS  - 1
SP  - 161
EP  - 162
DO  - 10.1007/s00198-008-0677-0
ER  - 
TY  - UNPB
T1  - Recommendation to restrict the use of Protelos / Osseor ( strontium ranelate ) CHMP confirms recommendation from the PRAC
A1  - Agency, European Medicines
Y1  - 2013///
KW  - Recommendation to restrict the use of Protelos/Oss
VL  - 44
IS  - April
SP  - 1
EP  - 3
UR  - http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2013/04/WC500142507.pdf
ER  - 
TY  - UNPB
T1  - Protelos / Osseor to remain available but with further restrictions
A1  - European Medicines Agency
Y1  - 2014///
VL  - 44
IS  - EMA/235924/2014
SP  - 1
EP  - 3
UR  - http://www.ema.europa.eu/docs/en_GB/document_library/Referrals_document/Protelos_and_Osseor/Opinion_provided_by_Committee_for_Medicinal_Products_for_Human_Use/WC500161968.pdf
ER  - 
TY  - JOUR
T1  - Fracture healing: a consensus report from the International Osteoporosis Foundation Fracture Working Group
A1  - Silverman, S. L.
A1  - Kupperman, E. S.
A1  - Bukata, S. V.
Y1  - 2016///
KW  - Fracture healing
KW  - Osteoporotic fracture
KW  - Trial design
JF  - Osteoporosis International
VL  - 27
IS  - 7
SP  - 2197
EP  - 2206
SN  - 1433-2965 (Electronic)\r0937-941X (Linking)
DO  - 10.1007/s00198-016-3513-y
N2  - We used the RAND UCLA appropriateness method to decide appropriateness of use of  osteoporosis medication after incident fracture and potential for fracture healing and make suggestions for trial design for clinical and preclinical research. PURPOSE: To develop appropriateness criteria to assist in the use and study of osteoporosis medications in patients with recent fracture and in the potential use of osteoporosis medications to enhance delayed fracture healing. To promote further research by suggesting preclinical and clinical trial design for studies where fracture healing is the endpoint. METHODS: DESIGN: RAND/UCLA appropriateness method (RUAM). PARTICIPANTS: A panel of experts, both members and non-members of the International Osteoporosis Foundation Fracture Working Group, were identified consisting of geriatricians, rheumatologists, orthopedists, endocrinologists, and internists. This resulted in a round 1 panel of 15 panelists, round 2 panel of 15 members, and a round 3 panel of 14 members. MAIN OUTCOME MEASURE: Agreement on statements and scenarios using RUAM. Three rounds of voting by panelists took place. Agreement in a third round was reached for 111 statements and scenarios, measured by median panel ratings and the amount of dispersion of panel ratings, based on the interpercentile range. RESULTS: An expert panel validated a set of statements and scenarios about the use of osteoporosis medications after incident fracture and use of these medications to enhance delayed fracture healing and made recommendations for study designs to investigate the effect of osteoporosis medications on fracture healing. CONCLUSIONS: The result of this exercise is intended to assist in improving patient care by identifying the appropriateness of use of osteoporosis medications after fracture and in fracture healing and to make suggestions for further preclinical and clinical research.
ER  - 
TY  - JOUR
T1  - Patient-Reported Outcome After Displaced Femoral Neck Fracture
A1  - Leonardsson, Olof
A1  - Rolfson, Ola
A1  - Hommel, Ami
A1  - Garellick, Göran
A1  - Åkesson, Kristina
A1  - Rogmark, Cecilia
Y1  - 2013///
JF  - The Journal of Bone and Joint Surgery-American Volume
VL  - 95
IS  - 18
SP  - 1693
EP  - 1699
SN  - 1535-1386 (Electronic)
DO  - 10.2106/JBJS.L.00836
UR  - http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00004623-201309180-00011
ER  - 
TY  - JOUR
T1  - Strategies to prevent falls and fractures in hospitals and care homes and effect of cognitive impairment: systematic review and meta-analyses
A1  - Oliver, D.
A1  - Connelly, J. B
A1  - Victor, C. R
A1  - Shaw, F. E
A1  - Whitehead, A.
A1  - Genc, Y.
A1  - Vanoli, A.
A1  - Martin, F. C
A1  - Gosney, M. A
Y1  - 2007///
JF  - Bmj
VL  - 334
IS  - 7584
SP  - 82
EP  - 82
SN  - 1468-5833 (Electronic)\r0959-535X (Linking)
DO  - 10.1136/bmj.39049.706493.55
UR  - http://www.bmj.com/cgi/doi/10.1136/bmj.39049.706493.55
N2  - Objectives To evaluate the evidence for strategies to prevent falls or fractures in residents in care homes and hospital inpatients and to investigate the effect of dementia and cognitive impairment.  Design Systematic review and meta-analyses of studies grouped by intervention and setting (hospital or care home). Meta-regression to investigate the effects of dementia and of study quality and design.  Data sources Medline, CINAHL, Embase, PsychInfo, Cochrane Database, Clinical Trials Register, and hand searching of references from reviews and guidelines to January 2005.  Results 1207 references were identified, including 115 systematic reviews, expert reviews, or guidelines. Of the 92 full papers inspected, 43 were included. Meta-analysis for multifaceted interventions in hospital (13 studies) showed a rate ratio of 0.82 (95% confidence interval 0.68 to 0.997) for falls but no significant effect on the number of fallers or fractures. For hip protectors in care homes (11 studies) the rate ratio for hip fractures was 0.67 (0.46 to 0.98), but there was no significant effect on falls and not enough studies on fallers. For all other interventions (multifaceted interventions in care homes; removal of physical restraints in either setting; fall alarm devices in either setting; exercise in care homes; calcium/vitamin D in care homes; changes in the physical environment in either setting; medication review in hospital) meta-analysis was either unsuitable because of insufficient studies or showed no significant effect on falls, fallers, or fractures, despite strongly positive results in some individual studies. Meta-regression showed no significant association between effect size and prevalence of dementia or cognitive impairment.  Conclusion There is some evidence that multifaceted interventions in hospital reduce the number of falls and that use of hip protectors in care homes prevents hip fractures. There is insufficient evidence, however, for the effectiveness of other single interventions in hospitals or care homes or multifaceted interventions in care homes.
ER  - 
TY  - JOUR
T1  - Impact of mechanical stretch on the cell behaviors of bone and surrounding tissues
A1  - Yu, H.-S.
A1  - Kim, J.-J.
A1  - Kim, H.-W.
A1  - Lewis, M. P.
A1  - Wall, I.
Y1  - 2016///
JF  - Journal of Tissue Engineering
VL  - 7
IS  - 0
DO  - 10.1177/2041731415618342
UR  - http://tej.sagepub.com/lookup/doi/10.1177/2041731415618342
N2  - Mechanical loading is recognized to play an important role in regulating the behaviors of cells in bone and surrounding tissues in vivo. Many in vitro studies have been conducted to determine the effects of mechanical loading on individual cell types of the tissues. In this review, we focus specifically on the use of the Flexercell system as a tool for studying cellular responses to mechanical stretch. We assess the literature describing the impact of mechanical stretch on different cell types from bone, muscle, tendon, ligament, and cartilage, describing individual cell phenotype responses. In addition, we review evidence regarding the mechanotransduction pathways that are activated to potentiate these phenotype responses in different cell populations.
ER  - 
TY  - JOUR
T1  - Endocrine Disorders in Adolescent and Young Female Athletes: Impact on Growth, Menstrual Cycles, and Bone Mass Acquisition
A1  - Maïmoun, Laurent
A1  - Georgopoulos, Neoklis A.
A1  - Sultan, Charles
Y1  - 2014///
JF  - The Journal of Clinical Endocrinology & Metabolism
VL  - 99
IS  - 11
SP  - 4037
EP  - 4050
DO  - 10.1210/jc.2013-3030
UR  - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2013-3030
N2  - CONTEXT: Puberty is a crucial period of dramatic hormonal changes, accelerated growth, attainment of reproductive capacity, and acquisition of peak bone mass. Participation in recreational physical activity is widely acknowledged to provide significant health benefits in this period. Conversely, intense training imposes several constraints, such as training stress and maintenance of very low body fat to maximize performance. Adolescent female athletes are therefore at risk of overtraining and/or poor dietary intake, which may have several consequences for endocrine function. The "adaptive" changes in the hypothalamic-pituitary-gonadal, -adrenal, and somatotropic axes and the secretory role of the adipose tissue are reviewed, as are their effects on growth, menstrual cycles, and bone mass acquisition. DESIGN: A systematic search on Medline between 1990 and 2013 was conducted using the following terms: "intense training," "physical activity," or "exercise" combined with "hormone," "endocrine," and "girls," "women," or "elite female athletes." All articles reporting on the endocrine changes related to intense training and their potential implications for growth, menstrual cycles, and bone mass acquisition were considered. RESULTS AND CONCLUSION: Young female athletes present a high prevalence of menstrual disorders, including delayed menarche, oligomenorrhea, and amenorrhea, characterized by a high degree of variability according to the type of sport. Exercise-related reproductive dysfunction may have consequences for growth velocity and peak bone mass acquisition. Recent findings highlight the endocrine role of adipose tissue and energy balance in the regulation of homeostasis and reproductive function. A better understanding of the mechanisms whereby intense training affects the endocrine system may orient research to develop innovative strategies (ie, based on nutritional or pharmacological approaches and individualized modalities of training and competition) to improve the medical care of these adolescents and protect their reproductive function.
ER  - 
TY  - JOUR
T1  - Effects of resistance and endurance exercise on bone mineral status of young women: A randomized exercise intervention trial
A1  - Snow???Harter, Christine
A1  - Bouxsein, Mary L.
A1  - Lewis, Barbara T.
A1  - Carter, Dennis R.
A1  - Marcus, Robert
Y1  - 1992///
JF  - Journal of Bone and Mineral Research
VL  - 7
IS  - 7
SP  - 761
EP  - 769
SN  - 1523-4681
DO  - 10.1002/jbmr.5650070706
N2  - A substantial body of cross-sectional data and a smaller number of intervention trials generally justify optimism that regular physical activity benefits the skeleton. We conducted an 8 month controlled exercise trial in a group of healthy college women (mean age = 19.9 years) who were randomly assigned to a control group or to progressive training in jogging or weight lifting. We measured the following variables: bone mineral density (BMD) of the spine (L2–4) and right proximal femur using dual-energy x-ray absorptiometry, dynamic muscle strength using the 1-RM method, and endurance performance using the 1.5 mile walk/run field test. A total of 31 women completed the 8 month study. For women completing the study, compliance, defined as the percentage of workout sessions attended, was 97% for the runners (range 90–1009/0) and 92% (range 88–100%) for the weight trainers. Body weight increased by approximately 2 kg in all groups (p < 0.05). Weight training was associated with significant increases (p < 0.01) in muscle strength in all muscle groups. Improvement ranged from 10% for the deep back to 54% for the leg. No significant changes in strength scores were observed in the control or running groups. Aerobic performance improved only in the running group (16%, p < 0.01). Lumbar BMD increased (p < 0.05) in both runners (1.3 ± 1.6%) and weight trainers (1.2 ± 1.8%). These results did not differ from each other but were both significantly greater than results in control subjects, in whom bone mineral did not change. No measure of bone mineral at the proximal femur changed significantly in any group. These results demonstrate that 8 months of supervised progressive training in either running or resistance exercise modestly increases lumbar spine mineral in young women.
ER  - 
TY  - JOUR
T1  - Effects of high-impact exercise on bone mineral density: A randomized controlled trial in premenopausal women
A1  - Vainionpää, Aki
A1  - Korpelainen, Raija
A1  - Leppäluoto, Juhani
A1  - Jämsä, Timo
Y1  - 2005///
KW  - Clinical trial
KW  - Mechanical loading
KW  - Osteoporosis
KW  - Population based
KW  - Premenopausal women
KW  - Prevention
JF  - Osteoporosis International
VL  - 16
IS  - 2
SP  - 191
EP  - 197
SN  - 3588537600
DO  - 10.1007/s00198-004-1659-5
N2  - INTRODUCTION: The purpose of this randomized controlled study was to assess the effects of high-impact exercise on the bone mineral density (BMD) of premenopausal women at the population level. MATERIALS AND METHODS: The study population consisted of a random population-based sample of 120 women from a cohort of 5,161 women, aged 35 to 40 years. They were randomly assigned to either an exercise or control group. The exercise regimen consisted of supervised, progressive high-impact exercises three times per week and an additional home program for 12 months. BMD was measured on the lumbar spine (L1-L4), proximal femur, and distal forearm, by dual-energy X-ray absorptiometry at baseline and after 12 months. Calcaneal bone was measured using quantitative ultrasound. RESULTS: Thirty-nine women (65%) in the exercise group and 41 women (68%) in the control group completed the study. The exercise group demonstrated significant change compared with the control group in femoral neck BMD (1.1% vs -0.4%; p=0.003), intertrochanteric BMD (0.8% vs -0.2%; p=0.029), and total femoral BMD (0.1% vs -0.3%; p=0.006). No exercise-induced effects were found in the total lumbar BMD or in the lumbar vertebrae L2-L4. Instead, L1 BMD (2.2% vs -0.4%; p=0.002) increased significantly more in the exercise group than in the control group. Calcaneal broadband ultrasound attenuation showed also a significant change in the exercise group compared with the control group (7.3% vs -0.6%; p=0.015). The changes were also significant within the exercise group, but not within the control group. There were no significant differences between or within the groups in the distal forearm. CONCLUSIONS: This study indicates that high-impact exercise is effective in improving bone mineral density in the lumbar spine and upper femur in premenopausal women, and the results of the study may be generalized at the population level. This type of training may be an efficient, safe, and inexpensive way to prevent osteoporosis later in life.
ER  - 
TY  - JOUR
T1  - Treatment failure in osteoporosis
A1  - Diez-Perez, A.
A1  - Adachi, J. D.
A1  - Agnusdei, D.
A1  - Bilezikian, J. P.
A1  - Compston, J. E.
A1  - Cummings, S. R.
A1  - Eastell, R.
A1  - Eriksen, E. F.
A1  - Gonzalez-Macias, J.
A1  - Liberman, U. A.
A1  - Wahl, D. A.
A1  - Seeman, E.
A1  - Kanis, J. A.
A1  - Cooper, C.
Y1  - 2012///
KW  - Bone mineral density
KW  - Fractures
KW  - Markers of bone turnover
KW  - Osteoporosis
KW  - Treatment
JF  - Osteoporosis International
VL  - 23
IS  - 12
SP  - 2769
EP  - 2774
SN  - 1433-2965 (Electronic)\r0937-941X (Linking)
DO  - 10.1007/s00198-012-2093-8
N2  - UNLABELLED: Guidelines concerning the definition of failure of therapies used to reduce the risk of fracture are provided.\n\nINTRODUCTION: This study aims to provide guidelines concerning the definition of failure of therapies used to reduce the risk of fracture.\n\nMETHODS: A working group of the Committee of Scientific Advisors of the International Osteoporosis Foundation was convened to define outcome variables that may assist clinicians in decision making.\n\nRESULTS: In the face of limited evidence, failure of treatment may be inferred when two or more incident fractures have occurred during treatment, when serial measurements of bone remodelling markers are not suppressed by anti-resorptive therapy and where bone mineral density continues to decrease.\n\nCONCLUSION: The provision of pragmatic criteria to define failure to respond to treatment provides an unmet clinical need and may stimulate research into an important issue.
ER  - 
TY  - JOUR
T1  - Overcoming resistance to bisphosphonates through the administration of alfacalcidol: Results of a 1-year, open follow-up study
A1  - Gaál, János
A1  - Bender, Tamás
A1  - Varga, József
A1  - Horváth, Irén
A1  - Kiss, Judit
A1  - Somogyi, Péter
A1  - Surányi, Péter
Y1  - 2009///
KW  - Alfacalcidol
KW  - Osteoporosis
KW  - Resistance to bisphosphonates
JF  - Rheumatology International
VL  - 30
IS  - 1
SP  - 25
EP  - 31
SN  - 1437-160X (Electronic)\r0172-8172 (Linking)
DO  - 10.1007/s00296-009-0892-9
N2  - This study intended to determine whether the replacement of vitamin D3 with alfacalcidol results in any bone mineral density (BMD) increase in 76 patients unresponsive to the combination of alendronate and conventional vitamin D3 treatment. In these patients the conventional vitamin D3 had been replaced with alfacalcidol (0.5 mug/day), and then the patients were followed up for a year. After treatment for 1 year, Wilcoxon test revealed a small but statistically significant (P < 0.001) increase in the BMD values of the forearm and lumbar vertebrae, in the serum calcium and urinary calcium/creatinine ratio in first-voided morning urine. However, the serum alkaline phosphatase activity, phosphorus, parathormone, osteocalcin levels and the urinary d-pyr/creatinine ratio decreased significantly (P < 0.001). As suggested by our results, combination therapy with alendronate and alfacalcidol increases bone density and improves the biochemical markers of bone turnover, without any substantial increase in the incidence of adverse effects.
ER  - 
TY  - JOUR
T1  - Management of proximal femoral fractures 2011: Association of Anaesthetists of Great Britain and Ireland
A1  - Griffiths, R.
A1  - Alper, J.
A1  - Beckingsale, A.
A1  - Goldhill, D.
A1  - Heyburn, G.
A1  - Holloway, J.
A1  - Leaper, E.
A1  - Parker, M.
A1  - Ridgway, S.
A1  - White, S.
A1  - Wiese, M.
A1  - Wilson, I.
Y1  - 2012///
JF  - Anaesthesia
VL  - 67
IS  - 1
SP  - 85
EP  - 98
SN  - 1365-2044 (Electronic)\r0003-2409 (Linking)
DO  - 10.1111/j.1365-2044.2011.06957.x
N2  - There should be protocol-driven, fast-track admission of patients with hip fractures through the emergency department. Patients with hip fractures require multidisciplinary care, led by orthogeriatricians. Surgery is the best analgesic for hip fractures. Surgical repair of hip fractures should occur within 48 hours of hospital admission. Surgery and anaesthesia must be undertaken by appropriately experienced surgeons and anaesthetists. There must be high-quality communication between clinicians and allied health professionals. Early mobilisation is a key part of the management of patients with hip fractures. Pre-operative management should include consideration of planning for discharge from hospital. Measures should be taken to prevent secondary falls. 10. Continuous audit and targeted research is required in order to inform and improve the management of patients with hip fracture.
ER  - 
TY  - BOOK
T1  - Диагностика и лечение переломов проксимального отдела бедра у лиц пожилого и старческого возраста. Методические рекомендации
A1  - Загородний Н.В., Голухов Г.Н., Волна А.А., и др.
Y1  - 2012///
PB  - Издательство РУДН
CY  - Москва
ER  - 
TY  - UNPB
T1  - The Care of Patients with Fragility Fracture
A1  - British Orthopaedic Association
Y1  - 2007///
SP  - 14
EP  - 52
CY  - London
DO  - 10.1136/bmj.2.5211.1518
ER  - 
TY  - JOUR
T1  - Effect of comorbidities and postoperative complications on mortality after hip fracture in elderly people: prospective observational cohort study
A1  - Roche, J J W
Y1  - 2005///
JF  - Bmj
VL  - 331
IS  - 7529
SP  - 1374
EP  - 0
SN  - 1468-5833 (Electronic)\r0959-535X (Linking)
DO  - 10.1136/bmj.38643.663843.55
UR  - http://www.bmj.com/cgi/doi/10.1136/bmj.38643.663843.55
ER  - 
TY  - JOUR
T1  - Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: A randomized blinded phase 2 clinical trial
A1  - Miller, Paul D.
A1  - Bolognese, Michael A.
A1  - Lewiecki, E. Michael
A1  - McClung, Michael R.
A1  - Ding, Beiying
A1  - Austin, Matthew
A1  - Liu, Yu
A1  - San Martin, Javier
Y1  - 2008///
KW  - Bone mineral density
KW  - Denosumab
KW  - Fully human monoclonal antibody
KW  - Osteoporosis
KW  - RANKL
JF  - Bone
VL  - 43
IS  - 2
SP  - 222
EP  - 229
SN  - 8756-3282 (Print)\r1873-2763 (Linking)
DO  - 10.1016/j.bone.2008.04.007
N2  - Introduction: Denosumab is a fully human monoclonal antibody that inhibits receptor activator of nuclear factor-kappa B ligand (RANKL), an essential mediator of osteoclast formation, function, and survival that has been shown to decrease bone turnover and increase bone mineral density (BMD) in treated patients. We assessed the long-term efficacy and safety of denosumab, and the effects of discontinuing and restarting denosumab treatment in postmenopausal women with low bone mass. Methods: Postmenopausal women with a lumbar spine T-score of -1.8 to -4.0 or proximal femur T-score of -1.8 to -3.5 were randomized to denosumab every 3 months (Q3M; 6, 14, or 30 mg) or every 6 months (Q6M; 14, 60, 100, or 210 mg); placebo; or open-label oral alendronate weekly. After 24 months, patients receiving denosumab either continued treatment at 60 mg Q6M for an additional 24 months, discontinued therapy, or discontinued treatment for 12 months then re-initiated denosumab (60 mg Q6M) for 12 months. The placebo cohort was maintained. Alendronate-treated patients discontinued alendronate and were followed. Changes in BMD and bone turnover markers (BTM) as well as safety outcomes were evaluated. Results: Overall, 262/412 (64%) patients completed 48 months of study. Continuous, long-term denosumab treatment increased BMD at the lumbar spine (9.4% to 11.8%) and total hip (4.0% to 6.1%). BTM were consistently suppressed over 48 months. Discontinuation of denosumab was associated with a BMD decrease of 6.6% at the lumbar spine and 5.3% at the total hip within the first 12 months of treatment discontinuation. Retreatment with denosumab increased lumbar spine BMD by 9.0% from original baseline values. Levels of BTM increased upon discontinuation and decreased with retreatment. Adverse event rates were similar among treatment groups. Conclusions: In postmenopausal women with low BMD, long-term denosumab treatment led to gains in BMD and reduction of BTM throughout the course of the study. The effects on bone turnover were fully reversible with discontinuation and restored with subsequent retreatment. ?? 2008 Elsevier Inc. All rights reserved.
ER  - 
TY  - JOUR
T1  - Co-managed care for fragility hip fractures (Rochester model)
A1  - Kates, S. L.
A1  - Mendelson, D. A.
A1  - Friedman, S. M.
Y1  - 2010///
KW  - Cost of care
KW  - Economics of hip fracture care
KW  - Geriatric fracture center
KW  - Hip fractures
KW  - Osteoporosis
KW  - Systems of care
JF  - Osteoporosis International
VL  - 21
IS  - SUPPL. 4
SN  - 1433-2965
DO  - 10.1007/s00198-010-1417-9
N2  - Hip fractures in older adults are a common event with a high risk of morbidity and mortality. Patients who sustain a hip fracture often present with multiple co-morbid conditions that can benefit from co-management by orthopedic surgeons and geriatricians. This manuscript describes a co-managed model of care for patients with hip fractures. This model of care will be explained, and the benefits and results will be described. Retrospective review of the care of all native non-pathological hip fracture patients aged 60 years and older admitted between April 2005 and March 2009 to a 261-bed community teaching hospital. The outcome measures include patient characteristics, length of stay, mortality, 30-day readmission, re-operation, and costs of care. Seven hundred fifty-eight patients were identified with an average age of 84.8 (SD 8.4); 77.8% of the patients were female, 94.7% Caucasian, and 37.3% from nursing homes, and the mean Charlson score is 2.9 (SD 2.1). The length of stay was 4.3 days, 30-day readmission rate was 10.4%, 17-month re-operation rate was 1.9%, and costs of care to the system were $15,188. The 1-year mortality rate was 21.2%. This model of care resulted in improvements in all measures studied. Previous studies have shown reduction in in-hospital complications. Additional studies are needed to show if this model of care can be translated to other systems or to other surgical conditions. Wide application of this model care could substantially improve the quality of care and cost of caring for frail elders with hip fractures.
ER  - 
TY  - JOUR
T1  - Новые направления в терапии остеопороза – применение моноклональных человеческих антител к RANKL (Деносумаб)
A1  - Белая, Ж Е
A1  - Рожинская, Л Я
Y1  - 2011///
PB  - Общество с ограниченной ответственностью" Редакция журнала" Остеопороз и остеопатии"
JF  - Остеопороз и остеопатии
IS  - 2
SP  - 23
EP  - 26
ER  - 
TY  - JOUR
T1  - A 24-Month Study Evaluating the Efficacy and Safety of Denosumab for the Treatment of Men With Low Bone Mineral Density: Results From the ADAMO Trial
A1  - Langdahl, Bente L.
A1  - Teglbjærg, Christence Stubbe
A1  - Ho, Pei-Ran
A1  - Chapurlat, Roland
A1  - Czerwinski, Edward
A1  - Kendler, David L.
A1  - Reginster, Jean-Yves
A1  - Kivitz, Alan
A1  - Lewiecki, E. Michael
A1  - Miller, Paul D.
A1  - Bolognese, Michael A.
A1  - McClung, Michael R.
A1  - Bone, Henry G.
A1  - Ljunggren, Östen
A1  - Abrahamsen, Bo
A1  - Gruntmanis, Ugis
A1  - Yang, Yu-Ching
A1  - Wagman, Rachel B.
A1  - Mirza, Faisal
A1  - Siddhanti, Suresh
A1  - Orwoll, Eric
Y1  - 2015///
JF  - The Journal of Clinical Endocrinology & Metabolism
VL  - 100
IS  - 4
SP  - 1335
EP  - 1342
SN  - 0021-972x
DO  - 10.1210/jc.2014-4079
UR  - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2014-4079
N2  - Context: One in 4 men in the US aged >50 will suffer an osteoporosis-related fracture. Less data are available on osteoporosis treatment in men than women. Objective: Evaluate denosumab therapy in men with low BMD. Design: Phase 3 study with two treatment periods: a previously reported 12-month double-blind, placebo-controlled phase and a 12-month open-label phase. Setting: Multicenter in North America and Europe. Participants: 228 men entered the open-label phase and 219 completed the study. Intervention: Men from the original denosumab (long-term) and placebo (crossover) groups received denosumab 60 mg SC every 6 months. Main Outcome Measures: BMD, serum C-telopeptide (sCTX), and safety. Results: During the open-label phase, continued BMD increases occurred with long-term denosumab treatment (2.2% lumbar spine; 0.9% total hip; 1.3% femoral neck; 1.3% trochanter; and 0.2% 1/3 radius), resulting in cumulative 24-month gains from baseline of 8.0%, 3.4%, 3.4%, 4.6%, and 0.7%, respectively (all P<0.01). The crossover group showed BMD gains after 12 months of denosumab treatment similar to the long-term denosumab group during the first treatment year. Significant reductions in sCTX were observed following denosumab administration. Adverse events rates were similar between groups and no new safety signals identified. Conclusions: In men with low BMD, denosumab treatment for a second year continued to increase BMD, maintained reductions in bone resorption, and was well tolerated. BMD increased in men initiating denosumab during the second year. These effects were similar to those previously seen in postmenopausal women with osteoporosis and men with prostate cancer on androgen deprivation therapy.
ER  - 
TY  - JOUR
T1  - Новые направления в терапии остеопороза – применение моноклональных человеческих антител к RANKL (Деносумаб)
A1  - Белая Ж.Е., Рожинская, Л.Я.
Y1  - 2011///
JF  - Остеопороз и остеопатии
IS  - 2
SP  - 23
EP  - 26
ER  - 
TY  - JOUR
T1  - A Randomized, Placebo-Controlled Study of the Effects of Denosumab for the Treatment of Men with Low Bone Mineral Density
A1  - Orwoll, Eric
A1  - Teglbjærg, Christence S.
A1  - Langdahl, Bente L.
A1  - Chapurlat, Roland
A1  - Czerwinski, Edward
A1  - Kendler, David L.
A1  - Reginster, Jean-Yves
A1  - Kivitz, Alan
A1  - Lewiecki, E. Michael
A1  - Miller, Paul D.
A1  - Bolognese, Michael A.
A1  - McClung, Michael R.
A1  - Bone, Henry G.
A1  - Ljunggren, Östen
A1  - Abrahamsen, Bo
A1  - Gruntmanis, Ugis
A1  - Yang, Yu-Ching
A1  - Wagman, Rachel B.
A1  - Siddhanti, Suresh
A1  - Grauer, Andreas
A1  - Hall, Jesse W.
A1  - Boonen, Steven
Y1  - 2012///
JF  - The Journal of Clinical Endocrinology & Metabolism
VL  - 97
IS  - 9
SP  - 3161
EP  - 3169
DO  - 10.1210/jc.2012-1569
UR  - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2012-1569
N2  - Context: Men with low bone mineral density (BMD) were treated with denosumab. Objective: Our objective was to investigate the effects of denosumab compared with placebo in men with low BMD after 1 yr of treatment. Design, Subjects, and Intervention: This was a placebo-controlled, phase 3 study to investigate the efficacy and safety of denosumab 60 mg every 6 months vs. placebo in men with low BMD. Main Outcome Measure: The primary endpoint was the percent change from baseline in lumbar spine (LS) BMD at month 12. Results: Of the 242 randomized subjects (mean age 65 yr), 228 (94.2%) completed 1 yr of denosumab therapy. After 12 months, denosumab resulted in BMD increases of 5.7% at the LS, 2.4% at the total hip, 2.1% at the femoral neck, 3.1% at the trochanter, and 0.6% at the one third radius (adjusted P ≤ 0.0144 for BMD percent differences at all sites compared with placebo). Sensitivity analyses done by controlling for baseline covariates (such as baseline testosterone levels, BMD T-scores, and 10-yr os...
ER  - 
TY  - JOUR
T1  - Comparison of the Effect of Denosumab and Alendronate on BMD and Biochemical Markers of Bone Turnover in Postmenopausal Women With Low Bone Mass: A Randomized, Blinded, Phase 3 Trial*
A1  - Brown, Jacques P
A1  - Prince, Richard L
A1  - Deal, Chad
A1  - Recker, Robert R
A1  - Kiel, Douglas P
A1  - de Gregorio, Luiz H
A1  - Hadji, Peyman
A1  - Hofbauer, Lorenz C
A1  - Álvaro-Gracia, Jose M
A1  - Wang, Huei
A1  - Austin, Matthew
A1  - Wagman, Rachel B
A1  - Newmark, Richard
A1  - Libanati, Cesar
A1  - San Martin, Javier
A1  - Bone, Henry G
Y1  - 2009///
JF  - Journal of Bone and Mineral Research
VL  - 24
IS  - 1
SP  - 153
EP  - 161
SN  - 1523-4681
DO  - 10.1359/jbmr.0809010
UR  - http://doi.wiley.com/10.1359/jbmr.0809010
N2  - Denosumab is a fully human monoclonal antibody that inhibits bone resorption by neutralizing RANKL, a key mediator of osteoclast formation, function, and survival. This phase 3, multicenter, doubleblind study compared the efficacy and safety of denosumab with alendronate in postmenopausal women with low bone mass. One thousand one hundred eighty-nine postmenopausal women with a T-score <or= -2.0 at the lumbar spine or total hip were randomized 1:1 to receive subcutaneous denosumab injections (60 mg every 6 mo [Q6M]) plus oral placebo weekly (n = 594) or oral alendronate weekly (70 mg) plus subcutaneous placebo injections Q6M (n = 595). Changes in BMD were assessed at the total hip, femoral neck, trochanter, lumbar spine, and one-third radius at 6 and 12 mo and in bone turnover markers at months 1, 3, 6, 9, and 12. Safety was evaluated by monitoring adverse events and laboratory values. At the total hip, denosumab significantly increased BMD compared with alendronate at month 12 (3.5% versus 2.6%; p < 0.0001). Furthermore, significantly greater increases in BMD were observed with denosumab treatment at all measured skeletal sites (12-mo treatment difference: 0.6%, femoral neck; 1.0%, trochanter; 1.1%, lumbar spine; 0.6%, one-third radius; p <or= 0.0002 all sites). Denosumab treatment led to significantly greater reduction of bone turnover markers compared with alendronate therapy. Adverse events and laboratory values were similar for denosumab- and alendronate-treated subjects. Denosumab showed significantly larger gains in BMD and greater reduction in bone turnover markers compared with alendronate. The overall safety profile was similar for both treatments.
ER  - 
TY  - JOUR
T1  - Atypical subtrochanteric and diaphyseal femoral fractures: Second report of a task force of the American society for bone and mineral research
A1  - Shane, Elizabeth
A1  - Burr, David
A1  - Abrahamsen, Bo
A1  - Adler, Robert A.
A1  - Brown, Thomas D.
A1  - Cheung, Angela M.
A1  - Cosman, Felicia
A1  - Curtis, Jeffrey R.
A1  - Dell, Richard
A1  - Dempster, David W.
A1  - Ebeling, Peter R.
A1  - Einhorn, Thomas A.
A1  - Genant, Harry K.
A1  - Geusens, Piet
A1  - Klaushofer, Klaus
A1  - Lane, Joseph M.
A1  - McKiernan, Fergus
A1  - McKinney, Ross
A1  - Ng, Alvin
A1  - Nieves, Jeri
A1  - O'Keefe, Regis
A1  - Papapoulos, Socrates
A1  - Howe, Tet Sen
A1  - Van Der Meulen, Marjolein C H
A1  - Weinstein, Robert S.
A1  - Whyte, Michael P.
Y1  - 2014///
KW  - Bisphosphonates
KW  - Denosumab
KW  - Fractures
KW  - Stress Fracture
KW  - Suppression Of Remodeling
JF  - Journal of Bone and Mineral Research
VL  - 29
IS  - 1
SP  - 1
EP  - 23
SN  - 0884-0431
DO  - 10.1002/jbmr.1998
N2  - Bisphosphonates (BPs) and denosumab reduce the risk of spine and nonspine fractures. Atypical femur fractures (AFFs) located in the subtrochanteric region and diaphysis of the femur have been reported in patients taking BPs and in patients on denosumab, but they also occur in patients with no exposure to these drugs. In this report, we review studies on the epidemiology, pathogenesis, and medical management of AFFs, published since 2010. This newer evidence suggests that AFFs are stress or insufficiency fractures. The original case definition was revised to highlight radiographic features that distinguish AFFs from ordinary osteoporotic femoral diaphyseal fractures and to provide guidance on the importance of their transverse orientation. The requirement that fractures be noncomminuted was relaxed to include minimal comminution. The periosteal stress reaction at the fracture site was changed from a minor to a major feature. The association with specific diseases and drug exposures was removed from the minor features, because it was considered that these associations should be sought rather than be included in the case definition. Studies with radiographic review consistently report significant associations between AFFs and BP use, although the strength of associations and magnitude of effect vary. Although the relative risk of patients with AFFs taking BPs is high, the absolute risk of AFFs in patients on BPs is low, ranging from 3.2 to 50 cases per 100,000 person-years. However, long-term use may be associated with higher risk (∼100 per 100,000 person-years). BPs localize in areas that are developing stress fractures; suppression of targeted intracortical remodeling at the site of an AFF could impair the processes by which stress fractures normally heal. When BPs are stopped, risk of an AFF may decline. Lower limb geometry and Asian ethnicity may contribute to the risk of AFFs. There is inconsistent evidence that teriparatide may advance healing of AFFs.
ER  - 
TY  - JOUR
T1  - Fracture Risk and Zoledronic Acid Therapy in Men with Osteoporosis
A1  - Boonen, Steven
A1  - Reginster, Jean-Yves
A1  - Kaufman, Jean-Marc
A1  - Lippuner, Kurt
A1  - Zanchetta, Jose
A1  - Langdahl, Bente
A1  - Rizzoli, Rene
A1  - Lipschitz, Stanley
A1  - Dimai, Hans Peter
A1  - Witvrouw, Richard
A1  - Eriksen, Erik
A1  - Brixen, Kim
A1  - Russo, Luis
A1  - Claessens, Frank
A1  - Papanastasiou, Philemon
A1  - Antunez, Oscar
A1  - Su, Guoqin
A1  - Bucci-Rechtweg, Christina
A1  - Hruska, Josef
A1  - Incera, Elodie
A1  - Vanderschueren, Dirk
A1  - Orwoll, Eric
Y1  - 2012///
JF  - New England Journal of Medicine
VL  - 367
IS  - 18
SP  - 1714
EP  - 1723
SN  - 1533-4406 (Electronic)\r0028-4793 (Linking)
DO  - 10.1056/NEJMoa1204061
UR  - http://www.nejm.org/doi/abs/10.1056/NEJMoa1204061
N2  - Osteoporosis is an important cause of morbidity and mortality among men.1,2 Among persons older than 50 years of age, approximately 40% of all osteoporotic fractures worldwide occur in men.3 Mortality after osteoporotic fracture is higher among men than among women.2,4 Previous studies involving men with osteoporosis have focused on the surrogate outcomes of bone mineral density and bone-turnover markers,5–9 but data from double-blind, randomized studies assessing antifracture efficacy are lacking. In addition, given the low awareness of the disease,10 the development of guidelines for the detection and treatment of osteoporosis in men has been limited.11 Hence, there . . .
ER  - 
TY  - JOUR
T1  - Ibandronate and the risk of non-vertebral and clinical fractures in women with postmenopausal osteoporosis: results of a meta-analysis of phase III studies
A1  - Harris, Steven T.
A1  - Blumentals, William A.
A1  - Miller, Paul D.
Y1  - 2008///
JF  - Current Medical Research and Opinion
VL  - 24
IS  - 1
SP  - 237
EP  - 245
SN  - 030079908X
DO  - 10.1185/030079908X253717
UR  - http://www.tandfonline.com/doi/full/10.1185/030079908X253717
N2  - OBJECTIVE: The marketed doses of ibandronate, 150 mg once-monthly oral and 3 mg quarterly intravenous (IV) injection, produce greater increases in lumbar spine bone mineral density than treatment with the 2.5 mg oral daily dose. This meta-analysis assessed whether these doses also reduce fracture risk relative to placebo. STUDY DESIGN AND METHODS: Individual patient data from the intent-to-treat populations of the BONE, IV fracture prevention, MOBILE, and DIVA studies were grouped into three dose levels based on annual cumulative exposure (ACE), defined as the annual dose (mg) x bioavailability (0.6%, oral; 100%, IV) or placebo. Six key non-vertebral fractures (NVFs) (clavicle, humerus, wrist, pelvis, hip, and leg), all NVFs, and all clinical fractures were examined. RESULTS: This meta-analysis included 8710 patients. Cox proportional-hazards models estimated the adjusted relative risk (RR) for fracture with ibandronate versus placebo, and time to fracture was compared using log-rank tests. The high-dose group (ACE > or = 10.8 mg) showed significant reductions in the adjusted RR of key NVFs (34.4%, p = 0.032), all NVFs (29.9%, p = 0.041), and clinical fractures (28.8%, p = 0.010) relative to placebo. The high-dose group also had significantly longer time to fracture versus placebo for key NVFs (p = 0.031), all NVFs (p = 0.025), and clinical fractures (p = 0.002). Study limitations included: not all studies were placebo-controlled; a limited number of baseline characteristics were available for multivariate analyses. CONCLUSION: Ibandronate at dose levels of ACE > or = 10.8 mg, which includes the marketed 150 mg once-monthly oral and 3 mg quarterly IV injection regimens, may provide significant non-vertebral and clinical fracture efficacy.
ER  - 
TY  - JOUR
T1  - Time course of bone mineral density changes with denosumab compared with other drugs in postmenopausal osteoporosis: A dose-response-based meta-analysis
A1  - Mandema, Jaap W.
A1  - Zheng, Jenny
A1  - Libanati, Cesar
A1  - Ruixo, Juan Jose Perez
Y1  - 2014///
JF  - Journal of Clinical Endocrinology and Metabolism
VL  - 99
IS  - 10
SP  - 3746
EP  - 3755
SN  - 0021-972x
DO  - 10.1210/jc.2013-3795
N2  - Objective: Our objective was to compare the time course of bone mineral density (BMD) changes at the lumbar spine (LS) and total hip (TH) in postmenopausal women during treatment with denosumab, bisphosphonates, selective estrogen receptor modulators, PTH, or calcitonin. Data Sources and Study Selection: Data were extracted from 142 randomized controlled trials for prevention or treatment of postmenopausal osteoporosis representing over 113 000 women. Data Extraction and Data Synthesis: The percent change from baseline in BMD was analyzed using a nonlinear least-squares random-effects meta-regression analysis. The dose-response relationship of BMD changes was well characterized by a maximal effect (EMax) model with a different EMax for LS and TH for each drug class. The ratio of LS and TH BMD changes was significantly different across the different drug classes. The time course of BMD changes was well characterized by an exponential onset with a different rate for LS and TH for each drug class. The dose-r...
ER  - 
TY  - JOUR
T1  - Adjuvant denosumab in breast cancer (ABCSG-18): A multicentre, randomised, double-blind, placebo-controlled trial
A1  - Gnant, Michael
A1  - Pfeiler, Georg
A1  - Dubsky, Peter C.
A1  - Hubalek, Michael
A1  - Greil, Richard
A1  - Jakesz, Raimund
A1  - Wette, Viktor
A1  - Balic, Marija
A1  - Haslbauer, Ferdinand
A1  - Melbinger, Elisabeth
A1  - Bjelic-Radisic, Vesna
A1  - Artner-Matuschek, Silvia
A1  - Fitzal, Florian
A1  - Marth, Christian
A1  - Sevelda, Paul
A1  - Mlineritsch, Brigitte
A1  - Steger, Günther G.
A1  - Manfreda, Diether
A1  - Exner, Ruth
A1  - Egle, Daniel
A1  - Bergh, Jonas
A1  - Kainberger, Franz
A1  - Talbot, Susan
A1  - Warner, Douglas
A1  - Fesl, Christian
A1  - Singer, Christian F.
Y1  - 2015///
JF  - The Lancet
VL  - 386
IS  - 9992
SP  - 433
EP  - 443
SN  - 0140-6736
DO  - 10.1016/S0140-6736(15)60995-3
N2  - Background Adjuvant endocrine therapy compromises bone health in patients with breast cancer, causing osteopenia, osteoporosis, and fractures. Antiresorptive treatments such as bisphosphonates prevent and counteract these side-effects. In this trial, we aimed to investigate the effects of the anti-RANK ligand antibody denosumab in postmenopausal, aromatase inhibitor-treated patients with early-stage hormone receptor-positive breast cancer. Methods In this prospective, double-blind, placebo-controlled, phase 3 trial, postmenopausal patients with early hormone receptor-positive breast cancer receiving treatment with aromatase inhibitors were randomly assigned in a 1:1 ratio to receive either denosumab 60 mg or placebo administered subcutaneously every 6 months in 58 trial centres in Austria and Sweden. Patients were assigned by an interactive voice response system. The randomisation schedule used a randomly permuted block design with block sizes 2 and 4, stratified by type of hospital regarding Hologic device for DXA scans, previous aromatase inhibitor use, and baseline bone mineral density. Patients, treating physicians, investigators, data managers, and all study personnel were masked to treatment allocation. The primary endpoint was time from randomisation to first clinical fracture, analysed by intention to treat. As an additional sensitivity analysis, we also analysed the primary endpoint on the per-protocol population. Patients were treated until the prespecified number of 247 first clinical fractures was reached. This trial is ongoing (patients are in follow-up) and is registered with the European Clinical Trials Database, number 2005-005275-15, and with ClinicalTrials.gov, number NCT00556374. Findings Between Dec 18, 2006, and July 22, 2013, 3425 eligible patients were enrolled into the trial, of whom 3420 were randomly assigned to receive denosumab 60 mg (n=1711) or placebo (n=1709) subcutaneously every 6 months. Compared with the placebo group, patients in the denosumab group had a significantly delayed time to first clinical fracture (hazard ratio [HR] 0·50 [95% CI 0·39-0·65], p<0·0001). The overall lower number of fractures in the denosumab group (92) than in the placebo group (176) was similar in all patient subgroups, including in patients with a bone mineral density T-score of -1 or higher at baseline (n=1872, HR 0·44 [95% CI 0·31-0·64], p<0·0001) and in those with a bone mineral density T-score of less than -1 already at baseline (n=1548, HR 0·57 [95% CI 0·40-0·82], p=0·002). The patient incidence of adverse events in the safety analysis set (all patients who received at least one dose of study drug) did not differ between the denosumab group (1366 events, 80%) and the placebo group (1334 events, 79%), nor did the numbers of serious adverse events (521 vs 511 [30% in each group]). The main adverse events were arthralgia and other aromatase-inhibitor related symptoms; no additional toxicity from the study drug was reported. Despite proactive adjudication of every potential osteonecrosis of the jaw by an international expert panel, no cases of osteonecrosis of the jaw were reported. 93 patients (3% of the full analysis set) died during the study, of which one death (in the denosumab group) was thought to be related to the study drug. Interpretation Adjuvant denosumab 60 mg twice per year reduces the risk of clinical fractures in postmenopausal women with breast cancer receiving aromatase inhibitors, and can be administered without added toxicity. Since a main side-effect of adjuvant breast cancer treatment can be substantially reduced by the addition of denosumab, this treatment should be considered for clinical practice. Funding Amgen.
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TY  - JOUR
T1  - Zoledronic Acid and Clinical Fractures and Mortality after Hip Fracture
A1  - Lyles, Kenneth W.
A1  - Colón-Emeric, Cathleen S.
A1  - Magaziner, Jay S.
A1  - Adachi, Jonathan D.
A1  - Pieper, Carl F.
A1  - Mautalen, Carlos
A1  - Hyldstrup, Lars
A1  - Recknor, Chris
A1  - Nordsletten, Lars
A1  - Moore, Kathy A.
A1  - Lavecchia, Catherine
A1  - Zhang, Jie
A1  - Mesenbrink, Peter
A1  - Hodgson, Patricia K.
A1  - Abrams, Ken
A1  - Orloff, John J.
A1  - Horowitz, Zebulun
A1  - Eriksen, Erik Fink
A1  - Boonen, Steven
Y1  - 2007///
JF  - New England Journal of Medicine
VL  - 357
IS  - 18
SP  - 1799
EP  - 1809
SN  - 1533-4406 (Electronic)\r0028-4793 (Linking)
DO  - 10.1056/NEJMoa074941
UR  - http://www.nejm.org/doi/abs/10.1056/NEJMoa074941
N2  - Background Mortality is increased after a hip fracture, and strategies that improve outcomes are needed. Methods In this randomized, double-blind, placebo-controlled trial, 1065 patients were assigned to receive yearly intravenous zoledronic acid (at a dose of 5 mg), and 1062 patients were assigned to receive placebo. The infusions were first administered within 90 days after surgical repair of a hip fracture. All patients (mean age, 74.5 years) received supplemental vitamin D and calcium. The median follow-up was 1.9 years. The primary end point was a new clinical fracture. Results The rates of any new clinical fracture were 8.6% in the zoledronic acid group and 13.9% in the placebo group, a 35% risk reduction with zoledronic acid (P=0.001); the respective rates of a new clinical vertebral fracture were 1.7% and 3.8% (P=0.02), and the respective rates of new nonvertebral fractures were 7.6% and 10.7% (P=0.03). In the safety analysis, 101 of 1054 patients in the zoledronic acid group (9.6%) and 141 of 105...
ER  - 
TY  - JOUR
T1  - Zoledronic Acid for the Prevention of Bone Loss in Postmenopausal Women With Low Bone Mass
A1  - McClung, Michael
A1  - Miller, Paul
A1  - Recknor, Chris
A1  - Mesenbrink, Peter
A1  - Bucci-Rechtweg, Christina
A1  - Benhamou, Claude-Laurent
Y1  - 2009///
JF  - Obstetrics & Gynecology
VL  - 114
IS  - 5
SP  - 999
EP  - 1007
DO  - 10.1097/AOG.0b013e3181bdce0a
UR  - http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00006250-200911000-00007
N2  - OBJECTIVE: To evaluate the efficacy of zoledronic acid in the prevention of bone loss in postmenopausal women with low bone mass. METHODS: In this 2-year, randomized, multicenter, double-blind, placebo-controlled study, postmenopausal women with low bone mass were selected randomly to receive either zoledronic acid 5 mg intravenously at randomization and at month 12 (zoledronic acid 2 x 5 mg), zoledronic acid 5 mg intravenously only at randomization and placebo at month 12 (zoledronic acid 1 x 5 mg), or placebo at randomization and at month 12 (placebo). The primary efficacy endpoint was the percentage change in lumbar spine bone mineral density (BMD) (lumbar spine BMD) at month 24 relative to baseline. RESULTS: Both zoledronic acid 2 x 5 mg and zoledronic acid 1 x 5 mg regimens significantly increased mean lumbar spine BMD compared with placebo at month 24 (5.18% and 4.42% compared with -1.32%, respectively, both P<.001). Similarly, significantly greater increases for both zoledronic acid regimens relative to placebo were observed for lumbar spine BMD at month 12 and for BMD at the proximal femur sites (total hip, femoral neck, trochanter) at month 12 and 24 (all P<.001). Both zoledronic acid regimens significantly reduced bone turnover markers over time relative to placebo (all P<.001), although changes with zoledronic acid 2 x 5 mg regimen were sustained greater during the second year relative to zoledronic acid 1 x 5 mg. The overall incidence of adverse events and serious adverse events were similar across all treatment groups. CONCLUSION: Both once-yearly dosing and a single dose of intravenous zoledronic acid 5 mg prevented bone loss for 2 years and were well-tolerated in postmenopausal women with low bone mass. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00132808. LEVEL OF EVIDENCE: I.
ER  - 
TY  - JOUR
T1  - Inhibition of RANKL as a treatment for osteoporosis: Preclinical and early clinical studies
A1  - McClung, Michael R.
Y1  - 2006///
JF  - Current Osteoporosis Reports
VL  - 4
IS  - 1
SP  - 28
EP  - 33
DO  - 10.1007/s11914-006-0012-7
N2  - Osteoporosis and several other bone disorders occur when there is an imbalance between the resorption and formation components of bone remodeling activity. Therapies available for some of these conditions modulate the activity of osteoclasts and/or osteoblasts. The recent discoveries of receptor activator of NF-kappaB ligand (RANKL), an endogenous activator of osteoclastogenenesis and osteoclast activity and its inhibitor, osteoprotegerin (OPG) as pivotal regulatory factors in the pathogenesis of bone diseases like osteoporosis provide unique targets for therapeutic agents. In laboratory animals and now in humans, administering forms of OPG markedly inhibits osteoclast activity and improves bone strength, documenting that the strategy of inhibiting RANKL activity has therapeutic promise. A highly specific, fully human antibody against RANKL has been produced (denosumab) that in early studies in humans reduces bone turnover and improves bone density. Attributes of denosumab in these clinical studies include a very rapid onset of action, sustained effects for several months after a single injection, and good tolerability. These results provide the basis for studies evaluating the effectiveness of denosumab in several clinical conditions characterized by increased osteoclastic activity.
ER  - 
TY  - JOUR
T1  - Bisphosphonate-Associated Osteonecrosis of the Jaw: Report of a Task Force of the American Society for Bone and Mineral Research
A1  - Khosla, Sundeep
A1  - Burr, David
A1  - Cauley, Jane
A1  - Dempster, David W
A1  - Ebeling, Peter R
A1  - Felsenberg, Dieter
A1  - Gagel, Robert F
A1  - Gilsanz, Vincente
A1  - Guise, Theresa
A1  - Koka, Sreenivas
A1  - McCauley, Laurie K
A1  - McGowan, Joan
A1  - McKee, Marc D
A1  - Mohla, Suresh
A1  - Pendrys, David G
A1  - Raisz, Lawrence G
A1  - Ruggiero, Salvatore L
A1  - Shafer, David M
A1  - Shum, Lillian
A1  - Silverman, Stuart L
A1  - Van Poznak, Catherine H
A1  - Watts, Nelson
A1  - Woo, Sook-Bin
A1  - Shane, Elizabeth
Y1  - 2007///
JF  - Journal of Bone and Mineral Research
VL  - 22
IS  - 10
SP  - 1479
EP  - 1491
SN  - 0884-0431 (Print)\r0884-0431 (Linking)
DO  - 10.1359/jbmr.0707onj
UR  - http://doi.wiley.com/10.1359/jbmr.0707onj
N2  - UNLABELLED: ONJ has been increasingly suspected to be a potential complication of bisphosphonate therapy in recent years. Thus, the ASBMR leadership appointed a multidisciplinary task force to address key questions related to case definition, epidemiology, risk factors, diagnostic imaging, clinical management, and future areas for research related to the disorder. This report summarizes the findings and recommendations of the task force. INTRODUCTION: The increasing recognition that use of bisphosphonates may be associated with osteonecrosis of the jaw (ONJ) led the leadership of the American Society for Bone and Mineral Research (ASBMR) to appoint a task force to address a number of key questions related to this disorder. MATERIALS AND METHODS: A multidisciplinary expert group reviewed all pertinent published data on bisphosphonate-associated ONJ. Food and Drug Administration drug adverse event reports were also reviewed. RESULTS AND CONCLUSIONS: A case definition was developed so that subsequent studies could report on the same condition. The task force defined ONJ as the presence of exposed bone in the maxillofacial region that did not heal within 8 wk after identification by a health care provider. Based on review of both published and unpublished data, the risk of ONJ associated with oral bisphosphonate therapy for osteoporosis seems to be low, estimated between 1 in 10,000 and <1 in 100,000 patient-treatment years. However, the task force recognized that information on incidence of ONJ is rapidly evolving and that the true incidence may be higher. The risk of ONJ in patients with cancer treated with high doses of intravenous bisphosphonates is clearly higher, in the range of 1-10 per 100 patients (depending on duration of therapy). In the future, improved diagnostic imaging modalities, such as optical coherence tomography or MRI combined with contrast agents and the manipulation of image planes, may identify patients at preclinical or early stages of the disease. Management is largely supportive. A research agenda aimed at filling the considerable gaps in knowledge regarding this disorder was also outlined.
ER  - 
TY  - ICOMM
T1  - New contraindication and updated warning on kidney impairment for Reclast (zoledronic acid)
A1  - Communication, FDA Drug Safety
JF  - 2011
UR  - https://www.fda.gov/Drugs/DrugSafety/ucm270199.htm
ER  - 
TY  - JOUR
T1  - The Effect of Teriparatide [Human Parathyroid Hormone (1-34)] Therapy on Bone Density in Men With Osteoporosis
A1  - Orwoll, ES
A1  - Scheele, WH
A1  - Paul, S
A1  - Adami, S
A1  - Syversen, U
A1  - Diez-Perez, A
A1  - Kaufman, J-M
A1  - Clancy, AD
A1  - Gaich, GA
Y1  - 2003///
JF  - Journal of Bone and Mineral Research
VL  - 18
IS  - 1
SP  - 9
EP  - 17
SN  - 0884-0431 (Print)\r0884-0431
DO  - 10.1359/jbmr.2003.18.1.9
UR  - http://doi.wiley.com/10.1359/jbmr.2003.18.1.9
N2  - Teriparatide [rhPTH(1-34)] increases bone mineral density and reduces the risk of vertebral fracture in women. We randomized 437 men with spine or hip bone mineral density more than 2 SD below the young adult male mean to daily injections of placebo, teriparatide 20 microg, or teriparatide 40 microg. All subjects also received supplemental calcium and vitamin D. The study was stopped after a median duration of 11 months because of a finding of osteosarcomas in rats in routine toxicology studies. Biochemical markers of bone formation increased early in the course of therapy and were followed by increases in indices of osteoclastic activity. Spine bone mineral density was greater than in placebo subjects after 3 months of teriparatide therapy, and by the end of therapy it was increased by 5.9% (20 microg) and 9.0% (40 microg) above baseline (p < 0.001 vs. placebo for both comparisons). Femoral neck bone mineral density increased 1.5% (20 microg; p = 0.029) and 2.9% (40 microg; p < 0.001), and whole body bone mineral content increased 0.6% (20 microg; p = 0.021) and 0.9% (40 microg;p = 0.005) above baseline in the teriparatide subjects. There was no change in radial bone mineral density in the teriparatide groups. Bone mineral density responses to teriparatide were similar regardless of gonadal status, age, baseline bone mineral density, body mass index, smoking, or alcohol intake. Subjects experienced expected changes in mineral metabolism. Adverse events were similar in the placebo and 20-microg groups, but more frequent in the 40-microg group. This study shows that teriparatide treatment results in an increase in bone mineral density and is a potentially useful therapy for osteoporosis in men.
ER  - 
TY  - JOUR
T1  - Teriparatide or Alendronate in Glucocorticoid-Induced Osteoporosis
A1  - Saag, Kenneth G.
A1  - Shane, Elizabeth
A1  - Boonen, Steven
A1  - Marín, Fernando
A1  - Donley, David W.
A1  - Taylor, Kathleen A.
A1  - Dalsky, Gail P.
A1  - Marcus, Robert
Y1  - 2007///
JF  - New England Journal of Medicine
VL  - 357
IS  - 20
SP  - 2028
EP  - 2039
SN  - 1533-4406 (Electronic)\r0028-4793 (Linking)
DO  - 10.1056/NEJMoa071408
UR  - http://www.nejm.org/doi/abs/10.1056/NEJMoa071408
N2  - Background Bisphosphonate therapy is the current standard of care for the prevention and treatment of glucocorticoid-induced osteoporosis. Studies of anabolic therapy in patients who are receiving long-term glucocorticoids and are at high risk for fracture are lacking. Methods In an 18-month randomized, double-blind, controlled trial, we compared teriparatide with alendronate in 428 women and men with osteoporosis (ages, 22 to 89 years) who had received glucocorticoids for at least 3 months (prednisone equivalent, 5 mg daily or more). A total of 214 patients received 20 μg of teriparatide once daily, and 214 received 10 mg of alendronate once daily. The primary outcome was the change in bone mineral density at the lumbar spine. Secondary outcomes included changes in bone mineral density at the total hip and in markers of bone turnover, the time to changes in bone mineral density, the incidence of fractures, and safety. Results At the last measurement, the mean (±SE) bone mineral density at the lumbar spin...
ER  - 
TY  - JOUR
T1  - Effects of teriparatide versus alendronate for treating glucocorticoid-induced osteoporosis: Thirty-six-month results of a randomized, double-blind, controlled trial
A1  - Saag, Kenneth G.
A1  - Zanchetta, Jose R.
A1  - Devogelaer, Jean Pierre
A1  - Adler, Robert A.
A1  - Eastell, Richard
A1  - See, Kyoungah
A1  - Krege, John H.
A1  - Krohn, Kelly
A1  - Warner, Margaret R.
Y1  - 2009///
JF  - Arthritis and Rheumatism
VL  - 60
IS  - 11
SP  - 3346
EP  - 3355
SN  - 0004-3591 (Print)\r0004-3591 (Linking)
DO  - 10.1002/art.24879
N2  - OBJECTIVE: To compare the bone anabolic drug teriparatide (20 microg/day) with the antiresorptive drug alendronate (10 mg/day) for treating glucocorticoid-induced osteoporosis (OP). METHODS: This was a 36-month, randomized, double-blind, controlled trial in 428 subjects with OP (ages 22-89 years) who had received > or =5 mg/day of prednisone equivalent for > or =3 months preceding screening. Measures included changes in lumbar spine and hip bone mineral density (BMD), changes in bone biomarkers, fracture incidence, and safety. RESULTS: Increases in BMD from baseline were significantly greater in the teriparatide group than in the alendronate group, and at 36 months were 11.0% versus 5.3% for lumbar spine, 5.2% versus 2.7% for total hip, and 6.3% versus 3.4% for femoral neck (P < 0.001 for all). In the teriparatide group, median percent increases from baseline in N-terminal type I procollagen propeptide (PINP) and osteocalcin (OC) levels were significant from 1 to 36 months (P < 0.01), and increases in levels of C-terminal telopeptide of type I collagen (CTX) were significant from 1 to 6 months (P < 0.01). In the alendronate group, median percent decreases in PINP, OC, and CTX were significant by 6 months and remained below baseline through 36 months (P < 0.001). Fewer subjects had vertebral fractures in the teriparatide group than in the alendronate group (3 [1.7%] of 173 versus 13 [7.7%] of 169; P = 0.007), with most occurring during the first 18 months. There was no significant difference between groups in the incidence of nonvertebral fractures (16 [7.5%] of 214 subjects taking teriparatide versus 15 [7.0%] of 214 subjects taking alendronate; P = 0.843). More subjects in the teriparatide group (21%) versus the alendronate group (7%) had elevated predose serum calcium concentrations (P < 0.001). CONCLUSION: Our findings indicate that subjects with glucocorticoid-induced OP treated with teriparatide for 36 months had greater increases in BMD and fewer new vertebral fractures than subjects treated with alendronate.
ER  - 
TY  - JOUR
T1  - A Randomized Double-Blind Trial to Compare the Efficacy of Teriparatide [Recombinant Human Parathyroid Hormone (1–34)] with Alendronate in Postmenopausal Women with Osteoporosis
A1  - Body, Jean-Jacques
A1  - Gaich, Gregory A.
A1  - Scheele, Wim H.
A1  - Kulkarni, Pandurang M.
A1  - Miller, Paul D.
A1  - Peretz, Anne
A1  - Dore, Robin K.
A1  - Correa-Rotter, Ricardo
A1  - Papaioannou, Alexandra
A1  - Cumming, David C.
A1  - Hodsman, Anthony B.
Y1  - 2002///
JF  - The Journal of Clinical Endocrinology & Metabolism
VL  - 87
IS  - 10
SP  - 4528
EP  - 4535
SN  - 0021-972X (Print)\r0021-972X (Linking)
DO  - 10.1210/jc.2002-020334
UR  - https://academic.oup.com/jcem/article-lookup/doi/10.1210/jc.2002-020334
ER  - 
TY  - JOUR
T1  - Skeletal changes in rats given daily subcutaneous injections of recombinant human parathyroid hormone (1-34) for 2 years and relevance to human safety.
A1  - Vahle, John L
A1  - Sato, Masahiko
A1  - Long, Gerald G
A1  - Young, Jamie K
A1  - Francis, Paul C
A1  - Engelhardt, Jeffery A
A1  - Westmore, Michael S
A1  - Linda, Yanfei
A1  - Nold, James B
Y1  - 2002///
JF  - Toxicologic pathology
VL  - 30
IS  - 3
SP  - 312
EP  - 21
SN  - 0192-6233 (Print)\r0192-6233 (Linking)
DO  - 10.1080/01926230252929882
UR  - http://www.ncbi.nlm.nih.gov/pubmed/12051548
N2  - Fischer 344 rats (60/sex/group) were given daily subcutaneous injections of recombinant human parathyroid hormone (PTH)(1-34) for 2 years at doses of 0, 5, 30, or 75 microg/kg. Treatment caused substantial increases in bone mass consistent with the known pharmacologic effects of once-daily administration. As determined by quantitative computed tomography (QCT) and histomorphometry, bone mass was markedly increased. Substantial new bone formation resulted in a large decrease in marrow space accompanied by altered bone architecture. Bone proliferative lesions were observed in all PTH( 1-34)-treated groups. Osteosarcoma occurred in 3, 21, and 31 male rats and in 4, 12, and 23 female rats in the 5-, 30-, and 75-microg/kg treatment groups, respectively. Focal osteoblast hyperplasia, osteoma, and osteoblastoma were much less frequent. Although the specific cellular or molecular mechanisms responsible for the rat bone tumors have not been fully elucidated, the data suggest that these lesions resulted from the long duration of treatment and the exaggerated pharmacologic response of the rat skeleton to daily treatment with PTH(1-34). Important differences between the rat study and clinical use in adult humans suggest that the increased incidence of bone neoplasia in rats treated for 2 years is likely not predictive of an increased risk of bone cancer in skeletally mature adult humans being given PTH(1-34) for a limited period of time in the treatment of osteoporosis.
ER  - 
TY  - JOUR
T1  - Commentary on Clinical Safety of Recombinant Human Parathyroid Hormone 1-34 in the Treatment of Osteoporosis in Men and Postmenopausal Women
A1  - Tashjian, Armen H.
A1  - Chabner, Bruce A.
Y1  - 2002///
JF  - Journal of Bone and Mineral Research
VL  - 17
IS  - 7
SP  - 1151
EP  - 1161
DO  - 10.1359/jbmr.2002.17.7.1151
UR  - http://doi.wiley.com/10.1359/jbmr.2002.17.7.1151
ER  - 
TY  - JOUR
T1  - Comparative Safety and Effectiveness of Denosumab Versus Zoledronic Acid in Patients With Osteoporosis: A Cohort Study
A1  - Choi, Nam-Kyong
A1  - Solomon, Daniel H
A1  - Tsacogianis, Theodore N
A1  - Landon, Joan E
A1  - Song, Hong Ji
A1  - Kim, Seoyoung C
Y1  - 2017///
JF  - Journal of Bone and Mineral Research
DO  - 10.1002/jbmr.3019
UR  - http://doi.wiley.com/10.1002/jbmr.3019
ER  - 
TY  - JOUR
T1  - Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy
A1  - Kendler, David L
A1  - Roux, Christian
A1  - Benhamou, Claude Laurent
A1  - Brown, Jacques P
A1  - Lillestol, Michael
A1  - Siddhanti, Suresh
A1  - Man, Hoi-Shen
A1  - Martin, Javier San
A1  - Bone, Henry G
Y1  - 2010///
JF  - Journal of Bone and Mineral Research
VL  - 25
IS  - 1
SP  - 72
EP  - 81
SN  - 1523-4681 (Electronic)\r0884-0431 (Linking)
DO  - 10.1359/jbmr.090716
UR  - http://doi.wiley.com/10.1359/jbmr.090716
N2  - Patients treated with bisphosphonates for osteoporosis may discontinue or require a switch to other therapies. Denosumab binds to RANKL and is a potent inhibitor of bone resorption that has been shown to increase bone mineral density (BMD) and decrease fracture risk in postmenopausal women with osteoporosis. This was a multicenter, international, randomized, double-blind, double-dummy study in 504 postmenopausal women > or = 55 years of age with a BMD T-score of -2.0 or less and -4.0 or more who had been receiving alendronate therapy for at least 6 months. Subjects received open-label branded alendronate 70 mg once weekly for 1 month and then were randomly assigned to either continued weekly alendronate therapy or subcutaneous denosumab 60 mg every 6 months and were followed for 12 months. Changes in BMD and biochemical markers of bone turnover were evaluated. In subjects transitioning to denosumab, total hip BMD increased by 1.90% at month 12 compared with a 1.05% increase in subjects continuing on alendronate (p < .0001). Significantly greater BMD gains with denosumab compared with alendronate also were achieved at 12 months at the lumbar spine, femoral neck, and 1/3 radius (all p < .0125). Median serum CTX levels remained near baseline in the alendronate group and were significantly decreased versus alendronate (p < .0001) at all time points with denosumab. Adverse events and serious adverse events were balanced between groups. No clinical hypocalcemic adverse events were reported. Transition to denosumab produced greater increases in BMD at all measured skeletal sites and a greater reduction in bone turnover than did continued alendronate with a similar safety profile in both groups.
ER  - 
TY  - JOUR
T1  - The effect of teriparatide compared with risedronate on reduction of back pain in postmenopausal women with osteoporotic vertebral fractures
A1  - Hadji, P.
A1  - Zanchetta, J. R.
A1  - Russo, L.
A1  - Recknor, C. P.
A1  - Saag, K. G.
A1  - McKiernan, F. E.
A1  - Silverman, S. L.
A1  - Alam, J.
A1  - Burge, R. T.
A1  - Krege, J. H.
A1  - Lakshmanan, M. C.
A1  - Masica, D. N.
A1  - Mitlak, B. H.
A1  - Stock, J. L.
Y1  - 2012///
KW  - Back pain
KW  - Bisphosphonate
KW  - Osteoporosis
KW  - Teriparatide
KW  - Vertebral fracture
JF  - Osteoporosis International
VL  - 23
IS  - 8
SP  - 2141
EP  - 2150
SN  - 0937-941X
DO  - 10.1007/s00198-011-1856-y
N2  - The effect of teriparatide and risedronate on back pain was tested, and there was no difference in the proportion of patients experiencing a reduction in back pain between groups after 6 or 18 months. Patients receiving teriparatide had greater increases in bone mineral density and had fewer vertebral fractures. Introduction This study aimed to understand the effect of teriparatide in reducing back pain in patients with prevalent back pain and vertebral fracture compared to risedronate. Methods In an 18-month randomized, double-blind, double-dummy trial, we investigated the effects of teriparatide (20 μg/ day) vs. risedronate (35 mg/week) in postmenopausal women with back pain likely due to vertebral fracture. The primary objective was to compare the proportion of subjects reporting ≥30% reduction in worst back pain severity from baseline to 6 months as assessed by a numeric rating scale in each treatment group. Pre-specified secondary and exploratory outcomes included assessments of average and worst back pain at additional time points, disability and quality of life, bone mineral density, incidence of fractures, and safety. Results At 6 months, 59% of teriparatide and 57% of risedronate patients reported ≥30% reduction in worst back pain and there were no differences between groups in the proportion of patients experiencing reduction in worst or average back pain at any time point, disability, or quality of life. There was a greater increase from baseline in bone mineral density at the lumbar spine (p00.001) and femoral neck (p00.02) with teriparatide compared to risedronate and a lower incidence of vertebral fractures at 18 months (4% teriparatide and 9% risedronate; p00.01). Vertebral fractures were less severe (p00.04) in the teriparatide group. There was no difference in the overall incidence of adverse events. Conclusions Although there were no differences in back pain-related endpoints, patients receiving teriparatide had greater skeletal benefit than those receiving risedronate.
ER  - 
TY  - JOUR
T1  - Longterm reduction of back pain risk in women with osteoporosis treated with teriparatide compared with alendronate
A1  - Miller, Paul D.
A1  - Shergy, William J.
A1  - Body, Jean Jacques
A1  - Chen, Peiqi
A1  - Rohe, Mark E.
A1  - Krege, John H.
Y1  - 2005///
KW  - Alendronate
KW  - Back pain
KW  - Bone formation
KW  - Osteoporosis
KW  - Teriparatide
JF  - Journal of Rheumatology
VL  - 32
IS  - 8
SP  - 1556
EP  - 1562
SN  - 0315-162X
N2  - OBJECTIVE: To compare the effects on back pain of teriparatide versus alendronate, we analyzed the reporting of back pain in a head to head comparator trial and a followup study., METHODS: In the comparator trial, women were randomized to receive either daily self-injected teriparatide 40 microg plus an oral placebo (n = 73), or daily oral alendronate 10 mg plus self-injected placebo (n = 73). Treatment was for a median 14 months. After completion of the comparator trial, 72{%} of these patients enrolled in a nontreatment followup study. Adverse events were recorded at each comparator trial visit and followup study visit, and the incidence of new or worsening back pain in each group was compared., RESULTS: During the comparator trial, compared with women randomized to alendronate 10 mg, women randomized to teriparatide 40 microg had reduced risk for any back pain (relative risk 0.27, 95{%} CI 0.09-0.82) and moderate or severe back pain (relative risk 0.19, 95{%} CI 0.04-0.86). The differences in the reporting of back pain between the teriparatide treated women and the alendronate treated women were sustained during an interval including the comparator trial plus 18 additional months. During an interval including the comparator trial plus 30 additional months, teriparatide treated patients had numerically fewer occurrences of back pain and moderate or severe back pain., CONCLUSION: Compared with women randomized to alendronate 10 mg, women randomized to teriparatide 40 microg had reduced risk of back pain during the trial and 2.5 years of followup.
ER  - 
TY  - JOUR
T1  - Comparative effects of teriparatide, denosumab, and combination therapy on peripheral compartmental bone density, microarchitecture, and estimated strength: The DATA-HRpQCT study
A1  - Tsai, Joy N.
A1  - Uihlein, Alexander V.
A1  - Burnett-Bowie, Sherri Ann M
A1  - Neer, Robert M.
A1  - Zhu, Yuli
A1  - Derrico, Nicholas
A1  - Lee, Hang
A1  - Bouxsein, Mary L.
A1  - Leder, Benjamin Z.
Y1  - 2015///
KW  - Denosumab
KW  - High-Resolution Peripheral Quantitative Computed T
KW  - Microarchitecture
KW  - Osteoporosis
KW  - Teriparatide
JF  - Journal of Bone and Mineral Research
VL  - 30
IS  - 1
SP  - 39
EP  - 45
SN  - 1523-4681 (Electronic) 0884-0431 (Linking)
DO  - 10.1002/jbmr.2315
N2  - Combined teriparatide and denosumab increases spine and hip bone mineral density more than either drug alone. The effect of this combination on skeletal microstructure and microarchitecture, however, is unknown. Because skeletal microstructure and microarchitecture are important components of skeletal integrity, we performed high-resolution peripheral quantitative computed tomography (HR-pQCT) assessments at the distal tibia and radius in postmenopausal osteoporotic women randomized to receive teriparatide 20 µg daily (n = 31), denosumab 60 mg every 6 months (n = 33), or both (n = 30) for 12 months. In the teriparatide group, total volumetric bone mineral density (vBMD) did not change at either anatomic site but increased in both other groups at both sites. The increase in vBMD at the tibia was greater in the combination group (3.1 ± 2.2%) than both the denosumab (2.2 ± 1.9%) and teriparatide groups (-0.3 ± 1.9%) (p < 0.02 for both comparisons). Cortical vBMD decreased by 1.6 ± 1.9% at the tibia and by 0.9 ± 2.8% at the radius in the teriparatide group, whereas it increased in both other groups at both sites. Tibia cortical vBMD increased more in the combination group (1.5 ± 1.5%) than both monotherapy groups (p < 0.04 for both comparisons). Cortical thickness did not change in the teriparatide group but increased in both other groups. The increase in cortical thickness at the tibia was greater in the combination group (5.4 ± 3.9%) than both monotherapy groups (p < 0.01 for both comparisons). In the teriparatide group, radial cortical porosity increased by 20.9 ± 37.6% and by 5.6 ± 9.9% at the tibia but did not change in the other two groups. Bone stiffness and failure load, as estimated by finite element analysis, did not change in the teriparatide group but increased in the other two groups at both sites. Together, these findings suggest that the use of denosumab and teriparatide in combination improves HR-pQCT measures of bone quality more than either drug alone and may be of significant clinical benefit in the treatment of postmenopausal osteoporosis.
ER  - 
TY  - JOUR
T1  - Signaling pathways affecting skeletal health
A1  - Marie, Pierre J.
Y1  - 2012///
KW  - Cadherins
KW  - Calciumsensing receptor
KW  - Connexins
KW  - Dkk1
KW  - Ephrins
KW  - Growth factors
KW  - Integrins
KW  - MAPKs
KW  - Osteoblasts
KW  - Osteoclasts
KW  - Osteocytes
KW  - Osteoporosis
KW  - PI3K
KW  - Parathyroid hormone
KW  - Pathways
KW  - Sclerostin
KW  - Signaling
KW  - Skeletal health
KW  - Wnt
JF  - Current Osteoporosis Reports
VL  - 10
IS  - 3
SP  - 190
EP  - 198
SN  - 1544-2241 (Electronic)\r1544-1873 (Linking)
DO  - 10.1007/s11914-012-0109-0
N2  - Skeletal health is dependent on the balance between bone resorption and formation during bone remodeling. Multiple signaling pathways play essential roles in the maintenance of skeletal integrity by positively or negatively regulating bone cells. During the last years, significant advances have been made in our understanding of the essential signaling pathways that regulate bone cell commitment, differentiation and survival. New signaling anabolic pathways triggered by parathyroid hormone, local growth factors, Wnt signaling, and calcium sensing receptor have been identified. Novel signals induced by interactions between bone cells-matrix (integrins), osteoblasts/osteocytes (cadherins, connexins), and osteoblasts/osteoclast (ephrins, Wnt-RhoA, semaphorins) have been discovered. Recent studies revealed the key pathways (MAPK, PI3K/Akt) that critically control bone cells and skeletal mass. This review summarizes the most recent knowledge on the major signaling pathways that control bone cells, and their potential impact on the development of therapeutic strategies to improve human bone health.
ER  - 
TY  - JOUR
T1  - Анаболическая терапия остеопороза. Терипаратид: эффективность, безопасность и область применения
A1  - Белая, Ж Е
A1  - Рожинская, Л Я
Y1  - 2013///
PB  - Общество с ограниченной ответственностью" Редакция журнала" Остеопороз и остеопатии"
JF  - Остеопороз и остеопатии
IS  - 2
SP  - 32
EP  - 40
ER  - 
TY  - JOUR
T1  - Анаболическая терапия остеопороза. Терипаратид: эффективность, безопасность и область применения
A1  - Белая Ж.Е., Рожинская, Л.Я.
Y1  - 2013///
JF  - Остеопороз и остеопатии
IS  - 2
SP  - 32
EP  - 40
ER  - 
TY  - JOUR
T1  - The Skeletal Response to Teriparatide Is Largely Independent of Age, Initial Bone Mineral Density, and Prevalent Vertebral Fractures in Postmenopausal Women With Osteoporosis
A1  - Marcus, Robert
A1  - Wang, Ouhong
A1  - Satterwhite, Julie
A1  - Mitlak, Bruce
Y1  - 2003///
JF  - Journal of Bone and Mineral Research
VL  - 18
IS  - 1
SP  - 18
EP  - 23
DO  - 10.1359/jbmr.2003.18.1.18
UR  - http://doi.wiley.com/10.1359/jbmr.2003.18.1.18
N2  - In a recent study of women with postmenopausal osteoporosis, treatment with teriparatide for a median of 19 months increased bone mineral density and decreased the risk of vertebral and nonvertebral fractures. Using the same cohort, the current study evaluated the relationship between these therapeutic effects and the patient's baseline age, vertebral bone mineral density, and prevalent vertebral fractures. In women over 65 years of age, treatment resulted in a greater increase in vertebral bone mineral density than in younger women (treatment-by-age interaction, p = 0.037), but baseline age had no effect on the relative risk reduction for vertebral fractures (treatment-by-age interaction, p = 0.558). In women receiving placebo (with calcium and vitamin D), there was an inverse relationship between baseline vertebral bone mineral density and vertebral fracture risk. When compared across bone mineral density tertiles, the effects of teriparatide on the relative risk for developing new vertebral fractures and increase in vertebral bone mineral density did not differ significantly (p = 0.817 and p = 0.615, respectively). Teriparatide treatment significantly decreased vertebral fracture risk in patients with a vertebral bone mineral density T score of less than -33 or a score between -2.1 and -3.3 (p < 0.001 and p = 0.027, respectively) and showed a trend toward reduced fracture risk in the group with a T score greater than -2.1 (p = 0.115). Placebo-treated women with two or more prevalent vertebral fractures had a significantly greater risk of developing new vertebral fractures than women with zero or one prevalent vertebral fracture (p < 0.001). When compared within prevalent vertebral fracture subgroups, the effects of teriparatide on the relative risk for developing new vertebral fractures were similar. The results of this study indicate that teriparatide offers clinical benefit to patients across a broad range of age and disease severity.
ER  - 
TY  - JOUR
T1  - Teriparatide reduces the fracture risk associated with increasing number and severity of osteoporotic fractures
A1  - Gallagher, J. Christopher
A1  - Genant, Harry K.
A1  - Crans, Gerald G.
A1  - Vargas, Socorro Juan
A1  - Krege, John H.
Y1  - 2005///
JF  - Journal of Clinical Endocrinology and Metabolism
VL  - 90
IS  - 3
SP  - 1583
EP  - 1587
SN  - 0021-972X (Print)\r0021-972X (Linking)
DO  - 10.1210/jc.2004-0826
N2  - The relationship between prior fractures and risk of new fractures was evaluated in 931 postmenopausal women with prevalent vertebral fractures randomized to daily placebo or teriparatide (20 mug) in the Fracture Prevention Trial. The median observation time was 21 months. Among placebo patients with one, two, or three or more prevalent vertebral fractures, 7%, 16%, and 23%, respectively, developed vertebral fractures (by Cochran-Armitage trend test, P < 0.001), and 3%, 9%, and 17% developed moderate or severe vertebral fractures (P < 0.001). Among placebo patients with mild, moderate, or severe prevalent vertebral fractures, 10%, 13%, and 28%, respectively, developed vertebral fractures (P < 0.001), and 4%, 8%, and 23% developed moderate or severe vertebral fractures (P < 0.001). Among placebo patients with zero, one, or two or more prior nonvertebral fragility fractures, 4%, 8%, and 18%, respectively, developed nonvertebral fragility fractures (P < 0.001). In the teriparatide-treated group, there was no significant increase in vertebral or nonvertebral fracture risk in these subgroups. In summary, the number and severity of prevalent vertebral fractures independently predicted the risk for new vertebral fractures, and the number of prior nonvertebral fractures predicted the risk for new nonvertebral fractures in placebo patients. However, in teriparatide-treated patients, the increased fracture risk associated with prior number and severity of fracture was not observed.
ER  - 
TY  - JOUR
T1  - Pretreatment Levels of Bone Turnover and the Antifracture Efficacy of Alendronate: The Fracture Intervention Trial
A1  - Bauer, Douglas C
A1  - Garnero, Patrick
A1  - Hochberg, Marc C
A1  - Santora, Art
A1  - Delmas, Pierre
A1  - Ewing, Susan K
A1  - Black, Dennis M
Y1  - 2005///
JF  - Journal of Bone and Mineral Research
VL  - 21
IS  - 2
SP  - 292
EP  - 299
SN  - 0884-0431
DO  - 10.1359/JBMR.051018
UR  - http://doi.wiley.com/10.1359/JBMR.051018
N2  - UNLABELLED The influence of pretreatment bone turnover on alendronate efficacy is not known. In the FIT, we examined the effect of pretreatment bone turnover on the antifracture efficacy of daily alendronate given to postmenopausal women. The nonspine fracture efficacy of alendronate was significantly greater among both osteoporotic and nonosteoporotic women with higher baseline levels of the bone formation marker PINP. INTRODUCTION Previous trials have shown that high bone turnover is associated with greater increases in BMD among bisphosphonate-treated women. The influence of pretreatment bone turnover levels on antifracture efficacy has not been well studied. MATERIALS AND METHODS We randomized women 55-80 years of age with femoral neck BMD T scores < or = -1.6 to alendronate (ALN), 5-10 mg/day (n = 3105), or placebo (PBO; n = 3081). At baseline, 3495 women were osteoporotic (femoral neck BMD T score < or = -2.5 or prevalent vertebral fracture), and 2689 were not osteoporotic (BMD T score > -2.5 and no prevalent vertebral fracture). Pretreatment levels of bone-specific alkaline phosphatase (BSALP), N-terminal propeptide of type 1 collagen (PINP), and C-terminal cross-linked telopeptide of type 1 collagen (sCTx) were measured in all participants using archived serum (20% fasting). The risk of incident spine and nonspine fracture was compared in ALN- and PBO-treated subjects stratified into tertiles of baseline bone marker level. RESULTS AND CONCLUSIONS During a mean follow-up of 3.2 years, 492 nonspine and 294 morphometric vertebral fractures were documented. Compared with placebo, the reduction in nonspine fractures with ALN treatment differed significantly among those with low, intermediate, and high pretreatment levels of PINP levels (p = 0.03 for trend). For example, among osteoporotic women in the lowest tertile of pretreatment PINP (<41.6 ng/ml), the ALN versus PBO relative hazard for nonspine fracture was 0.88 (95% CI: 0.65, 1.21) compared with a relative hazard of 0.54 (95% CI: 0.39, 0.74) among those in the highest tertile of PINP (>56.8 ng/ml). Results were similar among women without osteoporosis at baseline. Although they did not reach statistical significance, similar trends were observed with baseline levels of BSALP. Conversely, spine fracture treatment efficacy among osteoporotic women did not differ significantly according to pretreatment marker levels. Spine fracture treatment efficacy among nonosteoporotic women was related to baseline BSALP (p = 0.05 for trend). In summary, alendronate nonspine fracture efficacy is greater among both osteoporotic and nonosteoporotic women with high pretreatment PINP. If confirmed in other studies, these findings suggest that bisphosphonate treatment may be most effective in women with elevated bone turnover.
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TY  - JOUR
T1  - Relationship Between Pretreatment Bone Resorption and Vertebral Fracture Incidence in Postmenopausal Osteoporotic Women Treated With Risedronate
A1  - Seibel, Markus J
A1  - Naganathan, Vasi
A1  - Barton, Ian
A1  - Grauer, Andreas
Y1  - 2003///
JF  - Journal of Bone and Mineral Research
VL  - 19
IS  - 2
SP  - 323
EP  - 329
DO  - 10.1359/JBMR.0301231
UR  - http://doi.wiley.com/10.1359/JBMR.0301231
N2  - It is unclear whether the antifracture efficacy of bisphosphonates depends on pretreatment bone turnover. We analyzed the risedronate phase III clinical programs using the urinary excretion of deoxypyridinoline (uDPD) as an index of pretreatment bone resorption rates. Risedronate reduced incident vertebral fractures in women with postmenopausal osteoporosis independent from pretreatment bone resorption. INTRODUCTION: Earlier studies on postmenopausal osteoporosis have suggested that the therapeutic efficacy of antiresorptive therapies might be influenced by pretreatment bone turnover. Because all of these studies have used bone mineral density (BMD) as the primary endpoint, it remains unclear whether this association holds true for incident fractures. MATERIALS AND METHODS: This study aims to answer this question in a post hoc analysis of a subset of the risedronate phase III clinical programs, using the urinary excretion of deoxypyridinoline (uDPD) as an index of pretreatment bone resorption (PBR). A total of 1593 women with postmenopausal osteoporosis that had baseline uDPD values and paired spinal radiographs available were pooled, in similar proportions, from the risedronate multinational and North American VERT, and from the risedronate HIP trials. Patients from treatment and placebo groups were stratified by the uDPD premenopausal normative median. The four resulting groups were balanced for age, years since menopause, body mass index, baseline femoral neck BMD, and number of prevalent fractures, but baseline lumbar spine BMD was significantly higher in patients with low PBR rates. RESULTS: In all groups, the proportion of patients with new vertebral fractures was higher in patients with baseline uDPD levels above the normative median. The incidence of vertebral fracture was significantly lower in groups assigned to risedronate compared with placebo. This effect was independent of PBR: in patients with high PBR, the relative risk (RR) of vertebral fracture after 1 year of risedronate was 0.28 (p = 0.03 compared with controls, absolute risk reduction 7.1%). In patients with low PBR, the RR of fracture after 1 year was 0.33 (p < 0.001, absolute risk reduction 4%). After 3 years, the RR of fracture was 0.52 (p = 0.042, absolute risk reduction 8.3%) in patients with high PBR, and 0.54 (p = 0.002, absolute risk reduction 7.1%) in patients with low PBR. Results were similar after adjusting for age, baseline lumbar spine BMD, and prevalent fractures. The number needed to treat to avoid one vertebral fracture at 12 months was 15 in the group of patients with high PBR and 25 in patients with low PBR. Risedronate significantly increased lumbar spine BMD. During the first year of treatment, women with high PBR gained lumbar spine BMD at a faster rate than patients with low PBR. Treatment-by-PBR status interactions were not significantly different over time. CONCLUSION: The efficacy of risedronate to reduce incident vertebral fractures in women with postmenopausal osteoporosis is largely independent of pretreatment bone resorption rates.
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TY  - JOUR
T1  - Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures
A1  - Black, Dennis M.
A1  - Cummings, Steven R.
A1  - Karpf, David B.
A1  - Cauley, Jane A.
A1  - Thompson, Desmond E.
A1  - Nevitt, Michael C.
A1  - Bauer, Douglas C.
A1  - Genant, Harry K.
A1  - Haskell, William L.
A1  - Marcus, Robert
A1  - Ott, Susan M.
A1  - Torner, James C.
A1  - Quandt, Sara A.
A1  - Reiss, Theodore F.
A1  - Ensrud, Kristine E.
Y1  - 1996///
JF  - Lancet
VL  - 348
IS  - 9041
SP  - 1535
EP  - 1541
SN  - 01406736
DO  - 10.1016/S0140-6736(96)07088-2
N2  - Background. Previous studies have shown that alendronate can increase bone mineral density (BMD) and prevent radiographically defined (morphometric) vertebral fractures. The Fracture Intervention Trial aimed to investigate the effect of alendronate on the risk of morphometric as well as clinically evident fractures in postmenopausal women with low bone mass. Methods. Women aged 55-81 with low femoral-neck BMD were enrolled in two study groups based on presence or absence of an existing vertebral fracture. Results for women with at least one vertebral fracture at baseline are reported here. 2027 women were randomly assigned placebo (1005) or alendronate (1022) and followed up for 36 months. The dose of alendronate (initially 5 mg daily) was increased (to 10 mg daily) at 24 months, with maintenance of the double blind. Lateral spine radiography was done at baseline and at 24 and 36 months. New vertebral fractures, the primary endpoint, were defined by morphometry as a decrease of 20% (and at least 4 mm) in at least one vertebral height between the baseline and latest follow-up radiograph. Non-spine clinical fractures were confirmed by radiographic reports. New symptomatic vertebral fractures were based on self-report and confirmed by radiography. Findings. Follow-up radiographs were obtained for 1946 women (98% of surviving participants). 78 (8.0%) of women in the alendronate group had one or more new morphometric vertebral fractures compared with 145 (15.0%) in the placebo group (relative risk 0.53 [95% CI 0.41-0.68]). For clinically apparent vertebral fractures, the corresponding numbers were 23 (2.3%) alendronate and 50 (5.0%) placebo (relative hazard 0.45 [0.27-0.72]). The risk of any clinical fracture, the main secondary endpoint, was lower in the alendronate than in the placebo group (139 [13.6%] vs 183 [18.2%]; relative hazard 0.72 [0.58-0.90]). The relative hazards for hip fracture and wrist fracture for alendronate versus placebo were 0.49 (0.23-0.99) and 0.52 (0.31-0.87). There was no significant difference between the groups in numbers of adverse experiences, including upper-gastrointestinal disorders. Interpretation. We conclude that among women with low bone mass and existing vertebral fractures, alendronate is well tolerated and substantially reduces the frequency of morphometric and clinical vertebral fractures, as well as other clinical fractures.
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TY  - JOUR
T1  - Effects of Risedronate Treatment on Vertebral and Nonvertebral Fractures in Women With Postmenopausal Osteoporosis&lt;SUBTITLE&gt;A Randomized Controlled Trial&lt;/SUBTITLE&gt;
A1  - Harris, Steven T.
Y1  - 1999///
JF  - Jama
VL  - 282
IS  - 14
SP  - 1344
EP  - 1344
SN  - 0098-7484 (Print)\r0098-7484 (Linking)
DO  - 10.1001/jama.282.14.1344
UR  - http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.282.14.1344
N2  - Context Risedronate, a potent bisphosphonate, has been shown to be effective in the treatment of Paget disease of bone and other metabolic bone diseases but, to our knowledge, it has not been evaluated in the treatment of established postmeno- pausal osteoporosis. Objective To test the efficacy and safety of daily treatment with risedronate to re- duce the risk of vertebral and other fractures in postmenopausal women with estab- lished osteoporosis. Design, Setting, and Participants Randomized, double-blind, placebo-con- trolled trial of 2458 ambulatory postmenopausal women younger than 85 years with at least 1 vertebral fracture at baseline who were enrolled at 1 of 110 centers in North America conducted between December 1993 and January 1998. Interventions Subjects were randomly assigned to receive oral treatment for 3 years with risedronate (2.5 or 5 mg/d) or placebo. All subjects received calcium, 1000 mg/d. Vitamin D (cholecalciferol, up to 500 IU/d) was provided if baseline levels of 25- hydroxyvitamin D were low. MainOutcomeMeasures Incidence of new vertebral fractures as detected by quan- titative and semiquantitative assessments of radiographs; incidence of radiographi- cally confirmed nonvertebral fractures and change from baseline in bone mineral den- sity as determined by dual x-ray absorptiometry. Results The 2.5 mg/d of risedronate arm was discontinued after 1 year; in the placebo and5mg/dof risedronate arms,450and489subjects, respectively, completed all3years of the trial. Treatment with5mg/dof risedronate,comparedwith placebo, decreased the cumulative incidence of new vertebral fractures by 41% (95% confidence interval [CI], 18%-58%)over3years(11.3%vs16.3%;P=.003).Afracture reduction of65%(95% CI, 38%-81%) was observed after the first year (2.4% vs 6.4%; P?.001). The cumula- tive incidence of nonvertebral fractures over 3 years was reduced by39%(95%CI,6%- 61%)(5.2%vs8.4%;P=.02).Bonemineral density increased significantlycomparedwith placebo at the lumbar spine (5.4% vs 1.1%), femoral neck (1.6% vs −1.2%), femoral trochanter (3.3% vs −0.7%), and midshaft of the radius (0.2% vs −1.4%). Bone formed during risedronate treatment was histologically normal. The overall safety profile of ris- edronate, including gastrointestinal safety, was similar to that of placebo. Conclusions These data suggest that risedronate therapy is effective and well tol- erated in the treatment of women with established postmenopausal osteoporosis.
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TY  - JOUR
T1  - Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis
A1  - Reginster, J. Y.
A1  - Minne, H. W.
A1  - Sorensen, O. H.
A1  - Hooper, M.
A1  - Roux, C.
A1  - Brandi, M. L.
A1  - Lund, B.
A1  - Ethgen, D.
A1  - Pack, S.
A1  - Roumagnac, I.
A1  - Eastell, R.
Y1  - 2000///
KW  - Bisphosphonates
KW  - Bone mineral density
KW  - Osteoporosis
KW  - Postmenopausal women
KW  - Risedronate
KW  - Vertebral fracture
JF  - Osteoporosis International
VL  - 11
IS  - 1
SP  - 83
EP  - 91
SN  - 0937-941X (Print)
DO  - 10.1007/s001980050010
N2  - The purpose of this randomized, double- masked, placebo-controlled study was to determine the efficacy and safety of risedronate in the prevention of vertebral fractures in postmenopausal women with established osteoporosis. The study was conducted at 80 study centers in Europe and Australia. Postmeno- pausal women (n = 1226) with two or more prevalent vertebral fractures received risedronate 2.5 or 5 mg/day or placebo; all subjects also received elemental calcium 1000 mg/day, and up to 500 IU/day vitamin D if baseline levels were low. The study duration was 3 years; however, the 2.5 mg group was discontinued by protocol amendment after 2 years. Lateral spinal radiographs were taken annually for assessment of vertebral fractures, and bone mineral density was measured by dual-energy X-ray absorptiometry at 6-month intervals. Risedronate 5 mg reduced the risk of new vertebral fractures by 49% over 3 years compared with control (pS0.001). A significant reduction of 61% was seen within the first year (p = 0.001). The fracture reduction with risedronate 2.5 mg was similar to that in the 5 mg group over 2 years. The risk of nonvertebral fractures was reduced by 33% compared with control over 3 years (p = 0.06). Risedronate significantly increased bone mineral density at the spine and hip within 6 months. The adverse-event profile of risedronate, including gastrointestinal adverse events, was similar to that of control. Risedronate 5 mg provides effective and well- tolerated therapy for severe postmenopausal osteo- porosis, reducing the incidence of vertebral fractures and improving bone density in women with established disease.
ER  - 
TY  - JOUR
T1  - Effect of Parathyroid Hormone (1-34) on Fractures and Bone Mineral Density in Postmenopausal Women with Osteoporosis
A1  - Neer, Robert M.
A1  - Arnaud, Claude D.
A1  - Zanchetta, Jose R.
A1  - Prince, Richard
A1  - Gaich, Gregory A.
A1  - Reginster, Jean-Yves
A1  - Hodsman, Anthony B.
A1  - Eriksen, Erik F.
A1  - Ish-Shalom, Sophia
A1  - Genant, Harry K.
A1  - Wang, Ouhong
A1  - Mellström, Dan
A1  - Oefjord, Erik S.
A1  - Marcinowska-Suchowierska, Ewa
A1  - Salmi, Jorma
A1  - Mulder, Henk
A1  - Halse, Johan
A1  - Sawicki, Andrzej Z.
A1  - Mitlak, Bruce H.
Y1  - 2001///
JF  - New England Journal of Medicine
VL  - 344
IS  - 19
SP  - 1434
EP  - 1441
SN  - 2001051034
DO  - 10.1056/NEJM200105103441904
UR  - http://www.nejm.org/doi/abs/10.1056/NEJM200105103441904
N2  - Background Once-daily injections of parathyroid hormone or its amino-terminal fragments increase bone formation and bone mass without causing hypercalcemia, but their effects on fractures are unknown. Methods We randomly assigned 1637 postmenopausal women with prior vertebral fractures to receive 20 or 40 μg of parathyroid hormone (1-34) or placebo, administered subcutaneously by the women daily. We obtained vertebral radiographs at base line and at the end of the study (median duration of observation, 21 months) and performed serial measurements of bone mass by dual-energy x-ray absorptiometry. Results New vertebral fractures occurred in 14 percent of the women in the placebo group and in 5 percent and 4 percent, respectively, of the women in the 20-μg and 40-μg parathyroid hormone groups; the respective relative risks of fracture in the 20-μg and 40-μg groups, as compared with the placebo group, were 0.35 and 0.31 (95 percent confidence intervals, 0.22 to 0.55 and 0.19 to 0.50). New nonvertebral fragili...
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TY  - JOUR
T1  - Reduction of Vertebral Fracture Risk in Postmenopausal Women With Osteoporosis Treated With Raloxifene: Results From a 3-Year Randomized Clinical Trial
A1  - Ettinger, Bruce
A1  - Black, Dennis M
A1  - Mitlak, Bruce H
A1  - Knickerbocker, Ronald K
A1  - Nickelsen, Thomas
A1  - Genant, Harry K
A1  - Christiansen, Claus
A1  - Delmas, Pierre D
A1  - Zanchetta, Jose R
A1  - Stakkestad, Jacob
A1  - Gluer, Claus C
A1  - Krueger, Kathryn
A1  - Cohen, Fredric J
A1  - Eckert, Stephen
A1  - Ensrud, Kristine E
A1  - Avioli, Louis V
A1  - Lips, Paul
A1  - Cummings, Steven R
A1  - for the Multiple Outcomes of Raloxifene Evaluation, Investigators
Y1  - 1999///
JF  - Jama
VL  - 282
IS  - 7
SP  - 637
EP  - 645
SN  - 0098-7484 (Print)\n0098-7484 (Linking)
DO  - 10.1001/jama.282.7.637
UR  - http://jama.ama-assn.org/cgi/content/abstract/282/7/637
N2  - Context Raloxifene hydrochloride, a selective estrogen receptor modulator, prevents bone loss in postmenopausal women, but whether it reduces fracture risk in these women is not known. Objective To determine the effect of raloxifene therapy on risk of vertebral and nonvertebral fractures. Design The Multiple Outcomes of Raloxifene Evaluation (MORE) study, a multicenter, randomized, blinded, placebo-controlled trial. Setting and Participants A total of 7705 women aged 31 to 80 years in 25 countries who had been postmenopausal for at least 2 years and who met World Health Organization criteria for having osteoporosis. The study began in 1994 and had up to 36 months of follow-up for primary efficacy measurements and nonserious adverse events and up to 40 months of follow-up for serious adverse events. Interventions Participants were randomized to 60 mg/d or 120 mg/d of raloxifene or to identically appearing placebo pills; in addition, all women received supplemental calcium and cholecalciferol. Main Outcome Measures Incident vertebral fracture was determined radiographically at baseline and at scheduled 24- and 36-month visits. Nonvertebral fracture was ascertained by interview at 6-month-interim visits. Bone mineral density was determined annually by dual-energy x-ray absorptiometry. Results At 36 months of the evaluable radiographs in 6828 women, 503 (7.4%) had at least 1 new vertebral fracture, including 10.1% of women receiving placebo, 6.6% of those receiving 60 mg/d of raloxifene, and 5.4% of those receiving 120 mg/d of raloxifene. Risk of vertebral fracture was reduced in both study groups receiving raloxifene (for 60-mg/d group: relative risk [RR], 0.7; 95% confidence interval [CI], 0.5-0.8; for 120-mg/d group: RR, 0.5; 95% CI, 0.4-0.7). Frequency of vertebral fracture was reduced both in women who did and did not have prevalent fracture. Risk of nonvertebral fracture for raloxifene vs placebo did not differ significantly (RR, 0.9; 95% CI, 0.8-1.1 for both raloxifene groups combined). Compared with placebo, raloxifene increased bone mineral density in the femoral neck by 2.1% (60 mg) and 2.4% (120 mg) and in the spine by 2.6% (60 mg) and 2.7% (120 mg) P<0.001 for all comparisons). Women receiving raloxifene had increased risk of venous thromboembolus vs placebo (RR, 3.1; 95% CI, 1.5-6.2). Raloxifene did not cause vaginal bleeding or breast pain and was associated with a lower incidence of breast cancer. Conclusions In postmenopausal women with osteoporosis, raloxifene increases bone mineral density in the spine and femoral neck and reduces risk of vertebral fracture.
ER  - 
TY  - JOUR
T1  - Effects of Oral Ibandronate Administered Daily or Intermittently on Fracture Risk in Postmenopausal Osteoporosis
A1  - Chesnut, Charles H
A1  - Skag, Arne
A1  - Christiansen, Claus
A1  - Recker, Robert
A1  - Stakkestad, Jacob A
A1  - Hoiseth, Arne
A1  - Felsenberg, Dieter
A1  - Huss, Hermann
A1  - Gilbride, Jennifer
A1  - Schimmer, Ralph C
A1  - Delmas, Pierre D
Y1  - 2004///
JF  - Journal of Bone and Mineral Research
VL  - 19
IS  - 8
SP  - 1241
EP  - 1249
SN  - 0884-0431 (Print)\r0884-0431
DO  - 10.1359/JBMR.040325
UR  - http://doi.wiley.com/10.1359/JBMR.040325
N2  - Oral daily (2.5 mg) and intermittent ibandronate (between-dose interval of >2 months), delivering a similar cumulative exposure, were evaluated in 2946 osteoporotic women with prevalent vertebral fracture. Significant reduction in incident vertebral fracture risk by 62% and 50%, respectively, was shown after 3 years. This is the first study to prospectively show antifracture efficacy for the intermittent administration of a bisphosphonate. INTRODUCTION: Bisphosphonates are important therapeutics in postmenopausal osteoporosis. However, they are currently associated with stringent dosing instructions that may impair patient compliance and hence therapeutic efficacy. Less frequent, intermittent administration may help to overcome these deficiencies. This study assessed the efficacy and safety of oral ibandronate administered either daily or intermittently with a dose-free interval of >2 months. MATERIALS AND METHODS: This randomized, double-blind, placebo-controlled, parallel-group study enrolled 2946 postmenopausal women with a BMD T score < or = -2.0 at the lumbar spine in at least one vertebra (L1-L4) and one to four prevalent vertebral fractures (T4-L4). Patients received placebo or oral ibandronate administered either daily (2.5 mg) or intermittently (20 mg every other day for 12 doses every 3 months). RESULTS AND CONCLUSIONS: After 3 years, the rate of new vertebral fractures was significantly reduced in patients receiving oral daily (4.7%) and intermittent ibandronate (4.9%), relative to placebo (9.6%). Thus, daily and intermittent oral ibandronate significantly reduced the risk of new morphometric vertebral fractures by 62% (p = 0.0001) and 50% (p = 0.0006), respectively, versus placebo. Both treatment groups also produced a statistically significant relative risk reduction in clinical vertebral fractures (49% and 48% for daily and intermittent ibandronate, respectively). Significant and progressive increases in lumbar spine (6.5%, 5.7%, and 1.3% for daily ibandronate, intermittent ibandronate, and placebo, respectively, at 3 years) and hip BMD, normalization of bone turnover, and significantly less height loss than in the placebo group were also observed for both ibandronate regimens. The overall population was at low risk for osteoporotic fractures. Consequently, the incidence of nonvertebral fractures was similar between the ibandronate and placebo groups after 3 years (9.1%, 8.9%, and 8.2% in the daily, intermittent, and placebo groups, respectively; difference between arms not significant). However, findings from a posthoc analysis showed that the daily regimen reduces the risk of nonvertebral fractures (69%; p = 0.012) in a higher-risk subgroup (femoral neck BMD T score < -3.0). In addition, oral ibandronate was well tolerated. Oral ibandronate, whether administered daily or intermittently with an extended between-dose interval of >2 months, is highly effective in reducing the incidence of osteoporotic fractures in postmenopausal women. This is the first time that significant fracture efficacy has been prospectively shown with an intermittently administered bisphosphonate in the overall study population of a randomized, controlled clinical trial. Thus, oral ibandronate holds promise as an effective and convenient alternative to current bisphosphonate therapies.
ER  - 
TY  - JOUR
T1  - Rapid bone loss is associated with increased levels of biochemical markers
A1  - Ross, P D
A1  - Knowlton, W
Y1  - 1998///
KW  - Absorptiometry, Photon
KW  - Adult
KW  - Aged
KW  - Aged, 80 and over
KW  - Alkaline Phosphatase/*blood
KW  - Amino Acids/*urine
KW  - Biological Markers/blood/urine
KW  - Bone Density/*physiology
KW  - Calcaneus/metabolism
KW  - Female
KW  - Humans
KW  - Longitudinal Studies
KW  - Middle Aged
KW  - Odds Ratio
KW  - Osteocalcin/*blood
KW  - Osteoporosis, Postmenopausal/blood/*metabolism/uri
KW  - Regression Analysis
JF  - J Bone Miner Res
VL  - 13
IS  - 2
SP  - 297
EP  - 302
SN  - 0884-0431 (Print)
DO  - 10.1359/jbmr.1998.13.2.297
UR  - http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=9495524
N2  - We examined associations of biochemical markers of bone turnover with rapid bone loss, as measured by changes in bone mineral density (BMD). To improve the precision of bone loss estimates, calcaneal BMD was measured up to eight times over a long interval (13 years) among postmenopausal women (mean age = 62 years at baseline). Women with fractures during the previous year, and users of corticosteroids, active vitamin D, bisphosphonates or calcitonin were excluded to avoid potential transient effects on marker levels. Among the remaining 354 women, markers were measured for 100 women with the fastest BMD loss (rapid loss group; mean = 2.2%/year) and 100 with the slowest loss (mean = 0.4%/year). Two markers of bone formation, serum bone alkaline phosphatase (Alkphase-B; BAP) and osteocalcin (NovoCalcin; OC), and two markers of bone resorption, urinary creatinine-corrected free deoxypyridinoline (Pyrilinks-D; DPD) and free pyridinolines (Pyrilinks; PYD), were measured. In separate logistic regression models, each of the markers was strongly associated with rapid loss: the odds of rapid loss increased by 1.8 to 2.0 times for each 1.0 standard deviation (SD) increase of the marker. For BAP levels 2 SD above the mean, the probability of rapid bone loss was 80%; in contrast, the probability was only 20% at 2 SD below the mean. The other markers yielded similar results. We conclude that these markers are associated with rapid bone loss; this relationship appears to be continuous, with progressively greater risk of rapid bone loss with increasing levels of biomarkers. Prospective studies that include the entire distribution of bone loss rates are warranted to confirm these findings.
ER  - 
TY  - JOUR
T1  - Role of peak bone mass and bone loss in postmenopausal osteoporosis: 12 year study.
A1  - Hansen, M A
A1  - Overgaard, K
A1  - Riis, B J
A1  - Christiansen, C
Y1  - 1991///
KW  - Age Factors
KW  - Alkaline Phosphatase
KW  - Alkaline Phosphatase: blood
KW  - Bone Density
KW  - Bone Density: physiology
KW  - Bone and Bones
KW  - Bone and Bones: metabolism
KW  - Calcium
KW  - Calcium: urine
KW  - Creatinine
KW  - Creatinine: urine
KW  - Female
KW  - Fractures, Spontaneous
KW  - Fractures, Spontaneous: prevention & control
KW  - Humans
KW  - Hydroxyproline
KW  - Hydroxyproline: urine
KW  - Middle Aged
KW  - Osteoporosis, Postmenopausal
KW  - Osteoporosis, Postmenopausal: metabolism
KW  - Predictive Value of Tests
KW  - Risk
JF  - BMJ (Clinical research ed.)
VL  - 303
IS  - 6808
SP  - 961
EP  - 4
DO  - 10.1136/bmj.303.6808.961
UR  - http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1671323&tool=pmcentrez&rendertype=abstract
N2  - OBJECTIVE: To examine the role of peak bone mass and subsequent postmenopausal bone loss in the development of osteoporosis and the reliability of identifying women at risk from one bone mass measurement and one biochemical assessment of the future bone loss.\n\nDESIGN: Population based study.\n\nSETTING: Outpatient clinic for research into osteoporosis.\n\nSUBJECTS: 178 healthy early postmenopausal women who had participated in a two year study in 1977. 154 of the women underwent follow up examination in 1989, of whom 33 were excluded because of diseases or taking drugs known to affect calcium metabolism.\n\nMAIN OUTCOME MEASURES: Bone mineral content of the forearm and values of biochemical markers of bone turnover.\n\nRESULTS: The average reduction in bone mineral content during 1977-89 was 20%, but the fast losers had lost 10.0% more than had the slow loser group (mean loss 26.6% in fast losers and 16.6% in slow losers; p less than 0.001). Prediction of future bone mineral content using baseline bone mineral content and estimated rate of loss gave results almost identical with the actual bone mineral content measured in 1989. Seven women had had a Colles' fracture and 20 a spinal compression fracture. The group with Colles' fracture had low baseline bone mineral content (34.7 (95% confidence interval 31.3 to 38.1) units v 39.4 (38.1 to 40.8) units in women with no fracture) whereas the group with spinal fracture had a normal baseline bone mineral content (38.1 (35.0 to 41.1) units) but an increased rate of loss (-2.4 (-3.5 to -1.3)%/year v -1.8 (-2.1 to -1.5)%/year in women with no fracture).\n\nCONCLUSIONS: One baseline measurement of bone mass combined with a single estimation of the rate of bone loss can reliably identify the women at menopause who are at highest risk of developing osteoporosis later in life. The rate of loss may have an independent role in likelihood of vertebral fracture.
ER  - 
TY  - JOUR
T1  - Markers of bone turnover predict postmenopausal forearm bone loss over 4 years: the OFELY study.
A1  - Garnero, P
A1  - Sornay-Rendu, E
A1  - Duboeuf, F
A1  - Delmas, P D
Y1  - 1999///
JF  - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
VL  - 14
IS  - 9
SP  - 1614
EP  - 1621
DO  - 10.1359/jbmr.1999.14.9.1614
N2  - The ability of biochemical markers to predict the rate of postmenopausal bone loss is still controversial. To investigate this issue further, baseline levels of a panel of specific and sensitive biochemical bone markers were correlated to the rate of change of forearm bone mineral density (BMD) assessed by four measurements over a 4-year period using dual-energy X-ray absorptiometry in a large population-based prospective cohort of 305 women aged 50-88 years (mean 64 years), 1-38 years postmenopausal. In the whole population, higher baseline levels of bone formation (serum osteocalcin and serum type I collagen N-terminal propeptide) and bone resorption markers (urinary N-telopeptides; urinary and serum C-telopeptides) were significantly associated with faster BMD loss (r = -0.19 to -0.30, p < 0.001), independently of age. In women within 5 years of menopause that have the highest rate of bone loss, the predictive value of bone markers was increased with correlation coefficients reaching 0.53. Women with an abnormally high bone turnover, i.e., with levels of bone markers at baseline 2 SD above the mean of premenopausal women, had a rate of bone loss that was 2- to 6-fold higher than women with a low turnover (p = 0.01-0.0001) according to the marker. When the population was categorized according to quartiles of bone markers at baseline, a similar relationship between increased levels of bone markers and faster rate of bone loss was found (p = 0.008-0.0001). In the logistic regression model, the odds-ratio of fast bone loss, defined as the rate of bone loss in the upper tertile of the population, was increased by 1.8- to 3.2-fold for levels of biochemical markers in the high turnover group compared with levels within the premenopausal range, with, however, a limited value for identifying individual fast bone losers. We conclude that increased levels of some of the new biochemical markers of bone turnover are associated with greater radial bone loss. Because increased bone loss is associated with an increased risk of fracture, bone turnover markers may be useful to improve the prediction of the risk of osteoporosis in postmenopausal women.
ER  - 
TY  - JOUR
T1  - Potential for bone turnover markers to cost-effectively identify and select post-menopausal osteopenic women at high risk of fracture for bisphosphonate therapy
A1  - Schousboe, J. T.
A1  - Bauer, D. C.
A1  - Nyman, J. A.
A1  - Kane, R. L.
A1  - Melton, L. J.
A1  - Ensrud, K. E.
Y1  - 2007///
KW  - Bisphosphonates
KW  - Bone turnover
KW  - Cost-effectiveness
KW  - Non-vertebral fracture
KW  - Vertebral fracture
JF  - Osteoporosis International
VL  - 18
IS  - 2
SP  - 201
EP  - 210
SN  - 0937-941X (Print)\r0937-941X (Linking)
DO  - 10.1007/s00198-006-0218-7
N2  - INTRODUCTION AND HYPOTHESIS: Over half of all fractures among post-menopausal women occur in those who do not have osteoporosis by bone density criteria. Measurement of bone turnover may cost-effectively identify a subset of women with T-score >-2.5 for whom anti-resorptive drug therapy is cost-effective. METHODS: Using a Markov model, we estimated the cost per quality adjusted life year (QALY) for five years of oral bisphosphonate compared to no drug therapy for osteopenic post-menopausal women aged 60 to 80 years with a high (top quartile) or low (bottom 3 quartiles) level of a bone turnover marker. RESULTS: For women with high bone turnover, the cost per QALY gained with alendronate compared to no drug therapy among women aged 70 years with T-scores of -2.0 or -1.5 were $58,000 and $80,000 (U.S. 2004 dollars), respectively. If bisphosphonates therapy also reduced the risk of non-vertebral fractures by 20% among osteopenic women with high bone turnover, then the costs per QALY gained were $34,000 and $50,000 for women age 70 with high bone turnover and T-scores of -2.0 and -1.5, respectively. CONCLUSION: Measurement of bone turnover markers has the potential to identify a subset of post-menopausal women without osteoporosis by bone density criteria for whom bisphosphonate therapy to prevent fracture is cost-effective. The size of that subset highly depends on the assumed efficacy of bisphosphonates for fracture risk reduction among women with both a T-score >-2.5 and high bone turnover and the cost of bisphosphonate treatment.
ER  - 
TY  - JOUR
T1  - BMD changes and predictors of increased bone loss in postmenopausal women after a 5-year course of alendronate
A1  - McNabb, Brian Louis
A1  - Vittinghoff, Eric
A1  - Schwartz, Ann V.
A1  - Eastell, Richard
A1  - Bauer, Douglas C.
A1  - Ensrud, Kristine
A1  - Rosenberg, Elizabeth
A1  - Santora, Arthur
A1  - Barrett-Connor, Elizabeth
A1  - Black, Dennis M.
Y1  - 2013///
KW  - ALENDRONATE/THERAPEUTIC USE
KW  - BISPHOSPHONATES
KW  - BONE DENSITY
KW  - DRUG HOLIDAY
KW  - DUAL-ENERGY X-RAY ABSORPTIOMETRY (DXA)
KW  - OSTEOPOROSIS
KW  - OSTEOPOROSIS, POSTMENOPAUSE
KW  - OSTEOPOROSIS/TREATMENT
JF  - Journal of Bone and Mineral Research
VL  - 28
IS  - 6
SP  - 1319
EP  - 1327
SN  - 1523-4681
DO  - 10.1002/jbmr.1864
N2  - Management of women discontinuing bisphosphonates after 3 to 5 years of treatment is controversial. Little is known about how much bone mineral density (BMD) is lost after discontinuation or whether there are risk factors for greater rates of bone loss post-discontinuation. We report patterns of change in BMD and prediction models for the changes in BMD in postmenopausal women during a 5-year treatment-free period after alendronate (ALN) therapy. We studied 406 women enrolled in the Fracture Intervention Trial (FIT) who had taken ALN for a mean of 5 years and were then enrolled in the placebo arm of the FIT Long-Term Extension (FLEX) trial for an additional 5 years, describing 5-year percent changes in total hip, femoral neck, and lumbar spine BMD over the treatment-free period. Prediction models of 5-year percent changes in BMD considered all linear combinations of candidate risk factors for bone loss such as BMD at the start of the treatment-free period, the change in BMD on ALN, age, and fracture history. Serum for three markers of bone turnover was available in 76 women, and these bone turnover markers were included as candidate predictors for these 76 women. Mean 5-year BMD changes were -3.6% at the total hip, -1.7% at the femoral neck, and 1.3% at the lumbar spine. Five-year BMD losses of >5% were experienced by 29% of subjects at the total hip, 11% of subjects at the femoral neck, and 1% of subjects at the lumbar spine. Several risk factors such as age and BMI were associated with greater bone loss, but no models based on these risk factors predicted bone loss rates. Although about one-third of women who discontinued ALN after 5 years experienced >5% bone loss at the total hip, predicting which women will lose at a higher rate was not possible.
ER  - 
TY  - JOUR
T1  - Evidence-based guidelines for the treatment of postmenopausal osteoporosis: a consensus document of the Belgian Bone Club
A1  - Boonen, Steven
A1  - Body, Jean-Jacques
A1  - Boutsen, Yves
A1  - Devogelaer, Jean-Pierre
A1  - Goemaere, Stefan
A1  - Kaufman, Jean-Marc
A1  - Rozenberg, Serge
A1  - Reginster, Jean-Yves
Y1  - 2005///
JF  - Osteoporosis International
VL  - 16
IS  - 3
SP  - 239
EP  - 254
DO  - 10.1007/s00198-004-1812-1
UR  - http://link.springer.com/10.1007/s00198-004-1812-1
ER  - 
TY  - JOUR
T1  - Fracture Prediction After Discontinuation of 4 to 5 Years of Alendronate Therapy
A1  - Bauer, Douglas C.
A1  - Schwartz, Ann
A1  - Palermo, Lisa
A1  - Cauley, Jane
A1  - Hochberg, Marc
A1  - Santora, Art
A1  - Cummings, Steven R.
A1  - Black, Dennis M.
Y1  - 2014///
JF  - JAMA Internal Medicine
VL  - 174
IS  - 7
SP  - 1126
EP  - 1126
SN  - 2168-6106
DO  - 10.1001/jamainternmed.2014.1232
UR  - http://archinte.jamanetwork.com/article.aspx?doi=10.1001/jamainternmed.2014.1232
N2  - IMPORTANCE: Discontinuation of bisphosphonate therapy after 3 to 5 years is increasingly considered, but methods to monitor fracture risk after discontinuation have not been established.\n\nOBJECTIVE: To test methods of predicting fracture risk among women who have discontinued alendronate therapy after 4 to 5 years.\n\nDESIGN, SETTING, AND PARTICIPANTS: The prospective Fracture Intervention Trial Long-term Extension (FLEX) study randomized postmenopausal women aged 61 to 86 years previously treated with 4 to 5 years of alendronate therapy to 5 more years of alendronate or placebo from 1998 through 2003; the present analysis includes only the placebo group. Hip and spine dual-energy x-ray absorptiometry (DXA) were measured when placebo was begun (FLEX baseline) and after 1 to 3 years of follow-up. Two biochemical markers of bone turnover, urinary type 1 collagen cross-linked N-telopeptide (NTX) and serum bone-specific alkaline phosphatase (BAP), were measured at FLEX baseline and after 1 and 3 years.\n\nMAIN OUTCOMES AND MEASURES: Symptomatic spine and nonspine fractures occurring after the follow-up measurement of DXA or bone turnover.\n\nRESULTS: During 5 years of placebo, 94 of 437 women (22%) experienced 1 or more symptomatic fractures; 82 had fractures after 1 year. One-year changes in hip DXA, NTX, and BAP were not related to subsequent fracture risk, but older age and lower hip DXA at time of discontinuation were significantly related to increased fracture risk (lowest tertile of baseline femoral neck DXA vs other 2 tertiles relative hazard ratio, 2.17 [95% CI, 1.38-3.41]; total hip DXA relative hazard ratio, 1.87 [95% CI, 1.20-2.92]).\n\nCONCLUSIONS AND RELEVANCE: Among postmenopausal women who discontinue alendronate therapy after 4 to 5 years, age and hip BMD at discontinuation predict clinical fractures during the subsequent 5 years. Follow-up measurements of DXA 1 year after discontinuation and of BAP or NTX 1 to 2 years after discontinuation are not associated with fracture risk and cannot be recommended.\n\nTRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00398931.
ER  - 
TY  - JOUR
T1  - Reassessment of fracture risk in women after 3 years of treatment with zoledronic acid: When is it reasonable to discontinue treatment?
A1  - Cosman, Felicia
A1  - Cauley, Jane A.
A1  - Eastell, Richard
A1  - Boonen, Steven
A1  - Palermo, Lisa
A1  - Reid, Ian R.
A1  - Cummings, Steven R.
A1  - Black, Dennis M.
Y1  - 2014///
JF  - Journal of Clinical Endocrinology and Metabolism
VL  - 99
IS  - 12
SP  - 4546
EP  - 4554
SN  - 0021-972x
DO  - 10.1210/jc.2014-1971
N2  - CONTEXT: Data are needed to guide therapeutic decisions about stopping bisphosphonates after an initial treatment period. OBJECTIVE: To define significant predictors of fracture and quantify fracture incidence in risk factor-defined subgroups of women who discontinue zoledronic acid (ZOL) after 3 years of treatment. To determine if continuing ZOL reduces fracture risk in subgroups. DESIGN: This study is based on data from the 3 year extension of HORIZON. SETTING: Subjects were in the ZOL arm of the Multicenter HORIZON trial. PARTICIPANTS: One thousand two hundred thirty three women who previously received 3 ZOL treatments during the Core trial. INTERVENTION: Randomization to three additional annual ZOL (Z6, n = 616) or placebo infusions (Z3P3, n = 617). MAIN OUTCOMES: The risk of morphometric vertebral fractures (MorphVertFx) and clinical nonvertebral fractures (NVF). RESULTS: The incidence of MorphVertFx in Z3P3 was predicted by femoral neck (FN) t-score </=-2.5 [OR 3.3 (1.4, 8.0), p = .008], total hip (TH) t-score </=-2.5 [OR 4.0 (1.8, 9.0), p = .0007], and incident MorphVertFx during Core [OR 4.75 (1.4, 16.8), p < .015]. Incidence of NVF was predicted by TH t-score [for 1 decline, HR 1.7 (1.2, 2.6), p = .008], incident NVF during Core [HR 2.5 (1.2, 5.3), p = .014], and prevalent vertebral fracture [HR 3.0 (1.4, 6.3), p = .005]. For MorphVertFx, there were no significant treatment subgroup interactions; absolute fracture reductions with continued ZOL were greatest in high-risk subgroups. For NVF, there were no significant treatment reductions overall or in subgroups and no significant interactions. CONCLUSIONS: After 3 years of ZOL, in women who have a TH t-score above -2.5, no recent incident fracture and no more than one risk factor (almost 55% of the population), risk for subsequent fracture (over three additional years) is low if treatment is discontinued (for MorphVertFx, average risk 3.2% and for NVF, average risk 5.8%). In these patients, discontinuation for up to 3 years is reasonable.
ER  - 
TY  - JOUR
T1  - Alendronate for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis
A1  - Saag, Kenneth G.
A1  - Emkey, Ronald
A1  - Schnitzer, Thomas J.
A1  - Brown, Jacques P.
A1  - Hawkins, Federico
A1  - Goemaere, Stefan
A1  - Thamsborg, Gorm
A1  - Liberman, Uri A.
A1  - Delmas, Pierre D.
A1  - Malice, Marie-Pierre
A1  - Czachur, Michelle
A1  - Daifotis, Anastasia G.
A1  - Lane, Nancy
A1  - Correa-Rotter, Ricardo
A1  - Yanover, Melissa
A1  - Westhovens, Rene
A1  - Epstein, Sol
A1  - Adachi, Jonathan D.
A1  - Poubelle, Patrice
A1  - Melo-Gomes, Jose
A1  - Rodriguez-Portales, Jose A.
Y1  - 1998///
JF  - New England Journal of Medicine
VL  - 339
IS  - 5
SP  - 292
EP  - 299
SN  - 0028-4793
DO  - 10.1056/NEJM199807303390502
UR  - http://www.nejm.org/doi/abs/10.1056/NEJM199807303390502
N2  - Background Osteoporosis is a common complication of long-term glucocorticoid therapy for which there is no well-proved preventive or restorative treatment. Methods We carried out two 48-week, randomized, placebo-controlled studies of two doses of alendronate in 477 men and women, 17 to 83 years of age, who were receiving glucocorticoid therapy. The primary end point was the difference in the mean percent change in lumbar-spine bone density from base line to week 48 between the groups. Secondary outcomes included changes in bone density of the hip, biochemical markers of bone turnover, and the incidence of new vertebral fractures. Results The mean (±SE) bone density of the lumbar spine increased by 2.1±0.3 percent and 2.9±0.3 percent, respectively, in the groups that received 5 and 10 mg of alendronate per day (P<0.001) and decreased by 0.4±0.3 percent in the placebo group. The femoral-neck bone density increased by 1.2±0.4 percent and 1.0±0.4 percent in the respective alendronate groups (P<0.01) and decre...
ER  - 
TY  - JOUR
T1  - Бисфосфонаты в терапии постменопаузального остеопороза
A1  - Белая Ж.Е., Рожинская, Л.Я.
Y1  - 2010///
JF  - Доктор.Ру.
IS  - 7-2 (58)
SP  - 29
EP  - 38
ER  - 
TY  - JOUR
T1  - Бисфосфонаты в терапии постменопаузального остеопороза
A1  - Белая, Жанна Евгеньевна
A1  - Рожинская, Людмила Яковлевна
Y1  - 2010///
PB  - Некоммерческое партнерство содействия развитию системы здравоохранения и медицины Русмедикал групп
JF  - Доктор. Ру
IS  - 7-2
SP  - 29
EP  - 38
ER  - 
TY  - JOUR
T1  - Once-Weekly Risedronate in Men With Osteoporosis: Results of a 2-Year, Placebo-Controlled, Double-Blind, Multicenter Study
A1  - Boonen, Steven
A1  - Orwoll, Eric S
A1  - Wenderoth, Dietrich
A1  - Stoner, Karen J
A1  - Eusebio, Rachelle
A1  - Delmas, Pierre D
Y1  - 2009///
JF  - Journal of Bone and Mineral Research
VL  - 24
IS  - 4
SP  - 719
EP  - 725
SN  - 0884-0431
DO  - 10.1359/jbmr.081214
UR  - http://doi.wiley.com/10.1359/jbmr.081214
N2  - Male osteoporosis is increasingly recognized as a major public health issue. This multinational, 2-yr, randomized, double-blind, placebo-controlled study was conducted to determine the efficacy and safety of 35 mg once-a-week risedronate in men with osteoporosis. Patients had to be men 30 yr old, with lumbar spine T-score 22.5 and femoral neck T-score 21 SD or lumbar spine T-score 21 and femoral neck T-score 22 SD (based on young normal men). Patients were randomized 2:1 to risedronate 35 mg once a week or placebo for 2 yr; all patients took 1000 mg elemental calcium and 400–500 IU vitamin D daily. Lumbar spine BMD at month 24 using last observation carried forward was the primary endpoint. Other endpoints included lumbar spine BMD at time points other than month 24, proximal femur BMD, bone turnover markers (BTMs), new vertebral fractures, clinical fractures, and adverse event (AE) assessment. There were 284 men enrolled in the study. Treatment with risedronate resulted in a significant increase from baseline to endpoint in lumbar spine BMD compared with placebo (4.5%; 95% CI: 3.5%, 5.6%; p < 0.001). Few new vertebral and nonvertebral fractures were reported, with no differences in fracture rates between the two groups. There was a significant (p < 0.01) reduction from baseline in BTMs for the risedronate group compared with placebo at all time points. No apparent differences in the pattern or distribution of AEs including serious and upper gastrointestinal AEs were observed. Risedronate therapy was well tolerated during this 2-yr study and was rapidly effective as indicated by significant BTM decreases at month 3 and BMD increases at month 6 (the earliest time points tested). The effects of risedronate treatment on BMD and BTMs in this study were similar to those previously shown to be associated with fracture risk reductions in women with postmenopausal osteoporosis.
ER  - 
TY  - JOUR
T1  - Prevention of Bone Loss with Risedronate in Glucocorticoid-Treated Rheumatoid Arthritis Patients
A1  - Eastell, R.
A1  - Devogelaer, J.-P.
A1  - Peel, N. F. A.
A1  - Chines, A. A.
A1  - Bax, D. E.
A1  - Sacco-Gibson, N.
A1  - Nagant de Deuxchaisnes, C.
A1  - Russell, R. G. G.
Y1  - 2000///
JF  - Osteoporosis International
VL  - 11
IS  - 4
SP  - 331
EP  - 337
DO  - 10.1007/s001980070122
UR  - http://link.springer.com/10.1007/s001980070122
N2  - The aim of the study was to assess risedronate's effect on bone mineral density in postmenopausal women with rheumatoid arthritis receiving glucocorticoids. We carried out a two center, 2 year, double-masked, placebo-controlled trial with a third year of nontreatment follow-up. We studied 120 women requiring long-term glucocorticoid therapy at > 2.5 mg/day prednisolone randomized to treatment with daily placebo; daily 2.5 mg risedronate; or cyclical 15 mg risedronate (2 out of 12 weeks). At 97 weeks, bone mineral density was maintained at the lumbar spine (+1.4%) and trochanter (+0.4%) in the daily 2.5 mg risedronate group, while significant bone loss occurred in the placebo group (-1.6%, p = 0.03; and 4.0%, p < 0.005, respectively). At the femoral neck, there was a nonsignificant bone loss in the daily 2.5 mg risedronate group (-1.0%) while in the placebo group bone mass decreased significantly (-3.6%, p < 0.001). The difference between placebo and daily 2.5 mg risedronate groups was significant at the lumbar spine (p = 0.009) and trochanter (p = 0.02) but did not reach statistical significance at the femoral neck. Although not significantly different from placebo at the lumbar spine, the overall effect of the cyclical regimen was similar to that of the daily 2.5 mg risedronate regimen. Treatment withdrawal led to bone loss in the risedronate groups that was significant at the lumbar spine. A similar number of patients experienced adverse events (including upper gastrointestinal events) across treatment groups and risedronate was generally well tolerated. Thus risedronate preserves bone mass in postmenopausal women with rheumatoid arthritis receiving glucocorticoids while patients receiving a placebo have significant bone loss.
ER  - 
TY  - JOUR
T1  - Once-monthly oral ibandronate provides significant improvement in bone mineral density in postmenopausal women treated with glucocorticoids for inflammatory rheumatic diseases: a 12-month, randomized, double-blind, placebo-controlled trial
A1  - Hakala, M
A1  - Kröger, H
A1  - Valleala, H
A1  - Hienonen-Kempas, T
A1  - Lehtonen-Veromaa, M
A1  - Heikkinen, J
A1  - Tuomiranta, T
A1  - Hannonen, P
A1  - Paimela, L
Y1  - 2012///
JF  - Scandinavian Journal of Rheumatology
VL  - 41
IS  - 4
SP  - 260
EP  - 266
SN  - 1502-7732 (Electronic)\r0300-9742 (Linking)
DO  - 10.3109/03009742.2012.664647
UR  - http://www.tandfonline.com/doi/full/10.3109/03009742.2012.664647
N2  - OBJECTIVES: To study the efficacy and safety of once-monthly oral ibandronate in the prevention of glucocorticoid (GC)-induced osteoporosis (GIOP) in postmenopausal women with inflammatory rheumatic diseases.\n\nMETHOD: A randomized, double-blind, placebo-controlled, parallel-group study of 140 postmenopausal women was conducted. At baseline, the mean lumbar spine (LS) (L1-L4) bone mineral density (BMD) was normal or osteopaenic (T-score ≥ -2.0) and the patients were receiving treatment with 5-15 mg/day of prednisone equivalent. Patients were randomized 1:1 to receive either monthly oral ibandronate 150 mg or placebo for 12 months. All patients received vitamin D and calcium supplements. The primary endpoint was the relative change in mean LS BMD from baseline to 12 months.\n\nRESULTS: Mean LS BMD increased significantly by 2.6% and 3.2% from baseline to 6 and 12 months with ibandronate compared to 0.3% and -0.1% with placebo, respectively (p < 0.001). Comparable significant mean increases were also found in trochanter, femoral neck and total hip BMDs at 12 months. Reductions in the serum levels of bone turnover markers C-terminal telopeptide of type I collagen (sCTX), N-terminal propeptide of type I procollagen (P1NP), and tartrate-resistant acid phosphatase (TRACP) were significantly more marked in the ibandronate group than in the placebo group at 1, 6, and 12 months. Adverse events (AEs) were reported at a similar frequency in both groups. A higher proportion of serious AEs (SAEs) were reported in the ibandronate group without emergence of any single SAE.\n\nCONCLUSIONS: Once-monthly oral ibandronate provides a significant increase in LS and total hip BMD with an acceptable safety profile in postmenopausal women treated with low-dose GCs for inflammatory rheumatic diseases.
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TY  - JOUR
T1  - Efficacy and safety of monthly ibandronate in men with low bone density
A1  - Orwoll, Eric S.
A1  - Binkley, Neil C.
A1  - Lewiecki, E. Michael
A1  - Gruntmanis, Ugis
A1  - Fries, Michael A.
A1  - Dasic, Gorana
Y1  - 2010///
KW  - Bone density
KW  - Ibandronate
KW  - Men
KW  - Osteoporosis
KW  - Treatment
JF  - Bone
VL  - 46
IS  - 4
SP  - 970
EP  - 976
SN  - 8756-3282
DO  - 10.1016/j.bone.2009.12.034
N2  - Introduction: Monthly oral ibandronate is indicated for the prevention and treatment of osteoporosis in postmenopausal women. The STudy Researching Osteoporosis iN Guys (STRONG) investigated the efficacy and safety of 150-mg monthly oral ibandronate in men with primary, idiopathic, or hypogonadism-related low bone density. Methods: STRONG was a 1-year, placebo-controlled, randomized (2 ibandronate: 1 placebo), double-blind study that enrolled ambulatory men > 30 years with baseline femoral neck (FN) bone mineral density (BMD) T-scores << 2.0 and lumbar spine (LS) BMD T-scores << 1.0 or LS BMD T-scores << 2.0, FN BMD T-scores << 1.0, and BMD T-scores >> 4.0 at any site assessed by dual-energy X-ray absorptiometry. The primary endpoint was mean percent change from baseline in LS BMD at 1 year (intent-to-treat [ITT] population). Secondary endpoints included mean BMD changes from baseline at the FN, total hip (TH), and trochanter (TR) and changes in bone turnover markers (BTMs), as measured by the bone resorption marker serum C-terminal telopeptide of type 1 collagen (sCTX) and the bone formation marker bone-specific alkaline phosphatase (BSAP). All men received twice daily calcium carbonate (1000 mg/day) and vitamin D (400 IU/day). Changes in BMD for treatment groups were compared using analysis of covariance with treatment, investigative site, and baseline testosterone as factors and baseline BMD as a covariate. Results: The ITT population consisted of 132 men; 47 received placebo and 85 received monthly ibandronate. Men who received ibandronate achieved greater increases in LS BMD at 12 months than those who received placebo (3.5% vs. 0.9%, respectively; difference, 2.6; p<0.001). The ibandronate group also achieved greater 12-month BMD increases than the placebo group, respectively, at the TH (1.8% vs. - 0.3%; difference, 2.1; p<0.001), FN (1.2% vs - 0.2%; difference, 1.4; p=0.012), and TR (2.2% vs. 0.4%; difference, 1.7; p<0.005). In men who completed the study and adhered to the protocol (per-protocol (PP) population), percent decreases in median sCTX and BSAP levels from baseline were also greater with ibandronate versus placebo (p<0.001 for both comparisons). Overall, monthly ibandronate was well tolerated. Conclusions: In men with low BMD, 1 year of treatment with oral once-monthly 150-mg ibandronate significantly increased BMD at the LS and hip (TH, TR, and FN), significantly reduced BTM levels in the PP population, and was generally well tolerated. ?? 2009 Elsevier Inc.
ER  - 
TY  - JOUR
T1  - Ibandronate for the prevention of nonvertebral fractures: A pooled analysis of individual patient data
A1  - Cranney, A.
A1  - Wells, G. A.
A1  - Yetisir, E.
A1  - Adami, S.
A1  - Cooper, C.
A1  - Delmas, P. D.
A1  - Miller, P. D.
A1  - Papapoulos, S.
A1  - Reginster, J. Y.
A1  - Sambrook, P. N.
A1  - Silverman, S.
A1  - Siris, E.
A1  - Adachi, J. D.
Y1  - 2009///
KW  - Ibandronate
KW  - Nonvertebral fractures
KW  - Postmenopausal osteoporosis
JF  - Osteoporosis International
VL  - 20
IS  - 2
SP  - 291
EP  - 297
SN  - 0019800806538
DO  - 10.1007/s00198-008-0653-8
N2  - This analysis was conducted to assess the effect of high versus lower doses of ibandronate on nonvertebral fractures. The results were adjusted for clinical fracture, age, and bone density. The treatment effect was dose-dependent. Higher doses of ibandronate significantly reduced the risk of nonvertebral fractures more effectively compared with lower doses. Introduction The objective of this study was to assess the efficacy of different doses of ibandronate on nonvertebral fractures in a pooled analysis. Methods Eight randomized trials of ibandronate were reviewed for inclusion. Alternative definitions of high versus low doses based on annual cumulative exposure (ACE) were explored. A time-to-event analysis was con-ducted using Kaplan–Meier methodology. Hazard ratios (HR) were derived using Cox regression and adjusted for covariates. Results Combining higher ACE doses of ≥ 10.8 mg (150 mg once monthly, 3 mg i.v. quarterly, and 2 mg i.v. every 2 months) versus ACE doses of 5.5 mg, from two trials, resulted in an HR 0.62 (95% CI 0.396–0.974, p= 0.038). There was a dose–response trend with increasing ACE doses (7.2–12 mg) versus ACE of 5.5 mg. Conclusions A dose–response effect on nonvertebral frac-tures was observed when comparing high with low ACE doses. A significant reduction in nonvertebral fractures was noted when pooling data from trials using ACE doses of ≥ 10.8 mg versus ACE ≤ 7.2 mg; and with ACE ≥ 10.8 mg versus ACE of 5.5 mg (38% reduction). Higher ibandronate dose levels (150 mg monthly or 3 mg i.v. quarterly) significantly reduced nonvertebral fracture risk in postmen-opausal women.
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TY  - JOUR
T1  - The Effects of Strontium Ranelate on the Risk of Vertebral Fracture in Women with Postmenopausal Osteoporosis
A1  - Meunier, Pierre J.
A1  - Roux, Christian
A1  - Seeman, Ego
A1  - Ortolani, Sergio
A1  - Badurski, Janusz E.
A1  - Spector, Tim D.
A1  - Cannata, Jorge
A1  - Balogh, Adam
A1  - Lemmel, Ernst-Martin
A1  - Pors-Nielsen, Stig
A1  - Rizzoli, René
A1  - Genant, Harry K.
A1  - Reginster, Jean-Yves
Y1  - 2004///
JF  - New England Journal of Medicine
VL  - 350
IS  - 5
SP  - 459
EP  - 468
SN  - 1533-4406 (Electronic)\r0028-4793 (Linking)
DO  - 10.1056/NEJMoa022436
UR  - http://www.nejm.org/doi/abs/10.1056/NEJMoa022436
N2  - BACKGROUND Osteoporotic structural damage and bone fragility result from reduced bone formation and increased bone resorption. In a phase 2 clinical trial, strontium ranelate, an orally active drug that dissociates bone remodeling by increasing bone formation and decreasing bone resorption, has been shown to reduce the risk of vertebral fractures and to increase bone mineral density. METHODS To evaluate the efficacy of strontium ranelate in preventing vertebral fractures in a phase 3 trial, we randomly assigned 1649 postmenopausal women with osteoporosis (low bone mineral density) and at least one vertebral fracture to receive 2 g of oral strontium ranelate per day or placebo for three years. We gave calcium and vitamin D supplements to both groups before and during the study. Vertebral radiographs were obtained annually, and measurements of bone mineral density were performed every six months. RESULTS New vertebral fractures occurred in fewer patients in the strontium ranelate group than in the placebo group, with a risk reduction of 49 percent in the first year of treatment and 41 percent during the three-year study period (relative risk, 0.59; 95 percent confidence interval, 0.48 to 0.73). Strontium ranelate increased bone mineral density at month 36 by 14.4 percent at the lumbar spine and 8.3 percent at the femoral neck (P<0.001 for both comparisons). There were no significant differences between the groups in the incidence of serious adverse events. CONCLUSIONS Treatment of postmenopausal osteoporosis with strontium ranelate leads to early and sustained reductions in the risk of vertebral fractures.
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TY  - JOUR
T1  - Once-Yearly Zoledronic Acid for Treatment of Postmenopausal Osteoporosis
A1  - Black, Dennis M.
A1  - Delmas, Pierre D.
A1  - Eastell, Richard
A1  - Reid, Ian R.
A1  - Boonen, Steven
A1  - Cauley, Jane A.
A1  - Cosman, Felicia
A1  - Lakatos, Péter
A1  - Leung, Ping Chung
A1  - Man, Zulema
A1  - Mautalen, Carlos
A1  - Mesenbrink, Peter
A1  - Hu, Huilin
A1  - Caminis, John
A1  - Tong, Karen
A1  - Rosario-Jansen, Theresa
A1  - Krasnow, Joel
A1  - Hue, Trisha F.
A1  - Sellmeyer, Deborah
A1  - Eriksen, Erik Fink
A1  - Cummings, Steven R.
Y1  - 2007///
JF  - New England Journal of Medicine
VL  - 356
IS  - 18
SP  - 1809
EP  - 1822
SN  - 1533-4406 (Electronic) 0028-4793 (Linking)
DO  - 10.1056/NEJMoa067312
UR  - http://www.nejm.org/doi/abs/10.1056/NEJMoa067312
N2  - BACKGROUND: A single infusion of intravenous zoledronic acid decreases bone turnover and improves bone density at 12 months in postmenopausal women with osteoporosis. We assessed the effects of annual infusions of zoledronic acid on fracture risk during a 3-year period. METHODS: In this double-blind, placebo-controlled trial, 3889 patients (mean age, 73 years) were randomly assigned to receive a single 15-minute infusion of zoledronic acid (5 mg) and 3876 were assigned to receive placebo at baseline, at 12 months, and at 24 months; the patients were followed until 36 months. Primary end points were new vertebral fracture (in patients not taking concomitant osteoporosis medications) and hip fracture (in all patients). Secondary end points included bone mineral density, bone turnover markers, and safety outcomes. RESULTS: Treatment with zoledronic acid reduced the risk of morphometric vertebral fracture by 70% during a 3-year period, as compared with placebo (3.3% in the zoledronic-acid group vs. 10.9% in the placebo group; relative risk, 0.30; 95% confidence interval [CI], 0.24 to 0.38) and reduced the risk of hip fracture by 41% (1.4% in the zoledronic-acid group vs. 2.5% in the placebo group; hazard ratio, 0.59; 95% CI, 0.42 to 0.83). Nonvertebral fractures, clinical fractures, and clinical vertebral fractures were reduced by 25%, 33%, and 77%, respectively (P<0.001 for all comparisons). Zoledronic acid was also associated with a significant improvement in bone mineral density and bone metabolism markers. Adverse events, including change in renal function, were similar in the two study groups. However, serious atrial fibrillation occurred more frequently in the zoledronic acid group (in 50 vs. 20 patients, P<0.001). CONCLUSIONS: A once-yearly infusion of zoledronic acid during a 3-year period significantly reduced the risk of vertebral, hip, and other fractures. (ClinicalTrials.gov number, NCT00049829.)
ER  - 
TY  - JOUR
T1  - Denosumab for Prevention of Fractures in Postmenopausal Women with Osteoporosis
A1  - Cummings, Steven R.
A1  - Martin, Javier San
A1  - McClung, Michael R.
A1  - Siris, Ethel S.
A1  - Eastell, Richard
A1  - Reid, Ian R.
A1  - Delmas, Pierre
A1  - Zoog, Holly B.
A1  - Austin, Matt
A1  - Wang, Andrea
A1  - Kutilek, Stepan
A1  - Adami, Silvano
A1  - Zanchetta, Jose
A1  - Libanati, Cesar
A1  - Siddhanti, Suresh
A1  - Christiansen, Claus
Y1  - 2009///
JF  - New England Journal of Medicine
VL  - 361
IS  - 8
SP  - 756
EP  - 765
SN  - 1533-4406 (Electronic)
DO  - 10.1056/NEJMoa0809493
UR  - http://www.nejm.org/doi/abs/10.1056/NEJMoa0809493
N2  - Background Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor-κB ligand (RANKL) that blocks its binding to RANK, inhibiting the development and activity of osteoclasts, decreasing bone resorption, and increasing bone density. Given its unique actions, denosumab may be useful in the treatment of osteoporosis. Methods We enrolled 7868 women between the ages of 60 and 90 years who had a bone mineral density T score of less than −2.5 but not less than −4.0 at the lumbar spine or total hip. Subjects were randomly assigned to receive either 60 mg of denosumab or placebo subcutaneously every 6 months for 36 months. The primary end point was new vertebral fracture. Secondary end points included nonvertebral and hip fractures. Results As compared with placebo, denosumab reduced the risk of new radiographic vertebral fracture, with a cumulative incidence of 2.3% in the denosumab group, versus 7.2% in the placebo group (risk ratio, 0.32; 95% confidence interval [CI], 0.26 to 0...
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TY  - JOUR
T1  - Effect of Alendronate on Risk of Fracture in Women With Low Bone Density but Without Vertebral Fractures&lt;SUBTITLE&gt;Results From the Fracture Intervention Trial&lt;/SUBTITLE&gt;
A1  - Cummings, Steven R.
Y1  - 1998///
JF  - Jama
VL  - 280
IS  - 24
SP  - 2077
EP  - 2077
DO  - 10.1001/jama.280.24.2077
UR  - http://jama.jamanetwork.com/article.aspx?doi=10.1001/jama.280.24.2077
ER  - 
TY  - JOUR
T1  - Effect of Risedronate on the Risk of Hip Fracture in Elderly Women
A1  - McClung, Michael R.
A1  - Geusens, Piet
A1  - Miller, Paul D.
A1  - Zippel, Hartmut
A1  - Bensen, William G.
A1  - Roux, Christian
A1  - Adami, Silvano
A1  - Fogelman, Ignac
A1  - Diamond, Terrence
A1  - Eastell, Richard
A1  - Meunier, Pierre J.
A1  - Wasnich, Richard D.
A1  - Greenwald, Maria
A1  - Kaufman, Jean-Marc
A1  - Chesnut, Charles H.
A1  - Reginster, Jean-Yves
Y1  - 2001///
JF  - New England Journal of Medicine
VL  - 344
IS  - 5
SP  - 333
EP  - 340
DO  - 10.1056/NEJM200102013440503
UR  - http://www.nejm.org/doi/abs/10.1056/NEJM200102013440503
N2  - Background Risedronate increases bone mineral density in elderly women, but whether it prevents hip fracture is not known. Methods We studied 5445 women 70 to 79 years old who had osteoporosis (indicated by a T score for bone mineral density at the femoral neck that was more than 4 SD below the mean peak value in young adults [–4] or lower than –3 plus a nonskeletal risk factor for hip fracture, such as poor gait or a propensity to fall) and 3886 women at least 80 years old who had at least one nonskeletal risk factor for hip fracture or low bone mineral density at the femoral neck (T score, lower than –4 or lower than –3 plus a hip-axis length of 11.1 cm or greater). The women were randomly assigned to receive treatment with oral risedronate (2.5 or 5.0 mg daily) or placebo for three years. The primary end point was the occurrence of hip fracture. Results Overall, the incidence of hip fracture among all the women assigned to risedronate was 2.8 percent, as compared with 3.9 percent among those assigned t...
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TY  - JOUR
T1  - Strontium ranelate reduces the risk of nonvertebral fractures in postmenopausal women with osteoporosis: Treatment of Peripheral Osteoporosis (TROPOS) study
A1  - Reginster, J. Y.
A1  - Seeman, E.
A1  - De Vernejoul, M. C.
A1  - Adami, S.
A1  - Compston, J.
A1  - Phenekos, C.
A1  - Devogelaer, J. P.
A1  - Curiel, M. Diaz
A1  - Sawicki, A.
A1  - Goemaere, S.
A1  - Sorensen, O. H.
A1  - Felsenberg, D.
A1  - Meunier, P. J.
Y1  - 2005///
JF  - Journal of Clinical Endocrinology and Metabolism
VL  - 90
IS  - 5
SP  - 2816
EP  - 2822
SN  - 0021-972X (Print)
DO  - 10.1210/jc.2004-1774
N2  - BACKGROUND: Strontium ranelate, a new oral drug shown to reduce vertebral fracture risk in postmenopausal women with osteoporosis, was studied in the Treatment of Peripheral Osteoporosis (TROPOS) study to assess its efficacy and safety in preventing nonvertebral fractures also. METHODS: Strontium ranelate (2 g/d) or placebo were randomly allocated to 5091 postmenopausal women with osteoporosis in a double-blind placebo-controlled 5-yr study with a main statistical analysis over 3 yr of treatment. FINDINGS: In the entire sample, relative risk (RR) was reduced by 16% for all nonvertebral fractures (P = 0.04), and by 19% for major fragility fractures (hip, wrist, pelvis and sacrum, ribs and sternum, clavicle, humerus) (P = 0.031) in strontium ranelate-treated patients in comparison with the placebo group. Among women at high risk of hip fracture (age > or = 74 yr and femoral neck bone mineral density T score < or = -3, corresponding to -2.4 according to NHANES reference) (n = 1977), the RR reduction for hip fracture was 36% (P = 0.046). RR of vertebral fractures was reduced by 39% (P < 0.001) in the 3640 patients with spinal x-rays and by 45% in the subgroup without prevalent vertebral fracture. Strontium ranelate increased bone mineral density throughout the study, reaching at 3 yr (P < 0.001): +8.2% (femoral neck) and +9.8% (total hip). Incidence of adverse events (AEs) was similar in both groups. CONCLUSION: This study shows that strontium ranelate significantly reduces the risk of all nonvertebral and in a high-risk subgroup, hip fractures over a 3-yr period, and is well tolerated. It confirms that strontium ranelate reduces vertebral fractures. Strontium ranelate offers a safe and effective means of reducing the risk of fracture associated with osteoporosis.
ER  - 
TY  - JOUR
T1  - Cytosolic Entry of Bisphosphonate Drugs Requires Acidification of Vesicles after Fluid-Phase Endocytosis
A1  - Thompson, K.
Y1  - 2006///
JF  - Molecular Pharmacology
VL  - 69
IS  - 5
SP  - 1624
EP  - 1632
DO  - 10.1124/mol.105.020776
UR  - http://molpharm.aspetjournals.org/cgi/doi/10.1124/mol.105.020776
ER  - 
TY  - JOUR
T1  - Management of postmenopausal osteoporosis: position statement of The North American Menopause Society
Y1  - 2002///
JF  - Menopause
SP  - 84
EP  - 101
SN  - 1072-3714
DO  - 10.1097/00042192-200203000-00003
UR  - http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00042192-200203000-00003
N2  - Objective: The North American Menopause Society (NAMS) established a goal to create an evidence-based position statement regarding the management of postmenopausal osteoporosis. Design: NAMS followed the general principles established for evidence-based guidelines to create this document. A MEDLINE search was conducted. Clinicians and researchers acknowledged to be experts in the field of osteoporosis were enlisted to review the evidence. The NAMS Board of Trustees reviewed and approved the final document. Results: Osteoporosis, which has its highest rate of occurrence in postmenopausal women, increases the risk for fractures, including hip and spine fractures. These injuries are often associated with particularly high morbidity and mortality. Given the health implications of osteoporotic fractures, the primary goal of osteoporosis therapy is to prevent fractures by slowing or preventing bone loss, maintaining bone strength, and minimizing or eliminating factors that may contribute to falls. The evaluation of postmenopausal women for osteoporosis risk requires the recording of a medical history, a physical examination, and diagnostic tests. Major risk factors for osteoporosis are age, genetics, lifestyle (especially nutrition), and menopausal status. Management focuses first on nonpharmacologic measures, such as a balanced diet including adequate calcium and vitamin D intakes, appropriate exercise, smoking cessation, avoidance of excessive alcohol intake, and fall prevention. If pharmacologic therapy is indicated, FDA-approved options are estrogens (prevention only), bisphosphonates and selective estrogen-receptor modulators (prevention and treatment), and calcitonin (treatment only). Conclusions: Management of postmenopausal osteoporosis involves identifying the potential risk for osteoporosis and osteoporotic fracture, followed by measures that focus on reducing modifiable risk factors through lifestyle changes and, if indicated, pharmacologic therapy.
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TY  - JOUR
T1  - Inhibition of Protein Prenylation by Bisphosphonates Causes Sustained Activation of Rac, Cdc42, and Rho GTPases
A1  - Dunford, James E
A1  - Rogers, Michael J
A1  - Ebetino, Frank H
A1  - Phipps, Roger J
A1  - Coxon, Fraser P
Y1  - 2006///
JF  - Journal of Bone and Mineral Research
VL  - 21
IS  - 5
SP  - 684
EP  - 694
SN  - 0884-0431 (Print)\r0884-0431 (Linking)
DO  - 10.1359/jbmr.060118
UR  - http://doi.wiley.com/10.1359/jbmr.060118
N2  - N-BPs, which inhibit bone resorption by preventing prenylation of small GTPases, unexpectedly cause the accumulation of GTP-bound, unprenylated Rho family GTPases in macrophages and osteoclasts. In macrophages, this also leads to sustained, Rac-mediated activation of p38. The antiresorptive activity of N-BPs may therefore be caused at least in part, by the accumulation of unprenylated small GTPases, causing inappropriate activation of downstream signaling pathways. INTRODUCTION: Nitrogen-containing bisphosphonates (N-BPs) are potent inhibitors of bone resorption that act by inhibiting farnesyl diphosphate synthase, thereby indirectly preventing the prenylation of Rho family GTPases that are required for the function and survival of bone-resorbing osteoclasts. However, the effect that these drugs have on the activity of Rho family GTPases has not been determined. MATERIALS AND METHODS: The effect of N-BPs on the activity of Rho family GTPases in J774 macrophages and osteoclasts was measured using a pull-down assay to isolate the GTP-bound forms. The effect of N-BPs, or decreasing Rac expression using siRNA, on downstream p38 activity was evaluated by Western blotting and apoptosis assessed by measurement of caspase 3/7 activity. RESULTS: Rather than inhibiting GTPase function, loss of prenylation after treatment with N-BPs caused an increase in the GTP-bound form of Rac, Cdc42, and Rho in J774 cells and osteoclast-like cells, which paralleled the rate of accumulation of unprenylated small GTPases. Activation of Rac also occurred with other inhibitors of prenylation of Rho-family proteins, such as mevastatin and the geranylgeranyl transferase I inhibitor GGTI-298. The Rac-GTP that increased after N-BP treatment was newly translated, cytoplasmic unprenylated protein, because it was not labeled with [(14)C] mevalonate, and the increase in Rac-GTP was prevented by cycloheximide. Furthermore, this unprenylated Rac-GTP retained at least part of its functional activity in J774 cells, because it mediated N-BP-induced activation of p38. Paradoxically, although risedronate induces apoptosis of J774 macrophages by inhibiting protein prenylation, the p38 inhibitor SB203580 enhanced N-BP-induced apoptosis, suggesting that Rac-induced p38 activation partially suppresses the pro-apoptotic effect of N-BPs in these cells. CONCLUSIONS: N-BP drugs may disrupt the function of osteoclasts in vivo and affect other cell types in vitro by inhibiting protein prenylation, thereby causing inappropriate and sustained activation, rather than inhibition, of some small GTPases and their downstream signaling pathways.
ER  - 
TY  - JOUR
T1  - Official Positions of the International Society for Clinical Densitometry
A1  - Baek, Ki Hyun
A1  - Kang, Moo-Il
Y1  - 2005///
JF  - Journal of Korean Society of Endocrinology
VL  - 20
IS  - 1
SP  - 1
EP  - 1
DO  - 10.3803/jkes.2005.20.1.1
UR  - http://synapse.koreamed.org/DOIx.php?id=10.3803/jkes.2005.20.1.1
ER  - 
TY  - JOUR
T1  - Official Positions of the International Society for Clinical Densitometry
A1  - Baek, Ki Hyun
A1  - Kang, Moo-Il
Y1  - 2005///
JF  - Journal of Korean Society of Endocrinology
VL  - 20
IS  - 1
SP  - 1
EP  - 1
DO  - 10.3803/jkes.2005.20.1.1
UR  - http://synapse.koreamed.org/DOIx.php?id=10.3803/jkes.2005.20.1.1
ER  - 
TY  - JOUR
T1  - Official positions of the International Society for Clinical Densitometry
A1  - Leib ES, Lewiecki EM, Binkley N, et al.
Y1  - 2004///
JF  - J Clin Densitom
VL  - 7
IS  - 1
SP  - 1
EP  - 5
DO  - 10.1385/JCD:7:1:1.
ER  - 
TY  - ICOMM
T1  - Official Positions of the International Society for Clinical Densitometry
A1  - Baek, Ki Hyun
A1  - Kang, Moo-Il
Y1  - 2005///
JF  - Journal of Korean Society of Endocrinology
VL  - 20
IS  - 1
SP  - 1
EP  - 1
DO  - 10.3803/jkes.2005.20.1.1
UR  - http://synapse.koreamed.org/DOIx.php?id=10.3803/jkes.2005.20.1.1
ER  - 
TY  - ICOMM
T1  - Official Positions of the International Society for Clinical Densitometry
A1  - Baek, Ki Hyun
A1  - Kang, Moo-Il
Y1  - 2005///
JF  - Journal of Korean Society of Endocrinology
VL  - 20
IS  - 1
SP  - 1
EP  - 1
DO  - 10.3803/jkes.2005.20.1.1
UR  - http://synapse.koreamed.org/DOIx.php?id=10.3803/jkes.2005.20.1.1
ER  - 
TY  - UNPB
T1  - Official positions of the International Society for Clinical Densitometry
A1  - Densitometry, International Society for Clinical
Y1  - 2007///
UR  - https://www.iscd.org/wp-content/uploads/2012/10/ISCD2007OfficialPositions-Combined-AdultandPediatric.pdf
ER  - 
TY  - JOUR
T1  - A systematic review of intervention thresholds based on FRAX: A report prepared for the National Osteoporosis Guideline Group and the International Osteoporosis Foundation
A1  - Kanis, John A.
A1  - Harvey, Nicholas C.
A1  - Cooper, Cyrus
A1  - Johansson, Helena
A1  - Odén, Anders
A1  - McCloskey, Eugene V.
A1  - The Advisory Board of the National Osteoporosis Guideline Group
A1  - Cooper, Cyrus
A1  - Harvey, Nicholas
A1  - McCloskey, Eugene
A1  - Poole, Ken E.
A1  - Kanis, John A.
A1  - Gittoes, Neil
A1  - Hope, Sally
Y1  - 2016///
KW  - Assessment guidelines
KW  - Calibration
KW  - Discrimination
KW  - FRAX
KW  - Intervention threshold
JF  - Archives of Osteoporosis
VL  - 11
IS  - 1
SN  - 1862-3514 (Electronic)
DO  - 10.1007/s11657-016-0278-z
N2  - UNLABELLED This systematic review identified assessment guidelines for osteoporosis that incorporate FRAX. The rationale for intervention thresholds is given in a minority of papers. Intervention thresholds (fixed or age-dependent) need to be country-specific. INTRODUCTION In most assessment guidelines, treatment for osteoporosis is recommended in individuals with prior fragility fractures, especially fractures at spine and hip. However, for those without prior fractures, the intervention thresholds can be derived using different methods. The aim of this report was to undertake a systematic review of the available information on the use of FRAX® in assessment guidelines, in particular the setting of thresholds and their validation. METHODS We identified 120 guidelines or academic papers that incorporated FRAX of which 38 provided no clear statement on how the fracture probabilities derived are to be used in decision-making in clinical practice. The remainder recommended a fixed intervention threshold (n = 58), most commonly as a component of more complex guidance (e.g. bone mineral density (BMD) thresholds) or an age-dependent threshold (n = 22). Two guidelines have adopted both age-dependent and fixed thresholds. RESULTS Fixed probability thresholds have ranged from 4 to 20 % for a major fracture and 1.3-5 % for hip fracture. More than one half (39) of the 58 publications identified utilised a threshold probability of 20 % for a major osteoporotic fracture, many of which also mention a hip fracture probability of 3 % as an alternative intervention threshold. In nearly all instances, no rationale is provided other than that this was the threshold used by the National Osteoporosis Foundation of the USA. Where undertaken, fixed probability thresholds have been determined from tests of discrimination (Hong Kong), health economic assessment (USA, Switzerland), to match the prevalence of osteoporosis (China) or to align with pre-existing guidelines or reimbursement criteria (Japan, Poland). Age-dependent intervention thresholds, first developed by the National Osteoporosis Guideline Group (NOGG), are based on the rationale that if a woman with a prior fragility fracture is eligible for treatment, then, at any given age, a man or woman with the same fracture probability but in the absence of a previous fracture (i.e. at the 'fracture threshold') should also be eligible. Under current NOGG guidelines, based on age-dependent probability thresholds, inequalities in access to therapy arise especially at older ages (≥70 years) depending on the presence or absence of a prior fracture. An alternative threshold using a hybrid model reduces this disparity. CONCLUSION The use of FRAX (fixed or age-dependent thresholds) as the gateway to assessment identifies individuals at high risk more effectively than the use of BMD. However, the setting of intervention thresholds needs to be country-specific.
ER  - 
TY  - JOUR
T1  - The Official Positions of the International Society for Clinical Densitometry: Perceptions and Commentary
A1  - Lewiecki, E. Michael
A1  - Baim, Sanford
A1  - Langman, Craig B.
A1  - Bilezikian, John P.
Y1  - 2009///
KW  - DXA
KW  - QUS
KW  - evidence-based medicine
KW  - osteoporosis
KW  - quality
JF  - Journal of Clinical Densitometry
VL  - 12
IS  - 3
SP  - 267
EP  - 271
SN  - 0937-941X (Print)\r0937-941X (Linking)
DO  - 10.1016/j.jocd.2009.03.098
N2  - The International Society for Clinical Densitometry (ISCD) periodically issues Official Positions (OPs) on the assessment of skeletal health in adults and children. OPs are recommendations regarding topics that include nomenclature, indications, acquisition, analysis, quality control, interpretation, reporting, and clinical utility of measuring bone density using different technologies. The purpose of these directives is to assist health care professionals in the practice of clinical densitometry. The OPs are established through a rigorous process of scientific literature review by ISCD task forces, each assigned to address a group of clinically relevant questions. The findings and recommendations of each task force are assessed and revised, as needed, by an international panel of experts. Recommendations that are felt to be appropriate for inclusion as ISCD OPs are sent to the ISCD Board of Directors for final approval. Despite having a major impact in the clinical application of bone densitometry, the ISCD OPs have not been universally adopted, in part because of misunderstanding of the process used to establish them and the way that they are intended for use in clinical practice. This is a review of the benefits and limitations of the ISCD OPs with emphasis on areas of controversy. © 2009 The International Society for Clinical Densitometry.
ER  - 
TY  - BOOK
T1  - Клинические рекомендации по профилактике и ведению больных с остеопорозом
A1  - Алексеева Л.И., Баранова И.А., Белова К.Ю., и др.
Y1  - 2012///
PB  - Литера
SP  - 23
EP  - 23
CY  - Ярославль
ER  - 
TY  - JOUR
T1  - Relationship of Early Changes in Bone Resorption to the Reduction in Fracture Risk With Risedronate
A1  - Eastell, R
A1  - Barton, I
A1  - Hannon, Ra
A1  - Chines, A
A1  - Garnero, P
A1  - Delmas, Pd
Y1  - 2003///
JF  - Journal of Bone and Mineral Research
VL  - 18
IS  - 6
SP  - 1051
EP  - 1056
DO  - 10.1359/jbmr.2003.18.6.1051
UR  - http://doi.wiley.com/10.1359/jbmr.2003.18.6.1051
N2  - Changes in the level of biochemical markers of bone resorption with risedronate treatment for osteoporosis were examined as a surrogate for the decrease in fracture risk. Greater decreases in bone resorption markers were associated with greater decreases in vertebral (and nonvertebral) fractures. Antifracture efficacy of antiresorptive therapies is only partially explained by increases in bone mineral density. Early decreases in bone resorption may also play a role. We tested this hypothesis by measuring two bone resorption markers, the C-telopeptide of type I collagen (CTX) and the N-telopeptide of type I collagen (NTX), in osteoporotic patients in risedronate vertebral fracture trials. We studied 693 women with at least one vertebral deformity (mean age, 69 +/- 7 years) who received calcium (and vitamin D if required) and placebo or risedronate 5 mg daily for 3 years. The reductions in urinary CTX (median, 60%) and NTX (51%) at 3-6 months with risedronate therapy were significantly associated (p < 0.05) with the reduction in vertebral fracture risk (75% over 1 year and 50% over 3 years). The changes in both CTX and NTX accounted for approximately one-half (CTX, 55%; NTX, 49%) of risedronate's effect in reducing the risk of vertebral fractures in the first year and approximately two-thirds (CTX, 67%; NTX, 66%) over 3 years compared with placebo. The changes in CTX and NTX accounted for 77% and 54%, respectively, of risedronate's effect in reducing the risk of nonvertebral fractures over 3 years compared with placebo. The relationships between vertebral fracture risk and changes from baseline in CTX and NTX were not linear (p < 0.05). There was little further improvement in fracture benefit below a decrease of 55-60% for CTX and 35-40% for NTX. The decrease in bone resorption in patients taking risedronate accounts for a large proportion of the reduction in fracture risk. There may be a level of bone resorption reduction below which there is no further fracture benefit.
ER  - 
TY  - JOUR
T1  - Assessment of Fractures Risk Using the Frax® Tool (a Ten-Year Retrospective Study)
A1  - Nikitinskaya, O. A.
A1  - Toroptsova, N. V.
Y1  - 2016///
JF  - Almanac of Clinical Medicine
IS  - 32
SP  - 50
EP  - 55
DO  - 10.18786/2072-0505-2014-32-50-55
UR  - http://opskoro.elpub.ru/jour/article/view/134
ER  - 
TY  - UNPB
T1  - Recommendations to DXA Manufacturers for FRAX® Implementation
A1  - National Osteoporosis Foundation
A1  - International Society for Clinical Densitometry
Y1  - 2010///
KW  - DXA
KW  - ISCD
KW  - NOF
KW  - guide
KW  - implementation
KW  - treated
KW  - untreated
JF  - National Osteoporosis Foundation
UR  - http://www.nof.org/sites/default/files/pdfs/NOF_FRAX_Implem_Guide.pdf
ER  - 
TY  - JOUR
T1  - Daily and intermittent oral ibandronate normalize bone turnover and provide significant reduction in vertebral fracture risk: Results from the BONE study
A1  - Delmas, P. D.
A1  - Recker, R. R.
A1  - Chesnut, C. H.
A1  - Skag, A.
A1  - Stakkestad, J. A.
A1  - Emkey, R.
A1  - Gilbride, J.
A1  - Schimmer, R. C.
A1  - Christiansen, C.
Y1  - 2004///
KW  - Bisphosphonate
KW  - Bone turnover
KW  - Ibandronate
KW  - Intermittent
KW  - Osteoporosis
JF  - Osteoporosis International
VL  - 15
IS  - 10
SP  - 792
EP  - 798
SN  - 0937-941X (Print)\r0937-941X (Linking)
DO  - 10.1007/s00198-004-1602-9
N2  - Increasing evidence suggests that a high rate of bone turnover is associated with low bone mineral density (BMD) and is strongly linked to fracture risk. Measurement of biochemical markers of bone turnover is therefore becoming a more widely used endpoint in clinical trials in postmenopausal osteoporosis. This multinational double-blind, fracture-prevention study enrolled 2946 postmenopausal women with osteoporosis. Patients were randomized to receive placebo or oral ibandronate administered daily (2.5 mg/day) or intermittently (20 mg every other day for 12 doses every 3 months). The primary endpoint was the incidence of new vertebral fractures after 3 years. Secondary outcome measures included changes in the rate of bone turnover as assessed by biochemical markers and increases in spinal and hip BMD. Daily and intermittent oral ibandronate significantly reduced the risk of vertebral fractures by 62% and 50%, respectively, and produced significant and sustained reductions in all the measured biochemical markers of bone turnover. By 3 months, the rate of bone turnover was reduced by approximately 50-60%, and this level of suppression was sustained throughout the remainder of the study. In summary, oral ibandronate, given daily or with a between-dose interval of >2 months, normalizes the rate of bone turnover, provides significant increases in BMD and a marked reduction in the incidence of vertebral fractures. Thus, intermittent ibandronate has potential to become an important alternative to currently licensed bisphosphonates in postmenopausal osteoporosis.
ER  - 
TY  - JOUR
T1  - Clinical utility of a pharmacostatistical model for Ibandronate in postmenopausal osteoporosis
A1  - Reginster J.-Y., Gieschke, R.
Y1  - 2006///
KW  - accuracy
KW  - alendronic acid
KW  - bisphosphonic acid derivative
KW  - bone density
KW  - bone mineral
KW  - calcium
KW  - carboxy terminal telopeptide
KW  - clinical trial
KW  - compartment model
KW  - drug bioavailability
KW  - drug blood level
KW  - drug distribution
KW  - drug dose regimen
KW  - drug efficacy
KW  - drug elimination
KW  - drug half life
KW  - drug mechanism
KW  - drug metabolism
KW  - drug safety
KW  - drug urine level
KW  - etidronic acid
KW  - fragility fracture
KW  - human
KW  - ibandronic acid
KW  - mathematical model
KW  - olpadronic acid
KW  - osteocalcin
KW  - pamidronic acid
KW  - pharmacodynamics
KW  - placebo
KW  - postmenopause osteoporosis
KW  - prediction
KW  - review
KW  - risedronic acid
KW  - risk reduction
KW  - simulation
KW  - spine fracture
KW  - validation study
KW  - vitamin D
KW  - vitamin supplementation
KW  - zoledronic acid
JF  - Current Drug Metabolism
VL  - 7
IS  - 7
SP  - 827
EP  - 836
DO  - 10.2174/138920006778520624
UR  - http://www.embase.com/search/results?subaction=viewrecord&from=export&id=L44509684%5Cnhttp://www.ingentaconnect.com/content/ben/cdm/2006/00000007/00000007/art00009%5Cnhttp://dx.doi.org/10.2174/138920006778520624%5Cnhttp://elvis.ubvu.vu.nl:9003/vulink?sid=
N2  - Ibandronate, a potent, nitrogen-containing bisphosphonate for the treatment of postmenopausal osteoporosis, is the subject of an ongoing clinical development program to explore novel oral and intravenous (i.v.) dosing regimens. As part of this program, an extensive modeling and simulation project was undertaken to develop and validate a pharmacologically realistic mathematical model for ibandronate in osteoporosis, the aim being to identify practical dosing regimens for clinical evaluation. A simplified kinetics of drug action or kinetic-pharmacodynamic (K-PD) model (developed from a 4-compartment pharmacokinetic-pharmacodynamic [PK-PD] model) accurately described the urinary excretion of the C-telopeptide of the α-chain of type I collagen (uCTX). The model was extended to consider the effects of supplemental calcium therapy and allow simultaneous fitting of i.v. and oral ibandronate data, and then externally validated. This model was used successfully in the selection of appropriate once-monthly doses for further clinical evaluation and recent clinical studies have confirmed the efficacy of the doses identified. Further development of the model may include investigating the effects of ibandronate on bone mineral density and fracture risk, which would further enhance its clinical utility and predictive value. Although modeling and simulation has been used to explore the efficacy of other bisphosphonates, the extensive program with ibandronate has produced a comprehensively validated model that is the first to be prospectively tested by evaluating novel dosing regimens. © 2006 Bentham Science Publishers Ltd.
ER  - 
TY  - JOUR
T1  - PINP as a biological response marker during teriparatide treatment for osteoporosis
A1  - Krege, J. H.
A1  - Lane, N. E.
A1  - Harris, J. M.
A1  - Miller, P. D.
Y1  - 2014///
KW  - Anabolics
KW  - Biochemical markers of bone turnover
KW  - Osteoporosis
KW  - PINP
KW  - Teriparatide
JF  - Osteoporosis International
VL  - 25
IS  - 9
SP  - 2159
EP  - 2171
SN  - 0937-941x
DO  - 10.1007/s00198-014-2646-0
N2  - Postmenopausal women with severe osteoporosis may require treatment with the bone anabolic drug teriparatide. While changes in bone mineral density (BMD) are one measure of response, BMD changes often require a minimum of one year to observe measureable changes. Biochemical markers of bone turnover change within 1 to 3 months of initiating osteoporosis therapy. Monitoring with a marker such as procollagen type I N propeptide (PINP), an osteoblast-derived protein, during teriparatide treatment may provide clinically useful information for managing patients with osteoporosis. Clinical trials have shown consistent increases in PINP within 3 months of initiating teriparatide, increases that are significantly greater than placebo and significantly different from baseline. Increases in PINP concentrations during teriparatide treatment correlate well with increases in skeletal activity assessed by radioisotope bone scans and quantitative bone histomorphometry parameters. Individuals treated with teriparatide in clinical trials usually experienced an increase in PINP > 10 mcg/L from baseline, while those given placebo usually did not. In the clinical setting, patients experiencing a significant increase in PINP > 10 mcg/L after initiating teriparatide therapy may receive an earlier confirmation of anabolic effect, while those who do not may be assessed for adherence, proper injection technique, or undetected secondary conditions that might mitigate an anabolic response. PINP monitoring may provide information supplemental to BMD monitoring and be a useful aid in managing patients receiving anabolic osteoporosis treatment in the same way that biochemical markers of bone resorption are useful in monitoring antiresorptive therapy. This review examines PINP as a biological response marker during teriparatide treatment for osteoporosis
ER  - 
TY  - JOUR
T1  - Poor bisphosphonate adherence for treatment of osteoporosis increases fracture risk: Systematic review and meta-analysis
A1  - Imaz, I.
A1  - Zegarra, P.
A1  - González-Enríquez, J.
A1  - Rubio, B.
A1  - Alcazar, R.
A1  - Amate, J. M.
Y1  - 2010///
KW  - Adherence
KW  - Bisphosphonates
KW  - Bone fracture
KW  - Compliance
KW  - Osteoporosis
KW  - Systematic review
JF  - Osteoporosis International
VL  - 21
IS  - 11
SP  - 1943
EP  - 1951
SN  - 0937-941x
DO  - 10.1007/s00198-009-1134-4
N2  - - Systematic review of adherence to bisphosphonates for the treatment of
ER  - 
TY  - JOUR
T1  - Evidence-based guidelines for the use of biochemical markers of bone turnover in the selection and monitoring of bisphosphonate treatment in osteoporosis: A consensus document of the Belgian Bone Club
A1  - Bergmann, P.
A1  - Body, J. J.
A1  - Boonen, S.
A1  - Boutsen, Y.
A1  - Devogelaer, J. P.
A1  - Goemaere, S.
A1  - Kaufman, J. M.
A1  - Reginster, J. Y.
A1  - Gangji, V.
Y1  - 2009///
JF  - International Journal of Clinical Practice
VL  - 63
IS  - 1
SP  - 19
EP  - 26
SN  - 1742-1241 (Electronic)\r1368-5031 (Linking)
DO  - 10.1111/j.1742-1241.2008.01911.x
N2  - OBJECTIVES: To review the clinical value of bone turnover markers (BTM), to initiate and/or monitor anti-resorptive treatment for osteoporosis compared with bone mineral density (BMD) and to evaluate suitable BTM and changes in BTM levels for significance of treatment efficiency.\n\nMETHODOLOGY: Consensus meeting generating guidelines for clinical practice after review and discussion of the randomised controlled trials or meta-analyses on the management of osteoporosis in postmenopausal women.\n\nRESULTS: Although the correlation between BMD and BTM is statistically significant, BTM cannot be used as predictive markers of BMD in an individual patient. Both are independent predictors of fracture risk, but BTM can only be used as an additional risk factor in the decision to treat. Current data do not support the use of BTM to select the optimal treatment. However, they can be used to monitor treatment efficiency before BMD changes can be evaluated. Early changes in BTM can be used to measure the clinical efficacy of an anti-resorptive treatment and to reinforce patient compliance.\n\nDISCUSSION: Determining a threshold of BTM reflecting an optimal long-term effect is not obvious. The objective should be the return to the premenopausal range and/or a decrease at least equal to the least significant change (30%). Preanalytical and analytical variability of BTM is an important limitation to their use. Serum C-terminal cross-linked telopeptide of type I collagen (CTX), procollagen 1 N terminal extension peptide and bone specific alkaline phosphatase (BSALP) appear to be the most suitable.\n\nCONCLUSION: Consensus regarding the use of BTM resulted in guidelines for clinical practice. BMD determines the indication to treat osteoporosis. BTM reflect treatment efficiency and can be used to motivate patients to persist with their medication.
ER  - 
TY  - JOUR
T1  - Systematic review of the use of bone turnover markers for monitoring the response to osteoporosis treatment: The secondary prevention of fractures, and primary prevention of fractures in high-risk groups
A1  - Burch, Jane
A1  - Rice, Stephen
A1  - Yang, Huiqin
A1  - Neilson, Aileen
A1  - Stirk, Lisa
A1  - Francis, Roger
A1  - Holloway, Paul
A1  - Selby, Peter
A1  - Craig, Dawn
Y1  - 2014///
JF  - Health Technology Assessment
VL  - 18
IS  - 11
SP  - 1
EP  - 180
SN  - 1366-5278
DO  - 10.3310/hta18110
N2  - Background: There is currently no standard practice for the monitoring of patients receiving treatment for osteoporosis. Repeated dual-energy X-ray absorptiometry (DXA) is commonly used for monitoring treatment response, but it has its limitations. Bone turnover markers have advantages over DXA as they are non-invasive, relatively cheap and can detect changes in bone turnover rates earlier. However, they do have disadvantages, particularly high within-and between-patient variability. The ability of bone turnover markers to identify treatment non-responders and predict future fracture risk has yet to be established. Objectives: We aimed to determine the clinical effectiveness, test accuracy, reliability, reproducibility and cost-effectiveness of bone turnover markers for monitoring the response to osteoporosis treatment. Data sources: We searched 12 electronic databases (including MEDLINE, EMBASE, The Cochrane Library and trials registries) without language restrictions from inception to March 2012. We hand-searched three relevant journals for the 12 months prior to May 2012, and websites of five test manufacturers and the US Food and Drug Administration (FDA). Reference lists of included studies and relevant reviews were also searched. Review methods: A systematic review of test accuracy, clinical utility, reliability and reproducibility, and cost-effectiveness of two formation and two resorption bone turnover markers, in patients being treated for osteoporosis with any of bisphosphonate [alendronate (Fosamax (R), MSD), risedronate (Actonel (R), Warner Chilcott Company), zolendronate (Zometa (R), Novartis)], raloxifene (Evista (R), Eli Lilly and Company Ltd), strontium ranelate (Protelos (R), Servier Laboratories Ltd), denosumab (Prolia (R), Amgen Ltd) or teriparatide (Forsteo (R), Eli Lilly and Company Ltd), was undertaken according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Given the breadth of the review question, a range of study designs and outcome measures were eligible. The development of a decision model was planned to determine the cost-effectiveness of bone turnover markers for informing changes in patient management if clinical effectiveness could be established. Results: Forty-two studies (70 publications) met the inclusion criteria; none evaluated cost-effectiveness. Only five were randomised controlled trials (RCTs); these assessed only the impact of bone marker monitoring on aspects of adherence. No RCTs evaluated the effectiveness of bone turnover marker monitoring on treatment management. One trial suggested that feedback of a good response decreased non-persistence [hazard ratio (HR) 0.71, 95% confidence interval (CI) 0.53 to 0.95], and feedback of a poor response increased non-persistence (HR 2.22, 95% CI 1.27 to 3.89); it is not clear whether or not the trial recruited a population representative of that seen in clinical practice. Thirty-three studies reported results of some assessment of test accuracy, mostly correlations between changes in bone turnover and bone mineral density. Only four studies reported on intra-or interpatient reliability and reproducibility in treated patients. Overall, the results were inconsistent and inconclusive, owing to considerable clinical heterogeneity across the studies and the generally small sample sizes. As clinical effectiveness of bone turnover monitoring could not be established, a decision-analytic model was not developed. Conclusions: There was insufficient evidence to inform the choice of which bone turnover marker to use in routine clinical practice to monitor osteoporosis treatment response. The research priority is to identify the most promising treatment-test combinations for evaluation in subsequent, methodologically sound, RCTs. In order to determine whether or not bone turnover marker monitoring improves treatment management decisions, and ultimately impacts on patient outcomes in terms of reduced incidence of fracture, RCTs are required. Given the large number of potential patient population-treatment-test combinations, the most promising combinations would initially need to be identified in order to ensure that any RCTs focus on evaluating those strategies. As a result, the research priority is to identify these promising combinations, by either conducting small variability studies or initiating a patient registry to collect standardised data.
ER  - 
TY  - JOUR
T1  - Biochemical Markers of Bone Turnover Reflect Femoral Bone Loss in Elderly Women
A1  - Dresner-Pollak, R
A1  - Parker, A R
A1  - Poku, M
A1  - Thompson, J
A1  - Seibel, J M
A1  - Greenspan, L S
Y1  - 1996///
JF  - Calcified Tissue International
VL  - 59
IS  - 5
SP  - 328
EP  - 333
DO  - 10.1007/s002239900135
UR  - http://dx.doi.org/10.1007/s002239900135
N2  - Although over 90{%} of hip fractures occur in patients over age 70, few data are available on femoral bone loss in this age group. To examine the relationship between biochemical markers of bone turnover and femoral bone loss in the elderly, 36 female and 17 male, healthy, community-dwelling elderly over age 65 (mean {\textpm} SD age: women 71 {\textpm} 4 years, men 75 {\textpm} 5 years) were followed for 3 years. Annual bone mineral density measurements of the hip and lumbar spine by dual-energy x-ray absorptiometry (DXA) were obtained and biochemical markers of bone resorption (urinary N-telopeptide crosslinks, free pyridinoline, total pyridinoline, total deoxypyridinoline, and hydroxyproline) and bone formation (serum osteocalcin, bone-specific alkaline phosphatase) were obtained at the end of year 3. In elderly women, longitudinal bone loss at the total hip was negatively correlated with markers of bone resorption (r =−0.39 to −0.52, P < 0.05), bone formation (r =−0.38, P < 0.05), and age (r =−0.39, P < 0.05). Markers of bone resorption were correlated with markers of bone formation (r = 0.63 to 0.74, P < 0.01). In multiple regression analysis, urinary N-telopeptide crosslinks (marker of resorption), serum osteocalcin (marker of formation), and serum parathyroid hormone explained 43{%} of the variability of bone loss at the total hip in women. These parameters were not related to bone loss in men. We conclude that femoral bone loss increases with age in women over 65. Measurements of specific biochemical markers of bone turnover are correlated with longitudinal bone loss in elderly women. These markers may help identify women at greatest risk for bone loss who would benefit most from therapeutic interventions.
ER  - 
TY  - RPRT
T1  - Evidence Synthesis Number 77 Screening for Osteoporosis: Systematic Review to Update the 2002 US Preventive Services Task Force Recommendation
A1  - Nelson, Heidi D
A1  - Haney, Elizabeth M
A1  - Chou, Roger
A1  - Dana, Tracey
A1  - Fu, Rochelle
A1  - Bougatsos, Christina
Y1  - 2010///
IS  - 77
UR  - http://scholar.google.com/scholar?hl=en&btnG=Search&q=intitle:Evidence+Synthesis+Number+77+Screening+for+Osteoporosis+:+Systematic+Review+to+Update+the+2002+U+.+S+.+Preventive+Services+Task+Force+Recommendation#6
ER  - 
TY  - BOOK
T1  - Bone Densitometry in Clinical Practice
A1  - Bonnick, Sydney Lou
Y1  - 2003///
PB  - Humana Press, Inc.
ET  - 2nd
SP  - 411
EP  - 411
CY  - New York
SN  - 978-1-60327-498-2
DO  - 10.1007/978-1-60327-499-9
UR  - http://link.springer.com/10.1007/978-1-60327-499-9
ER  - 
TY  - JOUR
T1  - Trabecular bone score (TBS): Available knowledge, clinical relevance, and future prospects
A1  - Bousson, V.
A1  - Bergot, C.
A1  - Sutter, B.
A1  - Levitz, P.
A1  - Cortet, B.
Y1  - 2012///
KW  - Bone microarchitecture
KW  - Bone quality
KW  - DXA
KW  - Osteoporosis
KW  - Trabecular bone
JF  - Osteoporosis International
VL  - 23
IS  - 5
SP  - 1489
EP  - 1501
SN  - 1433-2965 (Electronic) 0937-941X (Linking)
DO  - 10.1007/s00198-011-1824-6
N2  - The diagnosis of osteoporosis rests on areal bone mineral density (BMD) measurement using DXA. Cancellous bone microarchitecture is a key determinant of bone strength but cannot be measured using DXA. To meet the need for a clinical tool capable of assessing bone microarchitecture, the TBS was developed. The TBS is a texture parameter that evaluates pixel gray-level variations in DXA images of the lumbar spine. The TBS variations may reflect bone microarchitecture. We explain the general principles used to compute the TBS, and we report the correlations between TBS and microarchitectural parameters. Several limitations of the TBS as it is used now are pointed out. We discuss data from currently available clinical studies on the ability of the TBS to identify patients with fractures and to evaluate the fracture risk. We conclude that this new index emphasizes the failure of the BMD T-score to fully capture the fragility fracture risk. However, although microarchitecture may influence the TBS, today, to the best of our understanding, there is no sufficient evidence that a TBS measurement provides reliable information on the status of the bone microarchitecture for a given patient. The TBS depends on gray-level variations and in a projectional image obtained in vivo, these variations can have many causes. Nevertheless, as clinical studies suggest that the TBS predicts the risk of fracture even after adjustment for BMD, we are encouraged to learn more about this score. Additional studies will have to be performed to assess the advantages and limitations of the TBS, in order to ensure that it is used appropriately in clinical practice.
ER  - 
TY  - JOUR
T1  - A Meta-Analysis of Trabecular Bone Score in Fracture Risk Prediction and Its Relationship to FRAX
A1  - McCloskey, Eugene V.
A1  - Odén, Anders
A1  - Harvey, Nicholas C.
A1  - Leslie, William D.
A1  - Hans, Didier
A1  - Johansson, Helena
A1  - Barkmann, Reinhard
A1  - Boutroy, Stephanie
A1  - Brown, Jacques
A1  - Chapurlat, Roland
A1  - Elders, Petra J M
A1  - Fujita, Yuki
A1  - Glüer, Claus C.
A1  - Goltzman, David
A1  - Iki, Masayuki
A1  - Karlsson, Magnus
A1  - Kindmark, Andreas
A1  - Kotowicz, Mark
A1  - Kurumatani, Norio
A1  - Kwok, Timothy
A1  - Lamy, Oliver
A1  - Leung, Jason
A1  - Lippuner, Kurt
A1  - Ljunggren, Östen
A1  - Lorentzon, Mattias
A1  - Mellström, Dan
A1  - Merlijn, Thomas
A1  - Oei, Ling
A1  - Ohlsson, Claes
A1  - Pasco, Julie A.
A1  - Rivadeneira, Fernando
A1  - Rosengren, Björn
A1  - Sornay-Rendu, Elisabeth
A1  - Szulc, Pawel
A1  - Tamaki, Junko
A1  - Kanis, John A.
Y1  - 2016///
KW  - FRACTURE
KW  - FRAX
KW  - META-ANALYSIS
KW  - RISK
KW  - TBS
KW  - TRABECULAR BONE STRUCTURE
JF  - Journal of Bone and Mineral Research
VL  - 31
IS  - 5
SP  - 940
EP  - 948
SN  - 1523-4681 (Electronic)\r0884-0431 (Linking)
DO  - 10.1002/jbmr.2734
N2  - Trabecular bone score (TBS) is a grey-level textural index of bone microarchitecture derived from lumbar spine dual-energy X-ray absorptiometry (DXA) images. TBS is a BMD-independent predictor of fracture risk. The objective of this meta-analysis was to determine whether TBS predicted fracture risk independently of FRAX probability and to examine their combined performance by adjusting the FRAX probability for TBS. We utilized individual level data from 17,809 men and women in 14 prospective population-based cohorts. Baseline evaluation included TBS and the FRAX risk variables and outcomes during follow up (mean 6.7 years) comprised major osteoporotic fractures. The association between TBS, FRAX probabilities and the risk of fracture was examined using an extension of the Poisson regression model in each cohort and for each sex and expressed as the gradient of risk (GR; hazard ratio per 1SD change in risk variable in direction of increased risk). FRAX probabilities were adjusted for TBS using an adjustment factor derived from an independent cohort (the Manitoba Bone Density Cohort). Overall, the GR of TBS for major osteoporotic fracture was 1.44 (95% CI: 1.35-1.53) when adjusted for age and time since baseline and was similar in men and women (p > 0.10). When additionally adjusted for FRAX 10-year probability of major osteoporotic fracture, TBS remained a significant, independent predictor for fracture (GR 1.32, 95%CI: 1.24-1.41). The adjustment of FRAX probability for TBS resulted in a small increase in the GR (1.76, 95%CI: 1.65, 1.87 vs. 1.70, 95%CI: 1.60-1.81). A smaller change in GR for hip fracture was observed (FRAX hip fracture probability GR 2.25 vs. 2.22). TBS is a significant predictor of fracture risk independently of FRAX. The findings support the use of TBS as a potential adjustment for FRAX probability, though the impact of the adjustment remains to be determined in the context of clinical assessment guidelines. This article is protected by copyright. All rights reserved.
ER  - 
TY  - JOUR
T1  - Monitoring of alendronate treatment and prediction of effect on bone mass by biochemical markers in the early postmenopausal intervention cohort study
A1  - Ravn, P.
A1  - Hosking, D.
A1  - Thompson, D.
A1  - Cizza, G.
A1  - Wasnich, R. D.
A1  - McClung, M.
A1  - Yates, A. J.
A1  - Bjarnason, N. H.
A1  - Christiansen, C.
Y1  - 1999///
JF  - Journal of Clinical Endocrinology and Metabolism
VL  - 84
IS  - 7
SP  - 2363
EP  - 2368
SN  - 0021-972X (Print)0021-972x
DO  - 10.1210/jcem.84.7.5847
N2  - To establish whether biochemical markers could be used to monitor alendronate (ALN) treatment and predict long-term response in bone mass, we used results from an ongoing, randomized trial of ALN treatment for prevention of postmenopausal osteoporosis (n = 1202). In women treated with ALN (5 mg), change from baseline at month 6 in urine N-telopeptide cross-links of type I collagen (NTX) and osteocalcin (OC) correlated with change from baseline at month 24 in spine, hip, and total body bone mineral density (BMD) [r = -0.28 to -0.31 (NTX) and r = -0.16 to -0.25 (OC), P<0.001]. This corresponded to a 4- to 5-fold greater increase at month 24 in BMD in the tertiles, with the greatest decrease at month 6 in NTX or OC. In women treated with ALN (5 mg) who had a change at month 24 in spine BMD of at least 0%, 86% (NTX) and 79% (OC) had a decrease at month 6 of at least 40% (NTX) or 20% (OC) (sensitivity). The corresponding specificities were 48% (NTX) and 53% (OC). In conclusion, change at month 6 in NTX and OC, in groups of women treated with ALN, indicated the numeric long-term response in BMD within these groups. In individual women, a decrease at month 6, in NTX or OC below the cut-point, validly identified women who responded, on ALN treatment, with a stabilization or an increase in bone mass. However, lack of decrease below the cut-point in NTX or OC could not be used to identify women with a bone loss during ALN treatment.
ER  - 
TY  - JOUR
T1  - Differences in the Capacity of Several Biochemical Bone Markers to Assess High Bone Turnover in Early Menopause and Response to Alendronate Therapy
A1  - Fink, E.
A1  - Cormier, C.
A1  - Steinmetz, P.
A1  - Kindermans, C.
A1  - Le Bouc, Y.
A1  - Souberbielle, J.-C.
Y1  - 2000///
JF  - Osteoporosis International
VL  - 11
IS  - 4
SP  - 295
EP  - 303
SN  - 0937-941X (Print)\r0937-941X (Linking)
DO  - 10.1007/PL00004183
UR  - http://link.springer.com/10.1007/PL00004183
N2  - We measured bone mineral density (BMD), four markers of bone formation [bone alkaline phosphatase (bAP), osteocalcin (Oc), N- and C-terminal propeptide of type I procollagen (PINP and PICP respectively)] and five markers of bone resorption [serum C-terminal telopeptide of type I collagen (CTx), urinary CTx, N-terminal cross-linked telopeptide (NTx), free and total deoxypyridinoline (fDpd and tDpd respectively)] in 28 healthy premenopausal women (45.7 +/- 3.0 years), 15 early (< 7 years) healthy menopausal women (53.8 +/- 3.1 years) and 20 osteoporotic women (65.3 +/- 8.2 years). Bone markers and BMD were also measured in the osteoporotic women 4.1 +/- 0.2 and 12.6 +/- 1.2 months after the beginning of alendronate therapy (Fosamax, 10 mg/day) respectively (BMD in 16/20). We calculated the intra-individual coefficient of variation (iCV) and the least significant change (LSC) for each bone marker from a subset of 9 healthy premenopausal women (32 +/- 5 years) who had a first and a second morning void urine collection (FMV and SMV respectively) and a blood sample on 4 nonconsecutive days (mean interval 14 +/- 3 days). None of the bone markers was correlated with BMD (except p = 0.043 between serum Oc and hip BMD). All markers, except fDpd, were increased significantly in early menopausal women when compared with the premenopausal group. Serum CTx presented the highest increase at menopause (+67.8%) and identified the highest rate (11/15) of early menopausal women with bone turnover above the premenopausal range. The iCVs for bone formation markers (7.2-14.4%) were lower than those for bone resorption markers (14.6-22.3%). The iCVs obtained on FMV and SMV were not different. The decrease after 4 months of alendronate was significant for each bone marker but variable from one marker to another. Serum CTx showed the largest decrease (70.8%) and identified the highest number of biologically responding patients (change > LSC; n = 17/20). A significant change in serum CTx after 4 months of alendronate was the best predictor of a significant gain in spine BMD (i.e., > 27 mg/cm<ovid:sup>2</ovid:sup>) after 1 year of therapy, allowing 15 of 16 patients (94%) to be classified correctly (one false-positive). Urinary NTx/Cr was the second best predictor. Despite a moderately high iCV (20.6%), serum CTx appeared the most effective of the markers tested and could be of interest for the detection of high bone turnover and the longitudinal monitoring of alendronate therapy in the individual patient. It must be stressed that serum PINP and urinary NTx and tDpd compared very similarly with serum CTx for monitoring alendronate therapy.
ER  - 
TY  - UNPB
T1  - 2013 ISCD Official Positions – Adult
A1  - ISCD
Y1  - 2013///
UR  - http://www.iscd.org/official-positions/2013-iscd-official-positions-adult
ER  - 
TY  - JOUR
T1  - Change in Bone Turnover and Hip, Non-Spine, and Vertebral Fracture in Alendronate-Treated Women: The Fracture Intervention Trial
A1  - Bauer, Douglas C
A1  - Black, Dennis M
A1  - Garnero, Patrick
A1  - Hochberg, Marc
A1  - Ott, Susan
A1  - Orloff, John
A1  - Thompson, Desmond E
A1  - Ewing, Susan K
A1  - Delmas, Pierre D
Y1  - 2004///
JF  - Journal of Bone and Mineral Research
VL  - 19
IS  - 8
SP  - 1250
EP  - 1258
SN  - 0884-0431 (Print)\r0884-0431 (Linking)
DO  - 10.1359/JBMR.040512
UR  - http://doi.wiley.com/10.1359/JBMR.040512
N2  - UNLABELLED We used data from the Fracture Intervention Trial to assess the relationship change in bone turnover after 1 year of alendronate or placebo treatment and subsequent hip, non-spine, and spine fracture risk among 6186 postmenopausal women. In the alendronate group (n = 3105), greater reductions in one or more biochemical marker were associated with a lower risk of fracture. INTRODUCTION There are few data on the relationship between short-term change in biochemical markers of bone turnover and non-spine fracture risk among bisphosphonate-treated women, and the clinical use of such measurements is unknown. MATERIALS AND METHODS We measured biochemical markers of bone turnover (bone-specific alkaline phosphatase [bone ALP], intact N-terminal propeptide of type I collagen, and C-terminal crosslinked telopeptide of type 1 collagen) and BMD of the spine and hip at baseline and after 1 year of alendronate or placebo. During a mean follow-up of 3.6 years, 72 hip, 786 non-spine, and 336 vertebral fractures were documented. RESULTS AND CONCLUSIONS Each 1 SD reduction in 1-year change in bone ALP was associated with fewer spine (odds ratio = 0.74; CI: 0.63, 0.87), non-spine (relative hazard [RH] = 0.89; CI: 0.78, 1.00; p < 0.050), and hip fractures (RH = 0.61; CI: 0.46, 0.78). Alendronate-treated women with at least a 30% reduction in bone ALP had a lower risk of non-spine (RH = 0.72; CI: 0.55, 0.92) and hip fractures (RH = 0.26; CI: 0.08, 0.83) relative to those with reductions <30%. We conclude that greater reductions in bone turnover with alendronate therapy are associated with fewer hip, non-spine, and vertebral fractures, and the effect is at least as strong as that observed with 1-year change in BMD.
ER  - 
TY  - JOUR
T1  - Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial.
A1  - Rossouw, Jacques E
A1  - Anderson, Garnet L
A1  - Prentice, Ross L
A1  - LaCroix, Andrea Z
A1  - Kooperberg, Charles
A1  - Stefanick, Marcia L
A1  - Jackson, Rebecca D
A1  - Beresford, Shirley A A
A1  - Howard, Barbara V
A1  - Johnson, Karen C
A1  - Kotchen, Jane Morley
A1  - Ockene, Judith
A1  - Writing Group for the Women's Health Initiative Investigators
Y1  - 2002///
JF  - Jama
VL  - 288
IS  - 3
SP  - 321
EP  - 33
SN  - 0098748400987484
DO  - 10.1001/jama.288.3.321
UR  - http://www.ncbi.nlm.nih.gov/pubmed/12117397
N2  - CONTEXT Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain. OBJECTIVE To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States. DESIGN Estrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998. INTERVENTIONS Participants received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102). MAIN OUTCOMES MEASURES The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome. A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes. RESULTS On May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major clinical outcomes through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10 000 person-years. CONCLUSIONS Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.
ER  - 
TY  - JOUR
T1  - Effects of Ultralow-Dose Transdermal Estradiol on Bone Mineral Density: A Randomized Clinical Trial
A1  - Ettinger, Bruce
A1  - Ensrud, Kristine E.
A1  - Wallace, Robert
A1  - Johnson, Karen C.
A1  - Cummings, Steven R.
A1  - Yankov, Vladimir
A1  - Vittinghoff, Eric
A1  - Grady, Deborah
Y1  - 2004///
JF  - Obstetrics & Gynecology
VL  - 104
IS  - 3
SP  - 443
EP  - 451
SN  - 0029-7844 (Print)\r0029-7844 (Linking)
DO  - 10.1097/01.AOG.0000137833.43248.79
UR  - http://content.wkhealth.com/linkback/openurl?sid=WKPTLP:landingpage&an=00006250-200409000-00004
N2  - OBJECTIVE: Because small increments in levels of endogenous plasma estradiol are associated with higher postmenopausal bone mineral density, we investigated the safety and effectiveness in preventing bone loss of unopposed, very-low-dose transdermal estradiol for postmenopausal women. METHODS: This was a randomized, placebo-controlled, double-blind trial with 2-year follow-up at 9 United States clinical centers. The study population comprised 417 postmenopausal women, aged 60-80 years, with intact uterus and bone mineral density z scores of -2.0 or higher, who were randomly assigned to receive either unopposed transdermal estradiol at 0.014 mg/d (n = 208) or placebo (n = 209). All participants received calcium and vitamin D supplementation. Lumbar spine and total hip bone mineral density change was measured by dual-energy X-ray absorptiometry; endometrial hyperplasia incidence was assessed by endometrial biopsy. RESULTS: Median plasma estradiol level in the estradiol group increased from 4.8 pg/mL at baseline to 8.5 pg/mL at 1 year (P <.001 versus baseline) and to 8.6 pg/mL at 2 years (P <.001 versus baseline) and was unchanged in the placebo group. Lumbar spine bone mineral density increased 2.6% in the estradiol group and 0.6% in the placebo group (between-group difference 2.0%, P <.001). Mean total hip bone mineral density increased 0.4% in the estradiol group and decreased 0.8% in the placebo group (between-group difference 1.2%, P <.001). Osteocalcin levels and bone-specific alkaline phosphatase were lower in the estradiol group than the placebo group (P <.001 each). Endometrial hyperplasia developed in 1 woman in the estradiol group but in none of the placebo group (difference in 2-year rates 0.5%, 95% confidence interval 0-7.3%). CONCLUSION: Postmenopausal treatment with low-dose, unopposed estradiol increased bone mineral density and decreased markers of bone turnover without causing endometrial hyperplasia.
ER  - 
TY  - JOUR
T1  - 2016 IMS Recommendations on women’s midlife health and menopause hormone therapy
A1  - Baber, R. J.
A1  - Panay, N.
A1  - Fenton, A.
Y1  - 2016///
JF  - Climacteric
VL  - 19
IS  - 2
SP  - 109
EP  - 150
SN  - 1369-7137
DO  - 10.3109/13697137.2015.1129166
UR  - http://www.tandfonline.com/doi/full/10.3109/13697137.2015.1129166
N2  - AbstractThe International Menopause Society (IMS) has produced these new 2016 recommendations on women’s midlife health and menopause hormone therapy (MHT) to help guide health-care professionals in optimizing their management of women in the menopause transition and beyond. The term MHT has been used to cover therapies including estrogens, progestogens and combined regimens. For the first time, the 2016 IMS recommendations now include grades of recommendations, levels of evidence and 'good practice points', in addition to section-specific references. Where possible, the recommendations are based on and linked to the evidence that supports them, unless good-quality evidence is absent. Particular attention has been paid to published evidence from 2013 onwards, the last time the IMS recommendations were updated. Databases have been extensively searched for relevant publications using key terms specific to each specialist area within menopause physiology and medicine. Information has also been drawn from international consensus statements published by bodies such as the IMS, the European Menopause and Andropause Society and the North American Menopause Society. The recommendations have been produced by experts derived mainly from the IMS, with the assistance of key collaborators where deemed advantageous. In preparing these international recommendations, experts have taken into account geographical variations in medical care, prevalence of diseases, and country-specific attitudes of the public, medical community and health authorities towards menopause management. The variation in availability and licensing of MHT and other products has also been considered.
ER  - 
TY  - JOUR
T1  - Revised global consensus statement on menopausal hormone therapy
A1  - de Villiers, T. J.
A1  - Hall, J. E.
A1  - Pinkerton, J. V.
A1  - Pérez, S. Cerdas
A1  - Rees, M.
A1  - Yang, C.
A1  - Pierroz, D. D.
Y1  - 2016///
JF  - Maturitas
VL  - 91
SP  - 153
EP  - 155
SN  - 1369-7137
DO  - 10.1016/j.maturitas.2016.06.001
N2  - The following Consensus Statement is endorsed by The International Menopause Society, The North American Menopause Society, The Endocrine Society, The European Menopause and Andropause Society, The Asia Pacific Menopause Federation, The International Osteoporosis Foundation and The Federation of Latin American Menopause Societies.
ER  - 
TY  - JOUR
T1  - Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-Year results from the MORE trial
A1  - Cauley, J. A.
A1  - Norton, L.
A1  - Lippman, M. E.
A1  - Eckert, S.
A1  - Krueger, K. A.
A1  - Purdie, D. W.
A1  - Farrerons, J.
A1  - Karasik, A.
A1  - Mellstrom, D.
A1  - Ng, K. W.
A1  - Stepan, J. J.
A1  - Powles, T. J.
A1  - Morrow, M.
A1  - Costa, A.
A1  - Silfen, S. L.
A1  - Walls, E. L.
A1  - Schmitt, H.
A1  - Muchmore, D. B.
A1  - Jordan, V. C.
Y1  - 2001///
KW  - Breast cancer
KW  - MORE trial
KW  - Menopause
KW  - Osteoporosis
KW  - Raloxifene
KW  - SERM
KW  - STAR trial
KW  - Tamoxifen
JF  - Breast Cancer Research and Treatment
VL  - 65
IS  - 2
SP  - 125
EP  - 134
SN  - 0167-6806 (Print) 0167-6806 (Linking)
DO  - 10.1023/A:1006478317173
N2  - Raloxifene, a selective estrogen receptor modulator approved for the prevention and treatment of postmenopausal osteoporosis, has shown a significant reduction in breast cancer incidence after 3 years in this placebo-controlled, randomized clinical trial in postmenopausal women with osteoporosis. This article includes results from an additional annual mammogram at 4 years and represents 3,004 additional patient-years of follow-up in this trial. Breast cancers were ascertained through annual screening mammograms and adjudicated by an independent oncology review board. A total of 7,705 women were enrolled in the 4-year trial; 2,576 received placebo, 2,557 raloxifene 60 mg/day, and 2,572 raloxifene 120 mg/day. Women were a mean of 66.5-years old at trial entry, 19 years postmenopause, and osteoporotic (low bone mineral density and/or prevalent vertebral fractures). As of 1 November 1999, 61 invasive breast cancers had been reported and were confirmed by the adjudication board, resulting in a 72% risk reduction with raloxifene (relative risk (RR) 0.28, 95% confidence interval (CI) 0.17, 0.46). These data indicate that 93 osteoporotic women would need to be treated with raloxifene for 4 years to prevent one case of invasive breast cancer. Raloxifene reduced the risk of estrogen receptor-positive invasive breast cancer by 84% (RR 0.16, 95% CI 0.09, 0.30). Raloxifene was generally safe and well-tolerated, however, thromboembolic disease occurred more frequently with raloxifene compared with placebo (p=0.003). We conclude that raloxifene continues to reduce the risk of breast cancer in women with osteoporosis after 4 years of treatment, through prevention of new cancers or suppression of subclinical tumors, or both. Additional randomized clinical trials continue to evaluate this effect in postmenopausal women with osteoporosis, at risk for cardiovascular disease, and at high risk for breast cancer
ER  - 
TY  - JOUR
T1  - the Prevention, Diagnosis, and Treatment of Vitamin D and Calcium Deficiencies in the Adult Population of Russia and in Patients With Osteoporosis (According To the Materials of Prepared Clinical Recommendations)
A1  - Lesnyak, O. M.
A1  - Nikitinskaya, O. A.
A1  - Toroptsova, N. V.
A1  - Belaya, Zh. E.
A1  - Belova, K. Yu.
A1  - Bordakova, E. V.
A1  - Gilmanov, A. Zh.
A1  - Gurkina, E. Yu.
A1  - Dorofeikov, V. V.
A1  - Ershova, O. B.
A1  - Zazerskaya, I. E.
A1  - Zotkin, E. G.
A1  - Karonova, T. L.
A1  - Marchenkova, L. A.
A1  - Nazarova, A. V.
A1  - Pigarova, E. A.
A1  - Rozhinskaya, L. Ya.
A1  - Safonova, Yu. A.
A1  - Skripnikova, I. A.
A1  - Shirinyan, L. V.
A1  - Yureneva, S. V.
A1  - Yakushevskaya, O. V.
Y1  - 2015///
JF  - Rheumatology Science and Practice
VL  - 53
IS  - 4
SP  - 403
EP  - 403
DO  - 10.14412/1995-4484-2015-403-408
UR  - http://rsp.ima-press.net/index.php/rsp/article/view/2112
ER  - 
TY  - JOUR
T1  - Exercise and lumbar spine bone mineral density in postmenopausal women: A meta-analysis of individual patient data
A1  - Kelley, George A.
A1  - Kelley, Kristi S.
A1  - Tran, Zung V.
Y1  - 2002///
JF  - Journals of Gerontology - Series A Biological Sciences and Medical Sciences
VL  - 57
IS  - 9
SP  - 599
EP  - 604
DO  - 10.1093/gerona/57.9.M599
UR  - http://www.scopus.com/inward/record.url?eid=2-s2.0-0036728561&partnerID=tZOtx3y1
N2  - Background. Low bone mineral density (BMD) at the lumbar spine is a major public health problem among post-menopausal women. We conducted a meta-analysis of individual patient data (IPD) to examine the effects of exercise on lumbar spine BMD in postmenopausal women. Methods. IPD were requested from a previously developed database of summary means from randomized and non-randomized trials dealing with the effects of exercise on BMD. Two-way analysis of variance tests with pairwise comparisons (p ≤ .05) and 95% confidence intervals (CIs) were used to determine the statistical significance for changes in lumbar spine BMD. Results. Across 13 trials that included 699 subjects (355 exercise, 344 control), a statistically significant interaction was found between test and group (F = 15.232, p = .000). Pairwise comparisons (Bonferroni t tests) revealed a statistically significant increase in final minus initial BMD for the exercise group (X̄ ± SD = 0.005 ± 0.043 g/cm2, t = 2.46, p = .014, 95% CI = 0.001-0.009) and a statistically significant decrease in final minus initial BMD for the control group (X̄ ± SD = -0.007 ± 0.045 g/cm2, t = -3.051, p = .002, 95% CI = -0.012-0.002). Changes were equivalent to an approximate 2% benefit in lumbar spine BMD (exercise, + 1%, control, - 1%). Conclusions. The results of this IPD meta-analysis suggest that exercise helps to improve and maintain lumbar spine BMD in postmenopausal women.
ER  - 
TY  - JOUR
T1  - Effects of Raloxifene on Cardiovascular Events and Breast Cancer in Postmenopausal Women
A1  - Barrett-Connor, Elizabeth
A1  - Mosca, Lori
A1  - Collins, Peter
A1  - Geiger, Mary Jane
A1  - Grady, Deborah
A1  - Kornitzer, Marcel
A1  - McNabb, Michelle A.
A1  - Wenger, Nanette K.
Y1  - 2006///
JF  - New England Journal of Medicine
VL  - 355
IS  - 2
SP  - 125
EP  - 137
SN  - 0028-4793
DO  - 10.1056/NEJMoa062462
UR  - http://www.nejm.org/doi/abs/10.1056/NEJMoa062462
ER  - 
TY  - JOUR
T1  - Continuing outcomes relevant to Evista: Breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene
A1  - Martino, Silvana
A1  - Cauley, Jane A.
A1  - Barrett-Connor, Elizabeth
A1  - Powles, Trevor J.
A1  - Mershon, John
A1  - Disch, Damon
A1  - Secrest, Roberta J.
A1  - Cummings, Steven R.
A1  - Mautalen, Carlos A.
A1  - Zanchetta, J. R.
A1  - Hooper, Michael J.
A1  - Ng, Kong Wa
A1  - Prince, Richard L.
A1  - Nicholson, Geoffrey
A1  - Roberts, Anthony P.
A1  - Seeman, Ego
A1  - Williamson, Margaret
A1  - Boschitsch, E.
A1  - Leb, Georg
A1  - Body, J. J.
A1  - Devogelaer, J. P.
A1  - Geusens, P.
A1  - Kaufman, Jean Marc
A1  - Peretz, A.
A1  - Adachi, Jonathan
A1  - Bensen, William
A1  - Brown, Jacques P.
A1  - Cheung, Angela
A1  - Chik, Constance
A1  - Gee, Shirl
A1  - Hanley, David
A1  - Hawker, Gillian A.
A1  - Hodsman, Anthony B.
A1  - Joyce, Carol
A1  - Monchesky, Theodore C.
A1  - Olszynski, Wojciech P.
A1  - Roe, Bruce
A1  - Senikas, Vyte
A1  - Seminoski, Kerry
A1  - Wall, Jack
A1  - Stepan, Jan
A1  - Hyldstrup, L.
A1  - Langdahl, Bente
A1  - Sorensen, Tine Hog
A1  - Alhava, Esko
A1  - Kormano, Martti
A1  - Salmela, Pasi
A1  - Salmi, Jorma
A1  - Valimaki, Matti
A1  - Audran, M.
A1  - Briancon, D.
A1  - Delmas, P.
A1  - Fardellone, Patrice
A1  - Ribot, C.
A1  - De Vernejoul, M. C.
A1  - Balogh, Adam
A1  - Julesz, J.
A1  - Szuecs, J.
A1  - Karsik, Avraham
A1  - Fiore, Carmelo
A1  - Genazzani, Andrea Riccardo
A1  - Gennari, C.
A1  - Isaia, Giovanni Carlo
A1  - Melis, Gian Benedetto
A1  - Nuti, Ranuccio
A1  - Oriente, Pasquale
A1  - Passeri, Mario
A1  - Sartori, Leonardo
A1  - Corea-Rotter, R.
A1  - Gonzalez, Santos
A1  - Murillo, Alfonso
A1  - Jonker, J. J.
A1  - Lips, P.
A1  - Mulder, H.
A1  - Pols, H. A.
A1  - Halse, Johan Inge
A1  - Hoiseth, Arne
A1  - Jorde, Rolf
A1  - Olford, Erik Snorre
A1  - Skag, Arne
A1  - Stakkestad, Jacob Andreas
A1  - Wist, Erik
A1  - Badurski, Janusz Edward
A1  - Hoszowski, Krzysztof
A1  - Ogonowski, Jaroslaw
A1  - Bose, Kamal
A1  - Lee, Kok Onn
A1  - Dzurik, Rastislav
A1  - Kocijancic, Andreja
A1  - Cannata Andia, Jorge B.
A1  - Collado, Ramon Carreras
A1  - Carranza, Frederico Hawkins
A1  - Diez-Perez, Adolfo
A1  - Escobar-Jimenez, Fernando
A1  - Minguella, Jordi Farrerons
A1  - Solan, Xavier Nogues
A1  - Torres, Manuel Munoz
A1  - Larsson, Karin
A1  - Malströem, Dan
Y1  - 2004///
JF  - Journal of the National Cancer Institute
VL  - 96
IS  - 23
SP  - 1751
EP  - 1761
SN  - 1460-2105 (Electronic)\n0027-8874 (Linking)
DO  - 10.1093/jnci/djh319
N2  - BACKGROUND: The randomized, double-blind Multiple Outcomes of Raloxifene Evaluation (MORE) trial found that 4 years of raloxifene therapy decreased the incidence of invasive breast cancer among postmenopausal women with osteoporosis by 72% compared with placebo. We conducted the Continuing Outcomes Relevant to Evista (CORE) trial to examine the effect of 4 additional years of raloxifene therapy on the incidence of invasive breast cancer in women in MORE who agreed to continue in CORE. METHODS: Women who had been randomly assigned to receive raloxifene (either 60 or 120 mg/day) in MORE were assigned to receive raloxifene (60 mg/day) in CORE (n = 3510), and women who had been assigned to receive placebo in MORE continued on placebo in CORE (n = 1703). Breast cancer incidence was analyzed by a log-rank test, and a Cox proportional hazards model was used to compute hazard ratios (HRs) and 95% confidence intervals (CIs). All statistical tests were two-sided. RESULTS: During the CORE trial, the 4-year incidences of invasive breast cancer and estrogen receptor (ER)-positive invasive breast cancer were reduced by 59% (HR = 0.41; 95% CI = 0.24 to 0.71) and 66% (HR = 0.34; 95% CI = 0.18 to 0.66), respectively, in the raloxifene group compared with the placebo group. There was no difference between the two groups in incidence of ER-negative invasive breast cancer during CORE (P = .86). Over the 8 years of both trials, the incidences of invasive breast cancer and ER-positive invasive breast cancer were reduced by 66% (HR = 0.34; 95% CI = 0.22 to 0.50) and 76% (HR = 0.24; 95% CI = 0.15 to 0.40), respectively, in the raloxifene group compared with the placebo group. During the CORE trial, the relative risk of thromboembolism in the raloxifene group compared with that in the placebo group was 2.17 (95% CI = 0.83 to 5.70). This increased risk, also observed in the MORE trial, persisted over the 8 years of both trials. CONCLUSIONS: The reduction in invasive breast cancer incidence continues beyond 4 years of raloxifene treatment in postmenopausal women with osteoporosis. No new safety concerns related to raloxifene therapy were identified during CORE.
ER  - 
TY  - JOUR
T1  - Primary care-relevant interventions to prevent falling in older adults: A systematic evidence review for the U.S. Preventive Services Task Force
A1  - Michael, Yvonne L.
A1  - Whitlock, Evelyn P.
A1  - Lin, Jennifer S.
A1  - Fu, Rongwei
A1  - O'Connor, Elizabeth A.
A1  - Gold, Rachel
Y1  - 2010///
JF  - Annals of Internal Medicine
VL  - 153
IS  - 12
SP  - 815
EP  - 825
SN  - 1539-3704 (Electronic)\r0003-4819 (Linking)
DO  - 10.7326/0003-4819-153-12-201012210-00008
N2  - RESULTADOS Se incluyeron 54 ECA (con un total de 26 102 par- partici-) que puso a prueba las intervenciones de atención primaria de pre- ventilación caer. Sólo 41 de los 111 ensayos de la revisión chrane Cooperación (16) se incluyeron en nuestra revisión, debido a diferencias en los criterios de inclusión. Las razones más comunes para la exclusión de la revisión fueron que un grupo de control verdadera faltaba, la población estudiada fue institucionalizado o reclutados de pacientes hospitalizados, y las intervenciones no podía llevarse a cabo en atención primaria o ser referido desde la atención primaria. Mesas y tablas de los estudios excluidos para cada pregunta clave en la evidencia están disponibles en el informe completo (18). Los detalles de cada estudio incluido se resumen en el Apéndice Tablas 2 a 6 (disponible en www.annals.org). La tabla muestra un resumen de las pruebas por categoría intervención. Evaluación y Gestión multifactorial Se evaluaron 19 evaluación multifactorial y tión ensayos gestión (7099 participantes) con 21 grupos de intervención activas (23-41). Todos los ensayos excepto 1 se limitaron a las poblaciones en alto riesgo de caer (36). La mayoría de las intervenciones evaluadas principales factores de riesgo para las caídas que eran identificables durante la evaluación clínica: uso de medicamentos, la agudeza visual, entorno familiar, y la marcha y el equilibrio. Sobre la base de la evidencia de que las intervenciones multifactoriales de evaluación que incorporan estrategias de gestión integrales tienen más éxito en la prevención de caídas (13), las intervenciones se clasificaron en la fase de la abstracción por 2 investigadores independientes como la gestión integral (completa y activa de los factores y condiciones de riesgo caída identificado en la evaluación multifactorial, incluyendo la provisión de los gerentes de caso o enfermeras a domicilio) o no exhaustivas (proporcionar solamente par- cial o manejo limitado de factores de riesgo relacionados con el otoño-identificados). Los grupos de control recibieron principalmente la atención habitual, aunque 2 ensayos utilizaron grupos de control "atención" (30, 32) y 1 ensayo pro- porcionada "una intervención mínima de principalmente la educación" como un grupo de control (42). La mayoría de los estudios fueron calificados como de calidad justo. La mayoría de los estudios no informaron si la asignación del tratamiento fue www.annals.org
ER  - 
TY  - JOUR
T1  - Effective exercise for the prevention of falls: A systematic review and meta-analysis
A1  - Sherrington, Catherine
A1  - Whitney, Julie C.
A1  - Lord, Stephen R.
A1  - Herbert, Robert D.
A1  - Cumming, Robert G.
A1  - Close, Jacqueline C.T.
Y1  - 2008///
KW  - Exercise
KW  - Falls
KW  - Meta-analysis
JF  - Journal of the American Geriatrics Society
VL  - 56
IS  - 12
SP  - 2234
EP  - 2243
SN  - 1532-5415
DO  - 10.1111/j.1532-5415.2008.02014.x
N2  - OBJECTIVES: To determine the effects of exercise on falls prevention in older people and establish whether particular trial characteristics or components of exercise programs are associated with larger reductions in falls. DESIGN: Systematic review with meta-analysis. Randomized controlled trials that compared fall rates in older people who undertook exercise programs with fall rates in those who did not exercise were included. SETTING: Older people. PARTICIPANTS: General community and residential care. MEASUREMENTS: Fall rates. RESULTS: The pooled estimate of the effect of exercise was that it reduced the rate of falling by 17% (44 trials with 9,603 participants, rate ratio (RR)=0.83, 95% confidence interval (CI)=0.75-0.91, P<.001, I(2)=62%). The greatest relative effects of exercise on fall rates (RR=0.58, 95% CI=0.48-0.69, 68% of between-study variability explained) were seen in programs that included a combination of a higher total dose of exercise (>50 hours over the trial period) and challenging balance exercises (exercises conducted while standing in which people aimed to stand with their feet closer together or on one leg, minimize use of their hands to assist, and practice controlled movements of the center of mass) and did not include a walking program. CONCLUSION: Exercise can prevent falls in older people. Greater relative effects are seen in programs that include exercises that challenge balance, use a higher dose of exercise, and do not include a walking program. Service providers can use these findings to design and implement exercise programs for falls prevention.
ER  -