{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T22:25:17Z","timestamp":1785536717691,"version":"3.56.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2011,6,27]],"date-time":"2011-06-27T00:00:00Z","timestamp":1309132800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Various definitions of nonvertebral fracture have been used in osteoporosis trials, precluding comparisons of efficacy. Using only subgroups of nonvertebral fractures for trial outcomes may underestimate the benefits and cost-effectiveness of treatments. The objectives of this study were to determine (1) the effect of antiresorptive treatment on various nonvertebral fracture outcomes, (2) whether risk reduction from antiresorptive treatment is greater for nonvertebral fractures that have stronger associations with low BMD, and (3) sample size estimates for clinical trials of osteoporosis treatments. Study-level data were combined from five randomized fracture-prevention trials of antiresorptive agents that reduce the risk of nonvertebral fracture in postmenopausal women: alendronate, clodronate, denosumab, lasofoxifene, and zoledronic acid. Pooled effect estimates were calculated with random-effects models. The five trials included 30,118 women; 2997 women had at least one nonvertebral fracture. There was no significant heterogeneity between treatments for any outcome (all p\u2009&amp;gt;\u20090.10). Antiresorptive treatment had similar effects on all fractures (summary hazard ratio [HR]\u2009=\u20090.76, 95% CI 0.70\u20130.81), high-trauma fractures (HR\u2009=\u20090.74, 95% CI 0.57\u20130.96), low-trauma fractures (HR\u2009=\u20090.77, (95% CI 0.71\u20130.83), nonvertebral six (ie, hip, pelvis, leg, wrist, humerus, and clavicle) fractures (HR\u2009=\u20090.73, 95% CI 0.66\u20130.80), other than nonvertebral six fractures (HR\u2009=\u20090.78, 95% CI 0.70\u20130.87), and all fractures other than finger, face, and toe (HR\u2009=\u20090.75, 95% CI 0.70\u20130.81). Risk reduction was not greater for fractures with stronger associations with low BMD (p\u2009=\u20090.77). A trial of all nonvertebral fractures would require fewer participants (n\u2009=\u20092641 per arm) than one of a subgroup of six fractures (n\u2009=\u20093289), for example. In summary, antiresorptive treatments reduced all nonvertebral fractures regardless of degree of trauma or special groupings, supporting the use of all nonvertebral fractures as a standard endpoint of osteoporosis trials and the basis for estimating the benefits and cost-effectiveness of treatments. \u00a9 2011 American Society for Bone and Mineral Research<\/jats:p>","DOI":"10.1002\/jbmr.446","type":"journal-article","created":{"date-parts":[[2011,6,30]],"date-time":"2011-06-30T12:22:57Z","timestamp":1309436577000},"page":"2411-2418","source":"Crossref","is-referenced-by-count":41,"title":["Effects of antiresorptive treatment on nonvertebral fracture outcomes"],"prefix":"10.1093","volume":"26","author":[{"given":"Dawn C","family":"Mackey","sequence":"first","affiliation":[{"name":"San Francisco Coordinating Center, California Pacific Medical Center, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis M","family":"Black","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas C","family":"Bauer","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Francisco, San Francisco, CA, USA"},{"name":"Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eugene V","family":"McCloskey","sequence":"additional","affiliation":[{"name":"Academic Unit of Bone Metabolism, University of Sheffield, Sheffield, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Eastell","sequence":"additional","affiliation":[{"name":"Academic Unit of Bone Metabolism, University of Sheffield, Sheffield, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Mesenbrink","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John R","family":"Thompson","sequence":"additional","affiliation":[{"name":"Pfizer Global Research and Development, New London, CT, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven R","family":"Cummings","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA"},{"name":"San Francisco Coordinating Center, California Pacific Medical Center, San Francisco, CA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2011,6,27]]},"reference":[{"key":"2024020317565911800_bib1","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1016\/S0140-6736(96)07088-2","article-title":"Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group","volume":"348","author":"Black","year":"1996","journal-title":"Lancet."},{"key":"2024020317565911800_bib2","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1056\/NEJMoa067312","article-title":"Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis","volume":"356","author":"Black","year":"2007","journal-title":"N Engl J Med."},{"key":"2024020317565911800_bib3","doi-asserted-by":"crossref","first-page":"2077","DOI":"10.1001\/jama.280.24.2077","article-title":"Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial","volume":"280","author":"Cummings","year":"1998","journal-title":"JAMA."},{"key":"2024020317565911800_bib4","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1056\/NEJMoa0809493","article-title":"Denosumab for prevention of fractures in postmenopausal women with osteoporosis","volume":"361","author":"Cummings","year":"2009","journal-title":"N Engl J Med."},{"key":"2024020317565911800_bib5","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1056\/NEJMoa0808692","article-title":"Lasofoxifene in postmenopausal women with osteoporosis","volume":"362","author":"Cummings","journal-title":"N Engl J Med."},{"key":"2024020317565911800_bib6","doi-asserted-by":"crossref","first-page":"1344","DOI":"10.1001\/jama.282.14.1344","article-title":"Effects of risedronate treatment on vertebral and nonvertebral fractures in women with postmenopausal osteoporosis: a randomized controlled trial. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group","volume":"282","author":"Harris","year":"1999","journal-title":"JAMA."},{"key":"2024020317565911800_bib7","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1056\/NEJM200102013440503","article-title":"Effect of risedronate on the risk of hip fracture in elderly women. Hip Intervention Program Study Group","volume":"344","author":"McClung","year":"2001","journal-title":"N Engl J Med."},{"key":"2024020317565911800_bib8","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1007\/s001980050010","article-title":"Randomized trial of the effects of risedronate on vertebral fractures in women with established postmenopausal osteoporosis. Vertebral Efficacy with Risedronate Therapy (VERT) Study Group","volume":"11","author":"Reginster","year":"2000","journal-title":"Osteoporos Int."},{"key":"2024020317565911800_bib9","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1359\/jbmr.2003.18.11.1947","article-title":"BMD at multiple sites and risk of fracture of multiple types: long-term results from the Study of Osteoporotic Fractures","volume":"18","author":"Stone","year":"2003","journal-title":"J Bone Miner Res."},{"key":"2024020317565911800_bib10","first-page":"605","article-title":"Therapies for treatment of osteoporosis in US women: cost-effectiveness and budget impact considerations","volume":"14","author":"Tosteson","year":"2008","journal-title":"Am J Manag Care."},{"key":"2024020317565911800_bib11","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s00198-007-0550-6","article-title":"Cost-effective osteoporosis treatment thresholds: the United States perspective","volume":"19","author":"Tosteson","year":"2008","journal-title":"Osteoporos Int."},{"key":"2024020317565911800_bib12","doi-asserted-by":"crossref","first-page":"2381","DOI":"10.1001\/jama.298.20.2381","article-title":"High-trauma fractures and low bone mineral density in older women and men","volume":"298","author":"Mackey","year":"2007","journal-title":"JAMA."},{"key":"2024020317565911800_bib13","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.1359\/jbmr.1998.13.8.1337","article-title":"The exclusion of high trauma fractures may underestimate the prevalence of bone fragility fractures in the community: the Geelong Osteoporosis Study","volume":"13","author":"Sanders","year":"1998","journal-title":"J Bone Miner Res."},{"key":"2024020317565911800_bib14","doi-asserted-by":"crossref","first-page":"4118","DOI":"10.1210\/jcem.85.11.6953","article-title":"Fracture risk reduction with alendronate in women with osteoporosis: the Fracture Intervention Trial. FIT Research Group","volume":"85","author":"Black","year":"2000","journal-title":"J Clin Endocrinol Metab."},{"key":"2024020317565911800_bib15","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1359\/jbmr.061008","article-title":"Clodronate reduces the incidence of fractures in community-dwelling elderly women unselected for osteoporosis: results of a double-blind, placebo-controlled, randomized study","volume":"22","author":"McCloskey","year":"2007","journal-title":"J Bone Miner Res."},{"key":"2024020317565911800_bib16","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/0002-9343(93)90350-X","article-title":"Four-year study of intermittent cyclic etidronate treatment of postmenopausal osteoporosis: three years of blinded therapy followed by one year of open therapy","volume":"95","author":"Harris","year":"1993","journal-title":"Am J Med."},{"key":"2024020317565911800_bib17","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/S0002-9343(97)00278-7","article-title":"Cyclical etidronate in the treatment of postmenopausal osteoporosis: efficacy and safety after seven years of treatment","volume":"103","author":"Miller","year":"1997","journal-title":"Am J Med."},{"key":"2024020317565911800_bib18","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/BF01622291","article-title":"Effects of cyclical etidronate therapy on bone loss in early postmenopausal women who are not undergoing hormonal replacement therapy","volume":"7","author":"Pouilles","year":"1997","journal-title":"Osteoporos Int."},{"key":"2024020317565911800_bib19","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1359\/JBMR.040325","article-title":"Effects of oral ibandronate administered daily or intermittently on fracture risk in postmenopausal osteoporosis","volume":"19","author":"Chesnut","year":"2004","journal-title":"J Bone Miner Res."},{"key":"2024020317565911800_bib20","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1359\/JBMR.050313","article-title":"Monthly oral ibandronate therapy in postmenopausal osteoporosis: 1-year results from the MOBILE study","volume":"20","author":"Miller","year":"2005","journal-title":"J Bone Miner Res."},{"key":"2024020317565911800_bib21","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1136\/ard.2005.044958","article-title":"Efficacy and tolerability of once-monthly oral ibandronate in postmenopausal osteoporosis: 2 year results from the MOBILE study","volume":"65","author":"Reginster","year":"2006","journal-title":"Ann Rheum Dis."},{"key":"2024020317565911800_bib22","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1001\/jama.282.7.637","article-title":"Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators","volume":"282","author":"Ettinger","year":"1999","journal-title":"JAMA."},{"key":"2024020317565911800_bib23","first-page":"2001","author":"Egger","edition":"2nd ed"},{"key":"2024020317565911800_bib24","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/0197-2456(86)90046-2","article-title":"Meta-analysis in clinical trials","volume":"7","author":"DerSimonian","year":"1986","journal-title":"Control Clin Trials."},{"key":"2024020317565911800_bib25","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1007\/s00198-007-0543-5","article-title":"FRAX and the assessment of fracture probability in men and women from the UK","volume":"19","author":"Kanis","year":"2008","journal-title":"Osteoporos Int."}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbmr.446","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/26\/10\/2411\/56558160\/446_ftp.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/26\/10\/2411\/56558160\/446_ftp.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T15:08:10Z","timestamp":1710342490000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/26\/10\/2411-2418\/7597986"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,6,27]]},"references-count":25,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2011,6,27]]},"published-print":{"date-parts":[[2011,10,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.446","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2011,10,1]]},"published":{"date-parts":[[2011,6,27]]}}}