{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T03:48:08Z","timestamp":1792813688172,"version":"4.5.0"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2013,2,13]],"date-time":"2013-02-13T00:00:00Z","timestamp":1360713600000},"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":[[2013,8,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>\u2003<\/jats:title>\n                    <jats:p>Although there is strong evidence that bisphosphonates prevent certain types of osteoporotic fractures, there are concerns that these medications may be associated with rare atypical femoral fractures (AFF). Recent published studies examining this potential association are conflicting regarding the existence and strength of this association. We conducted a systematic review and meta-analysis of published studies examining the association of bisphosphonates with subtrochanteric, femoral shaft, and AFF. The random-effects model was used to calculate the pooled estimates of adjusted risk ratios (RR). Subgroup analysis was performed by study design, for studies that used validated outcome definitions for AFF, and for studies reporting on duration of bisphosphonate use. Eleven studies were included in the meta-analysis: five case-control and six cohort studies. Bisphosphonate exposure was associated with an increased risk of subtrochanteric, femoral shaft, and AFF, with adjusted RR of 1.70 (95% confidence interval [CI], 1.22\u20132.37). Subgroup analysis of studies using the American Society for Bone and Mineral Research criteria to define AFF suggests a higher risk of AFF, with bisphosphonate use with RR of 11.78 (95% CI, 0.39\u2013359.69) as compared to studies using mainly diagnosis codes (RR, 1.62; 95% CI, 1.18\u20132.22), although there is a wide confidence interval and severe heterogeneity (I2\u2009=\u200996.15%) in this subgroup analysis. Subgroup analysis of studies examining at least 5 years of bisphosphonate use showed adjusted RR of 1.62 (95% CI, 1.29\u20132.04). This meta-analysis suggests there is an increased risk of subtrochanteric, femoral shaft, and AFF among bisphosphonate users. Further research examining the risk of AFF with long-term use of bisphosphonates is indicated as there was limited data in this subgroup. The public health implication of this observed increase in AFF risk is not clear.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jbmr.1893","type":"journal-article","created":{"date-parts":[[2013,2,13]],"date-time":"2013-02-13T15:52:45Z","timestamp":1360770765000},"page":"1729-1737","source":"Crossref","is-referenced-by-count":213,"title":["Bisphosphonates and risk of subtrochanteric, femoral shaft, and atypical femur fracture: A systematic review and meta-analysis"],"prefix":"10.1093","volume":"28","author":[{"given":"Lydia","family":"Gedmintas","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Immunology and AllergyBrigham and Women's HospitalBoston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel H","family":"Solomon","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and PharmacoeconomicsBrigham and Women's HospitalBoston, MA"},{"name":"Division of Rheumatology, Immunology and AllergyBrigham and Women's HospitalBoston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seoyoung C","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Pharmacoepidemiology and PharmacoeconomicsBrigham and Women's HospitalBoston, MA"},{"name":"Division of Rheumatology, Immunology and AllergyBrigham and Women's HospitalBoston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2013,2,13]]},"reference":[{"key":"2024020318365813300_jbmr1893-bib-0001","volume-title":"America's Bone Health: The State of Osteoporosis and Low Bone Mass in Our Nation","author":"National Osteoporosis Foundation","year":"2002"},{"key":"2024020318365813300_jbmr1893-bib-0002","doi-asserted-by":"crossref","first-page":"S14","DOI":"10.1016\/j.amjmed.2008.12.003","article-title":"Efficacy of bisphosphonates in reducing fracture risk in postmenopausal osteoporosis","volume":"122","author":"Bilezikian","year":"2009","journal-title":"Am J Med."},{"issue":"1","key":"2024020318365813300_jbmr1893-bib-0003","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/jbmr.189","article-title":"Estimating bisphosphonate use and fracture reduction among US women aged 45 years and older, 2001-2008","volume":"26","author":"Siris","year":"2011","journal-title":"J Bone Miner Res."},{"key":"2024020318365813300_jbmr1893-bib-0004","doi-asserted-by":"crossref","first-page":"1294","DOI":"10.1210\/jc.2004-0952","article-title":"Severely suppressed bone turnover: a potential complication of alendronate therapy","volume":"90","author":"Odvina","year":"2005","journal-title":"J Clin Endocrinol Metab."},{"key":"2024020318365813300_jbmr1893-bib-0005","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1359\/jbmr.2000.15.4.613","article-title":"Suppressed bone turnover by bisphosphonates increases microdamage accumulation and reduces some biomechanical properties in dog rib","volume":"15","author":"Mashiba","year":"2000","journal-title":"J Bone Miner Res."},{"key":"2024020318365813300_jbmr1893-bib-0006","author":"Kelly"},{"key":"2024020318365813300_jbmr1893-bib-0007","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s00198-009-0962-6","article-title":"Fragility fractures of the hip and femur: incidence and patient characteristics","volume":"21","author":"Nieves","year":"2010","journal-title":"Osteoporos Int."},{"key":"2024020318365813300_jbmr1893-bib-0008","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1002\/jbmr.233","article-title":"Trends in incidence of subtrochanteric fragility fractures and bisphosphonate use among the US elderly, 1996-2007","volume":"26","author":"Wang","year":"2011","journal-title":"J Bone Miner Res."},{"key":"2024020318365813300_jbmr1893-bib-0009","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1001\/jama.2011.190","article-title":"Bisphosphonate use and the risk of subtrochanteric or femoral shaft fractures in older women","volume":"305","author":"Park-Wyllie","year":"2011","journal-title":"JAMA."},{"key":"2024020318365813300_jbmr1893-bib-0010","doi-asserted-by":"crossref","first-page":"1728","DOI":"10.1056\/NEJMoa1010650","article-title":"Bisphosphonate use and atypical fractures of the femoral shaft","volume":"364","author":"Schilcher","year":"2011","journal-title":"N Engl J Med."},{"key":"2024020318365813300_jbmr1893-bib-0011","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1007\/s00198-010-1512-y","article-title":"Risk of femoral shaft and subtrochanteric fractures among users of bisphosphonates and raloxifene","volume":"22","author":"Vestergaard","year":"2011","journal-title":"Osteoporos Int."},{"issue":"19","key":"2024020318365813300_jbmr1893-bib-0012","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1056\/NEJMoa1001086","article-title":"Bisphosphonates and fractures of the subtrochanteric or diaphyseal femur","volume":"362","author":"Black","year":"2010","journal-title":"N Engl J Med."},{"issue":"5","key":"2024020318365813300_jbmr1893-bib-0013","doi-asserted-by":"crossref","first-page":"993","DOI":"10.1002\/jbmr.288","article-title":"Oral bisphosphonates and risk of subtrochanteric or diaphyseal femur fractures in a population-based cohort","volume":"26","author":"Kim","year":"2011","journal-title":"J Bone Miner Res."},{"issue":"11","key":"2024020318365813300_jbmr1893-bib-0014","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1016\/j.clinthera.2011.09.006","article-title":"Hip and subtrochanteric or diaphyseal femoral fractures in alendronate users: a 10-year, nationwide retrospective cohort study in Taiwanese women","volume":"33","author":"Hsiao","year":"2011","journal-title":"Clin Ther."},{"key":"2024020318365813300_jbmr1893-bib-0015","doi-asserted-by":"crossref","first-page":"b2535","DOI":"10.1136\/bmj.b2535","article-title":"Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement","volume":"339","author":"Moher","year":"2009","journal-title":"BMJ."},{"key":"2024020318365813300_jbmr1893-bib-0016","author":"Wells"},{"issue":"19","key":"2024020318365813300_jbmr1893-bib-0017","doi-asserted-by":"crossref","first-page":"1690","DOI":"10.1001\/jama.280.19.1690","article-title":"What's the relative risk? A method of correcting the odds ratio in cohort studies of common outcomes","volume":"280","author":"Zhang","year":"1998","journal-title":"JAMA."},{"issue":"3","key":"2024020318365813300_jbmr1893-bib-0018","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."},{"issue":"11","key":"2024020318365813300_jbmr1893-bib-0019","doi-asserted-by":"crossref","first-page":"1539","DOI":"10.1002\/sim.1186","article-title":"Quantifying heterogeneity in a meta-analysis","volume":"21","author":"Higgins","year":"2002","journal-title":"Stat Med."},{"issue":"10","key":"2024020318365813300_jbmr1893-bib-0020","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1016\/S0895-4356(01)00377-8","article-title":"Funnel plots for detecting bias in meta-analysis: guidelines on choice of axis","volume":"54","author":"Sterne","year":"2001","journal-title":"J Clin Epidemiol."},{"issue":"15","key":"2024020318365813300_jbmr1893-bib-0021","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1001\/jama.283.15.2008","article-title":"Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group","volume":"283","author":"Stroup","year":"2000","journal-title":"JAMA."},{"issue":"5","key":"2024020318365813300_jbmr1893-bib-0022","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/j.bone.2010.12.033","article-title":"Atypical fractures and bisphosphonate therapy: a cohort study of patients with femoral fracture with radiographic adjudication of fracture site and features","volume":"48","author":"Giusti","year":"2011","journal-title":"Bone."},{"issue":"1","key":"2024020318365813300_jbmr1893-bib-0023","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.bone.2012.02.632","article-title":"Clinical correlates of atypical femoral fracture","volume":"51","author":"Lo","year":"2012","journal-title":"Bone."},{"issue":"12","key":"2024020318365813300_jbmr1893-bib-0024","doi-asserted-by":"crossref","first-page":"2544","DOI":"10.1002\/jbmr.1719","article-title":"Incidence of atypical nontraumatic diaphyseal fractures of the femur","volume":"27","author":"Dell","year":"2012","journal-title":"J Bone Miner Res."},{"issue":"8","key":"2024020318365813300_jbmr1893-bib-0025","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1007\/s00198-008-0805-x","article-title":"Association of low-energy femoral fractures with prolonged bisphosphonate use: a case control study","volume":"20","author":"Lenart","year":"2009","journal-title":"Osteoporos Int."},{"issue":"12","key":"2024020318365813300_jbmr1893-bib-0026","doi-asserted-by":"crossref","first-page":"930","DOI":"10.1001\/archinternmed.2012.1796","article-title":"Increasing occurrence of atypical femoral fractures associated with bisphosphonate use","volume":"172","author":"Meier","year":"2012","journal-title":"Arch Intern Med."},{"key":"2024020318365813300_jbmr1893-bib-0027","doi-asserted-by":"crossref","first-page":"977","DOI":"10.1002\/jbmr.1550","article-title":"Incidence and demography of femur fractures with and without atypical features","volume":"27","author":"Feldstein","year":"2012","journal-title":"J Bone Miner Res."},{"issue":"6","key":"2024020318365813300_jbmr1893-bib-0028","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1359\/jbmr.081247","article-title":"Subtrochanteric and diaphyseal femur fractures in patients treated with alendronate: a register-based national cohort study","volume":"24","author":"Abrahamsen","year":"2009","journal-title":"J Bone Miner Res."},{"issue":"12","key":"2024020318365813300_jbmr1893-bib-0029","doi-asserted-by":"crossref","first-page":"5258","DOI":"10.1210\/jc.2010-1571","article-title":"Cumulative alendronate dose and the long-term absolute risk of subtrochanteric and diaphyseal femur fractures: a register-based national cohort analysis","volume":"95","author":"Abrahamsen","year":"2010","journal-title":"J Clin Endocrinol Metab."},{"key":"2024020318365813300_jbmr1893-bib-0030","author":"Aspenberg"},{"issue":"11","key":"2024020318365813300_jbmr1893-bib-0031","doi-asserted-by":"crossref","first-page":"2267","DOI":"10.1002\/jbmr.253","article-title":"Atypical subtrochanteric and diaphyseal femoral fractures: report of a task force of the American Society for Bone and Mineral Research","volume":"25","author":"Shane","year":"2010","journal-title":"J Bone Miner Res."},{"key":"2024020318365813300_jbmr1893-bib-0032","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1056\/NEJMp1202619","article-title":"Bisphosphonates for osteoporosis. Where do we go from here?","volume":"366","author":"Whitaker","year":"2012","journal-title":"N Engl J Med."},{"issue":"22","key":"2024020318365813300_jbmr1893-bib-0033","doi-asserted-by":"crossref","first-page":"2051","DOI":"10.1056\/NEJMp1202623","article-title":"Continuing bisphosphonate treatment for osteoporosis\u2014for whom and for how long?","volume":"366","author":"Black","year":"2012","journal-title":"N Engl J Med."}],"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.1893","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/28\/8\/1729\/56563121\/jbmr1893.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/28\/8\/1729\/56563121\/jbmr1893.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T10:48:53Z","timestamp":1710326933000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/28\/8\/1729-1737\/7598628"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,2,13]]},"references-count":33,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2013,2,13]]},"published-print":{"date-parts":[[2013,8,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.1893","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.717978745.793480940","asserted-by":"object"}]},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2013,8,1]]},"published":{"date-parts":[[2013,2,13]]}}}