title: Oral bisphosphonates and risk of subtrochanteric or diaphyseal femur fractures in a population-based cohort.
abstract: Bisphosphonates are the primary therapy for postmenopausal and glucocorticoid-induced osteoporosis. Case series suggest a potential link between prolonged use of bisphosphonates and low-energy fracture of subtrochanteric or diaphyseal femur as a consequence of oversuppression of bone resorption. Using health care utilization data, we conducted a propensity score-matched cohort study to examine the incidence rates (IRs) and risk of subtrochanteric or diaphyseal femur fractures among oral bisphosphonate users compared with raloxifene or calcitonin users. A Cox proportional hazards model evaluated the risk of these fractures associated with duration of osteoporosis treatment. A total of 104 subtrochanteric or diaphyseal femur fractures were observed among 33,815 patients. The estimated IR of subtrochanteric or diaphyseal femur fractures per 1000 person-years was 1.46 [95% confidence interval (CI) 1.11-1.88] among the bisphosphonate users and 1.43 (95% CI 1.06-1.89) among raloxifene/calcitonin users. No significant association between bisphosphonate use and subtrochanteric or diaphyseal femur fractures was found [hazard ratio (HR) = 1.03, 95% CI 0.70-1.52] compared with raloxifene/calcitonin. Even with this large study size, we had little precision in estimating the risk of subtrochanteric or diaphyseal femur fractures in patients treated with bisphosphonates for longer than 5 years (HR = 2.02, 95% CI 0.41-10.00). The occurrence of subtrochanteric or diaphyseal femur fracture was rare. There was no evidence of an increased risk of subtrochanteric or diaphyseal femur fractures in bisphosphonate users compared with raloxifene/calcitonin users. However, this study cannot exclude the possibility that long-term bisphosphonate use may increase the risk of these fractures.
authors.affiliation: Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Boston, MA, USA. skim62@partners.org
authors.forename: Seo Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Sebastian
authors.initials: S
authors.lastname: Schneeweiss
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Katz
authors.forename: Raisa
authors.initials: R
authors.lastname: Levin
authors.forename: Daniel H
authors.initials: DH
authors.lastname: Solomon
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000009:adverse effects*; D015331:Cohort Studies; D018483:Diaphyses / Q000473:pathology*; D004164:Diphosphonates / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D005264:Femoral Fractures / Q000139:chemically induced* / Q000453:epidemiology; D006620:Hip Fractures / Q000139:chemically induced* / Q000453:epidemiology; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D010024:Osteoporosis / Q000150:complications / Q000188:drug therapy; D016016:Proportional Hazards Models; D012307:Risk Factors
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates