Oral bisphosphonates and risk of subtrochanteric or diaphyseal femur fractures in a population-based cohort

Authors

  • Seo Young Kim,

    Corresponding author
    1. Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Boston, MA, USA
    2. Division of Rheumatology, Allergy and Immunology, Brigham and Women's Hospital, Boston, MA, USA
    • MSCE, 1620 Tremont Street, Suite 3030, Boston MA 02120, USA.
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  • Sebastian Schneeweiss,

    1. Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Boston, MA, USA
    2. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
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  • Jeffrey N Katz,

    1. Division of Rheumatology, Allergy and Immunology, Brigham and Women's Hospital, Boston, MA, USA
    2. Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA
    3. Department of Orthopedic Surgery, Brigham and Women's Hospital, Boston, MA, USA
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  • Raisa Levin,

    1. Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Boston, MA, USA
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  • Daniel H Solomon

    1. Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Boston, MA, USA
    2. Division of Rheumatology, Allergy and Immunology, Brigham and Women's Hospital, Boston, MA, USA
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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. © 2011 American Society for Bone and Mineral Research.

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