Division of Pharmacoepidemiology and Pharmacoeconomics, Brigham and Women's Hospital, Boston, MA, USA.
J Bone Miner Res. 2011 May;26(5):993-1001. doi: 10.1002/jbmr.288.
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.
双磷酸盐是绝经后和糖皮质激素诱导的骨质疏松症的主要治疗药物。病例系列研究表明，长期使用双磷酸盐与由于骨吸收过度抑制而导致的转子下或骨干股骨低能量骨折之间存在潜在联系。我们使用医疗保健利用数据，通过倾向评分匹配队列研究，来检查与使用雷洛昔芬或降钙素的患者相比，口服双磷酸盐使用者转子下或骨干股骨骨折的发生率 (IR) 和风险。Cox 比例风险模型评估了与骨质疏松症治疗持续时间相关的这些骨折的风险。在 33815 名患者中，共观察到 104 例转子下或骨干股骨骨折。在双磷酸盐使用者中，每 1000 人年发生转子下或骨干股骨骨折的估计发生率为 1.46(95%置信区间 [CI]，1.11-1.88)，而雷洛昔芬/降钙素使用者为 1.43(95% CI，1.06-1.89)。与雷洛昔芬/降钙素相比，双磷酸盐的使用与转子下或骨干股骨骨折之间没有发现显著关联[风险比 (HR) = 1.03，95% CI 0.70-1.52]。即使这项研究规模较大，我们也几乎无法准确估计接受双磷酸盐治疗超过 5 年的患者发生转子下或骨干股骨骨折的风险(HR = 2.02，95% CI 0.41-10.00)。转子下或骨干股骨骨折的发生率较低。与雷洛昔芬/降钙素使用者相比，双磷酸盐使用者发生转子下或骨干股骨骨折的风险没有增加的证据。然而，本研究不能排除长期使用双磷酸盐可能会增加这些骨折风险的可能性。
