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.
Highlights
Bisphosphonates decrease bone turnover and increase bone mineral density (BMD) by inhibiting osteoclast-mediated bone resorption.[1]
There is always a reason why some patients received a prescription and some did not.[15,16,17] the outcomes of the patient groups would not be comparable, and the validity of any inferences drawn about the relative effects of treatment would be subject to unmeasured confounding.[15,17,18] Data from recent secondary analyses using three large placebo-controlled, randomized clinical trials (RCTs) of bisphosphonates showed that the occurrence of atypical subtrochanteric or diaphyseal femoral fracture was rare among 14,195 women (0.23 per 1000 person-years).(19) Of those, 3673 were treated with alendronate and 3875 with intravenous zoledronic acid
Given the limitations in the currently available data, we conducted a large population-based cohort study [1] to estimate the incidence rates (IRs) and hazard ratio (HR) of subtrochanteric and diaphyseal femoral fractures in elderly patients treated with oral bisphosphonates compared with those treated with either raloxifene or calcitonin nasal spray and [2] to examine the potential risk of these fractures associated with treatment duration
Summary
Bisphosphonates decrease bone turnover and increase bone mineral density (BMD) by inhibiting osteoclast-mediated bone resorption.[1]. There is always a reason why some patients received a prescription and some did not.[15,16,17] the outcomes of the patient groups would not be comparable, and the validity of any inferences drawn about the relative effects of treatment would be subject to unmeasured confounding (ie, confounding by indication).(15,17,18) Data from recent secondary analyses using three large placebo-controlled, randomized clinical trials (RCTs) of bisphosphonates showed that the occurrence of atypical subtrochanteric or diaphyseal femoral fracture was rare among 14,195 women (0.23 per 1000 person-years).(19) Of those, 3673 were treated with alendronate and 3875 with intravenous zoledronic acid. A propensity score is the estimated probability of starting treatment A versus starting treatment B based on preexisting patient characteristics.[17,21] Propensity score matching has been used increasingly as an effective way to adjust a large number of confounders simultaneously, even if the outcome is rare.[17,18]
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