University of California at San Francisco, San Francisco, CA 94107, USA.
N Engl J Med. 2010 May 13;362(19):1761-71. doi: 10.1056/NEJMoa1001086. Epub 2010 Mar 24.
A number of recent case reports and series have identified a subgroup of atypical fractures of the femoral shaft associated with bisphosphonate use. A population-based study did not support this association. Such a relationship has not been examined in randomized trials.
We performed secondary analyses using the results of three large, randomized bisphosphonate trials: the Fracture Intervention Trial (FIT), the FIT Long-Term Extension (FLEX) trial, and the Health Outcomes and Reduced Incidence with Zoledronic Acid Once Yearly (HORIZON) Pivotal Fracture Trial (PFT). We reviewed fracture records and radiographs (when available) from all hip and femur fractures to identify those below the lesser trochanter and above the distal metaphyseal flare (subtrochanteric and diaphyseal femur fractures) and to assess atypical features. We calculated the relative hazards for subtrochanteric and diaphyseal fractures for each study.
We reviewed 284 records for hip or femur fractures among 14,195 women in these trials. A total of 12 fractures in 10 patients were classified as occurring in the subtrochanteric or diaphyseal femur, a combined rate of 2.3 per 10,000 patient-years. As compared with placebo, the relative hazard was 1.03 (95% confidence interval [CI], 0.06 to 16.46) for alendronate use in the FIT trial, 1.50 (95% CI, 0.25 to 9.00) for zoledronic acid use in the HORIZON-PFT trial, and 1.33 (95% CI, 0.12 to 14.67) for continued alendronate use in the FLEX trial. Although increases in risk were not significant, confidence intervals were wide.
The occurrence of fracture of the subtrochanteric or diaphyseal femur was very rare, even among women who had been treated with bisphosphonates for as long as 10 years. There was no significant increase in risk associated with bisphosphonate use, but the study was underpowered for definitive conclusions.
最近的一些病例报告和系列研究已经确定了与双膦酸盐使用相关的股骨干非典型骨折亚组。一项基于人群的研究并未支持这种关联。这种关系尚未在随机试验中进行检查。
我们使用三项大型双膦酸盐试验的结果（骨折干预试验（FIT）、FIT 长期扩展试验（FLEX）和唑来膦酸每年一次降低骨折风险和提高生活质量的关键性骨折试验（HORIZON-PFT））进行了二次分析。我们回顾了所有髋部和股骨骨折的骨折记录和 X 光片（如有），以确定位于小转子以下和远端干骺端扩张部以上的骨折（转子下和骨干股骨骨折），并评估非典型特征。我们计算了每个研究中转子下和骨干股骨骨折的相对危险度。
我们在这些试验中的 14195 名女性中审查了 284 份髋部或股骨骨折记录。在 10 名患者中共有 12 处骨折被归类为发生在转子下或骨干股骨，总发生率为每 10000 患者年 2.3 例。与安慰剂相比，FIT 试验中使用阿伦膦酸钠的相对危险度为 1.03（95%置信区间[CI]，0.06 至 16.46），HORIZON-PFT 试验中使用唑来膦酸的相对危险度为 1.50（95%CI，0.25 至 9.00），FLEX 试验中继续使用阿仑膦酸钠的相对危险度为 1.33（95%CI，0.12 至 14.67）。虽然风险增加不显著，但置信区间较宽。
即使在接受双膦酸盐治疗长达 10 年的女性中，转子下或骨干股骨骨折的发生率也非常低。与双膦酸盐使用相关的风险没有显著增加，但该研究的效力不足以得出明确的结论。
