尽管有强有力的证据表明双膦酸盐可以预防某些类型的骨质疏松性骨折,有人担心这些药物可能与罕见的非典型股骨骨折(AFF)相关.最近发表的关于这种潜在关联的研究在这种关联的存在和强度方面存在矛盾。我们对已发表的研究双膦酸盐与转子下的相关性进行了系统评价和荟萃分析。股骨干,AFF。随机效应模型用于计算调整后风险比(RR)的合并估计值。通过研究设计进行亚组分析,对于使用AFF验证结果定义的研究,以及报告双膦酸盐使用持续时间的研究。荟萃分析中包括11项研究:5项病例对照研究和6项队列研究。双膦酸盐暴露与转子下的风险增加相关,股骨干,AFF,调整后的RR为1.70(95%置信区间[CI],1.22-2.37)。使用美国骨骼和矿物研究协会标准来定义AFF的亚组分析的研究表明,AFF的风险更高。与使用主要诊断代码的研究相比,使用双膦酸盐的RR为11.78(95%CI,0.39-359.69)(RR,1.62;95%CI,1.18-2.22),尽管在这个亚组分析中存在广泛的置信区间和严重的异质性(I(2)=96.15%).检查双膦酸盐使用至少5年的研究的亚组分析显示调整RR为1.62(95%CI,1.29-2.04)。这项荟萃分析表明,转子下的风险增加,股骨干,和AFF在双膦酸盐使用者中。由于此亚组的数据有限,因此表明了长期使用双膦酸盐的AFF风险的进一步研究。这种观察到的AFF风险增加对公共卫生的影响尚不清楚。
Although there is strong evidence that bisphosphonates prevent certain types of osteoporotic fractures, there are concerns that these medications may be associated with rare atypical femoral fractures (AFF). Recent published studies examining this potential association are conflicting regarding the existence and strength of this association. We conducted a systematic
review and meta-analysis of published studies examining the association of bisphosphonates with subtrochanteric, femoral shaft, and AFF. The random-effects model was used to calculate the pooled estimates of adjusted risk ratios (RR). Subgroup analysis was performed by study design, for studies that used validated outcome definitions for AFF, and for studies reporting on duration of bisphosphonate use. Eleven studies were included in the meta-analysis: five case-control and six cohort studies. Bisphosphonate exposure was associated with an increased risk of subtrochanteric, femoral shaft, and AFF, with adjusted RR of 1.70 (95% confidence interval [CI], 1.22-2.37). Subgroup analysis of studies using the American Society for Bone and Mineral Research criteria to define AFF suggests a higher risk of AFF, with bisphosphonate use with RR of 11.78 (95% CI, 0.39-359.69) as compared to studies using mainly diagnosis codes (RR, 1.62; 95% CI, 1.18-2.22), although there is a wide confidence interval and severe heterogeneity (I(2) = 96.15%) in this subgroup analysis. Subgroup analysis of studies examining at least 5 years of bisphosphonate use showed adjusted RR of 1.62 (95% CI, 1.29-2.04). This meta-analysis suggests there is an increased risk of subtrochanteric, femoral shaft, and AFF among bisphosphonate users. Further research examining the risk of AFF with long-term use of bisphosphonates is indicated as there was limited data in this subgroup. The public health implication of this observed increase in AFF risk is not clear.