Data from: Oral bisphosphonates are associated with increased risk of atypical femoral fractures in elderly women

Objectives: To evaluate the association between bisphosphonate use and the risk of atypical femoral fractures among women aged 65 or older. Design: Nested case–control study. Setting: General practice research database in Spain. Exposures Use of oral bisphosphonates before the occurrence of atypical fractures among cases or the corresponding index date among controls. Bisphosphonate use was categorised as ever versus never users. Ever users were divided according to the total time since first prescription. Main outcome measures: Cases were defined as women aged 65 years or older with a first diagnosis of subtrochanteric or diaphyseal fracture, recorded in the BIFAP database between 1 January 2005 and 31 December 2008, and with at least 1 year of follow-up before the index date. For each case, five age-matched and calendar-year-matched controls without a history of hip or atypical fracture were randomly selected from the database. Statistical analysis: OR of atypical femoral fracture by bisphosphonate use was determined using conditional logistic regression. Models were adjusted for comorbidities and use of other medications. Results: The analysis included 44 cases and 220 matched controls (mean age, 82 years). Ever use of bisphosphonates was more frequent in cases than controls (29.6% vs 10.5%). In multivariate analyses, OR (95% CI) of atypical femoral fracture was 4.30 (1.55 to 11.9) in ever versus never users of bisphosphonates. The risk increased with long-term use, with an OR of 9.46 (2.17 to 41.3) comparing those using bisphosphonates over 3 years versus no users (p for trend=0.01). Conclusions: Bisphosphonate use was associated with an increased risk of subtrochanteric or diaphyseal fractures in elderly women in a low fracture risk population, with a higher risk among long-term bisphosphonate users.研究目的：评估65岁及以上女性使用双膦酸盐（bisphosphonate）与非典型股骨骨折（atypical femoral fractures）风险之间的关联。研究设计：巢式病例对照研究（nested case–control study）。研究场景：西班牙全科医疗研究数据库。暴露因素：病例组为非典型骨折发生前口服双膦酸盐的使用者，对照组则以对应索引日期前的双膦酸盐使用情况作为暴露判定依据。双膦酸盐使用分为既往使用者与从未使用者，既往使用者按首次处方后的总用药时长进行分组。主要结局指标：病例定义为2005年1月1日至2008年12月31日期间，在BIFAP数据库中记录的首次诊断为转子下或股骨干骨折的65岁及以上女性，且在索引日期前至少拥有1年的随访记录。为每一例病例随机从数据库中选取5名年龄匹配、日历年度匹配且无髋部或非典型骨折病史的对照。统计学分析：采用条件logistic回归分析双膦酸盐使用与非典型股骨骨折的比值比（OR），模型对合并症及其他药物使用情况进行了校正。研究结果：本分析共纳入44例病例与220名匹配对照，受试者平均年龄为82岁。既往使用双膦酸盐的比例在病例组中高于对照组（29.6% vs 10.5%）。多变量分析显示，与从未使用者相比，既往使用双膦酸盐者发生非典型股骨骨折的OR（95%置信区间CI）为4.30（1.55~11.9）。骨折风险随用药时长延长而升高：用药超过3年者与未使用者相比，OR为9.46（2.17~41.3）（趋势检验p=0.01）。研究结论：在低骨折风险人群的老年女性中，双膦酸盐使用与转子下或股骨干骨折风险升高相关，且长期使用双膦酸盐者的风险更高。