OBJECTIVES Bisphosphonates (BPs) might have extra benefits in reducing mortality because of their anti-atherosclerotic effects, but studies reported conflicting results. We investigated the association between oral BP use and mortality risk following a major osteoporotic fracture (MOF) in the United Kingdom. DESIGN This was a population-based cohort study. SETTING AND PARTICIPANTS In total, 163,273 adults aged 50 years and older with an MOF between 2000 and 2018 from the Clinical Practice Research Datalink in the United Kingdom. METHODS Cox proportional hazards models were used to estimate the risk of all-cause mortality in current (0‒6 months), recent (7‒12 months), and past (>1 year) exposures to oral BPs after nonhip MOF and hip fracture. In addition, stratification by sex, BP type, and duration of follow-up was performed. RESULTS Compared with never users of oral BPs, current BP use was associated with a 7% higher all-cause mortality risk after nonhip MOF, whereas a 28% lower all-cause mortality risk was observed after hip fracture. Past BP exposure was associated with a 14% and 42% lower risk after nonhip MOF and hip fracture, respectively. When considering only the first 5 years of follow-up, mortality risk associated with current BP use was significantly lower for both fracture groups, and the greatest reduction in mortality risk was observed within the first year. Women had slightly lower risk compared with men. CONCLUSIONS AND IMPLICATIONS We found a slight increased risk of all-cause mortality with current BP exposure after a nonhip MOF; however, a protective effect was observed following a hip fracture. Both the timing and the effect size of an association based on the anti-atherosclerotic hypothesis of BPs are not supported by our results. The decreasing trend of the mortality risk with shorter durations of follow-up suggests that the observed association is likely due to unknown distortion or unknown pleiotropic properties of BPs.

中文翻译：

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英国发生重大骨质疏松性骨折后口服双膦酸盐的使用与死亡风险的关联：基于人群的队列研究

目标双膦酸盐 (BPs) 由于其抗动脉粥样硬化作用，可能在降低死亡率方面具有额外的益处，但研究报告的结果相互矛盾。我们调查了英国发生严重骨质疏松性骨折 (MOF) 后口服 BP 使用与死亡风险之间的关联。设计 这是一项基于人群的队列研究。设置和参与者 总共有 163,273 名 50 岁及以上的成年人在 2000 年至 2018 年期间拥有来自英国临床实践研究数据链的 MOF。方法 Cox 比例风险模型用于评估非髋关节 MOF 和髋部骨折后当前（0-6 个月）、近期（7-12 个月）和过去（>1 年）口服 BPs 暴露的全因死亡风险. 此外，还按性别、血压类型和随访时间进行了分层。结果 与从不使用口服 BP 相比，当前使用 BP 与非髋关节 MOF 后 7% 的全因死亡风险相关，而髋部骨折后观察到的全因死亡风险降低 28%。既往 BP 暴露与非髋关节 MOF 和髋部骨折风险分别降低 14% 和 42% 相关。仅考虑前 5 年的随访时，与当前使用 BP 相关的死亡风险在两个骨折组中均显着降低，并且在第一年内观察到的死亡风险降低幅度最大。与男性相比，女性的风险略低。结论和意义 我们发现非髋关节 MOF 后当前 BP 暴露会略微增加全因死亡风险；然而，在髋部骨折后观察到了保护作用。我们的结果不支持基于 BP 的抗动脉粥样硬化假设的关联的时间和效应大小。随着随访时间的缩短，死亡风险的下降趋势表明，观察到的关联可能是由于 BP 的未知扭曲或未知的多效性。