Recent studies suggest that the RANK/RANKL system impacts muscle function and/or mass. In the pivotal placebo‐controlled fracture trial of the RANKL inhibitor denosumab in women with postmenopausal osteoporosis, treatment was associated with a lower incidence of non‐fracture‐related falls (p = 0.02). This ad hoc exploratory analysis pooled data from five placebo‐controlled trials of denosumab to determine consistency across trials, if any, of the reduction of fall incidence. The analysis included trials in women with postmenopausal osteoporosis and low bone mass, men with osteoporosis, women receiving adjuvant aromatase inhibitors for breast cancer, and men receiving androgen deprivation therapy for prostate cancer. The analysis was stratified by trial, and only included data from the placebo‐controlled period of each trial. A time‐to‐event analysis of first fall and exposure‐adjusted subject incidence rates of falls were analyzed. Falls were reported and captured as adverse events. The analysis comprised 10,036 individuals; 5030 received denosumab 60 mg subcutaneously once every 6 months for 12 to 36 months and 5006 received placebo. Kaplan–Meier estimates showed an occurrence of falls in 6.5% of subjects in the placebo group compared with 5.2% of subjects in the denosumab group (hazard ratio = 0.79; 95% confidence interval 0.66–0.93; p = 0.0061). Heterogeneity in study designs did not permit overall assessment of association with fracture outcomes. In conclusion, denosumab may reduce the risk of falls in addition to its established fracture risk reduction by reducing bone resorption and increasing bone mass. These observations require further exploration and confirmation in studies with muscle function or falls as the primary outcome. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research..

中文翻译：

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来自 Denosumab 安慰剂对照试验的跌倒发生率汇总分析。

最近的研究表明，RANK/RANKL 系统影响肌肉功能和/或质量。在 RANKL 抑制剂地诺单抗对绝经后骨质疏松症女性进行的关键性安慰剂对照骨折试验中，治疗与非骨折相关跌倒的发生率降低相关（p= 0.02)。这项特别的探索性分析汇集了来自 5 项地诺单抗安慰剂对照试验的数据，以确定降低跌倒发生率的试验之间的一致性（如果有的话）。该分析包括绝经后骨质疏松症和低骨量女性、骨质疏松症男性、接受辅助芳香化酶抑制剂治疗乳腺癌的女性以及接受前列腺癌雄激素剥夺治疗的男性的试验。该分析按试验进行分层，并且仅包括来自每个试验的安慰剂对照期的数据。分析了首次跌倒的事件发生时间分析和经暴露调整的受试者跌倒发生率。跌倒被报告为不良事件。该分析包括 10,036 人；5030 每 6 个月一次皮下注射 60 mg 地诺塞麦，持续 12 至 36 个月，5006 接受安慰剂。p = 0.0061)。研究设计的异质性不允许对与骨折结果的关联进行整体评估。总之，狄诺塞麦除了通过减少骨吸收和增加骨量来降低骨折风险外，还可以降低跌倒的风险。这些观察结果需要在以肌肉功能或跌倒为主要结果的研究中进一步探索和确认。© 2020 作者。美国骨与矿物质研究学会出版的骨与矿物质研究杂志。