A recent observational study of the incidence of pneumonia in patients with previous hip fractures found that bisphosphonate use reduced pneumonia risk by about one-quarter, in comparisons with those either not receiving osteoporosis treatment or receiving treatment with non-bisphosphonate drugs. Mortality from pneumonia was similarly reduced. It was hypothesized that effects of these drugs on immune or inflammatory function might mediate this effect. We have used the adverse event database from our recent 6-year randomized controlled trial of zoledronate in 2000 women over the age of 65 years, to determine whether a similar effect is observed using this more rigorous study design. Seventy-five women had at least one episode of pneumonia (32 [3.2%] zoledronate, 43 [4.3%] placebo) and 119 women had at least one episode of either pneumonia or a lower respiratory tract infection (57 [5.7%] zoledronate, 62 [6.2%] placebo). There were 93 pneumonia events and 167 pneumonia/lower respiratory infection events. For pneumonia, the hazard ratio associated with randomization to zoledronate was 0.73 (95% confidence interval, 0.46–1.16; P = 0.18) and the rate ratio was 0.69 (0.45, 1.04; P = 0.073). For the composite endpoint of pneumonia or lower respiratory infection, the hazard ratio was 0.90 (0.61, 1.30; P = 0.58) and the rate ratio 0.74 (0.54, 0.997; P = 0.048). The proportion of people with events changed approximately linearly over time in both groups, suggesting a progressive divergence in cumulative incidence during the study. In conclusion, these findings lend support to the hypothesis that bisphosphonate use reduces the number of lower respiratory tract infections in older women, though the present study is under-powered for this endpoint and the findings are of borderline statistical significance. Further analysis of other trials of bisphosphonates is necessary to test this possibility further, and exploration of the possible underlying mechanisms is needed.

最近一项关于既往髋部骨折患者肺炎发生率的观察性研究发现，与未接受骨质疏松症治疗或接受非双膦酸盐药物治疗的患者相比，使用双膦酸盐可使肺炎风险降低约四分之一。肺炎死亡率也同样降低。据推测，这些药物对免疫或炎症功能的影响可能介导了这种影响。我们使用了最近对 2000 名 65 岁以上女性进行的为期 6 年的唑来膦酸随机对照试验中的不良事件数据库，以确定使用这种更严格的研究设计是否观察到类似的效果。75 名女性至少发生过一次肺炎（32 [3.2%] 唑来膦酸，43 [4. 3%] 安慰剂）和 119 名女性至少发生过一次肺炎或下呼吸道感染（57 名 [5.7%] 唑来膦酸，62 名 [6.2%] 安慰剂）。有 93 起肺炎事件和 167 起肺炎/下呼吸道感染事件。对于肺炎，随机分配至唑来膦酸的风险比为 0.73（95% 置信区间，0.46–1.16；P  = 0.18），比率为 0.69（0.45、1.04；P  = 0.073）。对于肺炎或下呼吸道感染的复合终点，风险比为 0.90 (0.61, 1.30; P  = 0.58) 和比率比为 0.74 (0.54, 0.997; P = 0.048）。两组中发生事件的人数比例随着时间的推移大致呈线性变化，表明研究期间累积发生率逐渐出现差异。总之，这些发现支持使用双膦酸盐可减少老年女性下呼吸道感染数量的假设，尽管本研究对该终点的效力不足，而且这些发现具有临界统计意义。有必要对其他双膦酸盐试验进行进一步分析以进一步检验这种可能性，并需要探索可能的潜在机制。