Faculty of Medical and Health Sciences, Department of Medicine, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Auckland District Health Board, Auckland, New Zealand.
Calcif Tissue Int. 2021 Jul;109(1):12-16. doi: 10.1007/s00223-021-00830-7. Epub 2021 Mar 12.
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.
最近一项观察性研究调查了既往髋部骨折患者肺炎的发生率，发现与未接受骨质疏松治疗或接受非双膦酸盐药物治疗的患者相比，使用双膦酸盐可降低约四分之一的肺炎风险。肺炎死亡率也相似降低。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作用。我们使用了最近在 2000 名年龄在 65 岁以上的女性中进行的唑来膦酸盐 6 年随机对照试验的不良事件数据库，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 名[3.2%]唑来膦酸盐，43 名[4.3%]安慰剂），119 名女性至少发生过一次肺炎或下呼吸道感染（57 名[5.7%]唑来膦酸盐，62 名[6.2%]安慰剂）。有 93 例肺炎事件和 167 例肺炎/下呼吸道感染事件。对于肺炎，随机分组至唑来膦酸盐的风险比为 0.73（95%置信区间，0.46-1.16；P=0.18），率比为 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），率比为 0.74（0.54，0.997；P=0.048）。两组人群的事件发生率随时间大致呈线性变化，表明研究期间累积发病率逐渐发散。总之，这些发现支持了这样一种假设，即双膦酸盐的使用减少了老年女性下呼吸道感染的数量，尽管本研究对这一终点的效力不足，且结果具有边缘统计学意义。需要进一步分析其他双膦酸盐试验，以进一步检验这种可能性，并探索可能的潜在机制。
