Duke University, Durham, NC, USA.
Mayo Clinic, Rochester, MN, USA.
Osteoporos Int. 2024 Jan;35(1):181-187. doi: 10.1007/s00198-023-06912-6. Epub 2023 Sep 13.
COVID-19 infection has resulted in significant morbidity and mortality globally, especially among older adults. Repurposed drugs have demonstrated activity in respiratory illnesses, including nitrogen-containing bisphosphonates. In this retrospective longitudinal study at 4 academic medical centers, we show no benefit of nitrogen-containing bisphosphonates regarding ICU admission, ventilator use, and mortality among older adults with COVID-19 infection. We specifically evaluated the intravenous bisphosphonate zoledronic acid and found no difference compared to oral bisphosphonates.
Widely used in osteoporosis treatment, nitrogen-containing bisphosphonates (N-BP) have been associated with reduced mortality and morbidity among older adults. Based on prior studies, we hypothesized that prior treatment with N-BP might reduce intensive care unit (ICU) admission, ventilator use, and death among older adults diagnosed with COVID-19.
This retrospective analysis of the PCORnet Common Data Model across 4 academic medical centers through 1 September 2021 identified individuals age >50 years with a diagnosis of COVID-19. The composite outcome included ICU admission, ventilator use, or death within 15, 30, and 180 days of COVID-19 diagnosis. Use of N-BP was defined as a prescription within 3 years prior. ICU admission and ventilator use were determined using administrative codes. Death included both in-hospital and out-of-hospital events. Patients treated with N-BP were matched 1:1 by propensity score to patients without prior N-BP use. Secondary analysis compared outcomes among those prescribed zoledronic acid (ZOL) to those prescribed oral N-BPs.
Of 76,223 COVID-19 patients identified, 1,853 were previously prescribed N-BP, among whom 559 were prescribed ZOL. After propensity score matching, there were no significant differences in the composite outcome at 15 days (HR 1.22, 95% CI: 0.89-1.67), 30 days (HR 1.24, 95% CI: 0.93-1.66), or 180 days (HR 1.17, 95% CI: 0.93-1.48), comparing those prescribed and not prescribed N-BP. Compared to those prescribed oral N-BP, there were no significant differences in outcomes among those prescribed ZOL.
Among older COVID-19 patients, prior exposure to N-BP including ZOL was not associated with a reduction in ICU admission, ventilator use, or death.
COVID-19 感染在全球范围内导致了显著的发病率和死亡率，尤其是在老年人中。已上市药物在呼吸系统疾病中具有活性，包括含氮双膦酸盐。在这项在 4 个学术医疗中心进行的回顾性纵向研究中，我们没有发现含氮双膦酸盐在 COVID-19 感染的老年人中对 ICU 入院、呼吸机使用和死亡率有任何益处。我们特别评估了静脉内双膦酸盐唑来膦酸，与口服双膦酸盐相比没有差异。
含氮双膦酸盐（N-BP）在骨质疏松症治疗中广泛应用，与老年人的死亡率和发病率降低有关。基于先前的研究，我们假设，在 COVID-19 诊断之前，使用 N-BP 治疗可能会降低老年人的 ICU 入院率、呼吸机使用率和死亡率。
本研究通过 4 个学术医疗中心的 PCORnet 通用数据模型，对 2021 年 9 月 1 日前诊断为 COVID-19 的 >50 岁人群进行回顾性分析。复合结局包括 COVID-19 诊断后 15、30 和 180 天内的 ICU 入院、呼吸机使用或死亡。N-BP 的使用定义为 3 年内的处方。ICU 入院和呼吸机使用通过行政代码确定。死亡包括院内和院外事件。接受 N-BP 治疗的患者按倾向评分与未接受 N-BP 治疗的患者 1:1 匹配。二次分析比较了接受唑来膦酸（ZOL）治疗和口服 N-BP 治疗的患者的结局。
在确定的 76223 例 COVID-19 患者中，有 1853 例患者之前曾使用过 N-BP，其中 559 例患者曾使用过 ZOL。经过倾向评分匹配后，在 15 天（HR 1.22，95%CI：0.89-1.67）、30 天（HR 1.24，95%CI：0.93-1.66）或 180 天（HR 1.17，95%CI：0.93-1.48）时，比较 N-BP 处方和未处方患者，复合结局无显著差异。与口服 N-BP 处方患者相比，ZOL 处方患者的结局无显著差异。
在 COVID-19 老年患者中，先前接触 N-BP 包括 ZOL 与 ICU 入院、呼吸机使用或死亡减少无关。
