Rodríguez Alexander J, Ernst Martin T, Nybo Mads, Prieto-Alhambra Daniel, Ebeling Peter R, Hermann Anne Pernille, Abrahamsen Bo
Bone and Muscle Health Research Group, Department of Medicine, School of Clinical Sciences, Monash University, Clayton, Victoria, Australia.
OPEN-Open Patient Data Explorative Network, Institute of Clinical Research, University of Southern Denmark, Odense, Denmark.
J Clin Endocrinol Metab. 2020 Oct 1;105(10). doi: 10.1210/clinem/dgaa481.
The cardiovascular (CV) safety of oral bisphosphonates (oBPs) is uncertain.
Determine the risk of CV events in oBP users referred for bone mineral density (BMD) testing compared with matched controls.
Cohort study.
Danish national prescription registry enriched with local hospital data from Odense.
Individuals aged ≥45 years referred for BMD testing.
oBP.
Hospitalization for any CV event. Secondary study outcomes were specific CV events. Negative (inguinal hernia surgery and ingrown toenail) and positive (fragility fracture) control outcomes assessed systemic bias. Cox proportional hazards models were fitted to estimate hazard ratio (HR) and 95% confidence intervals.
There were 2565 oBP users (82.6% women) and 4568 (82.3% women) propensity score-matched controls. Alendronate accounted for 96% of oBP prescription. A total of 406 (15.8%) CV events occurred in oBP users (rate = 73.48 [66.67-80.98]); rate = events divided by person-time; and 837 (18.3%) events in controls (rate = 104.73 [97.87-112.07]) with an adjusted HR of 0.68 (95% CI 0.60-0.77). Additional adjustment for BMD did not attenuate estimates (HR 0.67; 95% CI 0.58-0.78]. Similar results were seen for secondary outcomes where risk reductions were seen regarding atrial fibrillation, stroke, heart failure, and aneurysms. Positive and negative control outcome analyses identified minimal residual confounding.
Oral BP users experienced a 33% reduced risk of CV events. This observational real-world study adds to a growing body of evidence for cardioprotection by oBP that warrants testing in a randomized setting.
口服双膦酸盐（oBP）的心血管（CV）安全性尚不确定。
确定与匹配的对照组相比，接受骨密度（BMD）检测的oBP使用者发生CV事件的风险。
队列研究。
丹麦国家处方登记处，并补充了欧登塞当地医院的数据。
年龄≥45岁且接受BMD检测的个体。
oBP。
因任何CV事件住院。次要研究结局为特定CV事件。阴性（腹股沟疝手术和嵌甲）和阳性（脆性骨折）对照结局用于评估系统偏差。采用Cox比例风险模型估计风险比（HR）和95%置信区间。
共有2565名oBP使用者（82.6%为女性）和4568名（82.3%为女性）倾向评分匹配的对照组。阿仑膦酸钠占oBP处方的96%。oBP使用者中共有406例（15.8%）发生CV事件（发生率=73.
