The impact of Renin-Angiotensin System Inhibitors on bone fracture risk: a nationwide nested case-control study

Abstract

Abstract Background The therapeutic efficacy of renin-angiotensin system inhibitors (RASi) in elderly patients with hypertension and at risk of fractures has been in the limelight because of accumulating evidence that localized RAS activation in bone tissue leads to osteoclastic bone resorption, resulting in osteoporosis. This study set out to investigate the association between RASi use and fracture incidence in a large cohort. Methods We employed a nested case–control design to investigate the association between RASi use and newly developed fractures. A case was defined as a patient newly diagnosed with a fracture between January 2004 and December 2015. We selected 1,049 cases and controls using 1:1 propensity score matching. Conditional logistic regression analysis was conducted to estimate the association between RASi exposure and fracture incidence. Results Overall, RASi usage was significantly associated with lower odds for fracture incidence (ever-users vs never-users: OR, 0.73; 95% CI, 0.59–0.91). We found that ARB-only users experienced fewer fractures than RASi-never users (OR, 0.65; 95% CI, 0.49–0.86), whereas ACEi-only users or ARB/ACEi-ever users did not. In subgroup analysis, RASi-ever users without cerebrovascular disease, those with a BMI exceeding 23, and statin exposure had significantly lower ORs. Conclusions The present study established a significant association between RASi use and reduced fracture incidence, thus highlighting the potential clinical utility of RASi use as a preventive strategy in elderly patients at risk for osteoporotic fractures.

Keywords

• Renin-angiotensin system inhibitors
• Angiotensin II receptor blockers
• Fracture
• Defined daily doses
• Nested case–control study