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Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Observational studies have investigated the associations between antihypertensive drugs and fracture risk as well as bone mineral density (BMD), but yielding controversial results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, a comprehensive drug-target Mendelian randomization (MR) analysis was conducted to systematically examine the associations between genetic proxies for eight common antihypertensive drugs and three bone health-related traits (fracture, total body BMD [TB-BMD], and estimated heel BMD [eBMD]). The main analysis used the inverse-variance weighted (IVW) method to estimate the causal effect. Multiple MR methods were also employed to test the robustness of the results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The genetic proxies for angiotensin receptor blockers (ARBs) were associated with a reduced risk of fracture (odds ratio [OR] = 0.67, 95% confidence interval [CI]: 0.54 to 0.84; <jats:italic>P<\/jats:italic> = 4.42 \u00d7 10<jats:sup>-4<\/jats:sup>; <jats:italic>P-<\/jats:italic>adjusted = 0.004), higher TB-BMD (\u03b2 = 0.36, 95% CI: 0.11 to 0.61; <jats:italic>P<\/jats:italic> = 0.005; <jats:italic>P-<\/jats:italic>adjusted = 0.022), and higher eBMD (\u03b2 = 0.30, 95% CI: 0.21 to 0.38; <jats:italic>P<\/jats:italic> = 3.59 \u00d7 10<jats:sup>-12<\/jats:sup>; <jats:italic>P-<\/jats:italic>adjusted = 6.55 \u00d7 10<jats:sup>-11<\/jats:sup>). Meanwhile, genetic proxies for calcium channel blockers (CCBs) were associated with an increased risk of fracture (OR = 1.07, 95% CI: 1.03 to 1.12; <jats:italic>P<\/jats:italic> = 0.002; <jats:italic>P-<\/jats:italic>adjusted = 0.013). Genetic proxies for potassium sparing diuretics (PSDs) showed negative associations with TB-BMD (\u03b2 = -0.61, 95% CI: -0.88 to -0.33; <jats:italic>P<\/jats:italic> = 1.55 \u00d7 10<jats:sup>-5<\/jats:sup>; <jats:italic>P-<\/jats:italic>adjusted = 1.86 \u00d7 10<jats:sup>-4<\/jats:sup>). Genetic proxies for thiazide diuretics had positive associations with eBMD (\u03b2 = 0.11, 95% CI: 0.03 to 0.18; <jats:italic>P<\/jats:italic> = 0.006; <jats:italic>P-<\/jats:italic>adjusted = 0.022). No significant heterogeneity or pleiotropy was identified. The results were consistent across different MR methods.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These findings suggest that genetic proxies for ARBs and thiazide diuretics may have a protective effect on bone health, while genetic proxies for CCBs and PSDs may have a negative effect.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2023.1164387","type":"journal-article","created":{"date-parts":[[2023,3,28]],"date-time":"2023-03-28T05:47:26Z","timestamp":1679982446000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":20,"title":["Association of antihypertensive drugs with fracture and bone mineral density: A comprehensive drug-target Mendelian randomization 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