Association of antihypertensive drugs with fracture and bone mineral density: A comprehensive drug-target Mendelian randomization study

Frontiers in Endocrinology

Endocrinology

Weiming Gong¹  Tianxin Zhang¹  Xin Huang¹  Ping Guo¹  Zhongshang Yuan¹  Hengchao Zhu²  Meng Zhao³ 

[1] Department of Biostatistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China;Institute for Medical Dataology, Shandong University, Jinan, Shandong, China;Department of Biostatistics, School of Public Health, Yale University, New Haven, CT, United States;Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China;

关键词: antihypertensive drugs;    fracture;    bone mineral density;    drug-target mendelian randomization;    causal effect;   

DOI  :  10.3389/fendo.2023.1164387

 received in 2023-02-12, accepted in 2023-03-16,  发布年份 2023

来源: Frontiers

【 摘 要 】

BackgroundObservational studies have investigated the associations between antihypertensive drugs and fracture risk as well as bone mineral density (BMD), but yielding controversial results. MethodsIn 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.ResultsThe 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; P = 4.42 × 10-4; P-adjusted = 0.004), higher TB-BMD (β = 0.36, 95% CI: 0.11 to 0.61; P = 0.005; P-adjusted = 0.022), and higher eBMD (β = 0.30, 95% CI: 0.21 to 0.38; P = 3.59 × 10-12; P-adjusted = 6.55 × 10-11). 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; P = 0.002; P-adjusted = 0.013). Genetic proxies for potassium sparing diuretics (PSDs) showed negative associations with TB-BMD (β = -0.61, 95% CI: -0.88 to -0.33; P = 1.55 × 10-5; P-adjusted = 1.86 × 10-4). Genetic proxies for thiazide diuretics had positive associations with eBMD (β = 0.11, 95% CI: 0.03 to 0.18; P = 0.006; P-adjusted = 0.022). No significant heterogeneity or pleiotropy was identified. The results were consistent across different MR methods. ConclusionsThese 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.

【 授权许可】

Unknown   
Copyright © 2023 Huang, Zhang, Guo, Gong, Zhu, Zhao and Yuan