Association of antihypertensive drugs with fracture and bone mineral density: A comprehensive drug-target Mendelian randomization study.
Front Endocrinol (Lausanne)
; 14: 1164387, 2023.
Article
em En
| MEDLINE
| ID: mdl-37056679
ABSTRACT
Background:
Observational studies have investigated the associations between antihypertensive drugs and fracture risk as well as bone mineral density (BMD), but yielding controversial results.Methods:
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.Results:
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; P = 4.42 × 10-4; P-adjusted = 0.004), higher TB-BMD (ß = 0.36, 95% CI 0.11 to 0.61; P = 0.005; P-adjusted = 0.022), and higher eBMD (ß = 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 (ß = -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 (ß = 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.Conclusions:
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.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Densidade Óssea
/
Fraturas Ósseas
Tipo de estudo:
Clinical_trials
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article