Associations between Atrial Fibrillation and Bone Mineral Density at Different Sites: A Mendelian Randomization Study
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Abstract
Background: Observational studies have suggested that anti-osteoporosis therapies may increase the risk of atrial fibrillation (AF); however, whether bone mineral density (BMD) itself exerts a causal effect on AF remains unclear. This study systematically investigated the univariable causal relationship between AF and BMD at different skeletal sites, including the femoral neck, lumbar spine, forearm, and total body, to clarify the relationship between bone status and AF risk.
Methods: We conducted a two-sample univariable Mendelian randomization (MR) analysis to evaluate the causal associations between AF and BMD measured at the femoral neck (FN-BMD), lumbar spine (LS-BMD), forearm (FA-BMD), and total body (TB-BMD). Summary statistics were obtained from large-scale genome-wide association studies (GWASs). The inverse variance-weighted (IVW) method was used as the primary method, with sensitivity analyses including Cochran’s Q test, the MR-Egger intercept test, and leave-one-out analyses.
Results: The IVW analysis indicated positive associations of FN-BMD (odds ratio [OR] = 1.17, 95% confidence interval [CI]: 1.05–1.29, P = 0.003) and FA-BMD (OR = 1.15, 95% CI: 1.03–1.29, P = 0.01) with an increased AF risk. In contrast, lumbar spine bone mineral density (LS‑BMD) had a suggestive causal association with AF(OR = 1.12, 95% CI: 1.02‑1.23, P = 0.014).In contrast, no significant associations were detected for TB-BMD (OR = 1.02, 95% CI: 0.95–1.09, P = 0.64). Sensitivity analyses supported the robustness of these findings.
Conclusion: This MR study provides genetic evidence that increased FN-BMD and FA-BMD is causally associated with an increased risk of AF, whereas lumbar spine bone mineral density (LS‑BMD) exerted a suggestive causal effect, whereas total‑body bone mineral density (TB‑BMD) showed no significant causal effect.. These results highlight novel links between skeletal health and cardiovascular disease.