Objective A number of observational studies have previously reported an association between atrial fibrillation (AF), long‐term warfarin therapy, and an increased risk of osteoporosis (OP). The proposed mechanisms behind this association involve chronic inflammation or vitamin K‐dependent bone metabolism. However, the presence of confounding factors and methodological limitations precludes the drawing of causal conclusions. The present Mendelian randomisation (MR) study investigates the existence of genetic evidence for causal links between AF, warfarin use and OP development. Methods The two‐sample MR was performed using summary statistics from European‐ancestry genome‐wide association studies. Genetic instruments for AF (111 independent SNPs) and warfarin use (9 SNPs) were selected at stringent significance thresholds ( p 0.05) or heterogeneity (Cochran’s Q p > 0.05) was identified. Iterative leave‐one‐out analyses demonstrated that no individual SNP exerted a disproportionate influence on the estimates. Conclusions This study, informed by genetic research, challenges established causal relationships between AF, warfarin use and the risk of OP. The observed clinical associations may be attributable to residual confounding or comorbidities present in ageing populations, rather than direct pharmacological effects. These findings provide a scientific basis for the clinical prioritisation of the management of thromboembolic risk over speculative concerns regarding bone health in the treatment of AF.
Hu et al. (Thu,) studied this question.