The Association between Treatment with Bisphosphonates and the Risk of Atrial Fibrillation: A Meta-Analysis of Observational Studies

BACKGROUND: Osteoporosis is one of the most common diseases of the skeletal system, particularly occurring in older adults. Bisphosphonates are frequently used to treat osteoporosis and prevent bone fractures. Studies evaluating the association between treatment with bisphosphonate and the risk of atrial fibrillation have reported conflicting results. This meta-analysis of observational studies was performed to assess this association. METHODS: Databases were searched to find relevant observational studies, and the identified articles were selected according to the selection criteria. Sensitivity and subgroup analysis based on various confounding factors were performed. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of atrial fibrillation were estimated using a random-effects model. RESULTS: We selected 12 studies, including four case-control and eight cohort studies, for the meta-analysis. Assessment of the estimated effect size yielded an OR of 1.171 (95% CI, 1.011–1.356; P=0.035), with substantial heterogeneity (I(2) =84.74%, P<0.001). When the studies were excluded one-after-another, the pooled OR remained unchanged in only six studies. In addition, subgroup analyses found that treatment with bisphosphonates was positively associated with the risk of atrial fibrillation in studies performed in Western countries (OR, 1.263; 95% CI, 1.092–1.462) and lower-quality studies (OR, 1.214; 95% CI, 1.035–1.423). No publication bias was observed. CONCLUSION: This meta-analysis showed that treatment with bisphosphonates may be associated with an increased risk of atrial fibrillation. Therefore, bisphosphonates should be carefully prescribed to patients at a high risk of atrial fibrillation.