Bisphosphonates and risk of atrial fibrillation: a meta-analysis

Arthritis Res Ther. 2010;12(1):R30. doi: 10.1186/ar2938. Epub 2010 Feb 19.


Introduction: Bisphosphonates are the most commonly used drugs for the prevention and treatment of osteoporosis. Although a recent FDA review of the results of clinical trials reported no clear link between bisphosphonates and serious or non-serious atrial fibrillation (AF), some epidemiologic studies have suggested an association between AF and bisphosphonates.

Methods: We conducted a meta-analysis of non-experimental studies to evaluate the risk of AF associated with bisphosphonates. Studies were identified by searching MEDLINE and EMBASE using a combination of the Medical Subject Headings and keywords. Our search was limited to English language articles. The pooled estimates of odds ratios (OR) as a measure of effect size were calculated using a random effects model.

Results: Seven eligible studies with 266,761 patients were identified: three cohort, three case-control, and one self-controlled case series. Bisphosphonate exposure was not associated with an increased risk of AF [pooled multivariate OR 1.04, 95% confidence interval (CI) 0.92-1.16] after adjusting for known risk factors. Moderate heterogeneity was noted (I-squared score = 62.8%). Stratified analyses by study design, cohort versus case-control studies, yielded similar results. Egger's and Begg's tests did not suggest an evidence of publication bias (P = 0.90, 1.00 respectively). No clear asymmetry was observed in the funnel plot analysis. Few studies compared risk between bisphosphonates or by dosing.

Conclusions: Our study did not find an association between bisphosphonate exposure and AF. This finding is consistent with the FDA's statement.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural

MeSH terms

  • Atrial Fibrillation / chemically induced*
  • Atrial Fibrillation / epidemiology*
  • Bone Density Conservation Agents / adverse effects*
  • Diphosphonates / adverse effects*
  • Female
  • Humans
  • Male
  • Osteoporosis / drug therapy
  • Risk Factors
  • United States


  • Bone Density Conservation Agents
  • Diphosphonates