Bisphosphonate use in women and the risk of atrial fibrillation: a systematic review and meta-analysis

Int J Cardiol. 2010 Jul 23;142(3):213-7. doi: 10.1016/j.ijcard.2009.11.041. Epub 2010 Jan 3.


Background: Bisphosphonates are used for the prevention and treatment of osteoporosis, but there have been concerns about a potential link between bisphosphonate therapy and atrial fibrillation. Data on the effects of bisphosphonate on the risk of atrial fibrillation are conflicting and the association of serious atrial fibrillation (defined as events resulting in hospitalization or disability or judged to be life-threatening) with the use of bisphosphonates is uncertain.

Hypothesis: We aimed to systematically evaluate the association of bisphosphonate use with the risk of atrial fibrillation.

Methods: We performed a systematic literature search for clinical trials using bisphosphonates and providing data on the outcome of atrial fibrillation. Four randomized controlled trials and 3 population based case-control studies were included in the final analysis. A meta-analysis was performed with the 4 randomized controlled trials to determine the risk of serious atrial fibrillation.

Results: For the purpose of meta-analysis, the studies were homogenous; therefore the Mantel-Haenszel fixed-effect model was used to calculate combined relative risk (RR). A two-sided alpha error of less than 0.05 was considered to be statistically significant (p<0.05). Four studies with 26126 postmenopausal women were included in the meta-analysis. Meta-analysis revealed that serious atrial fibrillation occurred more frequently in the bisphosphonate group compared to the placebo group (RR 1.525; 95% CI, 1.166 to 1.997; p=0.002). Two out of 3 observational studies indicated a statistically significant increase in the risk of atrial fibrillation with bisphosphonate therapy.

Conclusions: Bisphosphonate use is associated with a significant increase in the risk of serious atrial fibrillation in postmenopausal women.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Atrial Fibrillation / chemically induced*
  • Atrial Fibrillation / epidemiology*
  • Diphosphonates / adverse effects*
  • Female
  • Humans
  • Osteoporosis, Postmenopausal / epidemiology*
  • Osteoporosis, Postmenopausal / prevention & control*
  • Risk Factors


  • Diphosphonates