Relationship of Bisphosphonate Therapy and Atrial Fibrillation/Flutter: Outcomes of Sleep Disorders in Older Men (MrOS Sleep) Study

Chest. 2016 May;149(5):1173-80. doi: 10.1016/j.chest.2015.11.022. Epub 2015 Dec 12.


Background: Prior studies suggested an association between bisphosphonates and atrial fibrillation/flutter (AF) in women. This relationship in men, including those with sleep-disordered breathing (SDB), remains unclear. This study evaluated the relationship between bisphosphonate use and prevalent (nocturnal) and incident (clinically relevant) AF in a population of community-dwelling older men.

Methods: A total of 2,911 male participants (mean age, 76 years) of the prospective observational Osteoporotic Fractures in Men Study sleep cohort with overnight in-home polysomnography (PSG) constituted the analytic cohort. Nocturnal AF from ECGs during PSG and incident AF events were centrally adjudicated. The association of bisphosphonate use and AF was examined using multivariable-adjusted logistic regression for prevalent AF and Cox proportional hazards regression for incident AF.

Results: A total of 123 (4.2%) men were current bisphosphonate users. Prevalent nocturnal AF was present in 138 participants (4.6%). After multivariable adjustment, there was a significant association between current bisphosphonate use and prevalent AF (OR, 2.33; 95% CI, 1.13-4.79). In the subset of men with moderate to severe SDB, this association was even more pronounced (OR, 3.22; 95% CI, 1.29-8.03). However, the multivariable-adjusted relationship between bisphosphonate use and incident AF did not reach statistical significance (adjusted hazard ratio, 1.53; 95% CI, 0.96-2.45).

Conclusions: These results support an association between bisphosphonate use and prevalent nocturnal AF in community-dwelling older men. The data further suggest that those with moderate to severe SDB may be a particularly vulnerable group susceptible to bisphosphonate-related AF. Similar associations were not seen for bisphosphonate use and clinically relevant incident AF.

Keywords: atrial fibrillation; bisphosphonates; sleep-disordered breathing.

Publication types

  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Atrial Fibrillation / epidemiology*
  • Atrial Flutter / epidemiology*
  • Bone Density Conservation Agents / therapeutic use*
  • Diphosphonates / therapeutic use*
  • Electrocardiography
  • Humans
  • Incidence
  • Logistic Models
  • Male
  • Multivariate Analysis
  • Osteoporosis / drug therapy*
  • Polysomnography
  • Prevalence
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • Sleep Apnea Syndromes / epidemiology*


  • Bone Density Conservation Agents
  • Diphosphonates