Atrial fibrillation and bisphosphonate therapy

Bisphosphonates are the most commonly used treatment for osteoporosis and have proven efficacy in the reduction of vertebral and nonvertebral fractures. Recently, concerns have been raised about a possible association between bisphosphonate therapy and atrial fibrillation (AF) following the report of a significant increase in risk of serious AF in women treated with zoledronic acid in the HORIZON study. Subsequent studies have produced conflicting results but have not excluded the possibility of such an association. Currently there is no direct evidence that bisphosphonates exert either acute or chronic effects on cardiac electrophysiology. Nevertheless, altered intracellular electrolyte homeostasis and proinflammatory, profibrotic, and antiangiogenic effects provide potential mechanisms by which atrial conduction could be affected in patients treated with bisphosphonates. In studies in which an increase in risk of AF has been identified, there is no evidence that this translates into increased mortality or increased risk of stroke, and the risk-benefit balance of bisphosphonate therapy in patients with osteoporosis and other forms of metabolic bone disease remains strongly positive.