Published: Oct 8, 2013
By Cole Petrochko

Full Story:  http://www.medpagetoday.com/Endocrinology/Osteoporosis/42142

Bisphosphonate use was associated with significantly increased risks of atrial fibrillation and serious atrial fibrillation, researchers found.

A systematic review of randomized controlled studies and observational studies showed use of bisphosphonates was associated with a 27% increased risk of atrial fibrillation (95% CI 1.16-1.39) in observational studies and, in randomized controlled trials alone, with a 40% increased odds of serious atrial fibrillation (95% CI 1.02-1.93), according to Abhishek Sharma, MD, of Maimonides Medical Center in Brooklyn, N.Y., and colleagues.

Patients receiving bisphosphonates were not at increased risk for stroke or cardiovascular mortality, they wrote in the October issue of Chest.

Prior research has shown a trend toward atrial fibrillation risks with bisphosphonate use, but data were not significant.

Bisphosphonates are indicated for the prevention and treatment of osteoporosis, but have been associated with risks of atypical femur fractures.

The authors conducted a systematic review of studies evaluating risks of atrial fibrillation and cardiovascular events with bisphosphonate use, which included six observational studies with 149,856 total participants and six randomized controlled trials with 41,375 total participants.

Observational studies showed oral bisphosphonate use increased serious risk of atrial fibrillation among patients who had no prior history of atrial fibrillation but had history of fractures. Patients with cancer who received the drug intravenously and had no history of atrial fibrillation had increased atrial fibrillation risk compared with cancer patients without drug exposure who were age-, sex-, and cancer type-matched.

There was no association seen with drug use and atrial fibrillation in a population-based retrospective cohort of osteoporotic women or in two prospective databases.

The authors noted that non-oral administration of bisphosphonates “induces a release of tumor necrosis factor alpha, interleukin 6, and inhibition farnesyl pyrophosphate synthase in the mevalonate pathway, leading to the accumulation of pyrophosphate,” which, when increased in concentration, can “activate an inflammatory cascade and alter the expression of proteins that handle intracellular calcium” and increase risk for arrhythmias.

They also warned that the lack of association between stroke and bisphosphonate use may have been due to shorter-term follow-up with patients, as follow-up was an average of 2 to 6 years, which may not be sufficient to record stroke data when “one would have expected a higher rate of stroke in older patients with atrial fibrillation.”

They also cautioned that osteoporotic patients are at increased risk for cardiovascular disease — a risk that is “directly proportional to the severity of osteoporosis.”

The review may have been confounded by varying baseline factors, as well as under-reporting of events in some studies, patients’ other cardiovascular risk factors, and absent definitions of serious atrial fibrillation versus atrial fibrillation in some studies.

The review was also limited by included studies where cardiovascular outcomes were not primary or secondary outcomes.