Bisphosphonates, commonly used class of drugs against osteoporosis, may increase the risk of future irregular heart beats or serious atrial fibrillation, according to a study presented at CHEST 2008, the 74th annual international scientific assembly of the American College of Chest Physicians (ACCP), held at Philadelphia, during October 25 to 30, 2008.
Bisphosphonates, a group of non-hormonal drugs, inhibit osteoclastic activity, maintain or increase bone density and reduce the risk of fractures. Some generic drugs of the bisphosphonate family include alendronate, clodronate, etidronate, pamidronate, and tiludronate. The drugs are widely used in the treatment of osteoporosis, Paget disease, bone metastasis, multiple myeloma, and in conditions characterized by bone fragility.
Jennifer Miranda, lead scientist at the Jackson Memorial Hospital, University of Miami, Florida, and coworkers, conducted a meta-analysis to determine the association between bisphosphonates and atrial fibrillation (AF). The researchers selected 1,646 randomized clinical trial studies, in which bisphosphonates were compared to placebo, with AF as an adverse effect. Three studies, involving 16,322 patients with a mean age range of 69 to 75 years, met the eligibility criteria. In this group, 76 to 100% were women using bisphosphonates such as alendronate and zoledronic acid for osteoporosis. It was found that the odds ratio of incident AF and serious AF was 1.19 and 1.68, respectively for bisphosphonates in comparison with placebo. Results showed that 2.5 to 3% of patients taking bisphosphonates experienced atrial fibrillation, while 1 to 2% encountered serious AF, inclusive of hospitalization or death. Based on the findings, it was concluded that the osteoporosis drugs enhance the risk of serious AF; however, the population at risk, the underlying mechanism, and impact of the adverse effect have to be further examined.
Recently, Heckbert, et al. (Archives of Internal Medicine, 2008) conducted a case-control study in Washington State to assess the relationship between alendronate sodium ever use and the risk of incident AF in women. The scientists demonstrated that the ever use of alendronate raises the risk of incident AF in postmenopausal osteoporotic women.
In a recent contradictory study, Sørensen, et al. (British Medical Journal, 2008) found no evidence to associate the enhanced risk of atrial fibrillation with bisphosphonates usage. The researchers evaluated the relationship between bisphosphonates usage in osteoporotic women and atrial fibrillation (and flutter) using medical databases from Denmark. The population-based case control study involved 68,054 controls and 13,586 atrial fibrillation and flutter patients, who had a complete hospital and prescription history. Among them, 3.2% of test cases and 2.9% of controls were bisphosphonate (etidronate and alendronate) users for osteoporosis. It was found that the adjusted relative risk of current use of bisphosphonates versus non-use was 0.95 and 0.75, respectively for new users. The study concluded that there was lack of evidence to link the increased risk of atrial fibrillation with bisphosphonates use.
Atrial fibrillation, a cardiac arrhythmia, affects approximately 2.2 million Americans, according to the American Heart Association. AF, occurring in 3 to 5% of people above 65 years, may cause palpitation, shortness of breath, fatigue, confusion, angina leading to heart failure and stroke.
Osteoporosis, also known as the silent disease, increases the susceptibility of fractures to any bone, especially the hip, spine and wrist. The National Osteoporosis Foundation estimates that 10 million individuals in US have the disease, while almost 34 million more have low bone mass, thereby increasing their risk for osteoporosis. Currently, there is no cure for osteoporosis, but it can be managed by anabolic medications like teriparatide, or antiresorptive medications such as bisphosphonates, calcitonin, and estrogen.
Since, there are contradictory reports on the potential link between bisphosphonates use and atrial fibrillation, further larger research is warranted to validate the current findings. This may help physicians prescribe the extensively used class of drugs for osteoporosis, by considering both the benefits and disadvantages, i.e., reduced fracture risk with occurrence of cardiac complications.
References
1. Miranda J, Tamariz L, Urena J, et al. A Meta-analysis of the Risk of Atrial Fibrillation in Bisphosphonate Users. Paper presented at: CHEST 2008, the 74th annual international scientific assembly of the American College of Chest Physicians (ACCP);October 27, 2008; Philadelphia.
2. Heckbert SR, Li G, Cummings SR, Smith NL, Psaty BM. Use of alendronate and risk of incident atrial fibrillation in women. Arch Intern Med. 2008 Apr 28;168(8):826-31.
3. Sørensen HT, Christensen S, Mehnert F, et al. Use of bisphosphonates among women and risk of atrial fibrillation and flutter: population based case-control study. BMJ. 2008 Apr 12;336(7648):813-6. Epub 2008 Mar 11.
