April 28, 2008 -- The osteoporosis drug Fosamax may be linked to increased risk of abnormal heart rhythms, a new study shows. But experts urge patients not to quit Fosamax or similar osteoporosis drugs based on the findings.
"We're not saying that this drug should be stopped and we certainly do not feel that patients should stop taking the drug," researcher Susan Heckbert, MD, PhD, tells WebMD. "But we did detect this adverse effect."
The FDA has been probing possible ties between bisphosphonate drugs, which include alendronate (sold generically and as Fosamax), and an irregular heart rhythm (atrial fibrillation) since last fall, with no firm conclusions yet. So what's an osteoporosis patient to do?
"The benefits of fracture prevention will generally outweigh the risk of atrial fibrillation" in patients at high risk of bone fracture who are already taking a bisphosphonate drug, says Heckbert, who works for the University of Washington's cardiovascular health research unit and epidemiology department.
"What physicians and patients need to do is to weigh the risks and benefits," Heckbert says. "The information is never perfect for patients or physicians. ... They can't find out exactly what the risk is for that individual patient, so they have to do the best job they can with the available information. And this is just additional information about a risk that appears to be present for alendronate."
Atrial Fibrillation Study
Heckbert's study, published in the Archives of Internal Medicine, included 719 women with confirmed atrial fibrillation and 966 women without atrial fibrillation. All of the women were members of the same health care system in Washington.
The researchers checked the women's medical records and found that 6.5% of the atrial fibrillation patients and about 4% of women without atrial fibrillation had taken Fosamax.
Compared with women who had never used any bisphosphonate drug, women who had ever taken Fosamax were 86% more likely to have atrial fibrillation.
Still, Fosamax wasn't a major risk factor for atrial fibrillation. "In this population of women, the proportion of atrial fibrillation cases that could have been explained by alendronate use was only 3%," Heckbert says.
The study doesn't prove that Fosamax caused atrial fibrillation. The study was observational, meaning that patients weren't randomly assigned to take Fosamax.
The results held when the researchers weighed other heart rhythm risk factors. "It was a robust finding," says Heckbert, cautioning that observational studies can't address every possible influence on the data.
Heckbert and colleagues did the study after other researchers last year reported an increased rate of atrial fibrillation associated with the osteoporosis drug Reclast, which, like Fosamax, is a bisphosphonate.
But in another recent study, Danish researchers found no evidence of increased risk of atrial fibrillation in women taking bisphosphonates.
"Medicine is like that," Heckbert says. "We don't always find the same things."
Real Risk or Fluke?
WebMD asked two independent experts to review Heckbert's study.
"The evidence here is interesting, but I'm not going to put this at a high level of confidence at this point," Edward Puzas, MD, tells WebMD. Puzas is a professor of orthopaedics, director of the Osteoporosis Center, and director of orthopaedic research at the University of Rochester School of Medicine in Rochester, N.Y.
"I think you're going to see articles coming out on both sides of this right now, and my prediction is that in the end, it's going to sort itself out that there's little if any risk associated with cardiovascular issues and these bisphosphonates," Puzas says.
"I'm not ready to believe that the bisphosphonates, certainly as a class, have got any real potential serious adverse event with regard to atrial fibrillation," Puzas says. "Sometimes, where there's smoke there's fire, but many times, when you retrospectively ... look at these articles, they really do amount to statistical fluke or a statistical fluctuation, and it's not until other people demonstrate them in other trials in a more prospective, rigorous fashion that you can actually believe the evidence.
"If I were treating a new patient and about to put them on a bisphosphonate, I would evaluate their cardiac status with an extra eye toward looking at atrial fibrillation," says Puzas, adding that he wouldn't rule out bisphosphonates based only on cardiovascular risk factors.
Henrik Toft Sorensen, MD, PhD, who worked on the Danish study published by BMJ (formerly called the British Medical Journal) in April 2008, notes that Heckbert's data "might be vulnerable" to factors not weighed by the researchers. "This study does not change my recommendations for treatment. More data are needed," Sorensen tells WebMD by email.
An editorial published in the Archives of Internal Medicine praises Heckbert's study. But like Heckbert, Puzas, Sorensen, and the FDA, the editorialists don't jump to conclusions about bisphosphonates and atrial fibrillation.
Drug Companies Respond
WebMD contacted Merck, the drug company that makes Fosamax, for its response to Heckbert's study.
In a statement emailed to WebMD, Merck notes that randomized clinical trials are "the gold standard" for evaluating drug safety and efficacy, and Heckbert's study was an observational study, not a randomized clinical trial. "We strongly recommend that if patients have concerns about Fosamax that they talk to their physician," states Merck, adding that "it's worth pointing out that authors of the editorial in the Archives of Internal Medicine conclude: 'At this time, it seems that the benefits of bisphosphonate treatment in patients with osteoporosis outweigh the risks of [atrial fibrillation].'"
Reclast is made by the drug company Novartis. In May 2007, when The New England Journal of Medicine published the results of the Novartis-sponsored Reclast clinical trial, Novartis issued a news release stating that though 1.3% of the Reclast patients in the trial developed atrial fibrillation, compared to 0.5% of those taking placebo, those findings didn't appear in other studies. Novartis also noted that Reclast's active ingredient, zoledronic acid, has been used by more than 1.5 million cancer patients, with no sign of increased risk of atrial fibrillation.