WebMD Medical News
Louise Chang, MD
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
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
"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."
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
The study doesn't prove that Fosamax caused atrial fibrillation. The study
was observational, meaning that patients weren't randomly assigned to take
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."
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
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
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
SOURCES:Heckbert, S. Archives of Internal Medicine, April 28, 2008; vol 168:
pp 826-831.Cauley, J. Archives of Internal Medicine, April 28, 2008; vol 168: pp
793-795.Sorensen, H. BMJ, April 2008; vol 336: pp 813-816.Black, D. The New England Journal of Medicine, May 3, 2007; vol 356:
pp 1809-1822.Cummings, The New England Journal of Medicine, May 3, 2007; vol 356:
pp 1895-1896.Edward Puzas, MD, professor of orthopaedics, director of the Osteoporosis
Center, and director of orthopaedic research at the University of Rochester
School of Medicine, Rochester, N.Y.E-mail from Henrik Toft Sorensen, MD, PhD, department of clinical
epidemiology, Aarhus University Hospital, Denmark.FDA: "Early Communication of an Ongoing Safety Review."Statement, Merck.News release, Novartis, May 2, 2007.
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