FDA Report Suggests Women Reassess Bone Drug Use Due To Serious Adverse Events
May 11, 2012

FDA Report Suggests Women Reassess Bone Drug Use Due To Serious Adverse Events

A new analysis of popular bone-building drugs by the US Food and Drug Administration (FDA) could prompt millions of women to rethink their use of such drugs, even though the agency fell short of issuing specific recommendations.

The FDA said doctors need to reassess which women are likely to benefit from bisphosphonates such as Fosamax, Actonel and Reclast, given the lack of concrete evidence that taking them over long periods really helps them and the possibility that they can put some women at risk for rare but severe side effects.

The FDA review, published online Wednesday in The New England Journal of Medicine (NEJM), draws concern that these so-called bone-building drugs could be causing a reverse effect on some women, leading to weaker bones and contributing to “serious adverse events,” including femoral fractures, esophageal cancer and osteonecrosis of the jaw, a painful, disfiguring crumbling of the jaw.

Although the drug safety concerns are not new, the FDA decided to perform its own systematic review on the effectiveness of bisphosphonates and its side effects after prolonged use (three to five years). The agency found that the drug offered little, if any benefit over that time, and could prompt doctors around the country to reassess prescription of such drugs.

Most doctors believe that for women with documented osteoporosis who are at very high risk for spinal fractures, the benefits far outweigh any risks. However, some women with moderate bone density and no other risk factors continue to take the drugs for years even though they offer little or no benefits.

Although the FDA didn´t issue specific guidelines for duration of use, the analysis did suggest doctors and women taking the drugs should have increased awareness of the risks of long term use.

“I think a lot of people are going to come off this drug,” Dr. Clifford J. Rosen, an endocrinologist and researcher at the Maine Medical Center Research Institute, told the New York Times.

Rosen and colleagues published an accompanying article in the NEJM offering more specifics, concluding that the women most likely to benefit from long-term use of the drugs are those who continue to have very low bone density after three to five years of treatment. Women with a history of spinal fracture or with an existing fracture also are most likely to benefit from long-term use of the drugs, the researchers concluded.

However, many women who are prescribed these bone drugs have been given a diagnosis of osteopenia, moderate to low bone density that is not low enough to be called osteoporosis. These women are unlikely to benefit from long-term use and should probably stop taking the drugs after about three years, Rosen said.

It isn´t clear how many women would be affected based on the recommendations, but many women tire of therapy and stop taking it on their own anyway, probably because of the inconvenient requirements involved, like remaining upright after taking the drugs and common side effects, including heartburn, nausea and flu-like symptoms.

Even so, Rosen and colleagues estimate that 60 to 70 percent of women who currently use the drugs are good candidates for stopping the treatments after three to five years.

After about age 30, a woman´s bones start to dissolve faster than they can be rebuilt, and after menopause she may develop thin, brittle bones that are easily broken. Bisphosphonates slow this process. The drugs are incorporated into newly formed bone and can persist there for years, long after a patient stops taking them.

The FDA recommendations are based on findings from two studies led by the University of California, San Francisco (UCSF). The first study focused on Fosamax, which is sold generically as alendronate, over a ten-year period. The second study focused on Reclast and continued for six years.

The FDA analysis showed that both studies showed significant reductions in fracture risks during the first three years of use, but little or no benefit after five years.

In the Fosamax trial, 10.6 percent of women using the drug suffered a fracture during the first three years of use, compared with 21 percent in the placebo group. But there was no benefit seen among women who continued the drug for the next five to ten years. Similar results were found in the Reclast study, according to the FDA.

The studies did not show any increased risk of serious side effects with long-term use, however. But experts said the studies simply were not large enough to detect a relatively rare adverse event. Even so, there have been numerous reports of the unusual fractures and other side effects, prompting widespread concern over the risks of long-term use. It remains unclear just how common the femur fractures are, but estimates have ranged from 1to 10 in 10,000 users.

Dennis M. Black, a professor of epidemiology and biostatistics at UCSF and the coauthor of the article that accompanied the FDA report, said women should be reassured that serious complications are rare.

“The reality is there is a lot of uncertainty in this situation,” said Black. “The FDA report was very general, and we tried to be much more specific and use evidence from the best trial available. Hopefully people who are using this drug will be reassured.”

Rosen added that even though the FDA report was vague on specific recommendations, he was pleased to see the analysis published.

“It´s a very new thing that they submit a paper to The New England Journal that presents all sides of the argument,” Rosen told Times reporter Tara parker-Pope. “I think it´s a good thing, because I´ve been on these advisory committees for years, and we get a big crowd in Washington, but the doctors never see the results.”

The FDA said additional research is needed before doctors can determine if interruption of treatments is helpful. For now, the FDA said women should be mindful of how long they have been on bisphosphonates and talk with their doctors about whether they should be continuing treatments. It has already placed a statement on bisphosphonates´ labels saying patients should be reevaluated by their doctors periodically.

Dr Beatrice Edwards, an associate professor of orthopedic surgery at the Northwestern University Feinberg School of Medicine, agreed with the FDA report and said she keeps a close eye on her patients who take bisphosphonates.

“We usually have a discussion about the benefits and risks and look at their bone density,” Edwards told ABC News. “We may give them a five-year treatment, and then take them off for one or two years.”

Women who have experienced complications from bisphosphonates, such as femoral fractures, are filing lawsuits against the drug makers. The law firm Bernstein Liebhard LLP is currently representing clients who suffered from bisphosphonate complications after long term Fosamax use. The Firm is actively filing cases on behalf of these individuals in the Superior Court of New Jersey, Atlantic County, in In re: Fosamax Litigation (No. 282 N.J. Super. Ct.).

Those who took Fosamax and sustained a femur fracture may be entitled to compensation for medical bills, pain and suffering, lost wages and other injuries. To learn more about filing a Fosamax lawsuit, visit: http://www.consumerinjurylawyers.com/.