FDA Still Cautious About Bone Drugs

May 10, 2012— -- The U.S. Food and Drug Administration says doctors need to reassess which women are likely to benefit from popular bone-building drugs, given the lack of evidence showing that taking them for the long term really helps and the possibility that they put some women at risk for rare but serious side effects.

In a report published in the New England Journal of Medicine on Wednesday, the U.S. Food and Drug Administration raised concerns about the potential for some serious side effects in women taking bone-building drugs called bisphosphonates, specifically Fosamax, Actonel and Reclast.

The published findings are not new. In 2011, the agency voiced concerns that taking the drugs long-term may actually make bones weaker and increase the risk of rare but serious side effects such as atypical fractures of the thigh bone, esophageal cancer and osteonecrosis of the jaw, a rare but painful condition in which the jaw bone crumbles. To investigate, the FDA reviewed data from women who had taken the drugs for six to 10 years.

In Wednesday's report, the agency repeated its 2011 conclusions: Women without osteoporosis seem to get few to no benefits to their bones from taking the drugs beyond five years. In light of the concerns about the potential side effects, the authors said some patients should be able to safely stop taking the drugs after that time, particularly if they are younger and at low risk of fractures.

They suggested that women who continue to have very low bone density, measured by a "T score" lower than minus 2.5, are the ones who may benefit the most from taking the drugs after five years.

A commentary accompanying the FDA's report said it is older women who have a history of fractures or are at an increased fracture risk, particularly of spine fractures, who stand to benefit from taking the drugs for longer than five years.

Dennis Black, a professor of epidemiology at the University of California, San Francisco and the lead author of the commentary, said the drugs appear to be safe and helpful for women taking them for a just few years at a time.

"These drugs in general have very strong proven benefits for the first five years," Black said. "I would want a patient with osteoporosis to not let the worry about these very rare side effects overwhelm the very strong benefits they would get."

The reports reflect overall uncertainty about the optimal length of time a patient should take these drugs. Clinical trials of bisphosphonates have studied large numbers of women for up to five years and have shown that the drugs are effective for that length of time. But the trials looking at the effects after five years have included a much smaller number of patients, meaning their results are less certain.

"The problem is we don't really know when to start or stop these drugs, and we don't know how common those serious adverse events are," said Dr. Rita Redberg, a professor of medicine at UCSF. "We think they're uncommon, but we don't really have strong data."

According to the FDA, doctors wrote more than 150 million prescriptions for bisphosphonates between 2005 and 2009. The drugs work by targeting the body's process of breaking down and regenerating bone cells. After age 30 or so, a woman's bones start to break down faster than the body can rebuild them, which can lead to the brittle, vulnerable bones of osteoporosis. The drugs work to slow down the bone-dissolving process, letting the cells that work to build bone mass catch up.