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FDA Considers Limits on Osteoporosis Drugs Due to Fracture Risk

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An advisory committee of the U.S. Food and Drug Administration (FDA) last week weighed the risks and benefits of bisphosphonate drugs such as alendronate (Fosamax) for managing osteoporosis. The committee recommended limiting the duration of bisphosphonate use, but did not agree on a time frame.

Bisphosphonate drugs have been shown to reduce the risk of fractures, including hip and spine breaks, among people with bone loss -- osteopenia or the more severe osteoporosis. Most of this research has looked at post-menopausal women, who tend to experience bone loss as they age. It is estimated that some 10% of women over age 55 use these medications.

A few trials, however, have found that alendronate also helps manage bone problems among people with HIV, who may experience bone loss related to prolonged viral infection itself, resulting persistent inflammation, or antiretroviral drugs.

Normally there is a balance between bone creation and bone resorption, or removal of minerals. Bone loss occurs when bone is destroyed faster than it can be built. Bisphosphonates work by inhibiting bone resorption. In addition to alendronate, this drug class includes ibandronate (Boniva), risedronate (Actonel, Atelvia), and zoledronic acid (Reclast).

Over the past few years bisphosphonates have been linked to atypical fractures of the femur, or thigh bone, and osteonecrosis (bone death) of the jaw. In addition to bone problems, bisphosphonates may also increase the risk of esophageal cancer, but data are conflicting. While such events are rare, these associations raise concerns about routine and prolonged use of these drugs.

On September 9, the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee held a joint meeting near Washington, DC, to discuss the risks and benefits of long-term bisphosphonate use (more than 3-5 years) for the treatment and prevention of osteoporosis in light of recent safety concerns.

The FDA has already required new label language warning that the optimal duration of bisphosphonate use has not yet been determined, and that patients taking these drugs should be periodically re-evaluated to see if they should continue treatment.

After hearing a review of evidence from clinical trials as well as personal testimony from individuals who experienced unexplained fractures while taking bisphosphonates, the joint advisory committee last week recommended with a 17-6 vote that the warning should be strengthened to indicate that the duration of bisphosphonate therapy should be limited. But they could not reach agreement about what that limit should be due to insufficient data.

Many bisphosphonate clinical trials have not followed participants for more than 5 years, making long-term outcomes uncertain. Some research indicates that the bone-preserving effect of these drugs may be sustained after stopping therapy, suggesting that periodic treatment interruptions or "drug holidays" might be beneficial.

"In light of the potential risks that may be associated with long-term use of bisphosphonates for the treatment and/or prevention of osteoporosis, the sum of available long-term efficacy data appears to suggest that bisphosphonate therapy could be safely discontinued for some period of time," the advisory committee concluded.

The full FDA is not required to accept advisory committee recommendation, but it usually does so.

9/13/11

Sources

U.S. FDA, CDER. September 9, 2011: Joint Meeting of the Reproductive Health Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee Meeting Announcement. http://www.fda.gov/AdvisoryCommittees/Calendar/ucm262477.htm.

EP Walker. FDA Panel Waffles on Limiting Duration of Bisphosphonate Use. MedPage Today. September 9, 2011.

R Rubin. FDA Panel: Osteoporosis Drugs Need Better Labels. WebMD. September 9, 2011.

 

D Wilson. Stronger Cautions Backed on Bone Drugs for Women. New York Times. September 9, 2011.