FDA Bisphosphonate Study Finds Few Benefits from Long-Term Use

A new U.S. Food & Drug Administration (FDA) analysis is raising serious concerns about the long-term use of bisphosphonates like Fosamax to treat weak bones. While the bisphosphonate analysis found little if any benefit from taking the drugs for more than three to five years, the FDA has stopped short of issuing any sort of recommendations about their long-term use. Still, the agency’s findings could change the way doctors prescribe Fosamax and similar drugs to women with osteoporosis.

Bisphosphonate Overview
It is estimated that bisphosphonates are taken by some 5 million people to treat osteoporosis and other bone weakening diseases. The drugs are sold under a variety of brand names, including:

• Fosamax
• Actonel
• Aredia
• Bonefos
• Boniva
• Didronel
• Reclast
• Skelid
• Zometa

Over the years, bisphosphonates have been linked to a number of side effects, some of which may be associated with long-term use:

• In 2005, warnings about a jaw disease called Ostenecrosis of the Jaw were added to labels for Fosamax and other bisphosphonates.
• In October 2010 the FDA asked the manufacturers of bisphosphonates used to treat osteoporosis to add information to the “Warnings and Precautions” section of the drugs’ labels describing the risk of atypical thigh fractures after a study linked long-term use of such drugs to this side effect.
• Last year, a study suggested long-term use of oral bisphosphonates might double the risk of esophageal cancer

FDA Bisphosphonate Analysis
The FDA analysis, which appears in the New England Journal of Medicine, involved a review of two previously released studies that involved more than 2,400 post-menopausal women. One of the studies involved Fosamax and continued for 10 years, while the second, a study of Reclast, continued for six years. In the Fosamax trial, 10.6 percent of those who received the drug suffered a fracture during the first three years of use, compared with 21 percent given a placebo. However, no benefit was seen in women who continued taking Fosamax beyond five years.

In the Reclast trial, 9.8 percent of women treated with the injectable drug suffered a fracture in the first three years of the study, compared with 20 percent of women who were taking a placebo. However, by 3 to 6 years of use, 8.6 percent of Reclast users experienced fractures, compared with 12 percent in the placebo group.

While neither study indicated a long-term risk of serious side effects with either drug, it’s likely they were not large enough to accurately assess the likelihood of adverse events.

Bisphosphonate Reccommendations

According to a report in The New York Times, the FDA analysis offered little specific guidance about long-term bisphosphonate use, stating that an individual’s risk should be discussed with their doctor. However, the agency say that women at low risk for fracture or with a bone density near normal may be good candidates to stop therapy after three to five years, while older patients at higher fracture risk and bone density “in the osteoporotic range” may benefit from continued therapy.

An accompanying editorial asserted that women most likely to benefit from long-term bisphosphonate therapy are those who continue to have very low bone density, as measured by something called a “T score” that is lower than minus 2.5 after three to five years of treatment. Those 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. Women with osteopenia are unlikely to benefit from long-term bisphosphonate therapy, and should probably stop taking the drugs after about three years, according to the editorial.

In statement issued in response to the FDA’s findings, the American Society for Bone and Mineral Research (ASBMR) urged doctors to:

“. . . to consider each patient’s case individually since the optimal length of bisphosphonate therapy remains unknown and must be considered on a case-by-case basis. Patients whose fracture risk has clearly been reduced by bisphosphonates might be candidates for discontinuing the drug. However, individuals who after three to five years of taking bisphosphonates still have a high risk for fracture may want to remain on the medication because the risks of stopping treatment may not be the best option for high-risk patients, there is strong data that the drug remains very useful in preventing fractures caused by osteoporosis.”