Minuscule risk, large benefits for osteoporosis drugs

Millions of women with low bone density take bisphosphonates, a class of drugs used to prevent osteoporosis. But a new analysis by the FDA may lead some of these women, and their doctors, to rethink their treatment plans: The review suggests that certain women may be better off taking these drugs for a shorter period of time, instead of on a long-term basis and some should stop taking them altogether.

Published in The New England Journal of Medicine, the analysis was based on two studies from the University of California, San Francisco, that focused on two brand-name versions of bisphosphonates: Fosamax (alendronate) and Reclast (zoledronic acid). The studies lasted 10 and six years, respectively, and assessed the benefits and risks of long-term use of the drugs. The numbers showed that neither drug offered a significant benefit in the long-term, but the short-term benefits were substantial: In the Fosamax study, during the first three years of treatment, only about 11 percent of women taking the drug suffered a fracture, as compared to 21 percent taking placebo. The numbers were similar for women on Reclast versus placebo. However, after the first three years, there was little to no benefit seen for women taking either drug. This led the FDA analysis to recommend that, for many women, longer treatment may not yield benefits.

The studies did not show any increased risk of serious side effects with long-term use. But the serious side effects that can result from the use of bisphosphonates, such as femur fractures, esophageal cancer, and crumbling of the jaw bone, are very rare; it s estimated that such complications occur at a rate of 1 in 1,000 to 1 in 10,000 people taking them. It s possible, then, that these studies may have been too small to determine any increase in risk.

Overall, the FDA analysis emphasizes that, considering such serious side effects occur only very rarely, the decision whether to take bisphosphonates, and for what period of time, must be made on an individual basis. For example, a woman who has osteopenia, which involves only a mildly or moderately reduced bone density not severe enough to be labeled osteoporosis, might benefit most from only three years on the medication. Yet a woman with osteoporosis and a very high risk of spinal, wrist, or hip fractures might benefit more from taking the drug for a longer duration, as compared to the remote risk of one of the described side effects.

As ACSH s Dr. Gilbert Ross explains, Serious complications from bisphosphonates are very rare, whereas the disease that these medications ameliorate is very common and very serious. Osteoporosis can lead to severe debilitation if a woman with osteoporosis breaks her hip, it doesn t heal in the same way as in a healthy young person; she s likely to wind up disabled. Of course, he concludes, the risk-benefit equation will depend on the individual s specific condition.