A recent meeting of an FDA advisory committee has asked wants the FDA to limit the duration of bisphosphonate therapy for treatment of osteoporosis, but the committee could not agree on a time limit to recommend.

Osteoporosis is a common side effect from androgen deprivation therapy (ADT). It is common practice for all men undergoing ADT to have periodic bone density evaluations to make sure they do not have osteoporosis which puts them in danger of having dangerous bone fractures.

The FDA has already required that all bisphosphonates used to prevent or treat osteoporosis carry warnnings on their labels that optimal duration of use hasn’t been determined. The warnings also state that all patients on bisphosphonate therapy should have their need for continued therapy re-evaluated periodically. This issue has become a hot potato for the FDA as reports have emerged linking long-time bisphosphonate therapy with increased risk of atypical fractures.

Last Friday the Advisory Committee for Reproductive Health Drugs and the Drug Safety and Risk Management Advisory Committee met to discuss whether emerging reports of adverse events should spur the FDA to change the label to indicate that the drug not be used long term, and the committee members voted 17-6 to endorse a label change. To add to the confusion they backed away from setting a hard deadline, citing a lack of data to pinpoint an ideal therapeutic time limit.

The committee stated that there is no strong clinical evidence that bisphosphonates work better after they’re used for a long period of time, nor is there firm evidence that long-term use causes harm, the panel said. The placebo-controlled trials typically provide data for only five years of therapy, thus long term use decisions are not backed by any usable data.

Bisphosphonates have been shown to reduce the risk of breaking a hip by 40% to 50% and fracturing a vertebra by between 40% and 70%. They work by inhibiting bone resorption to prevent loss of bone mass.

In 2010, the FDA required that bisphosphonate drugs add a warning to their labels about a small increased risk of atypical femur fractures after an American Society for Bone and Mineral Research task force concluded that the risk, although it is small, is real.

Because the FDA approvals for the use of bisphosphonate drugs is primarily limited to women the panel only reviewed data from women who were taking bisphosphonates to prevent osteoporosis. In all the reported cases reviewed the women reported that suddenly and painfully they broke their femurs. In each case presented at the hearing the women reported that they collapsed to the ground as their femurs snapped.

Since the review included only women there is no direct evidence that men on ADT share this concern, but there is no reason to think that men’s experiences are any different.

The panel was also concerned with the drug’s link to deterioration of the jawbone. In 2005, the FDA added a warning on bisphosphonates about osteonecrosis of the jaw, a rare disease in which the bone in the jaw dies. In data presented Friday, an FDA reviewer said the risk for osteonecrosis of the jaw appears more prevalent after four years or more of use.

The panel did determine there’s no clear answer on the long-term safety of bisphosphonate therapy for the prevention and treatment of osteoporosis. The panel called for more studies to hone in on the long-term risks and benefits of the drug.

The panel also discussed the idea of a “drug holiday” or taking a break for bisphosphonate treatment in order to minimize risks, but agreed there wasn’t enough evidence to warrant recommending a drug holiday as a treatment plan.

We also implore the FDA to include data on men’s experiences with bisphosphonate use.

Joel T. Nowak, M.A., M.S.W.