Possible Link Between Bisphosphonates, Esophageal Cancer Sparks FDA Review

The FDA once again is examining safety data related to the use of bisphosphonates. This time, the agency is reviewing conflicting reports regarding oral bisphosphonates and the risk for esophageal cancer.

Although the agency said in a July 21 safety announcement that its safety review is ongoing, at this time, the benefits the osteoporosis drugs provide in reducing the risk of serious fractures continue to outweigh the potential risks.

The largest studies the FDA has reviewed to date are two epidemiologic studies that used the same patient database -- the United Kingdom's General Practice Research Database -- but arrived at quite different conclusions. Although one of these studies found no increase in the risk of esophageal cancer with oral bisphosphonate use, the second study found a doubling of the esophageal cancer risk among patients who had 10 or more prescriptions for the drugs or who had taken them for more than three years.

Two other studies that used different patient databases reported either no increase in esophageal cancer risk or a reduced risk. Differences in study design and methodology may account for the discrepant findings, the FDA said. Because the studies are observational rather than randomized, for example, they are subject to bias and confounding.

The FDA issued the following information for physicians:

Other drugs in the class are alendronate, which is marketed as Fosamax; ibandronate, which is marketed as Boniva; etidronate, which is marketed as Didronel; risedronate, which is marketed as Actonel; and tiludronate, which is marketed as Skelid.

The FDA previously reviewed safety data related to nonserious atrial fibrillation with bisphosphonate use, but the agency found no clear association. Last year, the agency alerted physicians to the risk of atypical fractures of the femur in patients taking bisphosphonates.

Physicians are encouraged to report adverse events involving bisphosphonate drugs to the FDA's MedWatch program.