After eight operations on patients whose jawbones turned out to be dead, oral surgeon Salvatore Ruggiero began doing some research in February 2001. He scoured the patients’ medical records and discovered they had something in common: They were cancer patients taking a drug called Aredia to combat bone loss.
Dr. Ruggiero, chief of oral and maxillofacial surgery at the Long Island Jewish Medical Center, says that year he phoned the drug’s maker, Novartis AG, to find out if there were other reports of patients on Aredia suffering from osteonecrosis of the jaws, or jawbone death.
He says he also reported his cases on MedWatch, the Food and Drug Administration’s computer system for tracking dangerous side effects from drugs.
Since then, Dr. Ruggiero has gathered 90 cases in which patients taking Aredia and Novartis’s successor drug, Zometa, have experienced dental problems so severe they have lost portions of their jaws. Other oral surgeons have been reporting the same problem. It wasn’t until November 2003 that Novartis first noted the possible side effect on the drugs’ package inserts.
Dr. Ruggiero’s experience in bringing his patients’ jaw problems to the attention of Novartis and the FDA underscores how challenging it is — and how long it can take — for companies and regulators to act on potentially dangerous side effects of marketed drugs. The issue has been at the center of two pharmaceutical debacles this year: the drug industry’s delayed recognition of suicide risk associated with pediatric antidepressant use, and Merck & Co.’s withdrawal of the painkiller Vioxx after a clinical trial linked long-term use to the risk of heart attack and stroke.
In September of 2004, Novartis at the direction of the FDA added a “precaution” to the drugs’ labels and sent letters warning doctors of the potential side effect. “Osteonecrosis of the jaws has been reported in patients with cancer receiving treatment regimens including” Aredia and Zometa, the label says. Novartis says as of September it had received 500 case reports of jaw problems in people taking Aredia and Zometa.
The oral surgeons believe that the two Novartis drugs, which are useful in stopping cancer cells from dissolving bone, end up causing problems in the jaws of some patients precisely because they interfere with the bone-dissolving process. New cells don’t grow unless the old ones are killed off. The bone doesn’t heal following dental work and is more prone to infections.