Drug for Bones Is Newly Linked to Jaw Disease

In the last 10 years, millions of patients have taken a class of drugs that can prevent agonizing broken and deteriorating bones. The drugs once seemed perfectly safe and have transformed life for patients with cancer or osteoporosis.

Skip to next paragraph Enlarge this Image Herb Swanson for The New York Times

Joan McDevitt suffered badly after developing osteonecrosis of the jaw.

Multimedia Graphic: Top-Selling Bisphosphonates

But recently there have been reports of a serious side effect: death of areas of bone in the jaw.

Everyone agrees that the condition, osteonecrosis of the jaw, is an uncommon complication, but that its true incidence is not known. It is estimated that among the 500,000 American cancer patients who take the drugs because their disease is affecting their bones, 1 to 10 percent may develop the problem.

As for the millions of osteoporosis patients, who take lower doses, the condition seems less common. But no one knows how much less. Some oral surgeons have as many as a couple of dozen cases, but their clinics have become centers to which patients elsewhere are referred. Among people with osteoporosis, only 15 cases of the new ailment have been reported in the medical literature.

So for now, doctors and dentists are perplexed. Firm data are scarce to nonexistent, studies that may provide answers are only about to begin, and medical organizations and drug companies are scrambling to provide guidance, often based only on hunches. Some dentists are refusing to treat patients taking the drugs, fearful that the dental work will induce a case of osteonecrosis, and lawyers are lining up to sue the drugs' makers, saying they failed to give patients adequate warning.

Doctors say worried patients hearing about the ailment are starting to besiege them. The patients want to know whether they should stop taking the drugs, called bisphosphonates. They want to know whether they should shun invasive dental procedures, like tooth extractions and implants, which appear to set off the condition. They want to know whether osteonecrosis of the jaw can be treated and, if so, how likely it is that a person will recover.

Some patients who have not developed osteonecrosis have decided to stop taking the drugs until more is known.

"I'm giving myself a little holiday," said Judy Langley, 63, of Anacortes, Wash., who because of osteoporosis has been taking a bisphosphonate for seven years.

Doctors also say the level of alarm among patients, as well as some physicians and dentists, is itself alarming. "The whole thing has spun out of control," said Dr. Ethel Siris, director of the Toni Stabile Osteoporosis Center at Columbia University.

The Food and Drug Administration is aware of the issue, said Laura Alvey, a spokeswoman, and has required that all bisphosphonate labels disclose the link to osteonecrosis of the jaw. The problem is that patients cannot easily abandon the drugs.

Cancer patients, mostly those with multiple myeloma and breast cancer whose disease has spread to their bones, generally take one of two bisphosphonates, Zometa or the older Aredia, intravenously. The drugs, doctors say, largely prevent excruciating bone pain and fragile bones that break like kindling.

Osteoporosis patients, on the other hand, usually take bisphosphonates as pills, in much lower doses. Those drugs — Fosamax, Actonel and Boniva — reduce the risk of fractures of the spine or hip, injuries that can create a steady downward spiral in patients' condition.

Even if patients stop taking the drugs, they are not free of them. Bisphosphonates remain in bone for years, and no one knows how long the osteonecrosis risk remains. Some doctors and dentists suggest stopping the drugs for a few months before and after an invasive dental procedure. Others say six months to a year may be better.

As for what happened to patients who developed the condition, oral surgeons say some got better but many did not. It now appears that the best treatment is with antibiotic rinses; cutting away the dead bone just made things worse.

So little is known, said Dr. Bruce L. Pihlstrom, acting director of the division of clinical research at the National Institute of Dental and Craniofacial Research, that the most fundamental questions lack answers.

The institute is starting studies, but for now "we have to be careful that we're not too alarmist about this," Dr. Pihlstrom said. "We just don't have the information we need."

The story of bisphosphonates (pronounced bis-FOS-fo-nates) began in 2003 with a letter in The Journal of Oral Maxillofacial Surgery calling osteonecrosis of the jaw "a growing epidemic."

Its author, Dr. Robert E. Marx, chief of oral and maxillofacial surgery at the University of Miami, reported on 36 patients who had received intravenous bisphosphonates. All had "painful bone exposure," as is typical with the condition, and "were unresponsive to surgical or medical treatments," Dr. Marx wrote.

"The common denominator," he said in a telephone interview, "was that they all had cancer. Then we started looking at their treatment. The one common thread was bisphosphonates."

But not everyone was convinced.

"My first reaction was that maybe there is an association but this wasn't enough," said Dr. Regina Landesberg, an oral and maxillofacial surgeon at Columbia University. "I wanted to see more data."

12Next Page »