Osteonecrosis of the jaw linked to use of bisphosphonates

Washington -- Physicians continually weigh the risks and benefits certain drugs pose to a particular patient. Bisphosphonates are no exception.

Over the past few years, an apparent connection between these bone-building medications and osteonecrosis of the jaw has been making the calculation a touch trickier and patients a bit uneasy.

Most of the jaw problems seem to occur with the drugs' intravenous forms, used primarily for cancer patients. A few cases have been seen in patients taking the drugs orally for osteoporosis. How great the risk is for either group and whether it is triggered by a dental procedure, as evidence suggests, has yet to be determined.

The drugs' manufacturers were required last year to add safety information about ONJ to package inserts.

Meanwhile, a lawsuit was filed recently against Merck, which manufactures Fosamax, and numerous Internet sites have been encouraging more such action. The resulting publicity has led to greater awareness of the condition and more calls to physicians' offices from worried patients.

Bisphosphonates such as alendronate, marketed as Fosamax, and risedronate, or Actonel, have become the drugs of choice to help stop bone loss. Physicians who had prescribed estrogen to postmenopausal women turned to them as alternatives after the Women's Health Initiative determined that hormone replacement therapy increases a woman's risk of heart attack, stroke and cancer.

The oral medications have been on the market for more than 10 years and have enjoyed a favorable safety profile despite having stringent requirements. For instance, the pill has to be taken with a full glass of water on an empty stomach, and the patient must remain upright and refrain from eating for a half-hour or more afterwards. Instances of esophageal irritation are the most frequent complaint.

That safety record may continue, but no one can know as yet. "We are in the middle of a period with [ONJ] where we don't understand it very well," said Ethel Sirus, MD, president of the National Osteoporosis Foundation. Until the evidence of harm is clearer, the drugs remain valuable treatment tools, she said. "The risks seem very small compared with the benefit of reducing fractures." Dr. Sirus has consulted for Merck.

Since dental procedures apparently play a role in the condition, perhaps because bone in the jaw is exposed to the mouth's high bacteria content, the foundation recommends that patients who are taking bisphosphonates continue to get regular check-ups and let their dentist know about the medications they take.

Physicians are urged to evaluate the threat posed by osteoporosis when they are considering prescribing a bisphosphonate.

"A man with a hip fracture has a one-in-three chance of dying within a year and a woman with a hip fracture has a one-in-four chance," said Laura Tosi, MD, former chair of the American Academy of Orthopedic Surgeon's Women's Health Issues.

But the risk for ONJ among those taking oral bisphosphonates may turn out to be one in 100,000, said Dr. Tosi, who has been on a Merck advisory board and lectured on osteoporosis for the company.

Merck said in a statement that ONJ is not well understood and may occur for a number of reasons. Known risk factors include a diagnosis of cancer, cancer treatment, poor oral hygiene and preexisting conditions such as dental disease, anemia and infection. "Clinical trials of the medication that included more than 17,000 patients uncovered no reports of ONJ," said a spokesman.

Procter and Gamble, which markets Actonel, is continuing to collect information on its product, said a spokeswoman. The firm has also established a medical communications group to provide information to physicians about ONJ.

Until there are more definitive data, physicians considering prescribing the medication could separate patients into three categories, suggested Dr. Tosi. One category would include patients who have cancer, another, those who have already had fractures, and the third, those with osteoporosis.

Bisphosphonates given intravenously have done a very good job of suppressing cancer pain and have greatly improved the quality of life of cancer patients, she said. And for people who have had fragility fractures, all research indicates they are at risk for additional fractures. Prescribing a bisphosphonate for those patients has decided advantages, she added.

It's the third group, those with osteoporosis, for whom it is more difficult to determine the correct answer, said Dr. Tosi "We don't want every woman or man on this drug but we do want to be sure that everyone is maximizing their capacity to make good bone." She advises patients and physicians to look beyond bone density scores -- assessed via a DEXA scan -- when determining who in this category should take medications. Additional exploration may uncover a treatable condition such as vitamin D deficiency or a thyroid condition.

George Griffing, MD, director and professor of general internal medicine at Saint Louis University School of Medicine in Missouri, is checking patients' vitamin D levels more frequently now. He's finding that about half his patients lack sufficient amounts. Adding supplements rapidly increases levels.

"While we are seeing a lot of vitamin D deficiency, the question is: 'Are we going to prevent bone loss?' I think we'll be hearing a lot more on this," said Dr. Griffing. "Vitamin D is a hot topic now."