Drug used for advanced cancer could cause exposed bone in jaw

Condition affects up to 10 percent of advanced cancer patients, U-M researchers report

ANN ARBOR, Mich. -- A type of drug used to strengthen bones when cancer has spread there may be linked to a side effect that involves deterioration of the jaw bone, according to two new reviews of cancer literature. The condition, called osteonecrosis of the jaw, is marked by exposed bone in the jaw and can lead to infection, inflammation and pain.

While researchers do not fully understand the condition or what causes it, osteonecrosis of the jaw, or ONJ, appears to occur in individuals who have been treated with drugs called bisphosphonates, which are used to improve bone strength. When treating bone affected by cancer, the bisphosphonates are given intravenously and have been shown to decrease the risk of skeletal complications such as fracture.

"Osteonecrosis of the jaw is not a common condition. It appears to occur in 1 percent to 10 percent of patients with advanced cancer who are on intravenous bisphosphonate therapy – a number significant enough that most medical oncologists will see patients with this condition. It is important that researchers learn why it occurs and how best to prevent or treat it," says Catherine Van Poznak, M.D., assistant professor of internal medicine at the University of Michigan Medical School.

Van Poznak has authored two recent reviews of osteonecrosis of the jaw. One study appears in the October issue of Current Opinions in Orthopaedics. The other was published in August in the journal Oncology. Both papers synthesize the present data for an overview of what is known to date about this recently identified complication.

ONJ is marked by exposed, non-healing bone. Pain, swelling and inflammation are the most common symptoms but the lesions can have no symptoms. ONJ typically develops months or years after therapy with intravenous bisphosphonates begins. Researchers have noted that when ONJ occurs, it usually follows an invasive dental procedure such as an extraction where the wound does not heal in a normal fashion. To try to prevent ONJ, it has been suggested that patients maximize their oral health and take care of any invasive dental work before they begin bisphosphonate therapy.

"No reported treatment has proven successful for osteonecrosis of the jaw, which means for now the focus is on prevention or alleviating symptoms once it develops. We do not know how to predict who will develop ONJ or who is most at risk," says Van Poznak, a breast oncologist at the U-M Comprehensive Cancer Center who treats patients whose cancer has metastasized to bone.

"Some patients have resolution of the lesion but in other patients, it may remain stable or even progress," Van Poznak adds.

Patients with osteoporosis also take bisphosphonates, although their treatment is typically prescribed as a pill, rather than intravenously. Some cases of ONJ have been reported in patients with osteoporosis who are taking oral bisphosphonates, but the risk of ONJ to such patients appears to be very low.

Previous studies have noted anywhere from 0.6 percent to 10 percent of patients with cancer on bisphosphonates developed ONJ. Reporting is currently voluntary. The problem, Van Poznak says, is that the condition itself is poorly defined and no universal reporting mechanism exists.

To address these challenges, clinical trials are being designed to help better define the condition. These upcoming clinical trials investigating bisphosphonate therapy for advanced cancer will include monitoring for ONJ, and researchers hope to learn what causes the condition to develop.

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Van Poznak's co-author on the Current Opinions in Orthopaedics paper was Brent Ward, D.D.S., M.D., assistant professor and program director of Oral and Maxillofacial Surgery at U-M. Co-author on the Oncology paper was Cherry Estilo, D.M.D., from Memorial Sloan-Kettering Cancer Center.

Reference:
Current Opinion in Orthopaedics, 2006, Vol. 17, issue 5, pp. 462-468
Oncology, 2006, Vol. 20, issue 9, pp. 1053-1062


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