Findings could lead to a screening test
Researchers at the Columbia University College of Dental Medicine have identified a genetic variation that raises the risk of developing serious necrotic jaw bone lesions in patients who take bisphosphonates, a common class of osteoclastic inhibitors. The discovery paves the way for a genetic screening test to determine who can safely take these drugs. The study appears in the online version of the journal The Oncologist.
Oral bisphosphonates are currently taken by some 3 million women in the United States for the prevention or treatment of osteoporosis. In addition, intravenous bisphosphonates are given to thousands of cancer patients each year to control the spread of bone cancer and prevent excess calcium (hypercalcemia) from accumulating in the blood. Bisphosphonates work by binding to calcium in the bone and inhibiting osteoclasts, bone cells that break down the bone's mineral structure.
"These drugs have been widely used for years and are generally considered safe and effective," said study leader Athanasios I. Zavras, DMD, MS, DMSc, associate professor of Dentistry and Epidemiology and Director of the Division of Oral Epidemiology & Biostatistics at the Columbia University College of Dental Medicine. "But the popular literature and blogs are filled with stories of patients on prolonged bisphosphonate therapy who were trying to control osteoporosis or hypercalcemia only to develop osteonecrosis of the jaw."
Osteonecrosis of the jaw, or ONJ, often leads to painful and hard-to-treat bone lesions, which can eventually lead to loss of the entire jaw. Among people taking bisphosphonates, ONJ tends to occur in those with dental disease or those who undergo invasive dental procedures.
There are no reliable figures on the incidence of ONJ in patients taking oral bisphosphonates. Estimates range from 1 in 1,000 to 1 in 100,000 patients for each year of exposure to the medication, according to the American College of Rheumatology. ONJ is more common among cancer patients taking the intravenous form of the drug, affecting about 5 to 10 percent of these individuals, noted Dr. Zavras.
Studies have suggested that genetic factors play a major role in predisposing patients to ONJ. Delving deeper into this question, Dr. Zavras and his colleagues performed genome-wide analyses of 30 patients who were taking bisphosphonates and had developed ONJ and compared them with several bisphosphonate users who were disease free.