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Study pinpoints genetic variation that raises a risk linked to bisphosphonates
Date:1/27/2012

ing 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.

The researchers found that patients who had a small variation in the RBMS3 gene were 5.8 times more likely to develop ONJ than those without the variation. The study also identified small variations in two other genes, IGFBP7 and ABCC4, that may contribute to ONJ risk.

"Our ultimate goal is to develop a pharmacogenetic test that personalizes risk assessment for ONJ, a test that you could give to people before they start to use bisphosphonates," said Dr. Zavras. "Those who are positive for this genetic variation would select some other treatment, while those who are negative could take these medications with little fear of developing ONJ."

"At the moment, many women discontinue or avoid treatment for serious osteoporosis because they are afraid of losing their jaw bones," added Dr. Zavras. "There even are reports of dentists who have refused to perform certain invasive procedures in patients taking bisphosphonates. So there is a great need for a pharmacogenetic screening test to determine which patients are really at risk for ONJ."

The current study looked only at Caucasians. Further studies are needed to determine whether the RBMS3 gene variation is seen in other racial groups, according to the researchers.

The paper is entitled, "Genome-wide pharmacogenetics of bisphosphonate-induced osteonecrosis of the jaw: the role of RBMS3." The lead authors are Paola Nicoletti of CUMC and Vass
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Contact: Karin Eskenazi
ket2116@columbia.edu
212-342-0508
Columbia University Medical Center
Source:Eurekalert

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