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Main Category: Genetics
Also Included In: Bones / Orthopedics
Article Date: 02 Feb 2012 - 10:00 PST

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According to a study published in the online version of the journal The Oncologist, a genetic variation that increases the risk of individuals who take bisphosphonates, developing serious necrotic jaw bone lesions, has been identified by researchers at the Columbia University College of Dental Medicine.

Bisphosphonates are a common class of osteoclastic inhibitors that work by attaching to calcium in the bone and inhibiting osteoclasts, bone cells that disintegrate the bone's mineral structure. The finding opens the door for a genetic screening test to determine which individuals can take these medications safely.

At present, approximately 3 million women in the U.S. take oral bisphosphonates for the treatment or prevention of osteoporosis. Furthermore, each year, thousands of cancer patients are given intravenous bisphosphonates to prevent excess calcium (hypercalcemia) from gathering in the blood and to control the spread of bone cancer.

Lead researcher of the study, 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, explained:

"These drugs have been widely used for years and are generally considered safe and effective. 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."

Often, osteonecrosis of the jaw (ONJ) results in painful and difficult-to-treat bone lesions, which can ultimately result in entire jaw loss. Among individuals taking bisphosphonates, ONJ usually occurs in those who go through invasive dental procedures or those with dental disease.

At present, figures on the incidence of ONJ in individuals taking oral bisphosphonates are unreliable. According to the American College of Rheumatology, estimates vary from 1 in 1,000 to 1 in 100,000 patients each year of exposure to the drug. Approximately 5% to 10% of cancer patients taking intravenous bisphosphonates are affected by ONJ.

According to prior investigations, genetic factors play a significant role in predisposing patients to ONJ. Dr. Zavras and his team conducted genome-wide examination of 30 individuals who have developed ONJ while taking bisphosponates and compared them with several disease free individuals who used bisphosphonates.

Results showed that individuals who has a small variation in the RBMS3 gene were 5.8 times more likely to develop ONJ than individuals without the variation. The researchers also identified small variations in two other genes that may contribute to ONJ risk - IGFBP7 and ABCC4.

Dr. Zavras, explained:

"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.

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."

Dr. Zavras, continued:

"At the moment, many women discontinue or avoid treatment for serious osteoporosis because they are afraid of losing their jaw bones. 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 researchers explain that additional studies are required in order to determine if the RBMS3 gene variation is seen in other racial groups, as the current investigation only examined Caucasians.

The study was supported by the National Institute of Dental and Craniofacial Research.

Written by Grace Rattue
Copyright: Medical News Today
Not to be reproduced without permission of Medical News Today

Visit our genetics section for the latest news on this subject. “Genomewide Pharmacogenetics of Bisphosphonate-Induced Osteonecrosis of the Jaw: The Role of RBMS3” Paola Nicoletti et al.
The Oncologist, First Published Online January 20, 2012; doi: 10.1634/theoncologist.2011-0202

Source: Columbia University Medical Center

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Osteoporosis Drug Complications Linked To Genetic Factors

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