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, drugs that are commonly prescribed for osteoporosis.
These osteoclastic inhibitors are being taken by 3 million women in the United States, and more worldwide. They are mainly menopausal women who are prescribed them for the prevention or treatment of osteoporosis. They are also prescribed intravenously 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 but those who work with bioidentical hormones have seen little value in them. The side effects are not insignificant and the late Dr John Lee saw great success in building bone density simply through supplemental natural progesterone and maintained that their bone density records bore out its value as density increased year on year.
The New Risk
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 commented that although these drugs have been considered safe for years 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. 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. If that is meaningless to you – the point is that it means a test can be developed that personalizes risk assessment for ONJ that could be given to people before they start to use bisphosphonates,”
Dr. Zavras comments: “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.
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.”
Am I alone in wishing researchers could extend their study to the work done with osteoporosis patients and bioidentical natural progesterone? The evidence is anecdotal, as it has never been officially studied, but Dr John Lee had years of scans showing increased bone density in his patients and no side effects – surely worth looking at?
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