Bisphosphonate May Cause Osteonecrosis of the Jaw

A study from Columbia University College of Dental Medicine warns that patients who were on long term bisphosphonates medication for treating osteoporosis were at risk of developing necrosis of bones in the jaw if they carried a variation of a particular gene. It was also a caution to doctors to have their osteoporosis patients checked for this gene variation before prescribing long-term or high doses of bisphosphonates for them. (1)

So what is osteonecrosis?

Osteonecrosis is a disease caused by decreased blood flow to the bones and the joints. When there is limited blood flow your bone begins to break down and die.

Bisphosphonates are a common class of drug that bind to the bone of the patient taking them and inhibits the production of cells called osteoclasts which are responsible for the breakdown and resorption of bone. They are prescribed to treat bone conditions such as osteoporosis, Paget’s disease, multiple myeloma, bone metastasis as well as those suffering from hypercalcemia (excessive calcium deposition in bones) etc. They are sold by different drug manufacturers under brand names Fosomax, Boniva, Reclast, Actonel, Evista, Zometa, Didronel, Aclasta, Skelid.

The study has been published in the online version of the journal The Oncologist. Though bisphosphonates are generally considered safe in long-term usage through the oral route, it is now come to notice that administration of high dosages or long-term administration through the intravenous route in people with a particular genetic variation is dangerous as it pegs their chances of developing osteonecrosis of the jaw.

Risks of Osteonecrosis of the Jaw

Osteonecrosis (ONJ) could eventually lead to the loss of the entire jaw especially in those who have dental diseases or have had surgical procedures done to their teeth.

According to the author 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, “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.” (2)

Though the risks of development of osteonecrosis of the jaw are slim in persons on bisphosphonates without the gene variation, the risks are almost 6% pegged in groups with the small variation in genes RBMS3, IGFBP7 and ABCC4, that possibly add to ONJ risk. The study has covered only the Caucasian race currently and needs to expand it’s scope to include other races as well.

There are widespread reports that women are not going for bisphosphonates their doctors are prescribing and some who were on bisphosphonates programs are considering discontinuing them for the fear of losing their jaw bones. Some women are avoiding them after getting invasive dental procedures done.

As per Zavras, “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.” (3)

SOURCES:

1. Genetic Variation That Raises Risk of Serious Complication Linked to Osteoporosis Drugs Identified; Science Daily News; February 2012; http://www.sciencedaily.com/releases/2012/01/120127135805.htm
2. Study Pinpoints Genetic Variation that Raises Risk of Serious Complication Linked to Osteoporosis Drugs; Columbia University Medical Center – Newsroom; February 2012; http://www.cumc.columbia.edu/news-room/2012/01/study-pinpoints-genetic-variation-that-raises-risk-of-serious-complication-linked-to-osteoporosis-drugs/
3. Study Pinpoints Genetic Variation that Raises Risk of Serious Complication Linked to Osteoporosis Drugs; Newswise; February 2012; http://www.newswise.com/articles/study-pinpoints-genetic-variation-that-raises-risk-of-serious-complication-linked-to-osteoporosis-drugs

Technical report of the study may be accessed at:

1. Genomewide Pharmacogenetics of Bisphosphonate-Induced Osteonecrosis of the Jaw: The Role of RBMS3; The Oncologist (Journal); February 2012; http://theoncologist.alphamedpress.org/content/early/2012/01/19/theoncologist.2011-0202.abstract