Genetic Test May Help Patients with Multiple Myeloma and Other Cancers Avoid Jaw Osteonecrosis

A genetic test in development by Micromedic may help identify patients who are likely to develop bisphosphonate-associated osteonecrosis of the jaw.

According to its partner organization, BioLight, Micromedic has identified a set of gene markers that can help predict which patients are likely to experience a serious adverse event that rarely occurs with bisphosphonate therapy.^1,2

The adverse event, known as bone bisphosphonate-associated osteonecrosis of the jaw (BRONJ), may manifest as exposed, necrotic bone that does not heal within an 8-week period and is not related to radiation therapy (see example images here).³

The prevalence of BRONJ among patients with multiple myeloma, breast cancer, and prostate cancer ranges from 1.2% to 18.6%, substantially higher than the approximately 0.1% incidence reported among patients receiving bisphosphonates for osteoporosis.¹

Micromedic developed the test using genetic markers first investigated in a 2011 study by Katz et al. In the 2011 study, investigators found a relationship between single-nucleotide polymorphisms (SNPs) of 5 genes (COL1A1, RANK, MMP2, OPG, and OPN) and an increased risk of BRONJ among patients with multiple myeloma. Among patents with SNPs in all 5 genes, the risk of developing BRONJ was 57%, versus 10% among patients with SNPs of 4 or fewer genes.⁴

Researchers at Tel Hashomer Medical Center, Israel validated the test in a trial conducted among patients with cancer. Results of the trial have not yet been published, although researchers at Tel Hashomer have previously published studies of BRONJ among patients receiving dental implants.^1,5

The proprietary genetic marker may help physicians predict whether or not bisphosphonate therapy is an acceptable choice for a given patient. It is not known whether the test will be limited to use in patients with cancers, such as multiple myeloma, or if the test will also be used in patients taking bisphosphonates for osteoporosis.¹

References:

• BioLight announces Micromedic identifies new genetic markers to predict risk of developing BRONJ, a devastating side effect of certain cancer drugs [press release]. http://www.bio-light.co.il/wp-content/uploads/2014/05/052714-BRONJ-PR.pdf. Accessed June 2014.
• BRONJ - Bisphosphonate Related Osteonecrosis of the Jaw [press release]. http://www.m-medic.com/215646/BRONJ-Bisphosphonate-Related-Osteonecrosis-of-the-Jaw. Accessed June 2014.
• Ruggiero SL. Guidelines for the diagnosis of bisphosphonate-related osteonecrosis of the jaw (BRONJ). Clin Cases Miner Bone Metab. 2007;4(1):37-42.
• Katz J, Gong Y, Salmasinia D, et al. Genetic polymorphisms and other risk factors associated with bisphosphonate induced osteonecrosis of the jaw. Int J Oral Maxillofac Surg. 2011;40(6):605-611.
• Lazarovici TS, Yahalom R, Taicher S, Schwartz-Arad D, Peleg O, Yarom N. Bisphosphonate-related osteonecrosis of the jaw associated with dental implants. J Oral Maxillofac Surg. 2010;68(4):790-796.