Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a serious adverse effect that occurs in between 0.01% and 10% of patients taking bisphosphonates (BPs), which are usually used to treat bone metastasis. Incidence varies according to the dose and route of administration of the BP, with the highest rates seen in users of zoledronic acid. In this study, a genomewide association analysis was performed by taking DNA samples from a small number of patients with a firm diagnosis of BRONJ.1
Initially, the study focused on 30 cases in Caucasians, with a comparison made with 17 treatment-tolerant controls. The control set was later expanded to 60 genetically matched controls per BRONJ case. Analysis revealed a single nucleotide polymorphism (SNP) in the RBMS3 gene that increased the risk of BRONJ 5.8-fold (odds ratio: 5.8; CI 3.1–11.1). SNPs in two other genes were also implicated. RBMS3 variations appear to have an impact on bone density, so this gene may be important in bone turnover. The precise role of the gene in BRONJ development will need to be elucidated through further study.
Editor's comment: Genetic predisposition to bisphosphonate-related osteonecrosis of the jaw has been suggested previously; this genome-wide association study, even though it was done with a modest sample number, discovered a new locus that has a very significant impact on the risk of this adverse event.
References
- Nicoletti P, Cartsos VM, Palaska PK, Shen Y, Floratos A, Zavras AI. Genomewide pharmacogenetics of bisphosphonate-induced osteonecrosis of the jaw: the role of RBMS3. Oncologist 2012;17:279–287. [DOI] [PMC free article] [PubMed] [Google Scholar]