Genetic polymorphisms and other risk factors associated with bisphosphonate induced osteonecrosis of the jaw

• DOI: 10.1016/j.ijom.2011.02.002
• Publication Date: 2011-03-11T11:11:06Z
• Authors: J. Katz; Y. Gong; D. Salmasinia; W. Hou; B. Burkley; P. Ferreira; O. Casanova; T.Y. Langaee; J.S. Moreb
• Keywords: Adult; Male; Genetic polymorphisms; Collagen Type I; Cohort Studies; Cytochrome P-450 CYP2C8; 03 medical and health sciences; 0302 clinical medicine; Gene Frequency; Multiple myeloma; Humans; Aged; Bone Density Conservation Agents; Diphosphonates; Imidazoles; Osteonecrosis; Bisphosphonates; Middle Aged; 3. Good health; Collagen Type I, alpha 1 Chain; Osteonecrosis of the jaw (ONJ); Injections, Intravenous; Matrix Metalloproteinase 2; Female; Aryl Hydrocarbon Hydroxylases; Pharmacogenomics; Multiple Myeloma; Jaw Diseases

Bisphosphonate induced osteonecrosis of the jaw (BONJ) is a complication in patients taking bisphosphonate (BP) that affects their quality of life and compliance. In this cohort study, patients with multiple myeloma (MM) on intravenous BP therapy were enrolled over 1 year. Demographic and clinical data and genotyping of 10 single nucleotide polymorphisms (SNPs) from seven candidate genes associated with drug or bone metabolism were determined. Of the 78 patients enrolled, 12 had BONJ. The median time to developing BONJ was 28 months. Univariate and multivariate analysis revealed a significant association between BONJ and smoking (p=0.048) and type of BP treatment (p=0.03). A trend for higher odds for BONJ was found for SNPs in five genes: COL1A1 (rs1800012), RANK (rs12458117), MMP2 (rs243865), OPG (rs2073618) and OPN (rs11730582). Considering all five SNPs together, patients with genotype scores ≥ 5 had a BONJ event rate of 57%; those with scores < 5 had a rate of 10%. The adjusted odds ratio was 11.2 (95% confidence interval of 1.8-69.9; p value 0.0097). Smoking, type of BP and combined genotype score of COL1A1, RANK, MMP2, OPG and OPN were significantly associated with BONJ in MM patients undergoing BP therapy.