New approach to analyze genetic and clinical data in bisphosphonate-induced osteonecrosis of the jaw.

OBJECTIVES: Osteonecrosis of the jaw (ONJ) is a major complication associated with long-term use of bisphosphonates (BP). We aimed to investigate the effect of CYP2C8 rs1934951 SNP and its relationship to a number of clinical and biochemical factors in 46 Hungarian subjects with bisphosphonate-induced ONJ.

METHODS: Blood samples were collected from each subject and genomic DNA was extracted. SNP analysis of CYP2C8 gene was carried out by predesigned TaqMan primer/probe sets. The genetic data together with clinical and biochemical variables were evaluated by chi-square test, logistic regression, and principal component analysis (PCA).

RESULTS: The risk of mandibular localization of ONJ was 19.2-fold higher in subjects with AG genotype than in normal GG genotype. PCA revealed strong positive correlations between maxillar localization of ONJ and a group of variables including intravenous BP application and serum lipid markers. Mandibular localization of ONJ was correlated positively with serum calcium, 25-hydroxy-vitamin D and PTH levels, oral BP application, and the length of BP therapy. The degree of the disease and the number of recurrences were correlated with the application of hormone-deprivation therapy for breast cancer patients.

CONCLUSION: The statistical approach applying PCA to our data may contribute to the better understanding of factors playing role in the development of bisphosphonate-induced ONJ.