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

Oral Dis. 2012 Sep;18(6):580-5. doi: 10.1111/j.1601-0825.2012.01912.x. Epub 2012 Feb 20.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenine
  • Administration, Intravenous
  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Aryl Hydrocarbon Hydroxylases / genetics*
  • Bisphosphonate-Associated Osteonecrosis of the Jaw / enzymology
  • Bisphosphonate-Associated Osteonecrosis of the Jaw / genetics*
  • Bone Density Conservation Agents / administration & dosage
  • Bone Density Conservation Agents / adverse effects
  • Breast Neoplasms / drug therapy
  • Calcium / blood
  • Cytochrome P-450 CYP2C8
  • Diphosphonates / administration & dosage
  • Diphosphonates / adverse effects
  • Estrogen Receptor Modulators / therapeutic use
  • Female
  • Genotype
  • Guanine
  • Humans
  • Hungary
  • Lipids / blood
  • Male
  • Mandibular Diseases / enzymology
  • Mandibular Diseases / genetics
  • Maxillary Diseases / genetics
  • Middle Aged
  • Parathyroid Hormone / blood
  • Polymorphism, Single Nucleotide / genetics*
  • Principal Component Analysis
  • Recurrence
  • Time Factors
  • Vitamin D / analogs & derivatives
  • Vitamin D / blood

Substances

  • Antineoplastic Agents, Hormonal
  • Bone Density Conservation Agents
  • Diphosphonates
  • Estrogen Receptor Modulators
  • Lipids
  • Parathyroid Hormone
  • Vitamin D
  • Guanine
  • 25-hydroxyvitamin D
  • Aryl Hydrocarbon Hydroxylases
  • CYP2C8 protein, human
  • Cytochrome P-450 CYP2C8
  • Adenine
  • Calcium