Genetic Background of Medication-Related Osteonecrosis of the Jaw: Current Evidence and Future Perspectives

Int J Mol Sci. 2024 Sep 29;25(19):10488. doi: 10.3390/ijms251910488.

Abstract

Medication-related osteonecrosis of the jaw (MRONJ) is a rare side effect of antiresorptive drugs that significantly hinders the quality of life of affected patients. The disease develops in the presence of a combination of factors. Important pathogenetic factors include inflammation, inhibition of bone remodeling, or genetic predisposition. Since the first description of this rare side effect in 2003, a growing body of data has suggested a possible role for genetic factors in the disease. Several genes have been suggested to play an important role in the pathogenesis of MRONJ such as SIRT1, VEGFA, and CYP2C8. With the development of molecular biology, newer methods such as miRNA and gene expression studies have been introduced in MRONJ, in addition to methods that can examine the base sequence of the DNA. Describing the complex genetic background of MRONJ can help further understand its pathophysiology as well as identify new therapeutic targets to better manage this adverse drug reaction.

Keywords: gene expression; genetic background; medication-related osteonecrosis of the jaw; microRNA; single nucleotide polymorphism.

Publication types

  • Review

MeSH terms

  • Bisphosphonate-Associated Osteonecrosis of the Jaw* / etiology
  • Bisphosphonate-Associated Osteonecrosis of the Jaw* / genetics
  • Bone Density Conservation Agents / adverse effects
  • Cytochrome P-450 CYP2C8 / genetics
  • Cytochrome P-450 CYP2C8 / metabolism
  • Genetic Predisposition to Disease*
  • Humans
  • Sirtuin 1 / genetics
  • Sirtuin 1 / metabolism
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Cytochrome P-450 CYP2C8
  • Vascular Endothelial Growth Factor A
  • Sirtuin 1
  • CYP2C8 protein, human
  • SIRT1 protein, human
  • VEGFA protein, human
  • Bone Density Conservation Agents