Understanding the genetic basis of medication-related osteonecrosis of the jaw: A systematic review

Medication-related osteonecrosis of the jaw (MRONJ) is an adverse event often associated with the use of antiresorptive drugs. This systematic review aims to identify genes and their polymorphisms associated with the risk of developing MRONJ in patients with oncological or skeletal-related diseases treated with antiresorptive drugs. A systematic literature review was conducted in accordance with PRISMA guidelines. Three electronic databases (PubMed, Scopus, and Web of Science) were searched for studies published up to December 2024. The search strategy included terms such as "MRONJ", "bone density conservation agents", and "genetics". Eligible studies were case control in design, investigating genetic polymorphisms in MRONJ patients compared to controls, which included either healthy individuals or patients receiving antiresorptive drugs without developing MRONJ. Study quality was assessed using the Q-genie tool for genetic association studies. Out of 833 retrieved articles, 27 met the inclusion criteria for qualitative analysis. Most studies were of 'fair' quality, with common limitations including small sample sizes, suboptimal control group selection, and ethnic heterogeneity within study cohorts. A total of 136 genetic variants across 58 genes were identified, many of which are involved in biological processes such as immune response and inflammation, cellular function, bone homeostasis, and angiogenesis. However, due to inconsistent findings and a lack of replication across studies, no definitive conclusions regarding specific genetic risk factors could be drawn. The findings of this review suggest that MRONJ susceptibility is likely influenced by multiple variants affecting interconnected biological pathways, particularly involved in immunity, metabolism, angiogenesis, and bone remodelling.