Oral microbiome analysis in medication-related osteonecrosis of the jaw

Medication-related osteonecrosis of the jaw (MRONJ) is an intractable, progressive, and chronic inf lammatory disease.Although oral bacterial infection has been implicated in the development and progression of MRONJ, the causative bacteria remain unclear.As antibacterial agents are frequently used in the treatment of MRONJ, it is necessary to identify the bacterial species and the microbiome that cause MRONJ.We sought to clarify these issues in this investigation of 20 patients diagnosed with MRONJ, 21 patients being treated with a bone-modifying agent (BMA) , and 25 healthy individuals as controls.Saliva samples were collected from all participants, and the microbiome was evaluated by a 16SrRNA analysis and next-generation sequencing.A comparative statistical analysis was conducted for each group.In a UniFrac analysis, the diversity of the oral microbiome was significantly lower in the MRONJ and BMA groups compared to the control group.A linear discriminant analysis effect size (LEfSe) analysis identified bacterial species with significantly higher relative abundance in each group.The relative abundance of anaerobic bacteria increased in the order of healthy, BMA, and MRONJ, whereas the detected bacterial species showed a decreasing trend.These results suggest that BMA treatment (i) can be a factor in the relative increase in the levels of anaerobic bacteria and (ii) is a trigger for MRONJ in the oral microenvironment.The dysbiosis of the oral microbiome may begin at the time of BMA introduction.Our results suggest that appropriate oral management during a patient' s BMA regimen is important to prevent the development of MRONJ, and that these findings may be useful for the selection of antibacterial agents.