Comprehensive profiling of plasma and exosomal microRNAs in medication-related osteonecrosis of the jaw

The role of circulating microRNAs (miRNAs) in the pathophysiology of medication-related osteonecrosis of the jaw (MRONJ) remains to be elucidated. This study investigated the expression of plasma miRNAs in patients with MRONJ compared to healthy individuals. 16 patients with MRONJ and 15 healthy controls participated in this case-control study, which was conducted in three consecutive phases. As a pilot study, miRNA profiling was performed using quantitative real-time reverse transcriptase PCR (qPCR) array plates targeting 754 miRNAs in a subset of plasma samples. In the subsequent phases, individual qPCR assays validated the array results using plasma samples from the full cohort (second phase) and plasma-derived exosomes (third phase). The qPCR arrays revealed differential miRNA profiles between the MRONJ and control groups. We selected miR-153-3p, miR-1180-3p, miR-483-5p, miR-511-5p, miR-628-3p, miR-486-5p, miR-92b-5p, miR-16-3p, miR-23a-3p, and miR-23a-5p for additional assays. The expression of miR-483-5p, miR-92-5p, and miR-486-5p was elevated in patients with MRONJ compared to controls, whereas miR-628-3p was downregulated (q < 0.01). All four miRNAs consistently exhibited differences in expression in plasma-derived exosomes between MRONJ patients and controls. We identified four miRNAs that could serve as potential biomarkers for MRONJ: miR-483-5p, miR-92-5p, miR-628-3p, and miR-486-5p. These biomarkers may reflect key pathways in MRONJ pathogenesis and could be used to guide patient risk stratification and future therapeutic interventions for MRONJ.