Osteoimmuno-microbial feedback loops in medication-related osteonecrosis of the jaw: from dysbiosis to persistent structural osteonecrosis

Background Medication-related osteonecrosis of the jaw is a severe adverse event associated with antiresorptive, antiangiogenic and other targeted therapies. Although suppressed bone remodeling and impaired vascularity are central to its pathogenesis, these mechanisms alone do not fully explain the strong clinical associations among local trauma, infection, chronic inflammation and persistent bone exposure.Objective To synthesize evidence on microbial dysbiosis, host immune dysregulation, and bone metabolic imbalance in MRONJ, and to propose an integrated osteoimmuno-microbial feedback framework.Design This narrative review examined English-language clinical and experimental studies, reviews, and guidelines identified through PubMed, Web of Science, and Scopus, supplemented by reference-list screening. The final search was performed on May 31, 2026.Results The reviewed evidence suggests that reduced bone turnover, impaired mucosal repair, and altered immune defense create a vulnerable local niche that permits microbial persistence and multispecies biofilm formation. Dysbiotic biofilms may sustain macrophage-associated inflammatory signaling, disturb bone homeostasis, and contribute to pyroptosis- and necroptosis-related tissue injury. These processes may form a self-perpetuating cycle of microbial colonization, inflammation, bone exposure, and impaired repair. However, microbial dysbiosis has not been established as a universal initiating event.Conclusions The proposed framework may help explain progression from potentially reversible local imbalance to persistent structural osteonecrosis. It highlights potential phase-adapted strategies targeting microbial ecology, inflammatory amplification, bone repair, and tissue vitality beyond conventional infection control and debridement.