Unraveling the Pathogenesis of Medication-Related Osteonecrosis of the Jaw

Abstract

Medication-related osteonecrosis of the jaw (MRONJ) is a serious complication associated with bone-modifying and antiangiogenic therapies. As the use of these agents expands in osteoporosis management and cancer care, the population at risk of MRONJ is increasing. Despite its substantial clinical burden, effective prevention and treatment remain limited by an incomplete understanding of its pathogenesis and of the biological features that may confer susceptibility to the jaws. This review critically synthesizes current evidence across five potentially interacting pathogenic domains: impaired bone remodeling, compromised vascular and lymphatic support, impaired oral soft-tissue healing, microbial dysbiosis and biofilm formation, and immune dysregulation. Systemic comorbidities and concomitant therapies are also considered as potential modifiers of disease susceptibility and clinical course. In addition, we examine jaw-specific susceptibility by integrating evidence from developmental biology, comparative anatomy, cellular pharmacology, and local osteoimmune biology. Together, these observations support a multifactorial model of MRONJ in which drug-specific effects interact with local tissue characteristics and host factors, while the temporal sequence and relative contribution of individual mechanisms remain incompletely defined. A more precise understanding of these interactions may improve risk stratification and inform future preventive and therapeutic strategies.