Medication-Related Osteonecrosis of the Jaw: A Comprehensive Review of Pathophysiology, Diagnosis, and Management Strategies

<span style="font-weight: 400;">Medication-Related Osteonecrosis of the Jaw (MRONJ) represents a severe, potentially debilitating adverse drug reaction characterized by the progressive destruction of bone in the maxillofacial region. Originally identified as bisphosphonate-related osteonecrosis of the jaw (BRONJ) in the early 2000s, the nomenclature and understanding of this pathology have evolved significantly to encompass a broader range of pharmacologic agents, including RANK ligand inhibitors (denosumab) and antiangiogenic therapies used in oncology. This comprehensive review synthesizes the current scientific literature, integrating data from the 2022 American Association of Oral and Maxillofacial Surgeons (AAOMS) update, the 2024 MASCC/ISOO clinical practice guidelines, and recent systematic reviews to provide an exhaustive analysis of the condition. We explore the multifactorial pathophysiology of MRONJ, proposing a unifying model that integrates bone remodeling inhibition, angiogenesis suppression, and inflammation/infection. Critical risk factors&mdash;ranging from medication potency and duration to local dentoalveolar trauma and systemic comorbidities&mdash;are analyzed in depth, with specific attention to genetic polymorphisms such as </span><em><span style="font-weight: 400;">CYP2C8</span></em><span style="font-weight: 400;">. The review critically evaluates the diagnostic utility of imaging modalities and biomarkers, addressing the ongoing controversy surrounding serum C-terminal telopeptide (CTX) levels and the emergence of salivary biomarkers. Furthermore, we provide a nuanced examination of prevention strategies, specifically the contentious debate concerning "drug holidays," and compare the efficacy of conservative management versus early surgical intervention. Emerging adjunctive therapies, including fluorescence-guided surgery, leukocyte-platelet rich fibrin (L-PRF), and the pentoxifylline-tocopherol (PENTO) protocol, are assessed for their potential to improve clinical outcomes and Quality of Life (QoL). This article aims to bridge the gap between theoretical knowledge and clinical application, providing an exhaustive resource for dental and medical professionals managing patients at risk for or affected by MRONJ.</span>