Novel standardized method for inducing medication-related osteonecrosis of the jaw in rats and precise quantitative assessment of pathological outcomes.

Abstract

Medication-related osteonecrosis of the jaw (MRONJ) is a serious complication of antiresorptive therapies, characterized by delayed healing, bone necrosis, and infection following dental procedures. Progress in the understanding of its pathophysiology has been hindered by the lack of standardized animal models. Existing models involving first molar or multiple molar extractions disrupt anatomic landmarks and face technical challenges, such as retained root fragments and inconsistent surgical procedures, which reduce reproducibility. To address these limitations, we developed a novel rat MRONJ model using maxillary second molar extraction combined with standardized palatal gingiva resection. By preserving the adjacent first and third molars, anatomic landmarks were retained, enabling precise and reproducible evaluations. The modified extraction technique incorporating wedge insertion improved the success rate and minimized root fractures. Notably, our findings revealed that suppressed bone metabolism in the MRONJ model inhibited natural tooth movement observed in the control group, highlighting a unique pathologic hallmark of MRONJ. The model effectively reproduced MRONJ-specific features, including persistent bone exposure, impaired bone healing, necrotic bone formation, and inflammation. Three-dimensional micro-computed tomography and histologic analyses provided robust and quantitative assessments of bone pathology. By integrating anatomic standardization and precise quantitative assessments, this model addresses the key limitations of previous approaches. It also provides a reliable platform for investigating the pathogenesis of MRONJ and for assessing preventive and therapeutic strategies. This approach contributes to translational research and holds promise for improving clinical outcomes.