Rat Calvaria Model Mimicking the Intraoral Lesion of Medication-Related Osteonecrosis in the Jaw: A Preliminary Test

Abstract

Numerous preclinical intraoral models have been proposed to study medication-related osteonecrosis of the jaws (MRONJ). However, an extraoral animal model is necessary to investigate the effects of interventions such as grafts or direct therapeutics. This study aimed to establish a MRONJ rat model on the calvaria. Seven rats were allocated to either the control or MRONJ group. The MRONJ group received injections of zoledronic acid and dexamethasone to induce osteonecrosis over 4 weeks. Two weeks after these injections, the maxillary first molar was extracted, and two calvaria defects were created using a 4 mm trephine burr. One defect was left untreated, while the other was filled with harvested calvaria bone. A histological examination of all calvaria in the MRONJ group revealed avascular necrosis and the destruction of cortical bone. An independent t-test and Pearson’s correlation coefficient were used for statistical analysis and the evaluation of alveolar and calvaria defects. The total alveolar and calvaria defect volume in the control group was significantly smaller than that in the MRONJ group. A statistically significant correlation was observed between alveolar and calvaria defects (Pearson correlation = 0.6, p = 0.023). The autogenous grafts showed poor results in the MRONJ group since they failed to revascularize and exhibited necrosis. The calvaria in this study successfully mimicked MRONJ lesions with avascular necrosis. This preclinical model could be used to develop treatments that are applicable to MRONJ.