Standardized Analysis of Mandibular Osteoradionecrosis in a Rat Model

Abstract

Objective. To develop a rat model of mandibular osteoradionecrosis (ORN) that uses novel micro-computed tomography bone volume analysis and detailed histology to provide a more effective, quantifiable, and standardized way to study ORN in vivo. Study Design. Animal model. Setting. Academic medical center. Subjects and Methods. Modifications to our previously published rat model of mandibular ORN were done to develop an ideal protocol consisting of 10 rats (6 experimental and 4 controls) with their left middle mandibular molar removed 7 days after either 20 Gy high dose rate brachytherapy or sham irradiation. Rats were sacrificed 21 days after extraction for landmark defined bone volume and histologic analysis. Results. A standardized method of quantification was achieved in all samples. The radiated group (XRT) had a mean bone volume/total volume (BV/TV) of 13.8% compared to 65.9% for controls ( P < .001). There were increases in osteoclasts and fibrosis, decreases in osteoblasts, and less bone in radiated samples with a mean (SD) of 5.91 (3.77) osteoclasts/high-powered field (HPF) and 4.00 (1.83) osteoblasts/HPF in XRT samples compared to 1.08 (1.08) osteoclasts/HPF and 22.49 (6.00) osteoblasts/HPF for controls ( P < .001). Conclusion. Our updated model continues to be clinically analogous to human mandibular ORN and improves the radiologic and histologic analysis of bony defects, providing a method for quantification of bone loss. Further cell-specific staining, including immunohistochemistry, can be used with this model to study potential cellular mechanisms of mandibular ORN and test any future therapeutic options.