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.