The left mandibles of 20 adult Wistar rats were irradiated (single fraction 1500 cGy, total dose 60 Gy) by means of a hypofractionated stereotactic radiotherapy (hfSRT) over a period of 6 weeks. Follow-up was 6 weeks (group 1, n = 10) and 12 weeks (group 2, n = 10). The contralateral mandibles as well as 5 non-irradiated animals served as controls. Primary endpoints were fibrosis, loss of cell count, decreased immunohistochemical labelling for bone morphogenetic protein-2 (BMP-2) and osteocalcin as well as increased expression of transforming growth factor (TGF-β).
Cell loss, progressive fibrosis, and focal necrosis were detected in all irradiated sites. Quantitative measurement revealed 32.0 ± 8.7 % and 37.3 ± 9.5 % empty osteocyte lacunae for groups 1 and 2 resp., compared to 16.3 ± 4.7 % and 18.9 ± 4.9 % on the contralateral side and 7.9 ± 1.7 % for unirradiated controls (Mann–Whitney U test; p < .01). BMP-2 and osteocalcin labelling showed a marked decrease in irradiated and contralateral sides while TGF-β was expressed strongly in irradiated sites only (for all p < .05).
External hypofractionated irradiation with a total dose of 60 Gy is feasible in rats and yields all histologic changes attributed to osteoradionecrosis (ORN) after a follow-up of 6 weeks. The irradiation protocol is suitable for an assessment of regenerative options in severe radiogenic bone damage. As a split mouth design entails major inaccuracies healthy animals have to be used as controls.