Validation of histologic changes induced by external irradiation in mandibular bone. An experimental animal model

• Published in: Journal of cranio-maxillo-facial surgery 2010-01, Vol.38 (1), p.47-53
• Main Authors: Fenner, Matthias, MD, DDS, Park, Jung, DDS, PhD, Schulz, Norbert, Amann, Kerstin, MD, PhD, Grabenbauer, Gerhard G., MD, PhD, Fahrig, Antje, MD, PhD, Karg, Juergen, MS, Wiltfang, Joerg, MD, DDS, PhD, Neukam, Friedrich W., MD, DDS, PhD, Nkenke, Emeka, MD, DDS, PhD
• Format: Article
• Language: English
• Subjects: animal model; Animals; Biological and medical sciences; Bone Morphogenetic Protein 2 - metabolism; Case-Control Studies; Dentistry; Disease Models, Animal; Diseases of the osteoarticular system; Dose Fractionation; Immunohistochemistry; irradiation; mandible; Mandible - metabolism; Mandible - pathology; Mandible - radiation effects; Medical sciences; osteoradionecrosis; Osteoradionecrosis - pathology; Otorhinolaryngology. Stomatology; Rats; Reference Standards; Statistics, Nonparametric; Surgery; Vascular bone diseases
• ISSN: 1010-5182; 1878-4119
• DOI: 10.1016/j.jcms.2009.07.011

Summary The present experimental study sought to determine the effect of high-dose irradiation on the rat mandible in order to establish an experimental model of radiogenic bone damage. 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.