Establishment and observation of a combined rat model of osteoradionecrosis

Abstract

Objective To establish an osteoradionecrosis of jaws (ORNJ) rat model which could be used to simulate ORNJ at different clinical stages, according to the new clinical diagnostic standards. Methods Thirty six male SD rats were divided into 6 groups randomly. For group a1, b1 and c1, the left mandible of each rat weas irradiated at doses of 7.0 Gy for 5 fractions, which were equivalent to total doses of 70 Gy. Group a0, b0 and c0 were sham irradiated, serving as control groups. Six weeks after irradiation, rats in group a0 and a1 were sacrificed, meanwhile, left mandibular molars of rats in group b1, b0, c1 and c0 were extracted. 12 weeks and 18 weeks after irradiation, the rats in group b0, b1 and in group c0, c1 were sacrificed respectively. All the rats′ mandibles were taken. All samples were examined by clinical manifestation, micro-CT and histology methods. The data was analyzed with SPSS 18.0 software package. Results Alopecia and retardation of central incisor growth, at the irradiated site were seen in group a1. Exposed necrotic bone was found in all irradiated mandibles of group b1 and c1. Reduced condyle volume, dental sepsis and obviously loose, necrotic bone of the irradiated mandible were found in group c1. Fibrosis and inflammtions were found in medulla in all irradiated groups. In group b1, small pieces of sequestrum were seen around the tooth root. And large sequestrum, pathological fracture, overwhelming fibrosis and disrupted incisor root were seen in group c1. Significant increment of empty lacunae and decrement of osteocytes were observed in all irradiated groups, accompanying with the decreased BV/TV: a1 (0.401 ± 0.053) , a0 (0.615 ± 0.037) , b1 (0.309 ± 0.041) , b0 (0.717 ± 0.040) , c1 (0.200 ± 0.026) , c0 (0.724 ± 0.041) , Pa1、b1= 0.012, Pb1、c1= 0.034, Pc1、a1= 0.004, a1>b1>c1, results were accepted as statistically significant at a value of P<0.05. Conclusions A combined rat model that can stimulate three different stages of ORNJ was successfully established. This model could be served as a new platform for future studies on pathogenesis and treatment of ORNJ. Key words: Osteoradionecrosis; Jaw; Models, Animal; Fibrosis; Bone histomorphometric analysis