Effects of pentoxifylline and tocopherol on an osteoradionecrosis animal model

Purpose: Osteoradionecrosis (ORN) is known to be a refractory disease in the oral and maxillofacial field. The purpose of this study was to examine the effects of pentoxifylline (PTX) and tocopherol (TP) on an ORN animal model focused on bone healing. Materials and methods: A total of 48 Sprague-Dawley rats were used: 40 received a single irradiation dose of 35 Gy on the left mandible, and eight were used as the nonirradiated control group. The rats received PTX (T1, C1), TP (T2, C2), a combination of PTX and TP (T3, C3), or normal saline (T4, C4). Three weeks after irradiation, the mandibular posterior teeth were extracted. The rats were sacrificed 4 weeks after extraction. Results: In the T3 group, bone volume/tissue volume was 19.62 +/- 16.03 (%), bone mineral density was as 0.31 +/- 0.16 (g/cm(3)) in the micro-CT analysis, which were higher than that of other groups (p = 0.025, p = 0.012, respectively). In the histological analysis, bone regeneration was the most prominent in the T3 group. The ratio of empty lacunae was the highest in the T4 group, 68.77 +/- 15.47 (%, p = 0.004). Immunohistochemistry showed that the expression of TNF-alpha was relatively lower in the T3 than in the T4 or T2 groups. The RT-qPCR showed the expression level of PECAM, VEGF-A, and osteocalcin was more than twofold as high as in the T3 group compared to the other groups. Conclusion: The combination of PTX and TP appears to promote angiogenesis and osteogenesis in a rat ORN model. Therefore, PTX and TP might be useful in the treatment and prevention of ORN. (C) 2020 Published by Elsevier Ltd on behalf of European Association for Cranio-Maxillo-Facial Surgery.