Refined rat Model for Mandibular Osteoradionecrosis Study and Treatment

Objectives: Radiation therapy is widely used for head and neck cancer treatment. Despite its advantages, it can be responsible for many orofacial complications. OsteoRadioNecrosis (ORN), characterized by necrotic and exposed bone tissue without healing over a 3-month period, is considered the most devastating complication. Most management strategies of ORN involve surgical intervention, and recurrence is common, hence the need for new treatments. However, the lack of knowledge about ORN pathophysiology limits their development. In this study, we developed a rat mandibular ORN model to study bone and vascular changes, for better understanding of ORN pathogenesis, and to investigate the efficacy of a new potential treatment.
Methods: To define the ORN model, we tested the impact of radiation doses of 20 to 40Gy (medical linear accelerator delivering 4-10MV X-rays), combined with dental extraction, on the mandibles of Lewis rats during a 4-month period. Micro-computed tomography (µCT, Quantum GX2, Perkin Elmer) imaging system was used to obtain in vivo images for longitudinal tracking of bone volume and ex vivo images, after animal perfusion with barium sulphate contrast agent, to track the volume of the vascular network.
Results: We defined 25Gy as the minimum dose of irradiation combined with dental extraction required to develop non-regenerative bone necrosis. Quantitative µCT findings were correlated with clinical and histological analyses. The decrease in bone volume in irradiated rats from the first weeks was associated with an early decrease in vascular volume compared with controls, suggesting a role of ischemia on the biological manifestations of ORN. We also had preliminary data on the implementation of a local treatment with minimally-invasive surgery, based on an original biomaterial cell-assisted therapy procedure.
Conclusions: This refined model allowed us to study the development of ORN, which helps to better understand this pathology and to test the effectiveness of a new biomaterial cell-assisted therapy.