Combined Treatment of Amifostine and Deferoxamine Restores Bone Mineral Beyond Normal Fracture Healing

Abstract

Radiotherapy is a valuable tool in the management of Head and Neck Cancer (HNC) patients. Despite its usefulness in increasing survival for patients with HNC, the use of radiotherapy has been known to have detrimental effects to bone.1 Osteoradionecrosis and pathologic fractures are known to occur in 5%-10% of patients after high dose radiotherapy to the jaw. Currently there are no therapeutic options known to circumvent the development of ORN and pathologic fractures in this setting. Radiation is known to cause vascular diminution and reduction in the number and function of osteocytes, which can ultimately lead to the devastating sequelae of ORN and pathologic fractures.4.s A combined therapy of Deferoxamine (DFO)-a vascular augmentation therapy and Amifostine (AMF)-a cellular radioprotectant, was utilized on a radiation induced non-union rat model to investigate these aberrant effects. Micro Computed Tomography {JlCT} was used for tissue examination of bone for osteocyte count, and gross inspection of fractured mandibles after dissection was used to assess for bone union as outcome measures. A significant restoration of bone volume fraction (BVF) (p = 0.000) and osteocyte count (Oc) (p = 0.000) was found when comparing radiated fractures to radiated fractures treated with combination therapy. Further, these metrics were comparable to nonradiated bone that had undergone fracture repair (BVF-p = 0.746; Oc-p = 0.064), indicating that normal fracture healing was apparent despite the effects of radiotherapy in treated samples. Ultimately, on gross inspection, non-radiated fractures exhibited 100% bony union, radiated fractures exhibited 25% bony union, and radiated fractures with combination therapy exhibited 80% bony union. In conclusion, the combination of DFO and AMF may be a useful clinical therapeutic strategy in the management of ORN, pathologic fractures and prevention of nonunions after radiotherapy.