Amifostine protects vascularity and improves union in a model of irradiated mandibular fracture healing.

Deniz Sarhaddi, Catherine N Tchanque-Fossuo, Behdod Poushanchi, Alexis Donneys, Sagar S Deshpande, Daniela M Weiss, Steven R Buchman

Index: Plast. Reconstr. Surg. 132(6) , 1542-9, (2013)

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Abstract

Pathologic fractures of the mandible can be devastating to cancer patients and are due in large part to the pernicious effects of irradiation on bone vascularity. The authors' aim was to ascertain whether amifostine, a radioprotective drug, will preserve vascularity and improve bone healing in a murine model of irradiated mandibular fracture repair.Rats were randomized into three groups: nonirradiated fracture (n = 9), irradiation/fracture (n = 5), and amifostine/irradiation/fracture (n = 7). Animals in the irradiation groups underwent a human equivalent dose of radiation directed at the left hemimandible. Animals treated in the amifostine group received amifostine concomitantly with radiation. All animals underwent unilateral left mandibular osteotomy with external fixation set to a 2.1-mm fracture gap. Fracture healing was allowed for 40 days before perfusion with Microfil. Vascular radiomorphometrics were quantified with micro-computed tomography.When compared with the irradiated/fractured group, amifostine treatment more than doubled the rate of fracture unions to 57 percent. Amifostine treatment also resulted in an increase in vessel number (123 percent; p < 0.05) and a corresponding decrease in vessel separation (55.5 percent; p < 0.05) there was no statistical difference in the vascularity metrics between the amifostine/irradiation/fracture group and the nonirradiated/fracture group.Amifostine prophylaxis during radiation maintains mandibular vascularity at levels observed in nonirradiated fracture specimens, corresponding to improved unions. These results set the stage for clinical exploration of this targeted therapy alone and in combination with other treatments, to mitigate the effects of irradiation on bone healing and fracture repair.