Deferoxamine Administration Delivers Translational Optimization of Distraction Osteogenesis in the Irradiated Mandible

Abstract

The authors' laboratory has previously demonstrated that deferoxamine promotes angiogenesis and bone repair in the setting of radiation therapy coupled with distraction osteogenesis. However, clinically relevant effects of deferoxamine administration on union rate and micro-computed tomographic and biomechanical parameters are unknown. The authors posit that administration of deferoxamine will increase union rate, mineralization, and strength of the regenerate in an irradiated distraction osteogenesis model. Sprague-Dawley rats were randomized into three groups: distraction osteogenesis-control, distraction osteogenesis-radiation therapy, and distraction osteogenesis-radiation therapy-deferoxamine. All animals underwent an osteotomy and distraction osteogenesis across a 5.1-mm distraction gap. Irradiated animals received 35-Gy human-equivalent radiation therapy 2 weeks before surgery, and deferoxamine was injected postoperatively in the regenerate site of treatment animals. Animals were killed on postoperative day 40, and mandibles were harvested to determine rates of bony union and micro-computed tomographic and biomechanical parameters. Compared with irradiated mandibles, deferoxamine-treated mandibles exhibited a higher union rate (11 percent versus 92 percent, respectively). Across micro-computed tomographic and biomechanical parameters, significant diminutions were observed with administration of radiation therapy, whereas deferoxamine therapy resulted in significant restoration to levels of controls, with select metrics exhibiting significant increases even beyond controls. The authors' data confirm that deferoxamine restores clinically relevant metrics of bony union and micro-computed tomographic and biomechanical parameters in a model of irradiated distraction osteogenesis in the murine mandible. Their findings support a potential use for deferoxamine in treatment protocols to allow predictable and reliable use of distraction osteogenesis as a viable reconstructive option in patients with head and neck cancer.