Deferoxamine reverses radiation induced hypovascularity during bone regeneration and repair in the murine mandible.

Abstract

Deferoxamine (DFO) is an iron-chelating agent that has also been shown to increase angiogenesis. We hypothesize that the angiogenic properties of DFO will improve bone regeneration in distraction osteogenesis (DO) after x-ray radiation therapy (XRT) by restoring the vascularity around the distraction site. Three groups of Sprague-Dawley rats underwent distraction of the left mandible. Two groups received pre-operative fractionated XRT, and one of these groups was treated with DFO during distraction. After consolidation, the animals were perfused and imaged with micro-CT to calculate vascular radiomorphometrics. Radiation inflicted a severe diminution in the vascular metrics of the distracted regenerate and consequently led to poor clinical outcome. The DFO treated group revealed improved DO bone regeneration with a substantial restoration and proliferation of vascularity. This set of experiments quantitatively demonstrates the ability of DFO to temper the anti-angiogenic effect of XRT in mandibular DO. These exciting results suggest that DFO may be a viable treatment option aimed at mitigating the damaging effects of XRT on new bone formation.