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89th Annual Meeting Abstracts

Deferoxamine Treatment Restores Vascularity in Irradiated Mandibular Distraction Osteogenesis
Aaron S. Farberg, B.S.1, Xi Lin Jing, M.D.2, Laura A. Monson, M.D.1, Catherine N. Tchanque-Fossuo, M.D.1, Alexis Donneys, M.D.1, Sagar S. Deshponde1, Steven R. Buchman, M.D.1.
1University of Michigan, Ann Arbor, MI, USA, 2Henry Ford Hospital System, Detroit, MI, USA.

PURPOSE: The deleterious effects of radiation therapy (XRT) for treatment of head and neck cancer (HNC) currently preclude the use of distraction osteogenesis (DO) as a reconstructive option. Recent work in our lab has shown severe attenuation of microvasculature in DO after XRT. Deferoxamine (DFO) is an iron-chelating agent on formulary that has been shown to increase angiogenesis. We hypothesize that the angiogenic properties of DFO will improve bone regeneration in DO after XRT by restoring the vascularity around the distraction site. Our specific aim is to use micro-computed tomography (CT) vascular imaging to quantitatively evaluate the effectiveness of DFO to enhance angiogenesis of the regenerate (RG) in DO of the radiated murine mandible.
METHODS: 2 groups of Sprague-Dawley rats (n=12) underwent fractionated XRT of the left mandible, utilizing the human equivalent dose for HNC. Both groups underwent placement of an external fixator, mandibular osteotomy, and 5.1 mm distraction over an 8 day period. During active distraction, the experimental DFO group (n=7) was treated with a 200 Mm DFO injection into the RG QOD. After 28 days of consolidation, the animals were perfused with a radiopaque compound (Microfil). Left hemi-mandibles were imaged with micro-CT at 18micron resolution, and a 5.1mm VOI encompassing the RG was selected. Radiomorphometrics for vascularity, including vessel number (VN), vessel separation (VS), and vessel volume fraction (VVF) were calculated for each group.
RESULTS: We found a substantial proliferation of vascularity in the DFO treated group when compared to the RG of the control group. DFO effected a significant increase in VN (1.02 v 0.51; p<0.001) and an expected subsequent decrease in VS (0.94 v 2.07; p<0.001). Our data revealed a massive increase in the number of vessels which were now packed closer together in the experimental group. This strong increase of vascularity with DFO in the radiated RG could be appreciated grossly with micro-CT image reconstruction as well as objectively measured by the increased VVF (0.05 v 0.03; p<0.005).
CONCLUSION: 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 bone formation. Additionally, this study establishes DFO’s ability to propagate angiogenesis in a pathologic model where healing is not routinely observed. The ability of increased vascularity to abrogate the devastating effects of XRT on bone formation may suggest utility for a broader range of clinical skeletal repair.


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