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DEFEROXAMINE RESTORES BIOMECHANICAL PROPERTIES AND POTENTIATES UNION OF IRRADIATED BONE IN DISTRACTION OSTEOGENESIS
Presenter: Presenter: Noah S Nelson, BS
Co-Authors: Felice PA, Donneys A; Ahsan S; Deshpande SS; Perosky JE; Kozloff KM; Buchman SR
University of Michigan School of Medicine

Background: Our laboratory has shown the iron-chelating agent Deferoxamine (DFO) promotes angiogenesis and bone repair in the setting of radiation therapy (XRT) coupled with Distraction Osteogenesis (DO). While these studies demonstrate DFO improves vascular and histologic metrics for irradiated bone, the clinically impactful effect of DFO on union formation and biomechanics has never been examined. We hypothesize DFO administration will increase bony union and strengthen Biomechanical Properties (BPs) of the regenerate in an irradiated DO model.

Methods: Sprague Dawley rats are randomized into groups: Group 1, DO-Control (n=10); Group 2, DO-XRT (n=9); and Group 3, DO-XRT-DFO (n=12). All animals undergo a left hemi-mandible osteotomy with placement of an external distraction device. Distraction occurs q12hrs from post-operative day (POD) 4 through POD 12 to achieve a 5.1mm critical-size distraction gap. Groups 2 and 3 receive 35Gy human-equivalent XRT in 5 fractions prior to the osteotomy. Group 3 animals receive 5 separate 300 uL doses of DFO every other day starting POD 4. Animals are sacrificed at POD 40 and hemi-mandibles harvested to analyze BPs and union.

Results: Union is achieved in 10 (100%) DO-Control, 1 (11%) DO-XRT, and 11 (92%) DO-XRT-DFO hemi-mandibles (Fig.1). BPs analysis show significant increases in Yield Load, Ultimate Load, and Failure Load for DO-XRT-DFO specimens compared with DO-XRT (Fig.2). Additionally, we see no difference between DO-XRT-DFO and DO-Controls for Ultimate Load and Failure Load, while Yield Load is increased in DFO-treated specimens.

Conclusion: BPs are preserved at levels comparable with Controls and increased compared to DO-XRT specimens for DFO-treated hemi-mandibles. Furthermore, DFO administration vastly improves union across our distraction gap. These results demonstrate quantifiable improvement in the clinically relevant measures of strength and union in distracted, irradiated bone. Our findings support the potential use of DFO in treatment protocols to allow predictable and reliable use of DO as a viable reconstructive option for head and neck cancer patients.


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