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DEFEROXAMINE INDUCES THE RESTORATION OF MINERALIZATION METRICS OF IRRADIATED BONE IN DISTRACTION OSTEOGENESIS
Presenter: Erin E Page, 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 mandibles, clinically impactful effects of DFO on mineralization metrics have never been examined. We hypothesize DFO administration will restore the composition and mineralization of the bony regenerate in an irradiated model of DO.

Methods: Sprague Dawley rats are randomized into 3 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 ?L doses of DFO, administered every other day starting POD 4. Animals are sacrificed at POD 40 and left hemi-mandibles harvested for uCT analysis.

Results: Significant increases in Bone Mineral Content (BMC) and Tissue Mineral Content (TMC) are seen in DO-XRT-DFO specimens compared to DO-XRT, while no difference exists between DO-XRT-DFO specimens and DO-Controls (Fig.1). In addition, Bone Volume Fraction (BVF) and Bone Mineral Density (BMD) are bolstered in DO-XRT-DFO specimens compared with DO-XRT (Figs. 2, 3). Impressively, we note increased BVF and BMD in DFO-treated specimens compared to DO-Controls.

Conclusion: Irradiated mandibles treated with DFO during DO show restored mineralization metrics of TMC, BMC, BVF, and BMD to levels of Controls. Remarkably, BVF and BMD increase above Control levels for DFO-treated specimens. This study exhibits how DFO reestablishes regenerate mineralization metrics and composition, supporting the potential use of DFO in treatment protocols to allow predictable and reliable use of DO as a viable reconstructive option in patients with head and neck cancer.


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