Plastic Surgery Research Council
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PSRC 60th Annual Meeting
Program and Abstracts

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Combined Amifostine and Deferoxamine Therapy Preserves Biomechanics and Improves Union Rate in a Model of Distraction Osteogenesis Following Radiotherapy
Noah S. Nelson, BS, Yekaterina Polyatskaya, MD, Alexander R. Zheutlin, BS, Joseph E. Perosky, MS, Alexis Donneys, MD, MS, Jose J. Rodriguez, MD, Sagar S. Deshpande, BS, Kenneth M. Kozloff, PhD, Steven R. Buchman, MD.
University of Michigan, Ann Arbor, MI, USA.

PURPOSE:We have previously demonstrated amifostine and deferoxamine to be effective therapeutics when used singularly to combat the deleterious effects of radiation prior to distraction osteogenesis. Each therapy has improved the biomechanical properties and union rates beyond levels seen in non-treated, radiated, distracted bone. To this point the metrics have not been restored completely back to non-radiated levels. In this study, we combined our efficacious individual treatments in order to maximize their therapeutic potential. We hypothesized that the radioprotective properties of amifostine and the angiogenic potential of deferoxamine would function cooperatively to further improve biomechanical metrics and union rates following radiotherapy and distraction osteogenesis.
METHODS:Sprague Dawley rats (n=58) were divided into five groups: non-radiated distraction (DO), radiated distraction (XDO), radiated distraction with amifostine (AMF), radiated distraction with deferoxamine therapy (DFO), and radiated distraction with both therapies (Combined). The groups receiving radiation were administered a fractionated, human-equivalent dose of 35Gy over 5 days, comparable to 70Gy in humans. The rats then underwent a mandibular osteotomy and external fixation. Their left hemi-mandibles were distracted from post-operative day 4-12 to a distance of 5.1mm. The consolidation period lasted until post-operative day 40, at which time the animals were euthanized, and their mandibles were harvested, examined for bony union, and biomechanically tested. Yield Load (YL), Failure Load (FL), and Stiffness (S) were ascertained.
RESULTS:Bony Union: While 100% of the DO group demonstrated bony unions, only 11% of the XDO mandibles were unions. The union rates improved to 64%, 86%, and 93% in the AMF, DFO, and Combined groups, respectively. Biomechanical Testing: Compared to the DO group, the XDO mandibles showed decreased values for YL (25N vs. 48N), FL (22N vs. 62N), and S (240N/mm vs. 795N/mm). With AMF, the values were all increased closer to DO levels (42N, 53N, 301N/mm, respectively). The DFO group was significantly higher than the XDO group in YL (76N,p=.001), FL (92N,p=.000), and S (885N/mm,p=.020). The Combined group also was significantly higher than XDO for YL (62N,p=.026) and FL (87N,p=.001), but was not statistically significant for S (699N/mm,p=.173). The DFO group demonstrated marginally higher values in all three metrics than the Combined group. Additionally, none of the treatment groups were statistically different from the DO group for YL, FL, or S.
CONCLUSION:While AMF and DFO on their own each represent a viable option to mitigate radiation-induced impairment of bone regeneration during distraction osteogenesis, the combination of these two therapies may be more beneficial. Although the DFO group displayed higher overall biomechanical metrics, the Combined group had a superior union rate in addition to elevated biomechanical strength beyond amifostine alone. In order to fully appreciate the potential complementary effects of these treatments, additional metrics of bone healing will be investigated in the future.


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