Plastic Surgery Research Council
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A NOVEL COMBINATION OF AMIFOSTINE PROPHYLAXIS AND ANGIOGENIC DEFEROXAMINE PROTECTS AND RESTORES BIOMECHANICAL PROPERTIES OF BONE IN PATHOLOGIC FRACTURE HEALING AFTER RADIOTHERAPY
Presenter: Salman Ahsan, Student
Co-Authors: Donneys A; Deshpande SS; Felice PA; Figuredo C; Henry M; Page E; Buchman SR
University of Michigan

Purpose: Pathologic fractures and associated non-unions after radiotherapy for Head and Neck cancer pose a complex management dilemma for reconstructive surgeons. We have previously demonstrated a partial remediation of biomechanical strength and bony union formation with Deferoxamine (DFO), an angiogenic factor, in a murine model of fracture healing following radiotherapy. The purpose of this study was to investigate the synergistic potential of Amifostine (AMF), a cytoprotectant, in combination with DFO to produce a more robust biomechanical construct and predictable rate of bony union.

Methods: Sprague-Dawley rats (n=35) were divided into 3 groups. Fracture, radiated fracture and radiated fracture with combined therapy. Radiated groups received a human equivalent dose of radiotherapy 2 weeks prior to mandibular osteotomy and external fixation. The combined group received AMF prophylaxis prior to radiation and injections of DFO after surgery. Following a 40-day healing period, mandibles were dissected, assessed for bony-union and mechanically tested. The combined group was subsequently compared to a previously established DFO group. ANOVA was used for comparisons between groups and p < 0.05 was considered statistically significant.

Results: Combined therapy significantly restored Failure Load to control levels (p=0.003). Yield and Stiffness also showed significant restorations. Combined Stiffness was significantly higher than DFO therapy alone (p=0.006). The combined group displayed an 80% union rate; an improvement over DFO alone at 67% and a marked improvement over radiated fractures at 20%.

Conclusion: Our data support the contention that combination therapy acts synergistically to restore the biomechanical properties of fracture healing after radiotherapy. Furthermore, we demonstrate a more robust biomechanical construct and predictable rate of bony union with combination therapy than with DFO alone. Based on these findings, we support the continued investigation of this treatment paradigm in its potential translation for the management of pathologic fractures and associated non-unions after radiotherapy.


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