Abstract: Amifostine Demonstrates Significant Cytoprotection In An Irradiated Murine Model of Mandibular Distraction Osteogenesis (Plastic Surgery 2011 (September 23-27, 2011))

Saturday, September 24, 2011: 8:00 AM

Colorado Convention Center

Elizabeth Razdolsky, BS , Plastic Surgery, University of Michigan, Ann Arbor, MI

Catherine Tchanque-Fossuo, MD , Plastic Surgery, University of Michigan, Ann Arbor, MI

Alexis Donneys, MD , Plastic Surgery, University of Michigan, Ann Arbor, MI

Laura Monson, MD , Plastic Surgery, University of Michigan, Ann Arbor, MI

Aaron Farberg, BS , Plastic Surgery, University of Michigan, Ann Arbor, MI

Sagar Deshpande, BS , Plastic Surgery, University of Michigan, Ann Arbor, MI

Kelly Gallagher, MD , Plastic Surgery, University of Michigan, Ann Arbor, MI

Deniz Sarhaddi, BA , Plastic Surgery, University of Michigan, Ann Arbor, MI

Behdod Poushanchi, BS , Plastic Surgery, University of Michigan, Ann Arbor, MI

Steven Buchman, MD , F7859 Mott Children's Hospital, Ann Arbor, MI

Presentation PDF file

Introduction: Head and neck cancer (HNC) clinical management requires adjuvant radiation (XRT) therapy. Our previous studies have demonstrated the deleterious effect of a human equivalent dose of radiation (HEDR) on a murine mandibular model of distraction osteogenesis (DO). Here, we use quantitative histomorphometry (QHM) to objectively measure the radio-protective effects of Amifostine (AMF) on the cellular integrity in an irradiated and distracted regenerate. We posit that AMF will protect osteocytes, cells critical for bone regeneration and healing, from the damaging effects of XRT.

Methods: 16 Sprague Dawley rats were randomly assigned into 2 groups: Group 1 (n=6) and Group 2 (n=10) received a HEDR given in 5 fractionated doses. Group 2 was given AMF 45 minutes prior to XRT. Both groups underwent a left mandibular osteotomy with bilateral fixator placement. Distraction to 5.1mm was followed by a 28-day consolidation period. All left hemimandibles were harvested, sectioned and stained with Gomori Trichome. QHM was performed for osteocyte count (Oc) and empty lacunae (EL). Independent Samples t-test was used for group comparison with p < 0.05 considered statistically significant.

Results: Complete bony bridging was observed in all AMF pre-treated animals, whereas the irradiated group exhibited some specimens with fibrous unions and incomplete bridging. QHM analysis revealed a statistically significant higher Oc compared with irradiated mandibles (68.62 ą 9.6 vs. 43.8 ą 1.4 osteocytes, p=0.000). There was also a corresponding decrease in the number of EL between the AMF-treated and irradiated groups (3.95 ą 1.5 vs. 11.4 ą 6.1 EL; p= 0.002). (See Figures 1 and 2)

Conclusions: Our findings demonstrate the significant osseous cytoprotective capacity of AMF on distraction in the face of XRT. The maintenance of bone forming cells resulting from AMF pretreatment was associated with an increase in bony union and a complete elimination in the incidence of fibrous union. We posit that the demonstration of similar efficacy of AMF in the clinical arena may allow the successful implementation of DO as a viable reconstructive option for HNC in the future.

19551 Amifostine Demonstrates Significant Cytoprotection In An Irradiated Murine Model of Mandibular Distraction Osteogenesis