Abstract: Deferoxamine Augments Vascularity and Prevents Osteocyte Depletion Following Radiotherapy in a Mandibular Pathologic Fracture Model (Plastic Surgery 2012)

Saturday, October 27, 2012: 1:55 PM

Daniela M Weiss, BS , Plastic Surgery, University of Michigan, Ann Arbor, MI

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

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

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

Peter A Felice, MD , Plastic Surgery, University of Michigan, Ann Arbor, MI

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

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

Steven R. Buchman, MD , Plastic Surgery, F7859 Mott Children's Hospital, Ann Arbor, MI

Presentation PDF file

Purpose: The effects of radiation on bone formation and healing are mediated through the mechanisms of vascular damage, direct cellular depletion and diminished function of osteocytes. Over time, this accumulated damage predisposes patients to the debilitating problem of late pathologic fractures and non-unions. Here we employ the use of Deferoxamine (DFO), an angiogenic enhancing therapy, to bolster the vascular response during bone healing in this setting and posit that the untoward effects of radiotherapy on vascular density and osteocyte count can be mitigated with the addition of DFO.

Methods: 12 rats received fractionated radiotherapy to left hemi-mandibles. After recovery, fracture repair ensued with external fixator placement and mandibular osteotomy. DFO was injected into the callus site every other day from post-operative days 4-12. A 40-day healing period was allowed prior to vessel perfusion, micro-CT and histologic processing. Mandibles were dissected and gross union was assessed. Union was defined as bony bridging and the absence of motion across the fracture site. Outcome data was analyzed with ANOVA, and p≤0.05 was statistically significant. The DFO group was compared with two other groups: fracture-Fx and radiated fracture-X/Fx (n=12,12).

Results: Vascularity: The DFO treated group demonstrated a significant restoration to control level Vessel Volume when compared to X/Fx (p=0.029). Vessel Number, Thickness and Separation also showed significant restorative effects. Histomorphometry: Histology revealed a significant restoration to control level osteocyte count (p=0.000); and a corresponding decrease in empty lacunae (p=0.000) when comparing X/Fx/DFO to X/Fx. Bony Union: While Fx mandibles demonstrated 100% bony union, X/Fx mandibles only demonstrated 25% union. The X/Fx/DFO group demonstrated 67% bony union.

Conclusions: We observed a complete restoration of vascular density and osteocyte count with the addition of DFO. The most consequential finding was a 42% increase in bony unions in a model where healing was not routinely observed.

20704 Deferoxamine Augments Vascularity and Prevents Osteocyte Depletion Following Radiotherapy in a Mandibular Pathologic Fracture Model