Deferoxamine Treatment Increases Osteocyte Count in Mandibular Distraction Osteogenesis

Background: As distraction osteogenesis (DO) has evolved into a conventional reconstructive option, surgeons have continued to push the capabilities of the technique beyond its current limitations. Efforts to enhance the DO procedure would offer improved outcomes as well as potentially expand its therapeutic potential. One such way to improve upon and extend the reach of the DO procedure would be to augment the blood supply to the regenerate (RG). Deferoxamine (DFO) is an iron-chelator that has been shown to increase angiogenesis via the hypoxia inducible factor pathway. We posit that the angiogenic effect of DFO will function to improve bone regeneration in the mandible by augmenting the number of bone producing cells. Our specific aim is to use quantitative histomorphometry (QHM) to objectively measure the effectiveness of DFO to increase the osteocyte count of the RG in DO of the murine mandible. Methods: Two groups of male Sprague-Dawley rats (n=12) underwent surgical placement of an external fixator, mandibular osteotomy, and a 5.1 mm distraction over an 8-day period. During the distraction stage, the experimental DFO group (n=5) was treated with a 200 micromolar DFO injection into the distraction gap q.o.d. After 28 days of consolidation, mandibles were harvested decalcified, sectioned, and stained (Gomori trichrome). Point counting of osteocytes and empty lacunae were performed within a region of interest using Bioquant software. Results: We found a substantial proliferation of osteocytes in the DFO treated group when compared to the RG of the control group. DFO effected a significant increase in osteocytes per high powered field (49v27; p<0.001). The QHM data also demonstrated no significant difference in empty lacunae between the two groups (1.11v0.75). The robust increase in cellularity with DFO in the RG could also be appreciated grossly within the region of the increased RG formation. Conclusions: Our study demonstrates the effectiveness of DFO treatment to enhance the number of osteocytes within the RG in a murine mandibular DO model. Maintenance of full lacunae supports our findings of a robust cellular response to DFO therapy. These results suggest that the angiogenic capabilities of DFO translate into an increase number of bone forming cells in the RG. DFO may have utility in optimizing bone formation in DO which may in turn lead to superior reconstructive capabilities for craniofacial surgeons in the future.