title: Deferoxamine expedites consolidation during mandibular distraction osteogenesis.
abstract: BACKGROUND
  A limitation of mandibular distraction osteogenesis (DO) is the length of time required for consolidation. This drawback subjects patients to possible pin-site infections, as well as a prolonged return to activities of normal daily living. Developing innovative techniques to abridge consolidation periods could be immensely effective in preventing these problematic morbidities. Deferoxamine (DFO) is an angiogenic activator that triggers the HIF-1α pathway through localized iron depletion. We previously established the effectiveness of DFO in enhancing regenerate vascularity at a full consolidation period (28 days) in a murine mandibular DO model. To investigate whether this augmentation in vascularity would function to accelerate consolidation, we progressively shortened consolidation periods prior to μCT imaging and biomechanical testing (BMT).
  
  
  METHODS
  Three time points (14d, 21d and 28d) were selected and six groups of Sprague-Dawley rats (n = 60) were equally divided into control (C) and experimental (E) groups for each time period. Each group underwent external fixator placement, mandibular osteotomy, and a 5.1 mm distraction. During distraction, the experimental groups were treated with DFO injections into the regenerate gap. After consolidation, mandibles were imaged and tension tested to failure. ANOVA was conducted between groups, and p < 0.05 was considered statistically significant.
  
  
  RESULTS
  At 14 days of consolidation the experimental group demonstrated significant increases in bone volume fraction (BVF), bone mineral density (BMD) and ultimate load (UL) in comparison to non-treated controls. The benefit of treatment was further substantiated by a striking 100% increase in the number of bony unions at this early time-period (C:4/10 vs. E:8/10). Furthermore, metrics of BVF, BMD, Yield and UL at 14 days with treatment demonstrated comparable metrics to those of the fully consolidated 28d control group.
  
  
  CONCLUSIONS
  Based on these findings, we contend that augmentation of vascular density through localized DFO injection delivers an efficient means for accelerating bone regeneration without significantly impacting bone quality or strength.
authors.affiliation: Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI, USA.
authors.forename: Alexis
authors.initials: A
authors.lastname: Donneys
authors.forename: Sagar S
authors.initials: SS
authors.lastname: Deshpande
authors.forename: Catherine N
authors.initials: CN
authors.lastname: Tchanque-Fossuo
authors.forename: Kelsey L
authors.initials: KL
authors.lastname: Johnson
authors.forename: Jordan T
authors.initials: JT
authors.lastname: Blough
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Perosky
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Kozloff
authors.forename: Peter A
authors.initials: PA
authors.lastname: Felice
authors.forename: Noah S
authors.initials: NS
authors.lastname: Nelson
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Farberg
authors.forename: Benjamin
authors.initials: B
authors.lastname: Levi
authors.forename: Steven R
authors.initials: SR
authors.lastname: Buchman
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000494:pharmacology*; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D003676:Deferoxamine / Q000494:pharmacology*; D008297:Male; D008334:Mandible / Q000601:surgery*; D019857:Osteogenesis, Distraction / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017262:Siderophores / Q000494:pharmacology
chemical_list: D043925:Angiogenesis Inducing Agents; D017262:Siderophores; D003676:Deferoxamine