title: Targeting angiogenesis as a therapeutic means to reinforce osteocyte survival and prevent nonunions in the aftermath of radiotherapy.
abstract: BACKGROUND
  Radiotherapy (XRT) exerts detrimental collateral effects on bone tissue through mechanisms of vascular damage and impediments to osteocytes, ultimately predisposing patients to the debilitating problems of late pathologic fractures and nonunions. We posit that angiogenic therapy will reverse these pathologic effects in a rat model of radiated fracture healing.
  
  
  METHODS
  Three groups of rats underwent mandibular osteotomy. Radiated groups received a fractionated 35-Gy dose before surgery. The deferoxamine (DFO) group received local injections postoperatively. A 40-day healing period was allowed before histology. Analysis of variance (ANOVA; p < .05) was used for group comparisons.
  
  
  RESULTS
  Radiated fractures revealed a significantly decreased osteocyte count and corresponding increase in empty lacunae when compared to nonradiated fractures (p = .001). With the addition of DFO, these differences were not appreciated. Further, a 42% increase in bony unions was observed after DFO therapy.
  
  
  CONCLUSIONS
  Targeting angiogenesis is a useful means for promoting osteocyte survival and preventing bone pathology after XRT.
authors.affiliation: Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, Michigan.
authors.forename: Alexis
authors.initials: A
authors.lastname: Donneys
authors.affiliation: Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, Michigan.
authors.forename: Noah S
authors.initials: NS
authors.lastname: Nelson
authors.affiliation: Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, Michigan.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Page
authors.affiliation: Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, Michigan.
authors.forename: Sagar S
authors.initials: SS
authors.lastname: Deshpande
authors.affiliation: Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, Michigan.|Department of General Surgery, University of South Carolina School of Medicine, Columbia, South Carolina.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Felice
authors.affiliation: Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, Michigan.
authors.forename: Catherine N
authors.initials: CN
authors.lastname: Tchanque-Fossuo
authors.affiliation: Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, Michigan.
authors.forename: Joshua P
authors.initials: JP
authors.lastname: Spiegel
authors.affiliation: Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, Michigan.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Buchman
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001707:Biopsy, Needle; D002470:Cell Survival; D002478:Cells, Cultured; D003676:Deferoxamine / Q000494:pharmacology*; D004195:Disease Models, Animal; D019583:Dose Fractionation, Radiation; D017102:Fracture Healing / Q000502:physiology; D005599:Fractures, Ununited / Q000517:prevention & control; D007150:Immunohistochemistry; D015552:Injections, Intralesional; D008297:Male; D008334:Mandible / Q000473:pathology / Q000528:radiation effects* / Q000601:surgery; D063168:Mandibular Osteotomy / Q000379:methods; D009389:Neovascularization, Pathologic / Q000517:prevention & control*; D010011:Osteocytes / Q000187:drug effects* / Q000528:radiation effects*; D011300:Preoperative Care / Q000379:methods; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity
chemical_list: D003676:Deferoxamine
keywords: angiogenesis; deferoxamine; mandible; nonunion; radiation