title: Deferoxamine restores callus size, mineralization, and mechanical strength in fracture healing after radiotherapy.
abstract: BACKGROUND
  Therapeutic augmentation of fracture-site angiogenesis with deferoxamine has proven to increase vascularity, callus size, and mineralization in long-bone fracture models. The authors posit that the addition of deferoxamine would enhance pathologic fracture healing in the setting of radiotherapy in a model where nonunions are the most common outcome.
  
  
  METHODS
  Thirty-five Sprague-Dawley rats were divided into three groups. Fracture, irradiated fracture, and irradiated fracture plus deferoxamine. The irradiated fracture and irradiated fracture plus deferoxamine groups received a human equivalent dose of radiotherapy [7 Gy/day for 5 days, (35 Gy)] 2 weeks before mandibular osteotomy and external fixation. The irradiated fracture plus deferoxamine group received injections of deferoxamine into the fracture callus after surgery. After a 40-day healing period, mandibles were dissected, clinically assessed for bony union, imaged with micro-computed tomography, and tension tested to failure.
  
  
  RESULTS
  Compared with irradiated fractures, metrics of callus size, mineralization, and strength in deferoxamine-treated mandibles were significantly increased. These metrics were restored to a level demonstrating no statistical difference from control fractures. In addition, the authors observed an increased rate of achieving bony unions in the irradiated fracture plus deferoxamine-treated group when compared with irradiated fracture (67 percent and 20 percent, respectively).
  
  
  CONCLUSIONS
  The authors' data demonstrate nearly total restoration of callus size, mineralization, and biomechanical strength, and a threefold increase in the rate of union with the use of deferoxamine. The authors' results suggest that the administration of deferoxamine may have the potential for clinical translation as a new treatment paradigm for radiation-induced pathologic fractures.
authors: Ann Arbor, Mich. From the Plastic Surgery Section, Craniofacial Research Laboratory, and the Department of Orthopedic Surgery, Orthopedic Research Laboratory, University of Michigan.
authors: Alexis
authors: A
authors: Donneys
authors: Salman
authors: S
authors: Ahsan
authors: Joseph E
authors: JE
authors: Perosky
authors: Sagar S
authors: SS
authors: Deshpande
authors: Catherine N
authors: CN
authors: Tchanque-Fossuo
authors: Benjamin
authors: B
authors: Levi
authors: Ken M
authors: KM
authors: Kozloff
authors: Steven R
authors: SR
authors: Buchman
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D002146:Bony Callus / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D002113:Calcification, Physiologic / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D003676:Deferoxamine / Q000494:pharmacology*; D004195:Disease Models, Animal; D017102:Fracture Healing / Q000187:drug effects* / Q000528:radiation effects; D008297:Male; D008334:Mandible / Q000187:drug effects / Q000502:physiology / Q000601:surgery; D010027:Osteotomy; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D011878:Radiotherapy / Q000009:adverse effects*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017262:Siderophores / Q000494:pharmacology; D013718:Tensile Strength / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects
chemical_list: D017262:Siderophores; D003676:Deferoxamine
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