title: The effect of Amifostine prophylaxis on bone densitometry, biomechanical strength and union in mandibular pathologic fracture repair.
abstract: BACKGROUND
  Pathologic fractures (Fx) of the mandibles are severely debilitating consequences of radiation (XRT) in the treatment of craniofacial malignancy. We have previously demonstrated Amifostine's effect (AMF) in the remediation of radiation-induced cellular damage. We posit that AMF prophylaxis will preserve bone strength and drastically reverse radiotherapy-induced non-union in a murine mandibular model of pathologic fracture repair.
  
  
  METHODS
  Twenty-nine rats were randomized into 3 groups: Fx, XRT/Fx, and AMF/XRT/Fx. A fractionated human equivalent dose of radiation was delivered to the left hemimandibles of XRT/Fx and AMF/XRT/Fx. AMF/XRT/Fx was pre-treated with AMF. All groups underwent left mandibular osteotomy with external fixation and setting of a 2.1mm fracture gap post-operatively. Utilizing micro-computed tomography and biomechanical testing, the healed fracture was evaluated for strength.
  
  
  RESULTS
  All radiomorphometrics and biomechanical properties were significantly diminished in XRT/Fx compared to both Fx and AMF/XRT/Fx. No difference was demonstrated between Fx and AMF/XRT/Fx in both outcomes.
  
  
  CONCLUSIONS
  Our investigation establishes the significant and substantial capability of AMF prophylaxis to preserve and enhance bone union, quality and strength in the setting of human equivalent radiotherapy. Such novel discoveries establish the true potential to utilize pharmacotherapy to prevent and improve the treatment outcomes of radiation-induced late pathologic fractures.
authors.affiliation: University of Michigan Hospital and Health Systems, Pediatric Plastic Surgery Section, 1540 E. Hospital Drive, Ann Arbor, MI 48109, USA.
authors.forename: Catherine N
authors.initials: CN
authors.lastname: Tchanque-Fossuo
authors.forename: Alexis
authors.initials: A
authors.lastname: Donneys
authors.forename: Deniz
authors.initials: D
authors.lastname: Sarhaddi
authors.forename: Behdod
authors.initials: B
authors.lastname: Poushanchi
authors.forename: Sagar S
authors.initials: SS
authors.lastname: Deshpande
authors.forename: Daniela M
authors.initials: DM
authors.lastname: Weiss
authors.forename: Steven R
authors.initials: SR
authors.lastname: Buchman
mesh_terms: D004999:Amifostine / Q000627:therapeutic use*; D000818:Animals; D003720:Densitometry; D005598:Fractures, Spontaneous / Q000188:drug therapy* / Q000517:prevention & control*; D008297:Male; D008334:Mandible / Q000187:drug effects* / Q000528:radiation effects*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D011837:Radiation-Protective Agents; D004999:Amifostine
keywords: Amifostine; Biomechanical strength; Bone density; Osteoradionecrosis; Pathologic fracture