title: Amifostine preserves osteocyte number and osteoid formation in fracture healing following radiotherapy.
abstract: OBJECTIVE
  Radiation is known to decrease osteocyte count and function, leading to bone weakening. A treatment strategy to mitigate these consequences could have immense therapeutic ramifications. The authors previously reported significantly decreased osteocyte count and mineralization capacity in a rat model of fracture healing after radiotherapy. They hypothesized that amifostine (AMF) would preserve osteocyte number and function in this model.
  
  
  METHODS
  Thirty-six rats were divided into 3 groups: fracture, radiated fracture, and radiated fracture with AMF. Radiated groups underwent human-equivalent radiotherapy to the mandible before fixator placement and mandibular osteotomy. The AMF group received a subcutaneous injection before each dose of radiotherapy. After 40 days, mandibles were harvested for histologic processing. Quantification of osteocyte count (Oc), empty lacunae (EL), and osteoid ratio (osteoid volume [OV] to tissue volume [TV]) was performed and the results were compared using analysis of variance (P < .05).
  
  
  RESULTS
  Radiated fractures showed significantly decreased Oc, increased EL, and a decreased capacity to produce new osteoid at the fracture site as measured with OV/TV compared with nonradiated fractures. In mandibles treated with AMF, these metrics were not statistically different than the control, indicating a preservation of osteocyte number and function.
  
  
  CONCLUSIONS
  These results support the hypothesis that AMF preserves osteocyte number and function, thereby preventing the pernicious effects of radiotherapy on the cellular environment of fracture healing. Based on these findings, the authors encourage future investigation of this promising therapy for use in the prevention of pathologic fractures and osteoradionecrosis.
authors.affiliation: Research Fellow, Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI.
authors.forename: Alexis
authors.initials: A
authors.lastname: Donneys
authors.affiliation: Research Fellow, Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI.
authors.forename: Catherine N
authors.initials: CN
authors.lastname: Tchanque-Fossuo
authors.affiliation: Research Assistant, Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI.
authors.forename: Jordan T
authors.initials: JT
authors.lastname: Blough
authors.affiliation: Research Fellow, Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI.
authors.forename: Noah S
authors.initials: NS
authors.lastname: Nelson
authors.affiliation: Research Fellow, Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI.
authors.forename: Sagar S
authors.initials: SS
authors.lastname: Deshpande
authors.affiliation: M. Haskell Newman Collegiate Professor of Plastic Surgery, Professor of Surgery, and Professor of Neurosurgery, Craniofacial Research Laboratory, Plastic Surgery Section, University of Michigan, Ann Arbor, MI. Electronic address: sbuchman@med.umich.edu.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Buchman
mesh_terms: D004999:Amifostine / Q000627:therapeutic use*; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects / Q000528:radiation effects; D002113:Calcification, Physiologic / Q000187:drug effects / Q000528:radiation effects; D002452:Cell Count; D017102:Fracture Healing / Q000187:drug effects* / Q000528:radiation effects*; D008297:Male; D063168:Mandibular Osteotomy; D010011:Osteocytes / Q000187:drug effects* / Q000528:radiation effects*; D011837:Radiation-Protective Agents / Q000627:therapeutic use*; D011878:Radiotherapy / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D011837:Radiation-Protective Agents; D004999:Amifostine