title: Prophylactic amifostine preserves the biomechanical properties of irradiated bone in the murine mandible.
abstract: BACKGROUND
  The authors have previously demonstrated that amifostine prophylaxis mitigates the pernicious effects of radiation in settings of fracture repair and distraction osteogenesis. Expanding on these studies, the authors examined the biomechanical properties of uninjured bone exposed to both radiation and amifostine. The authors hypothesize that radiation will degrade the biomechanical properties of native bone, and further hypothesize that prophylactic amifostine will preserve biomechanical properties to levels of normal bone and protect against radiation-induced morbidities.
  
  
  METHODS
  Rats were randomized into control, irradiated, and amifostine pretreatment plus radiation (amifostine-pretreated) groups. Irradiated animals received a fractionated dosing schedule of 35 Gy, with amifostine-pretreated animals receiving amifostine before irradiation. Hemimandibles were harvested at 8 and 18 weeks for biomechanical testing and micro-computed tomographic analysis.
  
  
  RESULTS
  At 8 weeks, irradiated specimens displayed elevations above controls for all biomechanical properties. At 18 weeks, the biomechanical properties of irradiated specimens degraded in comparison with controls; at both time points, amifostine-pretreated specimens were maintained at levels comparable to controls. There was a significant decrease in tissue mineral density from 8- to 18-week irradiated specimens, whereas no such change existed for control and amifostine-pretreated specimens.
  
  
  CONCLUSIONS
  The authors' findings demonstrate paradoxical and transient elevations in the initial biomechanical properties of irradiated specimens that were not sustained through the later study time point. Amifostine pretreatment, however, provided uninterrupted preservation of the biomechanical properties of normal, native bone at both time points. This supports the contention that amifostine is capable of providing continuous protection to bone against the untoward effects of radiation therapy.
authors.affiliation: Ann Arbor, Mich.; and Columbia, S.C. From the Craniofacial Research Laboratory, Plastic Surgery Section, and the Orthopaedic Research Laboratory, Orthopaedic Surgery Section, University of Michigan; and the Department of General Surgery, University of South Carolina School of Medicine.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Felice
authors.forename: Salman
authors.initials: S
authors.lastname: Ahsan
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Perosky
authors.forename: Sagar S
authors.initials: SS
authors.lastname: Deshpande
authors.forename: Noah S
authors.initials: NS
authors.lastname: Nelson
authors.forename: Alexis
authors.initials: A
authors.lastname: Donneys
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Kozloff
authors.forename: Steven R
authors.initials: SR
authors.lastname: Buchman
mesh_terms: D004999:Amifostine / Q000008:administration & dosage*; D000818:Animals; D001696:Biomechanical Phenomena; D001847:Bone Diseases / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D018890:Chemoprevention; D019583:Dose Fractionation, Radiation; D008297:Male; D008334:Mandible / Q000187:drug effects* / Q000503:physiopathology / Q000528:radiation effects; D011833:Radiation Injuries, Experimental / Q000517:prevention & control*; D011837:Radiation-Protective Agents / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D011837:Radiation-Protective Agents; D004999:Amifostine