title: Standardized analysis of mandibular osteoradionecrosis in a rat model.
abstract: OBJECTIVE
  To develop a rat model of mandibular osteoradionecrosis(ORN) that uses novel micro-computed tomography bone volume analysis and detailed histology to provide a more effective, quantifiable, and standardized way to study ORN in vivo.
  
  
  METHODS
  Animal model.
  
  
  METHODS
  Academic medical center.
  
  
  METHODS
  Modifications to our previously published rat model of mandibular ORN were done to develop an ideal protocol consisting of 10 rats (6 experimental and 4 controls) with their left middle mandibular molar removed 7 days after either 20 Gy high dose rate brachytherapy or sham irradiation. Rats were sacrificed 21 days after extraction for landmark defined bone volume and histologic analysis.
  
  
  RESULTS
  A standardized method of quantification was achieved in all samples. The radiated group (XRT) had a mean bone volume/total volume (BV/TV) of 13.8% compared to 65.9% for controls (P < .001). There were increases in osteoclasts and fibrosis, decreases in osteoblasts,and less bone in radiated samples with a mean (SD)of 5.91 (3.77) osteoclasts/high-powered field (HPF) and 4.00(1.83) osteoblasts/HPF in XRT samples compared to 1.08(1.08) osteoclasts/HPF and 22.49 (6.00) osteoblasts/HPF for controls (P <.001).
  
  
  CONCLUSIONS
  Our updated model continues to be clinically analogous to human mandibular ORN and improves the radiologic and histologic analysis of bony defects, providing a method for quantification of bone loss. Further cell-specific staining, including immunohistochemistry, can be used with this model to study potential cellular mechanisms of mandibular ORN and test any future therapeutic options.
authors.affiliation: Division of Head and Neck Surgery, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA. Mtamplen@mednet.ucla.edu
authors.forename: Matthew
authors.initials: M
authors.lastname: Tamplen
authors.forename: Kelley
authors.initials: K
authors.lastname: Trapp
authors.forename: Ichiro
authors.initials: I
authors.lastname: Nishimura
authors.forename: Bob
authors.initials: B
authors.lastname: Armin
authors.forename: Michael
authors.initials: M
authors.lastname: Steinberg
authors.forename: John
authors.initials: J
authors.lastname: Beumer
authors.forename: Elliot
authors.initials: E
authors.lastname: Abemayor
authors.forename: Vishad
authors.initials: V
authors.lastname: Nabili
mesh_terms: D000818:Animals; D001707:Biopsy, Needle; D004195:Disease Models, Animal; D021621:Imaging, Three-Dimensional; D007150:Immunohistochemistry; D008297:Male; D008334:Mandible / Q000000981:diagnostic imaging / Q000473:pathology* / Q000528:radiation effects*; D008336:Mandibular Diseases / Q000209:etiology / Q000473:pathology*; D010025:Osteoradionecrosis / Q000473:pathology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D014057:Tomography, X-Ray Computed / Q000379:methods