title: Dose-response effect of human equivalent radiation in the mandible.
abstract: BACKGROUND
  Despite widespread use of adjuvant irradiation for head and neck cancer, the extent of damage to the underlying bone is not fully understood but is associated with pathologic fractures, nonunion, and osteoradionecrosis. The authors' laboratory previously demonstrated that radiation significantly impedes new bone formation in the murine mandible. We hypothesize that the detrimental effects of human equivalent radiation on the murine mandible results in a dose-dependent degradation in traditional micro-computed tomography (micro-CT) metrics.
  
  
  METHODS
  Fifteen male Sprague-Dawley rats were randomized into 3 radiation dosage groups: low (5.91 Gy), middle (7 Gy), and high (8.89 Gy), delivered in 5 daily fractions. These dosages approximated 75%, 100%, and 150%, respectively, of the biologically equivalent dose that the human mandible receives during radiation treatment. Hemimandibles were harvested 56 days after radiation and scanned using micro-CT. Bone mineral density, tissue mineral density, and bone volume fraction were measured along with microdensitometry measurements.
  
  
  RESULTS
  Animals demonstrated dose-dependent adverse effects of mucositis, alopecia, weight loss, and mandibular atrophy with increasing radiation. Traditional micro-CT parameters were not sensitive enough to demonstrate statistically significant differences between the radiated groups; however, microdensitometry analysis showed clear differences between radiated groups and statistically significant changes between radiated and nonradiated groups.
  
  
  CONCLUSIONS
  The authors report dose-dependent and clinically significant adverse effects of fractionated human equivalent radiation to the murine mandible. The authors further report the limited capacity of traditional micro-CT metrics to adequately capture key changes in bone composition and present microdensitometric histogram analysis to demonstrate significant radiation-induced changes in mineralization patterns.
authors.affiliation: From the *University of Pittsburgh, Pittsburgh, Pennsylvania; and †University of Michigan, Ann Arbor, Michigan.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Monson
authors.forename: X Lin
authors.initials: XL
authors.lastname: Jing
authors.forename: Alexis
authors.initials: A
authors.lastname: Donneys
authors.forename: Aaron S
authors.initials: AS
authors.lastname: Farberg
authors.forename: Steven R
authors.initials: SR
authors.lastname: Buchman
mesh_terms: D000818:Animals; D015519:Bone Density / Q000528:radiation effects; D004195:Disease Models, Animal; D004307:Dose-Response Relationship, Radiation; D006258:Head and Neck Neoplasms / Q000473:pathology / Q000532:radiotherapy; D006801:Humans; D008297:Male; D008334:Mandible / Q000000981:diagnostic imaging* / Q000473:pathology / Q000528:radiation effects*; D010025:Osteoradionecrosis / Q000000981:diagnostic imaging* / Q000473:pathology*; D011832:Radiation Injuries / Q000000981:diagnostic imaging* / Q000473:pathology*; D018714:Radiotherapy, Adjuvant / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D055114:X-Ray Microtomography
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