title: The effects of high dose and highly fractionated radiation on distraction osteogenesis in the murine mandible.
abstract: The ability of irradiated tissue to support bony growth remains poorly defined, although there are anecdotal cases reported showing mixed results for the use of mandibular distraction osteogenesis after radiation for head and neck cancer. Many of these reports lack objective measures that would allow adequate analysis of outcomes or efficacy. The purpose of this experiment was to utilize a rat model of mandibular distraction osteogenesis after high dose and highly fractionated radiation therapy and to evaluate and quantify distracted bone formation under these conditions. Male Sprague-Dawley rats underwent 12 fractions of external beam radiation (48 Gray) of the left mandible. Following a two week recovery period, an external frame distractor was applied and gradual distraction of the mandible was performed. Tissue was harvested after a twenty-eight day consolidation period. Gross, radiologic and histological evaluations were undertaken. Those animals subjected to pre-operative radiation showed severe attenuation of bone formation including bone atrophy, incomplete bridging of the distraction gap, and gross bony defects or non-union. Although physical lengthening was achieved, the irradiated bone consistently demonstrated marked damaging effects on the normal process of distraction osteogenesis. This murine model has provided reliable evidence of the injurious effects of high dose radiation on bone repair and regeneration in distraction osteogenesis utilizing accurate and reproducible metrics. These results can now be used to assist in the development of therapies directed at mitigating the adverse consequences of radiation on the regeneration of bone and to optimize distraction osteogenesis so it can be successfully applied to post-oncologic reconstruction.
authors.affiliation: Craniofacial Research Laboratory, University of Michigan, 2228 BSRB, 109 Zina Pitcher, Ann Arbor 48109, USA.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Monson
authors.forename: Christi M
authors.initials: CM
authors.lastname: Cavaliere
authors.forename: Sagar S
authors.initials: SS
authors.lastname: Deshpande
authors.forename: Alexander L
authors.initials: AL
authors.lastname: Ayzengart
authors.forename: Steven R
authors.initials: SR
authors.lastname: Buchman
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000528:radiation effects*; D019583:Dose Fractionation, Radiation; D008297:Male; D008334:Mandible / Q000000981:diagnostic imaging / Q000473:pathology / Q000528:radiation effects*; D063168:Mandibular Osteotomy; D010012:Osteogenesis / Q000528:radiation effects*; D019857:Osteogenesis, Distraction; D011833:Radiation Injuries, Experimental / Q000209:etiology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014057:Tomography, X-Ray Computed