Y. Polyatskaya1, S. Deshpande1, A. Donneys1, S. Kang1, N. Nelson1, S. Deshpande1, P. Felice1, S. Buchman1 1University Of Michigan,Plastic Surgery,Ann Arbor, MI, USA
Introduction:
Radiation therapy is known to be detrimental to bone and soft tissue repair, resulting in an unacceptably high incidence of devastating wound healing complications as well as the associated morbidity of late pathologic fractures and non-unions. Our global hypothesis is that the pathologic effects of radiation on bone formation and healing are mediated through a mechanism of direct cellular depletion as well as diminished function of the cells responsible for the generation and maintenance of osteogenesis. We sought to quantify the extent of this depletion via histomorphometric evaluation in an isogenic model of mandibular distraction osteogenesis for future analysis of cell-based therapies.
Methods:
20 male Lewis rats were randomly split into two groups, DO (n=10), XRT/DO (n=10). XRT underwent 5 day fractionated radiation of the left mandible at 7 Gy per day and were allowed to recover for two weeks. All groups underwent mandibular distractor placement. Groups were distracted at 0.3mm every 12 hrs to a 5.1mm (a critical-sized defect), and sacrificed on post-operative day 40. Coronal sections were stained using Gomori Trichrome. Quantitative histomorphometry was performed utilizing Bioquant. Statistical analysis was performed using student's t-test.
Results:
Radiation significantly decreased the ratio of Osteoid Volume / Total Volume (DO: 0.6774 ± 0.1193, XRT/DO: 0.4505 ± 0.08487, p=0.000), increased Bone Volume / Total Volume (DO: 0.3226 ± 0.11930 XRT/DO: 0.5495± 0.08487, p=0.000), and decreased Osteoid Volume / Bone Volume (DO: 2.7762 ± 2.31595, XRT/DO: 0.8578 ± 0.27674, p=0.017) .
Conclusion:
A robust endogenous substrate is essential to distraction osteogenesis. Osteoid formation was impaired by radiation therapy and irradiated bone demonstrated hypermineralization. Thus, we demonstrated quantitative metrics of radiation-induced diminution of the matrix of bone, establishing an isogenic model for future remediation with cell- and tissue-based reconstructive therapies.
