A Histomorphometric Analysis of Radiation Damage in an Isogenic Murine Model of Distraction Osteogenesis


Alexander R. Zheutlin, BS, Sagar S. Deshpande, BS, Noah S. Nelson, BS, Yekaterina Polyatskaya, MD, Jose J. Rodriguez, MD, Alexis Donneys, MD, MS, Steven R. Buchman, MD


Purpose The devastation radiation therapy (XRT) causes to endogenous tissue in head and neck cancer (HNC) patients can be a prohibitive obstacle in reconstruction of the mandible, demanding a better understanding of XRT-induced damage and options for reconstruction. Our study investigates the cellular damage caused by radiation in an isogenic murine model of mandibular distraction osteogenesis (DO). We posit that radiation will result in reduced osteocytes, with elevated empty lacunae and immature osteoid.

Methods Twenty Lewis rats were randomly assigned to two groups: DO (n=10) and XRT/DO (n=10). Both groups underwent an osteotomy and mandibular DO across a 5.1 mm gap. XRT was administered to the XRT/DO group at a fractionated, human equivalent dose of 35 Gy prior to surgery. Animals were sacrificed on postoperative day 40 and mandibles were harvested and sectioned for histological analysis.

Results Bone that underwent radiation revealed a significantly decreased osteocyte count and complementary increase in empty lacunae when compared to non-XRT bone (p=0.019, p=0.000). Additionally, XRT bone demonstrated increased immature osteoid and decreased mature woven bone when compared to non-radiated bone (p=0.001 and p=0.003, respectively). Furthermore, analysis of the ratio of immature osteoid to woven bone volume exhibited a significant increase in the XRT bone, further revealing the devastating damage brought by XRT (p=0.001).

Conclusion These results clearly demonstrate the cellular diminution that occurs as a result of radiation. This foundational study provides the groundwork upon which to investigate cellular therapies in an immunoprivileged model of mandibular DO.

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