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

Abstract

The devastation radiation therapy (XRT) causes to endogenous tissue in patients with head and neck cancer can be a prohibitive obstacle in reconstruction of the mandible, demanding a better understanding of XRT-induced damage and options for reconstruction. This study investigated the cellular damage caused by radiation in an isogenic murine model of mandibular distraction osteogenesis (DO). The authors posited that radiation would result in fewer osteocytes, with increased empty lacunae and immature osteoid. Twenty Lewis rats were randomly assigned to a DO group (n= 10) or aXRT/DO group (n= 10). These 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 35Gy before surgery. Animals were sacrificed on postoperative day 40 and mandibles were harvested and sectioned for histologic analysis. Bone that underwent radiation showed a significantly decreased osteocyte count and complementary increase in empty lacunae compared with non-XRT bone (P= .019 and P= .000). In addition, XRT bone exhibited increased immature osteoid and decreased mature woven bone compared with nonradiated bone (P= .001 and P= .003, respectively). Furthermore, analysis of the ratio of immature osteoid to woven bone volume exhibited a significant increase in the XRT bone, further showing the devastating damage from XRT (P= .001). These results clearly show the cellular diminution that occurs as a result of radiation. This foundational study provides the groundwork on which to investigate cellular therapies in an immuno-privileged model of mandibular DO.