Purpose: Distraction osteogenesis (DO) is a powerful tool for reconstructing mandibular defects. The primary application of DO has been in the setting of congenital mandibular deformities; however, the utilization of DO for tissue replacement after oncologic resection or as a reconstructive option for deformations secondary to irradiation could have immense therapeutic ramifications.
The potential role of DO following therapeutic radiation remains unknown. Although a small number of anecdotal clinical cases have been reported, a reproducible animal model is essential for scientific analysis and enhancement of the process. The following study was carried out to investigate the effects of pre-operative external beam irradiation on rat mandibular distraction osteogenesis.
Methods: Male Sprague-Dawley rats underwent 30 Gray (N=9) of external beam irradiation of the mandible (fractionated 3 Gray per day x 10 days). Following a 2-week healing period, an external frame distractor was applied and an osteotomy placed posterior to the molar teeth. The mandible was distracted 0.3 mm twice per day, a total distance of 5.1 mm. Controls (N=10) included rats undergoing DO without irradiation.
Results: Nine rats completed radiation and surgery without difficulty. No infections occurred and the post-operative course did not differ from controls. Following consolidation, morphologic assessment of the irradiated mandibles displayed successful lengthening, however, there were obvious holes within the gap tissue and the bone was thin and brittle relative to controls. Radiographic evaluation revealed marked differences in the distracted irradiated mandibles, demonstrating osteopenia and poor bone healing.
Histologic analysis confirmed and delineated significant differences when compared to controls including an increased incidence of nonunion.
Conclusion: The potential use of DO for reconstruction of oncologic defects is appealing, but little reliable information exists regarding the effects of therapeutic radiation on the regenerated bone. Our results demonstrate that bone formation does occur during DO of the irradiated rat mandible. However, animals subjected to a therapeutic dose of pre-operative irradiation showed suboptimal results including osteopenia, incomplete bridging of the distraction gap, and in some cases gross bony defects or nonunion. Although physical lengthening was achieved there was a consistent detrimental effect of irradiation on the normal process of DO and a significant risk of complication. This rat model provides an important system for investigating bone formation during distraction of an irradiated bed, lending itself to the analysis of molecular events and structural properties that will help define a scientific basis for the optimization of DO as a tool for oncologic reconstruction.
View Synopsis (.doc format, 25.0 kb)