Radiation-induced craniofacial bone growth inhibition: Development of an animal model

Craniofacial deformities caused by therapeutic radiation-induced bone growt h inhibition can occur in up to 100% of survivors of childhood head and nec k cancers. The mechanism of radiation-induced craniofacial bone growth inhi bition is poorly understood. The objective of this study is to establish a model of radiation-induced craniofacial bone growth inhibition to study the pathophysiology of radiation on growing membranous bone. Seven-week-old ma le New Zealand white rabbits were randomized into 4 groups (n = 10/group) a nd received a single dose of orthovoltage radiation (0, 15, 25, or 35 Gy) t o the right orbital-zygomatic complex. Serial radiographs and computed tomo graphy scans were performed for cephalometric analysis, bone volume, and bo ne density measurements until skeletal maturity at 21 weeks. Statistically significant (P < 0.05) reductions in orbital-zygomatic complex linear bone growth, bone volume, and bone density were found after radiation with 25 or 35 Gy compared with nonirradiated control animals. A significant (P < 0.05 ) decrease in orbital-zygomatic complex volume was noted after 15-Gy radiat ion but there were no significant effects on linear bone growth as assessed by cephalometric analysis at this dose. This study establishes the rabbit orbital-zygomatic complex as a suitable model for the study of radiation-in duced craniofacial bone growth inhibition and will permit investigation int o the underlying cellular and molecular basis of this injury.