Effects of Single-Dose Versus Hypofractionated Focused Radiation on Vertebral Body Structure and Biomechanical Integrity: Development of A Rabbit Radiation-Induced Vertebral Compression Fracture Model.

Abstract Purpose Vertebral compression fracture (VCF) is a common complication of spinal stereotactic body radiation therapy. Development of an in vivo model is crucial to fully understand how focal radiation treatment affects vertebral integrity and biology at various dose fractionation regimens. We present a clinically-relevant animal model to analyze the effects of localized, high-dose radiation on vertebral microstructure and mechanical integrity. Using this model, we test the hypothesis that fractionation of radiation dosing can reduce focused radiation therapy's harmful effects on the spine. Methods and Materials The L5 vertebra of NZW rabbits was treated with either a 24 Gy single-dose of focused radiation or three fractionated 8-Gy doses over three consecutive days via the small animal radiation research platform (SARRP, Xstrahl). Nonradiated rabbits were used as controls. Rabbits were euthanized 6-months post-irradiation, and their lumbar vertebrae harvested for radiological, histological, and biomechanical testing. Results Localized single-dose radiation led to decreased vertebral bone volume (BV) and trabecular number (Tb.N.) and a subsequent increase in trabecular spacing (Tb.Sp.) and thickness (Tb.Th.) at L5. Hypofractionation of the radiation dose similarly led to reduced Tb.N. and increased Tb.Sp. and Tb.Th., yet preserved normalized BV. Single-dose irradiated vertebrae displayed lower fracture loads and stiffness compared to those receiving hypofractionated irradiation and controls. Hypofractionated and control groups exhibited similar fracture load and stiffness. For all vertebral samples, BV, Tb.N., and Tb.Sp. were correlated with fracture loads and Young's modulii (p Conclusions Single-dose focal irradiation showed greater detrimental effects than hypofractionation on the micro-architectural, cellular, and biomechanical characteristics of irradiated vertebral bodies. Correlation between radiological measurements and biomechanical properties supported the reliability of this animal model of radiation-induced VCF which can be applied to future studies of preventative measures.