Radioprotectant combinations spare radiation-induced damage to the physis more than fractionation alone

Purpose: The aim of this study was to determine if fractionation and individual or combinations of radioprotectants could minimize damage to physeal longitudinal growth in an animal model to any greater extent than fractionation alone. Materials and methods: Sixty-three weanling male Sprague-Dawley rats were randomized into seven equal groups. Five groups received a total 25 Gy radiation exposure in three equal fractions to the right knee with the left as non-irradiated control. For each group, pentoxifylline, misoprostol, and amifostine were given individually and amifostine was also given in combination with each of the other drugs prior to the radiation fractions. One group each received 25 Gy in one or three fractions without radioprotection. At six weeks, limb lengths and histomorphometry were assessed. Results: The single fraction of 25 Gy caused a mean tibial length discrepancy of 24.4%. Fractionation decreased this to 18.8% (p < 0.001). Beyond fractionation alone, the mean femoral length discrepancies were significantly decreased by each of the added individual and combination radioprotectant drugs (p < 0.0004). The smallest absolute femoral length discrepancy (11%) was achieved with fractionation and the combination of amifostine and misoprostol. Conclusions: Radioprotectants may be beneficial in growth plate radioprotection, alone or in combination.