Amifostine before fractionated irradiation protects bone growth in rats better than fractionation alone
The aim of this study was to determine the independent and combined effects of 100 mg/kg and 200 mg/kg doses of the radioprotectant amifostine and radiotherapy dose fractionation in preserving the integrity of or minimizing damage to the physis during high-dose radiation exposure in an animal model. Thirty-six weanling four-week-old male Sprague-Dawley rats were randomized into six study groups of six animals each. The distal femur and proximal tibia in the right leg of each animal was exposed to X-irradiation, with the contralateral left leg serving as the nonirradiated control. Three groups received a single 25 Gy radiotherapy dose: one group alone, a second group preceded by 100 mg/kg amifostine, and a third preceded by 200 mg/kg amifostine. Three groups received a total of 25 Gy in three equal fractions: one group alone, a second group preceded by 100 mg/kg amifostine, and a third preceded by 200 mg/kg amifostine. Fractionation of the 25 Gy radiation dose reduced the mean percent overall limb growth loss to 44.8%, a statistically significant reduction compared to a mean 58.8% reduced growth with the single 25 Gy dose. Addition of amifostine at 100 and 200 mg/kg before each of the three fractions of radiotherapy further decreased the mean percent overall limb growth loss to 35.2% and 28.5%, respectively, both statistically significant reductions beyond that achieved by fractionation alone.