Transiently increased bone density after irradiation and the radioprotectant drug amifostine in a rat model

At therapeutic levels in pediatric patients, radiation causes damage to the growth plate and contributes to growth deformity and fractures. The purpose of this project was to examine the effects of x-ray irradiation on regional bone mineral density (BMD) and osteoclast histology of rat bone with and without radioprotectant amifostine (AMF) pretreatment. Seventy-two weanling rats had their right knee irradiated with single fraction 17.5 Gy, whereas the left leg was used as an internal control. Twelve animals were euthanized at each of 6 time periods (0.5-6 wk) after irradiation, half having received 100 mg/kg amifostine. BMD (g/cm3) was determined for both the right and left femurs using peripheral quantitative computed tomography (CT) (pQCT). Tibial sections were stained for osteoclasts/chondroclasts with tartrate-resistant acid phosphatase. Statistically significant increases in BMD within the radiation field were seen in the treatment groups' right irradiated legs over the control unirradiated left legs at all time points from 0.5 through 6 weeks. Anatomically, a peak in BMD occurs in the region immediately adjacent to the chondro-osseous junction at 2 weeks after irradiation and then moves proximally within the adjacent metaphysis after 3 weeks. Corresponding to these findings, histologically a 2-week nadir occurs after irradiation in osteoclasts/chondroclast numbers adjacent to the chondro-osseous junction with a 71.9% decrease compared with controls (p <0.05). At 3 weeks, the numbers of osteoclasts/chondroclasts in this region have increased to 47.4% greater than the control legs (p <0.03) The animals receiving amifostine had BMD that was consistently closer to controls only adjacent to the chondro-osseous junction at 0.5, 2, and 3 weeks and osteoclast/chondroclast numbers that were closer to controls only at 4 weeks.