Posters— Radiation Oncology

BONE DENSITY EFFECTS OF RADIATION AND THE RADIOPROTECTANT DRUG AMIFOSTINE IN A RAT MODEL

Morgan H, Damron TA, Margulies B, Spadaro J Upstate Medical University Department of Orthopaedic Surgery, Syracuse, NY 13224

Purpose: The purpose of this project was to examine the effects on the bone density measurements of irradiated rat femurs with and without the radioprotective drug amifostine (AMF).

Methods: Seventy-two weanling Spague-Dawley rats were randomized into treatment groups. In all treated animals, the right knee (distal femur and proximal tibia) was irradiated with single fraction 17.5 Gy while the left leg was used as an internal control. Animals were sacrificed at 0.5, 1, 2, 3, 4, and 6 weeks following irradiation, 12 per time period. One half of the animals in each of the groups received 100 mg/kg amifostine twenty minutes prior to irradiation. For the bone density analysis, the skeletonized femurs were placed into a cylindrical holder and suspended in deionized water. Bone density (g/cm ) was determined using peripheral quantitative computed tomography (pQCT, Norland XCT 2000, Fort Atkinson, WI), resolution 90 microns.

Results: The irradiated slices maintained a significantly higher BMD than controls through 6 weeks in the most proximal metaphysis and through 3 weeks in the distal metaphysis.(Fig. 1) The slice closest to the metaphyscal side of the physis demonstrated a unique early peak BMD at 2 weeks which decreased dramatically by 3 weeks. The BMD for rats that received amifostine was significantly lower through 3 weeks than for rats that received radiation alone (p<0.02 for 0.5, 2, and 3 weeks).

Discussion: Three conclusions are drawn from the current data. First, at early time periods following irradiation, BMD within the irradiatio field is greater than control in this animal model Second, a 2 week early peak in BMD occurs in the juxta-physeal metaphysis. Third, amifostine has a significant effect in holding BMD close to normal in the juxta-physeal region. We hypothesize that the sensitive marrow elements, particularly in this case the monocyte precursor. of osteoclasts, are more sensitive to irradiation damage than the osteoblasts, given the slower turnover of the latter cells. In addition, we hypothesize that the early 2 week peak in BMD occurs only in the distal metaphysis due to the greater relative contribution of provisional calcification to BMD there, since this calcificati is a passive process which is likely to continue despite radiation effects, particularly when unchecked by resorptive activity of chondroclasts and osteoclasts. These hypotheses are supported by histological observations.