A novel rat model for the study of intraosseous metastatic spine cancer

Abstract

Object. Although metastatic spinal disease constitutes a significant percentage of all spinal column tumors, an accessible and reproducible animal model has not been reported. In this study the authors describe the technique for creating an intraosseous spinal tumor model in rats and present a functional and histological analysis. Methods. Eighteen female Fischer 344 rats were randomized into two groups. Group 1 animals underwent a transabdominal exposure and implantation of CRL-1666 breast adenocarcinoma into the L-6 vertebral body (VB). Animals in Group 2 underwent a sham operation. Hindlimb function was tested daily by using the Basso-Beattie-Bresnahan scale. Sixteen days after tumor implantation, animals were killed and their spines were removed for histological assessment. Statistical analysis was performed using the Wilcoxon signed-rank test. By Day 15 functional analysis showed a significant decrease in motor function in Group 1 animals (median functional score 2 of 21) compared with Group 2 rats (median functional score 21 of 21) (p = 0.0217). The onset of paraparesis in Group 1 occurred within 14 to 16 days of surgery. Histopathological analysis showed tumor proliferation through the VB and into the spinal canal, with marked osteolytic activity and spinal cord compression. Conclusions. Analysis of these findings demonstrates the consistency of tumor growth in this model and validates the utility of functional testing for onset of paresis. This new rat model allows for the preclinical evaluation of novel therapeutic treatments for patients harboring metastatic spine disease.