Evaluating the effects of mixed osteolytic/osteoblastic metastasis on vertebral bone quality in a new rat model

Abstract

Spinal metastases often show mixed areas of enhanced (osteoblastic) bone growth adjacent to areas of thinning (osteolytic) bone. This study aims to quantitatively characterize bone quality and tumor burden within a new rat model of mixed osteolytic/osteoblastic spinal metastases. Mixed vertebral metastases were analyzed in nude rats 21-days post intracardiac injection of Ace-1 canine prostate cancer cells. Vertebral micro-architecture was assessed in µCT images. Histologic processing quantified tumor burden (PTHrP), osteoclast activity (TRAP), and osteoid formation (Goldner's Trichrome) in ½ of all samples. Remaining samples were mechanically tested to failure in compression. Metastatically involved vertebrae exhibited extreme osteolysis, evident through an increase in osteoclasts leading to significantly reduced trabecular bone volume. Metastatically involved vertebrae also exhibited increased osteoid characteristic of osteoblastic lesions. While mechanical properties in tumor-bearing vertebrae were not significantly decreased compared to controls, a strong correlation was found between trabecular volumetric BMD and ultimate force. The highly aggressive Ace-1 skeletal metastases demonstrated predominant osteolysis with some areas of immature, new osteoblastic bone formation. Bone quality resulting from these lesions consisted of decreased structural properties, but without a significant impact on mechanical integrity.