The Effect of Tumor-Induced Bone Remodeling and Efficacy of Anti-Resorptive and Chemotherapeutic Treatments in Metastatic Bone Loss

摘要

We investigated the changes in bone geometrical properties due to tumor-induced osteolysis and the efficacy of two different treatments, Ibandronate (anti-resorptive) and Paclitaxel (anti-cancer), in an experimental rat model. Osteolytic Walker 256 (W256) carcinosarcoma cells were surgically implanted into the right femur of 30 male Sprague Dawley rats, while another 12 received sham operation. Of the 30 tumor-bearing rats, 12 were untreated, 9 were administered with Ibandronate and 9 with Paclitaxel. Both femora were scanned using micro-computed tomography (micro-CT). Serum DPD (deoxypyridinoline) concentration was monitored via regular blood collection to observe the progress of bone resorption. Localized tumor growth in the distal femur was successfully induced in this rat model. Bone volume analysis indicated no bone loss in the sham-operated femora for the control group and in the tumor-bearing femora for the I-bandronate-treated group. However, a significantly lower bone volume by average 10.7% was observed in the operated as compared to the intact femur for the tumor-bearing untreated group, corresponding to a 13.4% increase in DPD concentration after 30 days. For the Ibandronate-treated group, bone volume was the highest for both femora and DPD concentration showed a drastic reduction of 38.2% after 30 days. Bone loss in the Paclitaxel-treated group seemed lower than in the tumor-bearing untreated group but there was a discrepancy between serum DPD concentration and micro-CT results, possibly due to incomplete data (rat mortality). Based on this experimental rat model with tumor-induced osteolysis, I-bandronate was more effective than Paclitaxel in reducing the rate of bone resorption, and hence preserving the structural integrity of the femur. This study has demonstrated the use of serum analysis and micro-CT as tools to monitor the biochemical and structural changes that accompany tumor-induced osteolysis respectively.