The effect of an osteolytic tumor on the three-dimensional trabecular bone morphology in an animal model

Objective. To investigate the application of micro-computed tomography (mu CT) for the assessment of density differences and deterioration of three-dimensional architecture of trabecular bone in an experimental rat model for tumor-induced osteolytic defects. Design and materials. Walker carcinosarcoma 256 malignant breast cancer cells (W256) were surgically implanted into the medullary canal of the left femur of 15 4-month-old rats. Twenty-eight days after surgery all animals were killed and both femora from each rat were harvested. A total of 30 specimens (left and right femur) were scanned in a desktop mu CT imaging system (mu CT 20, Scanco Medical) to assess densitometric and architectural parameters. For each specimen a total of 200 micro-tomographic slices with a resolution of 30 mum in the distal metaphysis was taken. Bone mineral content (BMC) was analyzed for both cortical and trabecular bone (ctBMC), and for trabecular bone only (tBMC). Architectural indices (BV/TV, Tb.N, Tb.Th, Tb.Sp) according to standard definitions used in histomorphometry were calculated for trabecular bone. Results. The quantitative analysis of density parameters revealed significantly (P<0.001) lower values for ctBMC and tBMC in the tumor-bearing group (T) of 26% and 31%, respectively, compared with the contralateral control group. The quantitative analysis revealed significant (P<0.001) changes in the architectural parameters in the tumor-bearing bones compared with the contralateral control group: BV/TV was 30% lower, Tb.N and BS/TV decreased by 24% and 21%, respectively, Tb.Th. decreased by 10% and Tb.Sp. increased by 94%. Conclusions. This study demonstrates that mu CT is able to provide three-dimensional parameters of bone mass and trabecular structure in an animal model for tumor-induced bone loss. Recent advances in therapeutic approaches for skeletal diseases such as osteoporosis and metastatic bone disease rely on an understanding of the effects: of the agents on the mechanical properties of bone. In order to quantify the structural changes of the affected bones the application of a non-destructive method is mandatory. The use of mu CT seems to be a great advantage, since biomechanical tests and further histologic analysis can be done for the same specimens.