Purpose: To identify local and systemic risk factors for the development of pathologic fractures and determine the value of the Tokuhashi Score in patients with known asymptomatic lytic spinal metastases secondary to breast cancer.

Method: A prospective cohort study was carried out on 51 patients with lytic spinal metastases secondary to breast cancer identified as having either purely lytic or mixed disease. The Tokuhashi Score, developed to estimate life expectancy for patients with symptomatic spinal metastases being considered for surgery, was calculated for each of the 51 patients. The score consists of six parameters each of which is rated from 0–2. Initial and follow up CT images and pain and function data were obtained every four months for one year. A final review of patient charts was performed two years later to determine if each patient was still alive.

Results: Tumour burden was predominantly blastic and mixed rather than lytic. There was no progression of lytic tumour burden over the 12-month period, however there was progression of blastic tumour load. Eleven compression fractures occurred in seven patients; no burst fractures occurred during the study. No correlation between tumour burden (lytic, blastic or both) and risk of fracture was found. A weak correlation between bone mineral density and length of time elapsed from diagnosis of metastatic disease and fracture risk was found. Pain and functional data results were not related to tumour load. Tokuhashi score did correlate with survival, however actual survival in our population was far longer than that found in previous studies. Negative progesterone status was found to be negatively associated with life expectancy.

Conclusion: Metastatic vertebral disease in breast cancer patients has a predominantly blastic and mixed appearance with current pharmacologic therapies. Pathologic fracture risk appears to be more related to bone mineral density than tumour burden in this population. Tokuhashi score does correlate with life expectancy in patients with relatively asymptomatic spinal metastases. Having a progesterone receptor negative tumour has a significantly negative impact on life expectancy.

Purpose: The distribution of weight bearing area within the acetabulum is of importance in addressing trauma to the acetabulum, hip joint deformities and causes of osteoarthritis. According to Wolf’s law, bone density can indicate loading patterns experienced. The objective of this study was to characterize distributions of acetabular bone density patterns by regions in the normal population.

Method: CT scans of 22 subjects, mean age 70.6 with no evidence to hip joint pathologies were analysed. Bone density distribution maps were generated within AmiraDEV4.1 image analysis software using custom written plugins (Visage Imaging, Carlsbad, USA). Acetabular cup surfaces were semi-automatically segmented from the reconstructed CT volumes with an atlas-based approach. The acetabular cups were expanded 2.5 mm into the acetabular bone, and surface bone densities were calculated as the average bone density within ±2.5mm. The distribution maps were analysed using zones to spatially classify areas of high and low bone density in a healthy population. The acetabular cups were aligned using the acetabular rim plane that was landmarked, and by rotating the cups, such that a 900 abduction angle and a 00 anteversion angle were achieved. The grid used was divided to quadrants, and subdivided into radial thirds of the average rim radius. The correspondence of left and right density maps was investigated by comparing the average bone density in corresponding zones and across the population.

Results: High bone densities were found around the roof of the acetabulum aligning with the femoral mechanical axis during standing. The highest average bone density were found to be the superior and posterior walls of the acetabulum, corresponding to regions 8, 9, and 12 compared to other regions of the acetabuli (P< 0.01). A strong correlation was found between left and right sides within subjects (R=0.91, P< 0.05); and weaker correlation was also found for overall average bone density, (R=0.77, P< 0.05).

Conclusion: The location of the zones with the highest average bone density agrees with cadaveral studies of the maximum contact stress in the acetabulum (zones 9 and 12). [1,2]. It may explain why trauma to these areas carries a higher risk for early arthritic changes.

Purpose: The objective of this study is to develop and utilize a highly automated microCT based analysis tool to quantify microstructural differences in bone due to metastatic involvement in whole rat vertebrae.

Method: First and Third lumbar vertebrae from healthy (n=4) and metastatically involved (n=4) rnu/rnu rats were excised for analysis (total of 8 vertebrae). Lytic metastases were developed via intracardiac injection of MT1 human breast cancer cells. The specimens were scanned using microCT at 17.5 microns isotropic resolution. A highly automated algorithm was developed for whole vertebral segmentation based on the microCT data, including the posterior elements (AmiraDev3.1). This was accomplished using an atlas-based method incorporating demons deformable registration followed by refinement through level set curvature evolution. Volumetric concurrency was used to compare segmentations generated by the automated algorithm to manually refined segmentations. The segmentations were up-sampled by 4 and edge-enhanced and further segmented using a thresholding technique to have a clear segmentation of the individual trabeculae without advancing into the bone marrow(AmiraDev3.1). The cortical shell was removed automatically before analyzing the trabecular structure. Cortical bone volume(CBV) was calculated by subtracting the volume of the full segmentation from the segmentation with no cortical shell. The interior segmentation was then used to calculate Trabecular Bone Volume(TBV), Trabecular Thickness(TbTh), Trabecular Separation(TbSp), Trabecular Number(TbN) based on the expressions described by Parfitt, et al(1983). Finally mean intercept length(MIL) was used to calculate the anisotropy of the trabecular tissue. Analysis were carried out on both the healthy and metastatically involved vertebrae.

Results: The automated algorithm including the level set method refinement produced good tracking of the boundaries of entire rat vertebrae. Consistent results yielded significant reduction in TBV, slight reduction in TbN and TbTh, and significant increase in TbS in metastatic vertebrae compared to healthy. no significant differences were observed in CBV. The metastatic vertebrae was also found to be significantly more anisotropic than the healthy group.

Conclusion: The accuracy of the highly automated algorithm developed in this study to analyze microstructure in whole rat vertebrae make it a suitable tool for further analyzing the effects of existing and new treatments for spinal metastases at a preclinical level.