Content area
Abstract
Approximately 1/3 of all cancer patients suffer from spinal metastases. These metastases impact the equilibrium of the bone remodeling process, exhibiting excess bone-formation (osteoblastic), excess bone-resorption (osteolytic) or a mixture of the two. Previous work has assessed the impact of metastatic involvement on bone microarchitecture and mineral content, establishing relationships between these characteristics and mechanical behaviour. However, less well characterized are the effects of metastatic growth on the intrinsic features of the composite that is bone tissue.
In combination with previously established methodologies to characterize the microarchitecture and mineral content of metastatic vertebrae, this work sought to utilize multiple imaging and analytical techniques to characterize the hydroxyapatite and collagen constituents of healthy and metastatic vertebral bone tissue from established athymic rat models of osteolytic and mixed vertebral metastases.
Whole-bone measured changes were observed in collagen cross-linking and mineral crystal dimensions, within osteolytic vertebrae compared to healthy controls. Locally measured collagen organization and mineralization of bone tissue were found to be modified with metastatic involvement; with pathological osteoblastic new bone growth demonstrating stark differences compared to healthy controls. Tissue-level collagen features, assessed both globally (collagen cross-linking, proline concentration) and locally measured (collagen organization), were correlated to whole vertebral mechanical behaviour and the material level behaviour of bone tissue respectively. These changes in collagen cross-linking and organization, secondary to metastasis, were shown to significantly impact both tissue-level and whole vertebral mechanical behaviour independent of mineral content and bone microarchitecture.
This work has created a robust characterization of the impact of metastasis on vertebral bone quality. As such, it provides a foundation from which it is possible to study the effects of treatments on metastatically-involved vertebral bone, which may ultimately improve the prediction of failure and direct treatment optimized to individual patients with spinal metastases.
