Mechanical behavior of metastatic vertebrae are influenced by tissue architecture, mineral content, and organic feature alterations

Abstract

Diminished vertebral mechanical behavior with metastatic involvement is typically attributed to modified architecture and trabecular bone content. Previous work has identified organic and mineral phase bone quality changes in the presence of metastases, yet limited work exists on the potential influence of such tissue level modifications on vertebral mechanical characteristics. This work seeks to determine correlations between features of bone (structural and tissue level) and mechanical behavior in metastatically involved vertebral bone. It is hypothesized that tissue level properties (mineral and organic) will improve these correlations beyond architectural properties and BMD alone. Twenty-four female athymic rats were inoculated with HeLa or Ace-1 cancer cells lines producing osteolytic (N = 8) or mixed (osteolytic/osteoblastic, N = 7) metastases, respectively. Twenty-one days post-inoculation L1-L3 pathologic vertebral motion segments were excised and μCT imaged. 3D morphometric parameters and axial rigidity of the L2 vertebrae were quantified. Sequential loading and μCT imaging measured progression of failure, stiffness and peak force. Relationships between mechanical testing (whole bone and tissue-level) and tissue-level material property modifications with metastatic involvement were evaluated utilizing linear regression models. Osteolytic involvement reduced vertebral trabecular bone volume, structure, CT-derived axial rigidity, stiffness and failure force compared to healthy controls (N = 9). Mixed metastases demonstrated similar trends. Previously assessed collagen cross-linking and proline-based residues were correlated to mechanical behavior and improved the predictive ability of the regression models. Similarly, collagen organization improved predictive regression models for metastatic bone hardness. This work highlights the importance of both bone content/architecture and organic tissue-level features in characterizing metastatic vertebral mechanics. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.

Biomechanical Properties of Metastatically Involved Osteolytic Bone

“…Other metastatic bone models have suggested reduced bone tissue modulus with breast cancer involvement [47]. In contrast, nanoindentation performed on osteolytic metastatic rat vertebrae found no significant tissue level differences between the hardness and modulus of osteolytic and healthy samples [20].…”

“…Collagen organization has also been shown to affect modulus and hardness [17,18]. Osteolytic metastatic involvement has been shown to impact collagen organization in both trabecular and cortical bone, with increased collagen fibril disorganization associated with reduced hardness and modulus [19][20][21][22]. While modifications in collagen fibril diameter have been associated with changes in intrafibrillar cross-linking, which in turn, have been associated with changes in bone strength and post-yield properties [23][24][25], no significant differences have been seen between the collagen fibril diameter of osteolytic and healthy bone [19].…”

“…This increase in localized mineral homogeneity could lead to increased bone brittleness and fracture risk [40,41]. Osteolytic bone has also been shown to reduce the tissue mineral content [39] which has a strong correlation to trabecular bone modulus and hardness [20].…”

“…Stereological parameters including trabecular thickness, trabecular number, trabecular spacing and trabecular bone volume have been used to quantify changes in architecture of bone in osteolytic murine models in the femurs and the spinal column [44,68]. The architecture of osteolytic trabecular bone has been characterized by decreased trabecular number and thickness and increased trabecular spacing when compared to non-pathologic bone [20,35,37,44,69,70].…”

“…There are limited experimental studies that have tested mechanical performance of osteolytic disease in human tissue due to the inaccessibility of specimens [35,76,77]. Animal models of skeletal metastatic disease have been widely used in this context as they can incorporate both architectural and tissue material differences to better replicate osteolytic lesions when compared to simulated defects [20,44,68,69,78].…”