Influence of Metastatic Bone Lesion Type and Tumor Origin on Human Vertebral Bone Architecture, Matrix Quality, and Mechanical Properties

Abstract

Metastatic spine disease is incurable, causing increased vertebral fracture risk and severe patient morbidity. Here, we demonstrate that osteolytic, osteosclerotic, and mixed bone metastasis uniquely modify human vertebral bone architecture and quality, affecting vertebral strength and stiffness. Multivariable analysis showed bone metastasis type dominates vertebral strength and stiffness changes, with neither age nor gender having an independent effect. In osteolytic vertebrae, bone architecture rarefaction, lower tissue mineral content and connectivity, and accumulation of advanced glycation end-products (AGEs) affected low vertebral strength and stiffness. In osteosclerotic vertebrae, high trabecular number and thickness but low AGEs, suggesting a high degree of bone remodeling, yielded high vertebral strength. Our study found that bone metastasis from prostate and breast primary cancers differentially impacted the osteosclerotic bone microenvironment, yielding altered bone architecture and accumulation of AGEs. These findings indicate that therapeutic approaches should target the restoration of bone structural integrity.

Chemotherapy and adjuvant therapies' impact on the internal remodeling process of bone and its mechanical behavior for breast cancer patients

“…Research into bone quality under the purview of reference 29 has demonstrated that bone metastasis from prostate and breast cancers significantly affects bone quality. This study identifies notable reductions in vertebral strength and stiffness under these conditions, which supports and justifies our observations in (Figure 5).…”

Sclerotic prostate cancer bone metastasis: woven bone lesions with a twist

“…The same group performed a higher resolution analysis at 6 um isometric voxel size, of 4 mm side cubes from vertebrae with PCBM obtained from two patients, and described a higher BV/TV, bone surface, trabecular number, trabecular connectivity, anisotropy and fractal dimensions in PCBM ( 10 ). More recently, mCT scanning at an isometric voxel size of 10.5 μm was used to analyzed 5 mm diameter cores obtained from cadaveric vertebra with metastasis from two men who died of PC, 3 patients who died of breast cancer and 3 from lung cancer ( 11 ). By complimenting this morphological analysis with mechanical testing and biochemical analysis, the PCBM cores were scored as sclerotic, lytic, or mixed, but for the statistical analysis, all samples were grouped according to imaging classification, thus no conclusion can be made from the specific cancer type.…”

“…Although informative, these are relatively low-resolution histologic descriptors, and only a handful of studies have ventured into high-resolution, or three-dimensional analysis of PCBMs. For instance, a series of synchrotron-based high-resolution micro-computer tomography (μCT) scans from two patient samples ( 9, 10 ), demonstrated alterations in bone mineral density and trabecular morphology and structure, and recently, a high-resolution μCT scan reported similar structural changes in PCBMs obtained from two patients ( 11 ). These highly relevant descriptions are limited by sample size, and they require further validation to draw definitive conclusions.…”

O-arm-guided percutaneous microwave ablation and cementoplasty for the treatment of pelvic acetabulum bone metastasis

“…With the development and advancement of various new anticancer drugs, next-generation sequencing, targeting, and immunotherapy, the treatment mode of patients with bone metastasis has gradually shifted to a chronic disease management mode. Long-term systemic follow-up and the continuous adjustment of drugs according to the patient's condition can confer long-term survival benefits, which is particularly important for improving tumor-bearing survival and QoL ( 6 ).…”