Influence of Metastatic Bone Lesion Type and Tumor Origin on Human Vertebral Bone Architecture, Matrix Quality, and Mechanical Properties.
Influence of Metastatic Bone Lesion Type and Tumor Origin on Human Vertebral Bone Architecture, Matrix Quality, and Mechanical Properties.
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DOI：
10.1002/jbmr.4539
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发表时间：
2022-05
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转移性脊柱疾病是无法治愈的，导致椎体骨折风险增加和严重的患者发病率。在此，我们证明溶骨性、骨转移性和混合性骨转移性改变了人类脊椎骨的结构和质量，影响了脊椎骨的强度和刚度。多因素分析显示，骨转移类型主导椎体强度和刚度的变化，年龄和性别均无独立影响。在溶骨性椎骨中，骨结构稀疏，组织矿物质含量和连接性降低，以及晚期糖基化终产物（AGEs）的积累影响了较低的椎骨强度和刚度。在骨质疏松的椎骨中，高骨小梁数量和厚度但低AGEs，提示高度的骨重建，产生高的椎骨强度。我们的研究发现，前列腺癌和乳腺癌原发性骨转移对骨硬化微环境的影响不同，导致骨结构改变和AGEs积累。这些发现表明，治疗方法应针对骨结构完整性的恢复。
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.
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