Glucocorticoid induced osteoporosis (GIOP) is the most common negative consequence of long-term glucocorticoid treatment, leading to increased fracture risk followed by loss of mobility and high mortality risk. These biologically induced changes in bone quality at molecular level lead to changes both in bone matrix architecture and bone matrix composition. However, the quantitative details of changes in bone quality - and especially their link to reduced macroscale mechanical properties are still largely missing. In this study, a mouse model for glucocorticoid-induced osteoporosis (GIOP) was used to investigate mechanical and material alterations in bone cortex (natural nanocomposite) at different scale. By combining quantitative backscattered electron (qBSE) imaging, nanoindentation and high brilliance synchrotron X-ray nanomechanical imaging on a genetically modified mouse model of GIOP, we were able to quantify the local indentation modulus, mineralization distribution and the alterations of nanoscale structures and deformation mechanisms in the mid-diaphysis of femur, and relate them to the macroscopic mechanical changes. Our results showed clear and significant changes in terms of material quality of bone at nanoscale and microscale, which manifests itself in development of spatial heterogeneities in mineralization and indentation moduli across the bone organ, with potential implications for increased fracture risk.

中文翻译：

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骨基质组成、结构和力学性能的研究反映了糖皮质激素诱导的骨质疏松症中皮质骨的结构-功能关系

糖皮质激素诱发的骨质疏松症 (GIOP) 是长期糖皮质激素治疗最常见的负面后果，导致骨折风险增加，其次是活动能力丧失和高死亡率风险。这些在分子水平上生物诱导的骨质量变化导致骨基质结构和骨基质组成的变化。然而，骨骼质量变化的定量细节——尤其是它们与宏观力学性能降低的联系，仍然在很大程度上缺失。在这项研究中，使用糖皮质激素诱导的骨质疏松症 (GIOP) 的小鼠模型来研究不同规模的骨皮质（天然纳米复合材料）的机械和材料变化。通过结合定量背散射电子 (qBSE) 成像，通过对 GIOP 转基因小鼠模型的纳米压痕和高亮度同步加速器 X 射线纳米力学成像，我们能够量化股骨骨干中部的局部压痕模量、矿化分布以及纳米级结构和变形机制的改变，并与它们对宏观的机械变化。我们的研究结果表明，纳米尺度和微米尺度的骨材料质量发生了明显而显着的变化，这体现在整个骨器官矿化和压痕模量的空间异质性发展中，这可能会增加骨折风险。股骨骨干中部的矿化分布和纳米级结构和变形机制的改变，并将它们与宏观力学变化联系起来。我们的研究结果表明，纳米尺度和微米尺度的骨材料质量发生了明显而显着的变化，这体现在整个骨器官矿化和压痕模量的空间异质性发展中，这可能会增加骨折风险。股骨骨干中部的矿化分布和纳米级结构和变形机制的改变，并将它们与宏观力学变化联系起来。我们的研究结果表明，纳米尺度和微米尺度的骨材料质量发生了明显而显着的变化，这体现在整个骨器官矿化和压痕模量的空间异质性发展中，这可能会增加骨折风险。