Influence of the ultrastructure on the fracture characteristics of human bone in physiological and pathological conditions

生理病理条件下超微结构对人体骨断裂特性的影响

• 批准号: 227070813
• 负责人: Professor Dr. Björn Busse
• 金额: --
• 依托单位: Institut für Osteologie und Biomechanik (IOBM)
• 依托单位国家: 德国
• 项目类别: Independent Junior Research Groups
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/227070813?language=en
• 关键词: Influence; ultrastructure; fracture; characteristics; human

Disease- and aging-related changes to the musculoskeletal system are known to increase its susceptibility to fracture. Such changes are especially critical in the elderly as the consequent fractures can lead to restrictions on quality of life as well as significant mortality. Traditional thinking on the deterioration of bone with aging and disease has focused predominantly on the question of bone quantity, which is currently used as a predictor of fracture risk in clinical settings. However, the increased fracture risk of bone with aging and disease is not solely dependent on bone quantity; indeed, the fracture resistance is additionally affected by both morphological and compositional changes, which describe the bone quality. Understanding how the nature of fracture is affected by bone quality requires characterization of the compositional and morphological features at each level of bone’s complex hierarchical structure, which has characteristic features from millimeter to nanometer levels, specifically evolving to its macroscopic form (>3 mm) from a nanostructure comprised of collagen and mineral (<500 nm) and a microstructure of lamellae, osteocyte lacunae (3-20 μm) and osteons (100-300 μm). We believe that a hierarchical characterization of aged and diseased bone will lead to a greater understanding of how these conditions cause an increase in fracture risk.We will use an integrated approach combining bone quality assessment techniques by using microcomputed tomography, synchrotron small-angle X-ray scattering/wide-angle X-ray scattering, backscattered electron imaging, deep ultraviolet Raman/Fourier transform infrared spectroscopy, high-performance liquid chromatography and enzyme-linked immunosorbent assay to characterize various levels of the hierarchical structure of skeletally intact and diseased bones. In this connection, we would like to address whether the ultrastructure in terms of the collagen and mineral’s characteristics is significantly altered in bone diseases, whether there are distinct changes in structural and material characteristics (e.g., inter- and intrafibrillar crosslinking), and how these changes can affect the mechanisms of fracture and hence the bone strength and toughness. Our hypothesis is that the primary mechanisms influencing fracture resistance in bone can be associated with the plasticity mechanisms of mineralized collagen fibril sliding at the nanoscale, fracture path properties at the microscale, and microcracking at both scales. Our aim is to provide new information on how distinct ultrastructural features affect the mechanical behavior of bone tissue. Additionally, as this is a departure from traditional bioengineering and medical studies of bone fracture, we hope that such materials-science-based studies can positively impact the medical field by providing new and different insights into bone-related diseases, and as such can help in the search for new cures and treatment options for bone diseases.

已知与疾病和衰老相关的肌肉骨骼系统变化会增加其骨折的易感性。这种变化在老年人中尤其重要，因为随之而来的骨折可能导致生活质量的限制以及显著的死亡率。关于骨骼随年龄增长和疾病恶化的传统观点主要集中在骨量问题上，骨量目前被用作临床环境中骨折风险的预测因子。然而，随着年龄的增长和疾病，骨的骨折风险增加并不仅仅取决于骨量;事实上，抗骨折性还受到描述骨质量的形态和成分变化的影响。了解骨折的性质如何受到骨骼质量的影响，需要表征骨骼复杂分层结构每个水平的组成和形态特征，该结构具有从毫米到纳米水平的特征，特别是从纳米结构演变为宏观形式（>3 mm）由胶原蛋白和矿物质组成的纳米结构（<500 nm）以及片层的微观结构，骨细胞陷窝（3-20 μm）和骨单位（100-300 μm）。我们相信，对老化和病变骨的分级表征将有助于更好地了解这些条件如何导致骨折风险增加。我们将使用一种综合方法，结合骨质量评估技术，使用微计算机断层扫描，同步加速器小角X射线散射/广角X射线散射，背散射电子成像，深紫外拉曼/傅立叶变换红外光谱，高效液相色谱法和酶联免疫吸附测定法，以表征不同水平的等级结构的骨骼完整和患病的骨头。在这方面，我们想解决的是，在骨疾病中，胶原和矿物质特征方面的超微结构是否发生了显著改变，结构和材料特征是否发生了明显变化（例如，纤维间和纤维内交联），以及这些变化如何影响骨折机制，从而影响骨强度和韧性。我们的假设是，影响骨抗断裂性的主要机制可能与矿化胶原纤维在纳米尺度下滑动的塑性机制、微观尺度下的断裂路径特性以及两种尺度下的微裂纹有关。我们的目的是提供关于不同的超微结构特征如何影响骨组织力学行为的新信息。此外，由于这与传统的生物工程和骨折医学研究不同，我们希望这种基于材料科学的研究能够通过提供对骨骼相关疾病的新的和不同的见解来积极影响医学领域，因此可以帮助寻找骨骼疾病的新疗法和治疗方案。

项目成果

Assessment of collagen quality associated with non-enzymatic cross-links in human bone using Fourier-transform infrared imaging.

• DOI: 10.1016/j.bone.2017.01.015
• 发表时间: 2017-04
• 期刊: Bone
• 影响因子: 4.1
• 作者: Schmidt FN;Zimmermann EA;Campbell GM;Sroga GE;Püschel K;Amling M;Tang SY;Vashishth D;Busse B
• 通讯作者: Busse B

Effects of long-term alendronate treatment on bone mineralisation, resorption parameters and biomechanics of single human vertebral trabeculae.

• DOI: 10.22203/ecm.v028a12
• 发表时间: 2014-09
• 期刊: European cells & materials
• 影响因子: 3.1
• 作者: M. Krause;M. Soltau;E. Zimmermann;M. Hahn;J. Kornet;A. Hapfelmeier;S. Breer;M. Morlock;B. Wulff;K. Püschel;Glueer Cc;M. Amling;B. Busse

Fracture resistance of human cortical bone across multiple length-scales at physiological strain rates.

• DOI: 10.1016/j.biomaterials.2014.03.066
• 发表时间: 2014-07
• 期刊: Biomaterials
• 影响因子: 14
• 作者: E. Zimmermann;B. Gludovatz;E. Schaible;B. Busse;R. Ritchie

Atypical fracture with long-term bisphosphonate therapy is associated with altered cortical composition and reduced fracture resistance

• DOI: 10.1073/pnas.1704460114
• 发表时间: 2017-08-15
• 期刊: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• 影响因子: 11.1
• 作者: Lloyd, Ashley A.;Gludovatz, Bernd;Donnelly, Eve
• 通讯作者: Donnelly, Eve