Post-yield Behavior vs. Bone Quality

产后行为与骨质量

• 批准号: 7895834
• 负责人: Xiaodu Wang
• 金额: $ 34.89万
• 依托单位: UNIVERSITY OF TEXAS SAN ANTONIO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-07-17 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7895834
• 关键词: Acute; Address; Adult; Advanced Glycosylation End Products; Affect; Age; Aging; Architecture; Behavior; Biopsy; Bone Density; Bone Diseases; Bone Tissue; Clinical Treatment; Collagen; Dehydration; Deterioration; Development; Elderly; Elderly woman; Exhibits; Failure; Fracture; Future; Gender; Healthcare; High Pressure Liquid Chromatography; Human; Hydration status; Implant; In Situ; In Vitro; Individual; Lead; Measurement; Measures; Mechanics; Minerals; Modeling; Modification; Molecular; Monitor; Musculoskeletal; Pathologic Processes; Pathway interactions; Phase; Physicians; Plastics; Play; Population; Property; Risk Assessment; Role; Scheme; Specimen; Staging; Stress; Synchrotrons; System; Techniques; Testing; Tissues; Variant; Water; Work; age related; aged; base; bone; bone age; bone mass; bone quality; bone toughness; clinically relevant; crosslink; experience; human male; interfacial; novel; prevent; public health relevance; research study; response; treatment strategy

DESCRIPTION (provided by applicant): Bone fractures are a major concern for the health care of elderly and women populations. One leading reason for bone fractures is deterioration of tissue quality (manifested by its toughness) in addition to changes in bone mineral density and architecture. Recent evidence has evinced that bone may experience two distinct stages in the post-yield deformation: it begins with acute increases in microdamage accumulation and viscous response (Stage I), followed by plastic deformation and saturation of the viscous response (Stage II). More intriguingly, the internal strains in individual mineral and collagen phases appear to be different and such a discrepancy increases considerably as bones yield, suggesting a possible interfacial deformation between the two phases. In addition, hydration state of bone exhibits a significant role in sustaining the toughness of bone, but such effects diminish for elderly bones. Moreover, evidence has shown that age-related accumulation of non-enzymatic collagen crosslinks in bone may have significant effects on the toughness of bone. In these cases, elderly bones tend to fail prematurely with very limited permanent (or plastic) deformation compared with the younger bones. Based on these recent findings, the central hypothesis of this study is that the capacity of post-yield energy dissipation in bone is mainly determined by the interaction between the mineral and collagen phases, and any adverse changes in such a interaction would consequently lead to an increased fragility of bone. Four specific aims will be addressed: Aim 1: To determine the mechanism of the post-yield behavior of bone under different loading modes. Working hypothesis: The post-yield behavior of bone is initiated with an acute increase in microdamage accumulation with large variation in viscous response (Stage I) and followed by a saturated viscous response associated with large plastic deformation (Stage II); and such a behavior is independent of loading modes. Aim 2: To determine the correlation of mineral/collagen interaction with the post-yield deformation and energy dissipation of bone. Working hypothesis: Deformation at the mineral and collagen interface is a major mechanism for energy dissipation during the post-yield deformation of bone. Aim 3: To determine the effect of dehydration on the interfacial behavior between the mineral and collagen phases in bone and its correlation with age. Working hypothesis: The interfacial interaction between the mineral and collagen phase of bone is significantly affected by dehydration, and such an effect diminishes with increasing age. Aim 4: To determine the role of non-enzymatic collagen crosslinks (AGEs) in affecting the post-yield behavior (toughness) of bone and its correlation with age. Working hypothesis: Age-related accumulation of AGEs significantly affects the interfacial behavior between the mineral and collagen phases, thus leading to the significantly reduced capacity for bone to dissipate energy during the post-yield deformation. Through this study, we expect to elucidate the post-yield and failure behavior of bone at ultrastructural levels, and to determine the ultrastructural factors that govern the fragility of bone. Such information would facilitate future development of clinical treatments and strategies for predicting and preventing bone fractures. PUBLIC HEALTH RELEVANCE: The scientific and clinical relevance of this study is manifested in the following aspects: This study will help elucidate the underlying mechanism of the post-yield and failure behavior of bone at ultrastructural levels, thus allowing for accurate modeling and failure prediction of bone in musculoskeletal and implant systems. In addition, the novel techniques of this study will provide a unique means to help identify the cellular/molecular pathways that cause such ultrastructural changes in bone during pathological processes and to evaluate the efficacy of clinical treatments to bone disorders. Finally, by further modifications this approach can be extended to assess ultrastructural changes in biopsy bone tissues quantitatively, thus helping physicians to make more accurate risk assessments of bone fractures.

描述(由申请人提供)：骨折是老年人和妇女群体健康保健的一个主要问题。骨折的一个主要原因是组织质量的恶化(表现为韧性)，以及骨密度和结构的变化。最近的证据表明，骨的屈服后变形可能经历了两个不同的阶段：首先是微损伤积累和粘性反应的急剧增加(阶段I)，然后是塑性变形和粘性反应的饱和(阶段II)。更有趣的是，不同矿物质和胶原蛋白的内部应变似乎是不同的，这种差异随着骨骼的屈服而显著增加，这表明这两个阶段之间可能存在界面变形。此外，骨骼的水化状态对维持骨骼的韧性具有重要作用，但这种作用在老年骨骼中会减弱。此外，有证据表明，随着年龄的增长，骨骼中非酶类胶原交联物的积累可能会对骨骼的韧性产生重大影响。在这些情况下，与年轻骨骼相比，老年骨骼往往过早失效，永久性(或塑性)变形非常有限。基于这些最新发现，本研究的中心假设是，骨的屈服后能量耗散能力主要由矿物质和胶原蛋白之间的相互作用决定，这种相互作用中的任何不利变化都将导致骨的脆性增加。目标1：确定骨在不同加载方式下屈服后行为的机制。工作假说：骨的屈服后行为开始于微损伤积累的急剧增加和粘性响应的较大变化(阶段I)，随后是与大塑性变形相关的饱和粘性响应(阶段II)；并且这种行为与加载模式无关。目的：探讨矿物质/胶原蛋白相互作用与骨屈服后变形和能量耗散的相关性。工作假说：在骨屈服后变形过程中，矿物质和胶原界面的变形是能量耗散的主要机制。目的：研究脱水对骨内矿物相和胶原相界面行为的影响及其与年龄的关系。工作假说：骨矿物质和胶原蛋白之间的界面相互作用受到脱水的显著影响，这种影响随着年龄的增长而减弱。目的：探讨非酶胶原交联物(AGEs)在影响骨屈服后行为(韧性)中的作用及其与年龄的相关性。工作假说：与年龄相关的AGEs的积累显著影响矿物质和胶原相之间的界面行为，从而导致骨在屈服后变形过程中耗散能量的能力显著降低。通过这项研究，我们期望在超微结构水平上阐明骨的屈服和破坏后的行为，并确定控制骨脆性的超微结构因素。这些信息将有助于未来临床治疗和预测和预防骨折的策略的发展。公共卫生相关性：这项研究的科学和临床相关性体现在以下几个方面：这项研究将有助于在超微结构水平上阐明骨屈服后和失效行为的潜在机制，从而允许在肌肉骨骼和植入系统中对骨进行准确的建模和失效预测。此外，这项研究的新技术将提供一种独特的手段，帮助识别在病理过程中导致骨骼超微结构变化的细胞/分子途径，并评估临床治疗骨病的疗效。最后，通过进一步的改进，该方法可以扩展到定量评估活检骨组织的超微结构变化，从而帮助医生对骨折做出更准确的风险评估。

项目成果

Post-yield nanomechanics of human cortical bone in compression using synchrotron X-ray scattering techniques.

• DOI: 10.1016/j.jbiomech.2010.11.003
• 发表时间: 2011-02-24
• 期刊: JOURNAL OF BIOMECHANICS
• 影响因子: 2.4
• 作者: Dong, X. Neil;Almer, Jon D.;Wang, Xiaodu
• 通讯作者: Wang, Xiaodu

Effect of age on mechanical properties of the collagen phase in different orientations of human cortical bone.

• DOI: 10.1016/j.bone.2013.04.006
• 发表时间: 2013-08
• 期刊: BONE
• 影响因子: 4.1
• 作者: Leng, Huijie;Reyes, Michael J.;Dong, Xuanliang N.;Wang, Xiaodu
• 通讯作者: Wang, Xiaodu

Random field assessment of nanoscopic inhomogeneity of bone.

• DOI: 10.1016/j.bone.2010.08.021
• 发表时间: 2010-12
• 期刊: BONE
• 影响因子: 4.1
• 作者: Dong, X. Neil;Luo, Qing;Sparkman, Daniel M.;Millwater, Harry R.;Wang, Xiaodu
• 通讯作者: Wang, Xiaodu

In situ mechanical behavior of mineral crystals in human cortical bone under compressive load using synchrotron X-ray scattering techniques.

• DOI: 10.1016/j.jmbbm.2012.05.003
• 发表时间: 2012-10
• 期刊: JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
• 影响因子: 3.9
• 作者: Giri, Bijay;Almer, Jonathan D.;Dong, X. Neil;Wang, Xiaodu
• 通讯作者: Wang, Xiaodu

Orientation dependence of progressive post-yield behavior of human cortical bone in compression.

• DOI: 10.1016/j.jbiomech.2012.08.034
• 发表时间: 2012-11-15
• 期刊: Journal of biomechanics
• 影响因子: 2.4
• 作者: Dong XN;Acuna RL;Luo Q;Wang X
• 通讯作者: Wang X