MODULATION OF LOCAL BONE TISSUE MATERIAL PROPERTIES

局部骨组织材料特性的调节

基本信息

  • 批准号:
    6383216
  • 负责人:
  • 金额:
    $ 28.12万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2001
  • 资助国家:
    美国
  • 起止时间:
    2001-08-01 至 2005-05-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Compact bone mineral density is distributed non-uniformly within the normal bone structure. This is reflected in local variation in mechanical properties (strength and stiffness) that we believe helps to limit bending to those planes where muscles and ligaments have maximal mechanical influence. Challenges to normal bone mineral metabolism may affect this material distribution, and have structural effects disproportionate to the overall mineral loss. For instance, in postmenopausal osteoporosis, there is increased turnover of bone, and a generalized loss of bone mass, but this fully explains neither the strong association with fracture incidence, nor the substantial overlap between unaffected and fracture patients in most clinical screening measures of bone quality. Given the pre-existing material heterogeneity, any change in material properties, be it random, uniform, or systematic, is likely to have significant effects on the mechanical behavior of the structure. Therefore, therapeutic interventions designed to simply affect an overall increase in bone mass without considering regional mechanical property variation may be ineffective in preventing fracture. In compact bone, an increase in bone turnover may be seen as a branching problem in angiogenesis: new osteons, and their blood vessels, must arise from pre-existing osteons and blood vessels. If estrogen depletion were associated with a global increase in vascular and osteonal branching, the major early effects of remodeling would be seen in regions with high concentrations of pre-existing osteons. Such a scenario would produce an immediate systematic change in regional bone density that would be related not to original density, but to pre-existing remodeling patterns. Furthermore, we hypothesize that the new bone that is laid down in the estrogen-depleted condition is less densely populated by osteocytes than in the intact animal. If changes in osteocyte density were associated with alterations in the final mineralization of new bone, a more permanent change in the distribution of material properties would then ensue. We will test these hypotheses using the ovariectomized-sheep model of estrogen depletion. The radius/ulna will be tested for structural damping, stiffness, and strength before sectioning into regions for materials testing and histology. Remodeling activity will be quantified by dynamic and static histomorphometry, and by analysis of osteonal density patterns. Finally, local osteocyte population densities will be determined and compared with osteonal mineral measurements, and with mineral-independent measurements of local tissue age. In this way, we will address the issue of compact bone material heterogeneity in postmenopausal osteoporosis at the structural, materials, cell population, and biochemical levels.
描述(申请人提供):致密骨密度为 在正常骨结构内分布不均匀。这一点得到了反映 在机械性能(强度和刚度)的局部变化中,我们 相信有助于将弯曲限制在肌肉和韧带有 最大机械影响。对正常骨矿物质代谢的挑战可能 影响这种材料分布,并具有不成比例的结构效果 对整体矿物质流失的影响。例如,在绝经后骨质疏松症中, 骨的周转率增加,骨量普遍丢失,但 这既不能充分解释与骨折发生率的强烈关联,也不能解释 在大多数情况下,未受影响的患者和骨折患者之间的大部分重叠 骨质量的临床筛查措施。鉴于先前存在的材料 异质性,材料属性的任何变化,无论是随机的、均匀的还是 系统性的,可能会对机械行为产生重大影响 这个结构。因此,旨在简单地影响 不考虑局部力学因素的整体骨量增加 特性变化在预防骨折方面可能无效。 在密质骨中,骨转换的增加可能被视为一种分支。 血管生成中的问题:新的骨骼和它们的血管必须从 预先存在的骨骼和血管。如果雌激素缺乏与 随着全球血管和骨性分支的增加,早期的主要 重塑的影响将在高浓度的 先前存在的骨骼。这样的情景将立即产生系统性的 局部骨密度的变化与原始密度无关, 而是对先前存在的重塑模式。此外,我们假设 在雌激素耗尽的情况下形成的新骨密度较低 与完好的动物相比,由骨细胞填充。如果骨细胞发生变化 密度与新矿化最终矿化的蚀变有关 骨,材料特性分布的更永久性的变化将 然后接踵而至。 我们将使用去势绵羊雌激素模型来验证这些假说。 耗尽。将对桡骨/尺骨进行结构减震、刚度、 和强度,然后剖分成区域进行材料测试和 组织学。重塑活动将通过动态和静态来量化 组织形态计量学,并通过分析骨密度模式。最后,本地化 骨细胞密度将被测定,并与骨细胞进行比较 矿物质测量,以及局部组织的矿物质无关测量 年龄。通过这种方式,我们将解决致密骨材料的问题 绝经后骨质疏松症在结构、材料、细胞上的异质性 人口和生化水平。

项目成果

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CLIFFORD MICHAEL LES其他文献

CLIFFORD MICHAEL LES的其他文献

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{{ truncateString('CLIFFORD MICHAEL LES', 18)}}的其他基金

Degradation and Recovery of Bone: OVX and Treatment
骨的退化和恢复:OVX 和治疗
  • 批准号:
    7387437
  • 财政年份:
    2005
  • 资助金额:
    $ 28.12万
  • 项目类别:
Degradation and Recovery of Bone: OVX and Treatment
骨的退化和恢复:OVX 和治疗
  • 批准号:
    7050616
  • 财政年份:
    2005
  • 资助金额:
    $ 28.12万
  • 项目类别:
Degradation and Recovery of Bone: OVX and Treatment
骨的退化和恢复:OVX 和治疗
  • 批准号:
    6924988
  • 财政年份:
    2005
  • 资助金额:
    $ 28.12万
  • 项目类别:
Degradation and Recovery of Bone: OVX and Treatment
骨的退化和恢复:OVX 和治疗
  • 批准号:
    7197332
  • 财政年份:
    2005
  • 资助金额:
    $ 28.12万
  • 项目类别:
Degradation and Recovery of Bone: OVX and Treatment
骨的退化和恢复:OVX 和治疗
  • 批准号:
    7600520
  • 财政年份:
    2005
  • 资助金额:
    $ 28.12万
  • 项目类别:
MODULATION OF LOCAL BONE TISSUE MATERIAL PROPERTIES
局部骨组织材料特性的调节
  • 批准号:
    6512163
  • 财政年份:
    2001
  • 资助金额:
    $ 28.12万
  • 项目类别:
MODULATION OF LOCAL BONE TISSUE MATERIAL PROPERTIES
局部骨组织材料特性的调节
  • 批准号:
    6632753
  • 财政年份:
    2001
  • 资助金额:
    $ 28.12万
  • 项目类别:
MODULATION OF LOCAL BONE TISSUE MATERIAL PROPERTIES
局部骨组织材料特性的调节
  • 批准号:
    6769328
  • 财政年份:
    2001
  • 资助金额:
    $ 28.12万
  • 项目类别:
MATERIAL PROPERTIES AND REMODELING IN THE METACARPUS
掌骨的材料特性和重塑
  • 批准号:
    2077977
  • 财政年份:
    1994
  • 资助金额:
    $ 28.12万
  • 项目类别:
MATERIAL PROPERTIES AND REMODELING IN THE METACARPUS
掌骨的材料特性和重塑
  • 批准号:
    2077976
  • 财政年份:
    1993
  • 资助金额:
    $ 28.12万
  • 项目类别:

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