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：
6632753
负责人：
CLIFFORD MICHAEL LES
金额：
$ 20.19万
依托单位：
HENRY FORD HEALTH SYSTEM
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（由申请人提供）：紧凑的骨矿物质密度为在正常骨结构内不均匀分布。这反映了在机械性能（强度和刚度）的局部变化中相信有助于将弯曲限制在肌肉和韧带具有的那些飞机上最大的机械影响。正常骨矿物质代谢的挑战可能影响这种材料分布，结构效应不成比例总体矿物质损失。例如，在绝经后骨质疏松症中，骨骼营业额增加，骨质的普遍损失，但这完全解释了与断裂发生率的紧密关联，也没有在大多数人中，未受影响和断裂患者之间的实质重叠骨质质量的临床筛查度量。鉴于先前存在的材料异质性，材料特性的任何变化，无论是随机，均匀或系统的，可能对结构。因此，旨在简单影响的治疗干预措施骨骼质量的总体增加而不考虑区域机械性质变化可能无效预防骨折。在紧凑的骨骼中，骨转换的增加可能被视为分支血管生成中的问题：新的骨及其血管必须由预先存在的骨和血管。如果雌激素耗竭是相关的随着全球血管和腾腾分支的增加，主要的早期重塑的影响将在高浓度的区域中看到预先存在的骨。这种情况将产生直接系统的区域骨密度的变化，这与原始密度无关，但要预先存在重塑模式。此外，我们假设在雌激素缺乏状态下放置的新骨头较少由骨细胞填充，而不是完整的动物。如果骨细胞的变化密度与新的最终矿化变化有关骨骼，材料特性的分布更加永久变化然后随之而来。我们将使用雌激素的卵巢切除 - 肩杆模型检验这些假设消耗。半径/尺寸将测试结构阻尼，刚度，在将材料测试的区域分为区域之前和组织学。重塑活性将通过动态和静态进行量化组织形态法，并通过分析骨密度模式。最后，本地将确定骨细胞种群密度并与Osteonal进行比较矿物质测量以及局部组织的矿物质测量值年龄。这样，我们将解决紧凑的骨骼材料的问题绝经后骨质疏松症的异质性在结构，材料，细胞人口和生化水平。