Effects of bone tissue mineral and matrix properties on fracture incidence

骨组织矿物质和基质特性对骨折发生率的影响

• 批准号: 7616789
• 负责人: Eve Donnelly
• 金额: $ 5.11万
• 依托单位: HOSPITAL FOR SPECIAL SURGERY
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-29 至 2011-09-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7616789
• 关键词: Affect; Age; Biopsy; Bone Diseases; Bone Tissue; Disease; Electrons; Fracture; Goals; Human; Image; Incidence; Logistic Regressions; Measures; Methods; Minerals; Molecular Structure; Osteoporosis; Pathology; Patients; Pharmacotherapy; Play; Prevention; Property; Proteins; Public Health; Relative (related person); Risk; Risk Reduction; Role; Spatial Distribution; Spectrum Analysis; Structure; Therapeutic Agents; Tissues; Woman; base; bisphosphonate; bone; bone mass; insight; skeletal; tomography

DESCRIPTION: Osteoporosis is a major skeletal pathology that not only reduces bone mass but also alters the properties of the constituent tissue. Antiresorptive drug therapies for osteoporosis moderately increase bone mass but substantially decrease fracture risk, suggesting that modified tissue properties may play a key role in fracture risk reduction in osteoporotic patients. The long-term objective of this application is to understand the relationship between bone fragility and disease- and treatment-induced changes in the structure and distribution of bone mineral and matrix. Accordingly, the following Specific Aims are proposed: To relate bone mineral and matrix properties, microarchitecture, and quantity to fracture incidence in (1) young, untreated bone tissue and (2) bone tissue treated with antiresorptive therapeutic agents. In Aim 1 iliac crest biopsies from young women of comparable BMD with and without fractures will be characterized with a) vibrational spectroscopy and backscattered electron imaging to assess mineral and matrix properties and b) microcomputed tomography (microCT) and histomorphometry to assess microarchitecture and bone volume fraction (BV/TV). Relationships among fracture incidence, BMD, mineral and matrix properties, and microarchitectural measures will be examined with a multiple logistic regression. In Aim 2 bisphosphonate-treated and age-matched control human biopsies will be characterized using the same methods described for Aim 1 to assess treatment-based differences in mineral and matrix parameters and microarchitectural measures. As before, the ability of these parameters to predict fracture will be assessed with a logistic regression. These studies will illuminate the relative contributions of mineral and matrix properties, microarchitecture, and bone quantity to fracture incidence in normal and osteoporotic tissue. In addition, they will provide crucial insights into the mechanisms by which osteoporosis increases bone fragility and by which bisphosphonates reduce fracture incidence in osteoporotic tissue. Relevance to Public Health: The goal of this study is to understand how changes in the molecular structure and spatial distribution of the mineral and protein in bone tissue affect the likelihood that it will fracture. Understanding the factors that contribute to skeletal fragility is essential for effective prevention and treatment of bone diseases like osteoporosis.

描述：骨质疏松症是一种主要的骨骼病理学，它不仅会减少骨量，还会改变组成组织的特性。骨质疏松症的抗吸收药物疗法可适度增加骨量，但显着降低骨折风险，表明改变的组织特性可能在骨质疏松症患者骨折风险降低中发挥关键作用。该应用的长期目标是了解骨脆性与疾病和治疗引起的骨矿物质和基质的结构和分布变化之间的关系。因此，提出以下具体目标： 将骨矿物质和基质特性、微结构和数量与 (1) 年轻的、未经治疗的骨组织和 (2) 用抗再吸收治疗剂治疗的骨组织中的骨折发生率联系起来。在目标 1 中，将通过 a) 振动光谱和背散射电子成像来评估矿物质和基质特性，b) 显微计算机断层扫描 (microCT) 和组织形态计量学来评估微结构和骨体积，对骨密度相当的有骨折和无骨折的年轻女性的髂嵴活检进行表征分数（BV/TV）。骨折发生率、BMD、矿物和基质特性以及微结构测量之间的关系将通过多元逻辑回归进行检查。在目标 2 中，将使用目标 1 中描述的相同方法对经过双膦酸盐处理和年龄匹配的对照人体活检进行表征，以评估基于处理的矿物质和基质参数以及微结构测量的差异。和以前一样，这些参数预测骨折的能力将通过逻辑回归进行评估。这些研究将阐明矿物质和基质特性、微结构和骨量对正常和骨质疏松组织骨折发生率的相对贡献。此外，他们还将提供关于骨质疏松症增加骨脆性以及双磷酸盐降低骨质疏松组织骨折发生率的机制的重要见解。与公共健康的相关性：本研究的目的是了解骨组织中矿物质和蛋白质的分子结构和空间分布的变化如何影响其骨折的可能性。了解导致骨骼脆弱的因素对于有效预防和治疗骨质疏松症等骨疾病至关重要。