Effects of bone tissue mineral and matrix properties on fracture incidence

描述：骨质疏松症是一种主要的骨骼病理，不仅减少骨量，而且改变组成组织的性质。骨质疏松症的抗吸收药物治疗适度增加骨量，但大大降低骨折风险，这表明改变组织性质可能在骨质疏松症患者骨折风险降低中发挥关键作用。本申请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结构和分布变化之间的关系。因此，提出了以下具体目的：将骨矿物质和基质性质、微结构和数量与（1）未处理的年轻骨组织和（2）用抗吸收治疗剂处理的骨组织中的骨折发生率相关联。在目标1中，将采用a）振动光谱和背散射电子成像对BMD相当的有骨折和无骨折的年轻女性的髂嵴活检进行表征，以评估矿物质和基质性质，以及B）显微计算机断层扫描（microCT）和组织形态测量学，以评估微结构和骨体积分数（BV/TV）。骨折发生率、骨密度、矿物质和基质性质以及微结构测量之间的关系将用多元逻辑回归进行检查。在目标2中，将使用目标1所述的相同方法对双膦酸盐治疗和年龄匹配的对照人类活检进行表征，以评估矿物质和基质参数以及微结构指标的治疗差异。如前所述，将使用逻辑回归评估这些参数预测骨折的能力。这些研究将阐明矿物质和基质性质、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，他们将提供关键的见解，骨质疏松症增加骨脆性的机制，双膦酸盐减少骨折的发生率在骨质疏松组织。与公共卫生的相关性：这项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骼疾病至关重要。

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.