Subchondral Trabecular Plate and Rod Abnormalities in Human Osteoarthritis

项目摘要 骨关节炎（OA）是膝关节常见病，也是一种给患者带来巨大负担的常见病.的 OA的发病机制在很大程度上仍不清楚，并且缺乏有效的疾病修饰疗法。最近 动物研究表明，骨吸收和微结构适应异常与OA有关 进展很少有研究全面量化了人类的软骨下骨微结构 膝关节骨性关节炎，特别是在早期阶段，没有人一起看软骨。体内定量 缺乏膝关节软骨下骨微结构的方法，这使得难以准确和 纵向评估人类膝关节OA发展中的微观结构变化。我们提出两个具体的 旨在解决膝关节OA的基础和临床科学知识差距。在具体目标1中，我们将使用 个体小梁分割（ITS）是一种先进的显微结构分析技术，基于 第二代高分辨率外周定量计算机断层扫描（2G HR-pQCT）作为一种新的 评估工具，并使用MRI对软骨进行全面量化。在 具体目标2，我们将使用相同的方法对OA患者进行纵向分析。这项研究的结果 可以提供关于该组中轻度/中度或无膝关节OA的亚组如何进展的临床见解。 假设1：体内2G HR-pQCT膝关节扫描的ITS分析检测到了 软骨下骨小梁板和杆的Kellgren和Lawrence KOA等级（0-IV）不同， 女性比男性严重。 具体目的1a：通过2G HR-pQCT定量体内软骨下骨ITS微结构，纹理 对48名女性进行X线摄影测量，并通过MRI测量关节软骨MOAKS、体积和厚度 48名男性Kellgren和Lawrence（KL）II-IV级膝关节骨性关节炎（通过X线摄影定义），12名 年龄匹配的女性和12名男性（0-I级）。 特定目标1b：使用目标1a的数据，量化基于ITS的HR-pQCT分析与 软骨下骨的X线纹理测量与基于MRI的软骨测量。 假设2：ITS分析检测到的软骨下骨小梁板和杆的显微结构差异 的体内2G HR-pQCT膝关节扫描可预测男性和女性从轻度到更严重OA的进展。 具体目标2a：量化OA等级、软骨下骨ITS微观结构、质地 在36名女性和36名男性中， 轻度和中度KOA（II-III级），年龄匹配的12名女性和12名男性（0-I级），来自目标1a。 具体目标2b：使用目标2a的数据，量化基于ITS的HR-pQCT分析与 软骨下骨的纹理测量与软骨的MRI测量，并确定最佳组合， 进展至KL III-IV级的预测因子。

PROJECT SUMMARY Osteoarthritis (OA), common in the knee, is a prevalent disease that incurs enormous burden. The pathogenesis of OA remains largely unclear, and effective disease modifying therapies are lacking. Recent animal studies show that abnormal bone resorption and microstructural adaptations have been linked to OA progression. Few studies have comprehensively quantified subchondral bone microstructure in the human knee OA, particularly at the early stage and none have looked at cartilage in conjunction. In vivo quantification methods of subchondral bone microstructure in the knee are lacking, making it difficult to accurately and longitudinally assess microstructural changes in human knee OA development. We propose two Specific Aims to address basic and clinical science knowledge gaps in knee OA. In Specific Aim 1, we will use Individual Trabecula Segmentation (ITS), an advanced microstructural analysis technique, based on the second generation high resolution peripheral quantitative computed tomography (2G HR-pQCT) as a novel evaluation tool for human knee OA and also perform comprehensive quantification of cartilage using MRI. In Specific Aim 2, we will use the same methods for longitudinal analysis of OA patients. Findings from the study may provide clinical insights into how a subset of this group with mild/moderate or no knee OA progresses. Hypothesis 1: ITS analysis of in vivo 2G HR-pQCT knee scans detects microstructural differences in subchondral trabecular plates and rods that differ by Kellgren and Lawrence KOA grades (0-IV) and are more severe in women than men. Specific Aim 1a: To quantify subchondral bone ITS microstructure in vivo by 2G HR-pQCT, textural measures by X-ray radiography and articular cartilage MOAKS, volume and thickness by MRI in 48 women and 48 men with Kellgren and Lawrence (KL) grade II-IV knee OA defined by X-ray radiography and in 12 women and 12 men (Grade 0-I) matched for age. Specific Aim 1b: Using data from Aim 1a, quantify the correlation of ITS-based HR-pQCT analysis and X-ray textural measures of subchondral bone to MRI-based cartilage measurements. Hypothesis 2: Microstructural differences in subchondral trabecular plates and rods detected by ITS analysis of in vivo 2G HR-pQCT knee scans predict progression from mild to more severe OA in men and women. Specific Aim 2a: To quantify annual changes in OA grade, subchondral bone ITS microstructure, textural measures, and articular cartilage changes in MRI over 3 years of follow-up in 36 women and 36 men with mild and moderate KOA (Grade II-III) and age-matched 12 women and 12 men (Grade 0-I) from Aim 1a. Specific Aim 2b: Using data from Aim 2a, quantify the correlation of ITS-based HR-pQCT analysis and textural measures of subchondral bone to MRI measures of cartilage and determine the best combination of predictors of progression to KL Grade III-IV.