Subchondral Trabecular Plate and Rod Abnormalities in Human Osteoarthritis

项目总结 骨关节炎(OA)，常见于膝关节，是一种造成巨大负担的流行疾病。这个 目前，骨性关节炎的发病机制仍不十分清楚，也缺乏有效的疾病治疗方法。近期 动物研究表明，异常的骨吸收和微结构适应与骨性关节炎有关 进步。很少有研究全面量化人类软骨下骨的微结构。 膝关节骨关节炎，特别是在早期阶段，没有人看过软骨联合。活体定量 目前尚缺乏膝关节软骨下骨微结构的研究方法，难以准确、准确地测量膝关节软骨下骨的微结构。 纵向评估人类膝骨性关节炎发育过程中的微结构变化。我们提出了两个具体的 旨在解决膝骨性关节炎的基础和临床科学知识差距。在具体目标1中，我们将使用 个体骨小梁分割(ITS)是一种先进的微结构分析技术，它基于 第二代高分辨率外周定量CT(2G HR-pQCT)作为一种新技术 它是人类膝关节骨性关节炎的评估工具，也是使用MRI对软骨进行全面量化的工具。在……里面 具体目标2，我们将用同样的方法对骨性关节炎患者进行纵向分析。该研究的发现 可能为这一组患有轻度/中度或无膝骨性关节炎的患者提供临床洞察力。 假设1：其对活体2G HR-pQCT膝关节扫描的分析检测到 Kellgren和Lawrence KOA分级(0-IV)不同的软骨下小梁板和棒 女性的情况比男性严重。 目的1a：利用2GHR-pQCT对软骨下骨的显微结构进行活体定量 48例女性X线片和MRI测量关节软骨的体积和厚度 X线片确定为Kellgren和Lawrence(KL)II-IV级膝骨性关节炎患者48例，其中12例 女性和12名男性(0-I级)年龄匹配。 具体目标1b：使用目标1a的数据，量化基于ITS的HR-pQCT分析和 软骨下骨的X射线纹理测量到基于MRI的软骨测量。 假设2：通过分析检测到软骨下小梁板和小梁棒的显微结构差异 在活体2G HR-pQCT膝关节扫描中，可以预测男性和女性从轻度到更严重的骨关节炎的进展。 具体目标2a：量化骨关节炎分级、软骨下骨及其微结构、质地的年变化 对36例女性和36例男性进行了3年以上的MRI测量和关节软骨变化 来自目标1a的轻、中度膝关节骨性关节炎(II-III级)和年龄匹配的12名女性和12名男性(0-I级)。 具体目标2b：使用目标2a的数据，量化基于ITS的HR-pQCT分析和 软骨下骨质地测量与MRI测量软骨的最佳组合 晋级至KL III-IV级的预测因素。

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.