Subchondral Trabecular Plate and Rod Abnormalities in Human Osteoarthritis

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.