Abstract
To investigate the association between markers of synovial inflammation and matrix turnover (MRI-based and serum biomarkers) and knee symptoms in established knee osteoarthritis (KOA). This cross-sectional study utilised data from a randomised, multicentre placebo-controlled trial (UK-VIDEO) of vitamin D therapy in symptomatic KOA. Data on serum biomarkers, type III collagen degradation (C3M), metabolite of C-reactive protein (CRPM) and cartilage oligomeric matrix protein (COMP), were available at baseline whilst contrast-enhanced (CE) MRI data were acquired in a subsample at baseline and annually. Knee symptoms were assessed using WOMAC at all visits. We examined the cross-sectional association between knee symptoms and three MRI-based and three serum markers of synovitis and matrix turnover, respectively. A total of 447 participants were included in the serum and 136 participants in the MRI analyses. MRI-defined medial perimeniscal synovitis was positively associated with knee pain and, suprapatellar and medial perimeniscal synovitis with knee function in multivariate analysis. We observed a statistically significant, negative association between a higher concentration of serum C3M and CRPM and knee pain, respectively. Furthermore, the highest CRPM quartile was negatively associated with knee function. Our findings suggest that, in established painful radiographic KOA, MRI-defined medial perimeniscal and suprapatellar synovitis were positively associated with knee symptoms. Serum-based C3M and CRPM markers were negatively associated with knee symptoms. Pain fluctuations are common in KOA and a better understanding of the relationship between markers of synovitis and matrix turnover and knee symptoms would facilitate a more accurate assessment of temporal changes in disease progression.
Highlights
Osteoarthritis (OA), the most common form of arthritis, is a leading cause of disability in adult populations [1]
Of 474 participants recruited to VIDEO, 447 (94.30%) had complete serum biomarker data, were of the Kellgren–Lawrence (KL) grades 1 to 4 and had knee pain and function data at baseline
Whilst the inclusion criteria for the original VIDEO trial specified that study participants must have a KL grade of 2–3, upon re-evaluation of the x-rays during the original study, some study participants were graded as KL 1 and 4
Summary
Osteoarthritis (OA), the most common form of arthritis, is a leading cause of disability in adult populations [1]. The emerging evidence suggests, in the most part, that synovitis and fibrosis plays an important role in the pathogenesis of OA and is related to clinical symptoms and structural progression [5,6,7,8,9,10,11]. Evidence from both observational and interventional studies suggest that synovial inflammation measured on MRI contributes to knee pain [13,14,15]. Synovial fibrosis associated with collagen synthesis and matrix turnover contributes heavily to joint pain [10]. To accurately assess the structure–pain relationship, there is a great need to identify less invasive markers, preferably imaged-based and/or serum biomarkers, that can be used as surrogates of synovial inflammation and matrix turnover
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