Association between Markers of Synovial Inflammation, Matrix Turnover and Symptoms in Knee Osteoarthritis: A Cross-Sectional Study

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.

[1]  M. Karsdal,et al.  Serum C-reactive protein metabolite (CRPM) is associated with incidence of contralateral knee osteoarthritis , 2021, Scientific Reports.

[2]  Yeri Alice Rim,et al.  The Role of Fibrosis in Osteoarthritis Progression , 2020, Life.

[3]  N. Arden,et al.  Quantitative and semi-quantitative assessment of synovitis on MRI and the relationship with symptoms in symptomatic knee osteoarthritis , 2020, Rheumatology.

[4]  D. Felson,et al.  Are Contrast-Enhanced And Non-Contrast MRI Findings Reflecting Synovial Inflammation In Knee Osteoarthritis: A Meta-Analysis Of Observational Studies. , 2020, Osteoarthritis and cartilage.

[5]  D. Felson,et al.  Association between Bone marrow lesions & synovitis and symptoms in symptomatic knee osteoarthritis , 2019, Osteoarthritis and cartilage.

[6]  Kevin Macdonald,et al.  Multiparameter Analysis Identifies Heterogeneity in Knee Osteoarthritis Synovial Responses , 2019, Arthritis & rheumatology.

[7]  D. Felson,et al.  Effect of Vitamin D supplementation on synovial tissue volume and subchondral bone marrow lesion volume in symptomatic knee osteoarthritis , 2019, BMC Musculoskeletal Disorders.

[8]  Ji-ye He,et al.  Inflammatory and fibrosis infiltration in synovium associated with the progression in developmental dysplasia of the hip. , 2019, Molecular medicine reports.

[9]  M. Karsdal,et al.  Biomarkers of collagen synthesis predict progression in the PROFILE idiopathic pulmonary fibrosis cohort , 2018, bioRxiv.

[10]  M. Karsdal,et al.  Effects of dietary weight loss with and without exercise on interstitial matrix turnover and tissue inflammation biomarkers in adults with knee osteoarthritis: the Intensive Diet and Exercise for Arthritis trial (IDEA). , 2017, Osteoarthritis and cartilage.

[11]  C. Doré,et al.  Associations Between Clinical Evidence of Inflammation and Synovitis in Symptomatic Knee Osteoarthritis: A Cross‐Sectional Substudy , 2016, Arthritis care & research.

[12]  C. Cooper,et al.  The effect of vitamin D supplementation on knee osteoarthritis, the VIDEO study: a randomised controlled trial. , 2016, Osteoarthritis and cartilage.

[13]  M. Karsdal,et al.  Sensitization and Serological Biomarkers in Knee Osteoarthritis Patients With Different Degrees of Synovitis , 2016, The Clinical journal of pain.

[14]  Ali Guermazi,et al.  Semiquantitative Imaging Biomarkers of Knee Osteoarthritis Progression: Data From the Foundation for the National Institutes of Health Osteoarthritis Biomarkers Consortium , 2016, Arthritis & rheumatology.

[15]  J. Niinimäki,et al.  Associations between MRI-defined structural pathology and generalized and localized knee pain - the Oulu Knee Osteoarthritis study. , 2016, Osteoarthritis and cartilage.

[16]  Ali Guermazi,et al.  Semi‐Quantitative Imaging Biomarkers of Knee Osteoarthritis Progression: Data from the FNIH OA Biomarkers Consortium , 2016 .

[17]  A. Hofman,et al.  Association between biomarkers of tissue inflammation and progression of osteoarthritis: evidence from the Rotterdam study cohort , 2016, Arthritis Research & Therapy.

[18]  A Guermazi,et al.  Synovitis and the risk of knee osteoarthritis: the MOST Study. , 2016, Osteoarthritis and cartilage.

[19]  F. Cicuttini,et al.  Cross-sectional and Longitudinal Associations between Knee Joint Effusion Synovitis and Knee Pain in Older Adults , 2016, The Journal of Rheumatology.

[20]  T. Spector,et al.  Serum cartilage oligomeric matrix protein and development of radiographic and painful knee osteoarthritis. A community-based cohort of middle-aged women , 2015, Biomarkers : biochemical indicators of exposure, response, and susceptibility to chemicals.

[21]  P. M. van der Kraan,et al.  Unravelling osteoarthritis-related synovial fibrosis: a step closer to solving joint stiffness. , 2015, Rheumatology.

[22]  S. Bierma-Zeinstra,et al.  What Are the Prognostic Factors for Radiographic Progression of Knee Osteoarthritis? A Meta-analysis , 2015, Clinical orthopaedics and related research.

[23]  M. Karsdal,et al.  Association Between Experimental Pain Biomarkers and Serologic Markers in Patients With Different Degrees of Painful Knee Osteoarthritis , 2014, Arthritis & rheumatology.

[24]  M. Henriksen,et al.  Knee pain and inflammation in the infrapatellar fat pad estimated by conventional and dynamic contrast-enhanced magnetic resonance imaging in obese patients with osteoarthritis: a cross-sectional study. , 2014, Osteoarthritis and cartilage.

[25]  M. Nevitt,et al.  Synovitis in Knee Osteoarthritis Assessed by Contrast-enhanced Magnetic Resonance Imaging (MRI) is Associated with Radiographic Tibiofemoral Osteoarthritis and MRI-detected Widespread Cartilage Damage: The MOST Study , 2014, The Journal of Rheumatology.

[26]  C. Christiansen,et al.  Identification and characterisation of osteoarthritis patients with inflammation derived tissue turnover. , 2014, Osteoarthritis and cartilage.

[27]  T. Neogi,et al.  The epidemiology and impact of pain in osteoarthritis. , 2013, Osteoarthritis and cartilage.

[28]  M. Nevitt,et al.  The association between meniscal damage of the posterior horns and localized posterior synovitis detected on T1-weighted contrast-enhanced MRI--the MOST study. , 2013, Seminars in arthritis and rheumatism.

[29]  M. Karsdal,et al.  Circulating Protein Fragments of Cartilage and Connective Tissue Degradation Are Diagnostic and Prognostic Markers of Rheumatoid Arthritis and Ankylosing Spondylitis , 2013, PloS one.

[30]  D. Loeuille,et al.  Comparing non-enhanced and enhanced sequences in the assessment of effusion and synovitis in knee OA: associations with clinical, macroscopic and microscopic features. , 2011, Osteoarthritis and cartilage.

[31]  Ali Guermazi,et al.  Presence of MRI-detected joint effusion and synovitis increases the risk of cartilage loss in knees without osteoarthritis at 30-month follow-up: the MOST study , 2011, Annals of the rheumatic diseases.

[32]  A R Poole,et al.  Application of Biomarkers in the Development of Drugs Intended for the Treatment of Osteoarthritis OARSI FDA Osteoarthritis Biomarkers Working Group , 2011 .

[33]  Ali Guermazi,et al.  Fluctuation of knee pain and changes in bone marrow lesions, effusions, and synovitis on magnetic resonance imaging. , 2011, Arthritis and rheumatism.

[34]  M. Nevitt,et al.  Assessment of synovitis with contrast-enhanced MRI using a whole-joint semiquantitative scoring system in people with, or at high risk of, knee osteoarthritis: the MOST study , 2010, Annals of the Rheumatic Diseases.

[35]  Frank P. Luyten,et al.  The bone–cartilage unit in osteoarthritis , 2011, Nature Reviews Rheumatology.

[36]  Francis Berenbaum,et al.  The role of synovitis in pathophysiology and clinical symptoms of osteoarthritis , 2010, Nature Reviews Rheumatology.

[37]  A. Guermazi,et al.  Anatomical distribution of synovitis in knee osteoarthritis and its association with joint effusion assessed on non-enhanced and contrast-enhanced MRI. , 2010, Osteoarthritis and cartilage.

[38]  J. Buckwalter,et al.  Relation of synovitis to knee pain using contrast-enhanced MRIs , 2010, Annals of the rheumatic diseases.

[39]  M. Barbe,et al.  Is osteoarthritis a heterogeneous disease that can be stratified into subsets? , 2010, Clinical Rheumatology.

[40]  T. Ochi,et al.  Regional differences in chondrocyte metabolism in osteoarthritis: a detailed analysis by laser capture microdissection. , 2008, Arthritis and rheumatism.

[41]  H. Genant,et al.  Synovitis detected on magnetic resonance imaging and its relation to pain and cartilage loss in knee osteoarthritis , 2007, Annals of the rheumatic diseases.

[42]  David T Felson,et al.  Clinical practice. Osteoarthritis of the knee. , 2006, The New England journal of medicine.

[43]  M. Dougados,et al.  Synovitis: a potential predictive factor of structural progression of medial tibiofemoral knee osteoarthritis -- results of a 1 year longitudinal arthroscopic study in 422 patients. , 2005, Osteoarthritis and cartilage.

[44]  K. Pavelka,et al.  Serum cartilage oligomeric matrix protein reflects the presence of clinically diagnosed synovitis in patients with knee osteoarthritis. , 2001, Osteoarthritis and cartilage.