Association between ultrasound-detected synovitis and knee pain: a population-based case-control study with both cross-sectional and follow-up data

Background: Recently an important role for synovial pathology in the initiation and progression of knee osteoarthritis (OA) has been emphasised. This study aimed to examine whether ultrasonographydetected synovial changes (USSCs) associate with knee pain (KP) in a community population. Methods: A case-control study was conducted to compare people with early KP (n=298), established KP (n=100) or no KP (n=94) at baseline. Multinomial logistic regression was used to estimate odds ratio (OR) and 95% confidence interval (CI) between groups adjusted for radiographic osteoarthritis (ROA) severity and other confounding factors. After one year 255 participants with early and established KP completed the followup questionnaire for changes in KP. Logistic regression with adjustment was used to determine predictors of KP worsening. Results: At baseline, effusion was associated with early (OR 2.64, 95%CI 1.57 to 4.45) and established KP (OR 5.07, 95%CI 2.74 to 9.38). Synovial hypertrophy was also associated with early (OR 5.43, 95%CI 2.12 to 13.92) and established KP (OR 13.27, 95%CI 4.97 to 35.43). The association with effusion diminished when adjusted for ROA. Power Doppler signal was uncommon (early KP 3%, established KP 2%, controls 0%). Baseline effusion predicted worsening of knee pain at one year (OR 1.95, 95% CI 1.05 to 3.64). However, after adjusting for ROA, the prediction was insignificant (aORs 0.95, 95%CI 0.44 to 2.02). Conclusion: US effusion and synovial hypertrophy are associated with KP, but only effusion predicts KP worsening. However, the association/prediction are not independent from ROA. Power Doppler signal is uncommon in people with KP. Further study is needed to understand whether synovitis is directly involved in different types of KP

Synovitis in osteoarthritis: current understanding with therapeutic implications

Modern concepts of osteoarthritis (OA) have been forever changed by modern imaging phenotypes demonstrating complex and multi-tissue pathologies involving cartilage, subchondral bone and (increasingly recognized) inflammation of the synovium. The synovium may show significant changes, even before visible cartilage degeneration has occurred, with infiltration of mononuclear cells, thickening of the synovial lining layer and production of inflammatory cytokines. The combination of sensitive imaging modalities and tissue examination has confirmed a high prevalence of synovial inflammation in all stages of OA, with a number of studies demonstrating that synovitis is related to pain, poor function and may even be an independent driver of radiographic OA onset and structural progression. Treating key aspects of synovial inflammation therefore holds great promise for analgesia and also for structure modification. This article will review current knowledge on the prevalence of synovitis in OA and its role in symptoms and structural progression, and explore lessons learnt from targeting synovitis therapeutically

Association between biomarkers of tissue inflammation and progression of osteoarthritis: evidence from the Rotterdam study cohort

Background: We aimed to investigate the prognostic value of two biomarkers of tissue inflammation, matrix metalloproteinase-dependent degradation of C-reactive protein (CRPM) and connective tissue type I collagen turnover (C1M), on the incidence and progression of radiographic osteoarthritis (OA) in the Rotterdam Study, a prospective cohort. Moreover, the independent effect of these biomarkers with respect to the established biomarkers of OA progression, like urinary type II collagen degradation (uCTX-II) and serum cartilage oligomeric protein (COMP), was evaluated. Methods: Serum levels of C1M, CRPM, COMP and CRP of 1335 participants aged >55 years were measured in fasting serum using ELISA. The commercial ELISA detecting CTX-II was used in urine. Radiographs at baseline and 5-year follow-up were scored for OA stage by Kellgren-Lawrence grade. The associations between progression and incidence of OA and the baseline biomarkers were examined using logistic regression and generalized estimating equations adjusted for age, sex, BMI, and possible other confounders. Results: The uCTX-II, COMP, and CRP concentrations were associated with the incidence and progression of OA. Moreover, OA progression was positively associated with CRPM (OR = 1.3, p = 0.01) and CRP (OR = 1.3, p = 0.01) levels with similar effect size as uCTX-II (OR = 1.3, p = 0.01) and COMP (OR = 1.2, p = 0.02). CRPM had prognostic value for progression of OA independent from the uCTX-II and COMP. Conclusions: Our study confirmed the associations between uCTX-II and COMP concentrations and OA progression. Importantly, we showed for the first time that CRPM predicts the risk of OA progression independent of the established biomarkers uCTX-II and COMP

Association between biomarkers of tissue inflammation and progression of osteoarthritis: evidence from the Rotterdam study cohort

Abstract Background We aimed to investigate the prognostic value of two biomarkers of tissue inflammation, matrix metalloproteinase-dependent degradation of C-reactive protein (CRPM) and connective tissue type I collagen turnover (C1M), on the incidence and progression of radiographic osteoarthritis (OA) in the Rotterdam Study, a prospective cohort. Moreover, the independent effect of these biomarkers with respect to the established biomarkers of OA progression, like urinary type II collagen degradation (uCTX-II) and serum cartilage oligomeric protein (COMP), was evaluated. Methods Serum levels of C1M, CRPM, COMP and CRP of 1335 participants aged >55 years were measured in fasting serum using ELISA. The commercial ELISA detecting CTX-II was used in urine. Radiographs at baseline and 5-year follow-up were scored for OA stage by Kellgren-Lawrence grade. The associations between progression and incidence of OA and the baseline biomarkers were examined using logistic regression and generalized estimating equations adjusted for age, sex, BMI, and possible other confounders. Results The uCTX-II, COMP, and CRP concentrations were associated with the incidence and progression of OA. Moreover, OA progression was positively associated with CRPM (OR = 1.3, p = 0.01) and CRP (OR = 1.3, p = 0.01) levels with similar effect size as uCTX-II (OR = 1.3, p = 0.01) and COMP (OR = 1.2, p = 0.02). CRPM had prognostic value for progression of OA independent from the uCTX-II and COMP. Conclusions Our study confirmed the associations between uCTX-II and COMP concentrations and OA progression. Importantly, we showed for the first time that CRPM predicts the risk of OA progression independent of the established biomarkers uCTX-II and COMP