Background Osteoarthritis (OA) is described as a non-inflammatory joint disease. It is now evident that a subset of patients has chronic tissue inflammation. C-reactive protein (CRP) has shown limited use in predicting disease severity, progression or response to anti-inflammatory treatment.

Objectives The aim was to segregate patients into groups dependent on the present or absence of systemic and/or chronic tissue inflammation and describe these groups by serological markers.

Methods A cross-sectional study including 342 patients: 281 patients had symptomatic knee OA and 61 OA patients underwent total knee replacement (TKR). Following biomarkers were measured by ELISA in serum: high sensitive CRP (hsCRP), CRP degradation fragment (CRPM, chronic tissue inflammation), matrix metalloproteinase-mediated degradation fragments of type I, II and III collagen; C1M (connective tissue), C2M (cartilage) and C3M (synovium). The associations between biomarkers and OA stage were investigated: KL0, Mild OA (n=12); KL1-2, Moderate OA (n=202); KL3-4, Severe OA (n=57); and KL3-4 with TKR (n=60). Cut-off values of CRPM and hsCRP were set as 12ng/mL and 5µg/mL (mean+2SD of controls). Patients were divided in 4 quartiles (Q, fig) based on the cut-off values. Reference values of the biomarkers were recorded for healthy controls.

Results hsCRP was only elevated in the TKR patients compared to controls. The mean levels of the CRPM were higher in all OA groups (10-14ng/mL) compared to controls (5ng/mL). C1M and C2M were significantly elevated in the TRKs compared to Moderate and Severe OA (p<0.001). There was no difference in the mean levels of C3M from controls. Patients in Q4 (fig) had significantly higher KL compared to patients in Q1 (p<0.0001), Q2 (P=0.017) and Q3 (p<0.0001). C1M, C2M and C3M were lower in Q1 compared to all other quartiles. Comparing Q2 with Q3 showed that C1M was higher (p=0.0005) in Q3, but C3M was lower (p=0.019). Thus, patients identified by CRPM were significantly different compared to those identified by hsCRP.

Conclusions All OA patients had surprisingly high levels of chronic tissue inflammation. OA patients could be divided into quartiles or 2 separate groups: i) those who may benefit from anti-inflammatory treatment (Q3, Q4) and ii) those eligible for a more tissue centric treatment (Q1, Q2). Patients with high chronic tissue inflammation (Q2 and Q4) had higher levels of the tissue degradation markers C1M and C2M suggesting that they had elevated tissue turnover. In alignment, those OA patients undergoing TKR had even higher levels of tissue turnover markers, suggesting a distinct TKR serological phenotype.

Disclosure of Interest A. S. Siebuhr Employee of: Nordic Bioscience, K. Petersen: None Declared, L. Arendt-Nielsen: None Declared, L. Egsgaard: None Declared, T. Eskehave: None Declared, C. Christiansen Shareholder of: Nordic Bioscience, O. Simonsen: None Declared, H. C. Hoeck Employee of: Center of Clinical and Basic Research, M. Karsdal Shareholder of: Nordic Bioscience, Employee of: Nordic Bioscience, A. C. Bay-Jensen Employee of: Nordic Bioscience