Background Osteoarthritis (OA) is heterogeneous disease characterized by pain and tissue destruction which is in some case concomitant with inflammation. However, the link between pain and tissue destruction is yet unknown, and there is a lack objective quantifiable parameters. Collagens are the main structural proteins of the joint extracellular matrix. The degradation type I (connective tissue), II (cartilage), III (synovium) and IV (basement membrane) collagens have been shown to be elevated in joint degenerative diseases.
Objectives To investigate whether biomarkers reflecting collagen degradation were associated with symptomatic knee OA representing with different pain and inflammatory phenotypes.
Methods 111 knee OA patients, 62% women, from NYUHJD progression cohort study with varying degree of OA were included: mean (SD) age, 32 (10); mean (SD) BMI, 27 (4); NSAID users, 23%; radiographic OA (KL≥2) 68%; and bilateral knee OA; 87%. Pain was assessed by VASpain and WOMAC at baseline (BL) at a 2-year follow-up (FU) visit. Median (IQR) were 39 (13–69) and 37 (13–52) for BL VASpain and WOMACpain. 4 BL serum biomarkers of type I, II, III and IV collagen degradation (C1M, C2M, C3M, C4M), and the 2 inflammatory biomarkers CRPM and hsCRP, were assessed. Data were log2 transformed. Associations between BL biomarkers, BL pain and change (CHG) pain scores were assessed by multivariate linear model including gender, age, BMI, KLsignal knee, bilateral knee OA and NSAID use. Patients with cont. mild/moderate pain had a BL VASpain<54 and FU VASpain<30, cont. moderate/severe pain had VASpain>30 at baseline and FU, and transitional severe pain had either VASpain_BL<30 and VASpain_FU>54 or VASpain_BL>54 and VASpain_FU<30 (ref). Patients with; low biochemical disease activity index (bDAI) low in CRPM (<12nM) moderate bDAI were high in CRPM but low in hsCRP (<5), and high bDAI (flare) were high in CRPM and hsCRP.
Results BL association between pain and biomarkers. C2M (β -17.9, p<0.0001) and KLsignal knee (β -5.4, p=0.0031) were significantly associated with WOMAC pain. C2M (β -12.4, p=0.0033), C3M (β -19.9, p=0.059), age (β -0.84, p<0.0018), KLsignal knee (β 8.9, p=0.0021) and bilateral knee OA (β -12.2, p=0.087) were associated with VASpain. Association between BL biomarkers and CHG pain. C2M (β 13.3, p=0.0016), age (β 0.5, p=0.029) and bilateral OA (β -12.0, p=0.043) were significantly associated with delta WOMACpain. Only age, BMI and NSAID use was associated with CHG VASpain. Association between pain phenotypes and BL biomarkers. Patients with cont. mild/moderate pain had significantly higher C2M compared patients with transitional severe pain (p=0.0014) and cont. moderate/severe pain (p=0.04). Biomarker, BL pain and CHG pain in patients w. inflammatory OA. Patient with low bDAI had lower WOMACpain (p<0.05) and VASpain (p<0.1). C1M was higher (p<0.05) in the flare group compared to the low and moderate bDAI groups. C3M was higher (p<0.05) in the moderate bDAI group than the low DAI group.
Conclusions Different collagen degradation products are linked differentially to different phenotypes. Cartilage degradation (C2M) was consistently linked to pain CHG and phenotypes, whereas it was not associated with an inflammatory phenotype. In contrast, C1M and C3M were linked to inflammatory OA and flared OA.
Disclosure of Interest A.-C. Bay-Jensen Shareholder of: Nordic Bioscience, Grant/research support from: DBOARD H2020, Employee of: Nordic Bioscienc, S. Abramson: None declared, J. Samuals: None declared, I. Byrjalsen Employee of: Nordic Bioscience, S. Krasnokutsky: None declared, T. Manon-Jensen Employee of: Nordic Bioscience, M. Karsdal Shareholder of: DBOARD H2020, Employee of: Nordic Bioscienc, M. Attur: None declared