Background/Purpose:  Osteoarthritis (OA) is a disease characterized by pain and tissue destruction, in some cases concomitant with inflammation. 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 of especially type I (connective tissue), II (cartilage), III (synovium) and IV (basement membrane) collagens have been shown to be elevated in OA. So we investigated whether biomarkers reflecting collagen degradation were associated with 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, 62 (10); mean(SD) BMI, 27(4); NSAID users, 23%; radiographic OA (KL≥2) 68%; and bilateral knee OA; 87%. Pain was assessed by VAS_pain 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 VAS_pain and WOMAC_pain. 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, KL_{signal 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 KL_{signal 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), KL_{signal knee} (β 8.9, p=0.0021) and bilateral knee OA (β -12.2, p=0.087) were associated with VAS_pain. 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 WOMAC_pain. Only age, BMI and NSAID use was associated with CHG VAS_pain. 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 WOMAC_pain (p<0.05) and VAS_pain(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.

Conclusion:  Different collagen degradation products are linked differentially to different phenotypes. Cartilage degradation (C2M) was consistently linked to CHG pain phenotypes, whereas it was not associated with an inflammatory phenotype. In contrast, C1M and C3M were linked to inflammatory and flared OA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/knee-osteoarthritis-pain-is-differentially-associated-with-tissue-degradation-and-joint-inflammation/