Inflammatory Biomarkers Have Differing Effects on Joint Symptoms and Structural Changes in Knee Osteoarthritis

woman receiving knee exam, osteoarthritis
woman receiving knee exam, osteoarthritis
Researchers investigated the longitudinal associations of serum inflammatory markers with joint symptoms and structures in patients with knee osteoarthritis.

Inflammatory markers and adipokines were found to have varying effects on osteoarthritis (OA) of the knee with regard to structural changes and joint symptoms, according to research results published in Rheumatology.

Patients (N=200; 46.5% women) aged between 50 and 79 years who had pain scores between 20 and 80 mm on a 100 mm visual analog scale, had knee OA for a minimum of 6 months, and had 25-hydroxyvitamin D serum levels between 12.5 and 60 nmol/L were enrolled in the current analysis from the Vitamin D Effect on OA (VIDEO) study. Several inflammatory markers (interleukin [IL]-1β, IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, IL-17A, IL-17F, IL-21, IL-22, IL-23), vitamin D levels, Western Ontario and McMaster Universities Index (WOMAC), joint magnetic resonance imaging (MRI), cartilage volume and defects, bone marrow lesions (BMLs), and effusion-synovitis were recorded at baseline and at 24 months to investigate knee OA pathogenesis.

Researchers found that for component 1 (proinflammatory cytokines), IL-1β, IL-2, IL-4, IL-6, IL-8, IL-17A, IL-17F, IL-21, IL-22, and IL-23 ranked highest and had a positive association with respect to function score (β, 24.67; 95% CI, 1.18-48.20), but did not have a positive association with stiffness, pain, and overall WOMAC scores. Based on MRI evaluations, a positive association was also found between the first component and BMLs (mean ratio [MR], 1.01; 95% CI, 1.005-1.022). Cartilage defects, volume, and effusion-synovitis were not found to be positively associated with component 1.

Researchers observed that IL-10, IL-12, and GM-CSF ranked highest for component 2 (IL-10-related anti-inflammatory). In addition, with respect to component 2 and total score, there was a negative association with total score (β, -25.98; 95% CI, -36.67 to -15.30), pain score (β, -3.51; 95% CI, -6.44 to -0.58), function score (β, -19.61; 95% CI, -27.90 to -11.32), and stiffness score (β, -2.82; 95% CI, -4.07 to -1.56). No association was found between the second component and cartilage defects or with BMLs when evaluating MRI structures. However, component 2 was associated with both cartilage volume (β, 0.06; 95% CI, 0.01-0.10) and effusion-synovitis (MR, 0.97; 95% CI, 0.94-0.99).

For component 3 (C-reactive protein [CRP]-related metabolic inflammation), CRP, leptin, and adipsin were positively associated with total score (β, 87.76; 95% CI, 35.25-140.28), pain score (β, 20.74; 95% CI, 9.14-32.33), function score (β, 61.02; 95% CI, 21.35-100.68), and stiffness score (β, 6.26; 95% CI, 0.18-12.33). Regarding MRI structures and component 3, no associations were observed.

Component 4 (”resistin-related” metabolic inflammation) was mainly loaded by resistin. No associations were observed between the fourth component and WOMAC score or cartilage volume or effusion-synovitis. However, component 4 was associated with cartilage defects (β, 0.61; 95% CI, 0.003-1.22) and BMLs (MR, 1.03; 95% CI, 1.00-1.06). For component 5 (adiponectin-related metabolic inflammation), apelin-36 and adiponectin were associated with BMLs (MR, 1.01; 95% CI, 1.003-1.024).

Study limitations included the fact that it was conducted post-hoc within a randomized controlled trial, which may have affected the results; only some inflammatory biomarkers were included in the analysis; and the study findings may be generalizable to the general knee OA population.

Researchers concluded that, “various inflammatory and metabolic components were associated differently with joint symptoms and structural changes in knee OA, suggesting complex inflammatory and metabolic interrelationship in the pathogenesis of knee OA.”


Zhu J, Ruan G, Cen H, et al. Association of serum levels of inflammatory markers and adipokines with joint symptoms and structures in participants with knee osteoarthritis. Rheumatology. Published online June 11, 2021. doi:10.1093/rheumatology/keab479