Abstract
BackgroundThe identification of biomarkers of post-traumatic osteoarthritis (PTOA) progression is of clinical importance. The aims of this study were: (1) to assess the abilities of various soluble proinflammatory mediators in plasma to distinguish patients with knee PTOA from controls; (2) to determine the correlations between the mediators in plasma and those mediators in synovial fluid (SF); and (3) to explore the associations of the mediators with radiographic PTOA severity.Materials and methodsThe concentrations of IL-1β, IL-6, IL-18, TNFα, and leptin were measured using ELISA. Nitric oxide was determined as nitrite/nitrate (NOx) using the Griess reaction.ResultsWe included 171 subjects (134 PTOA patients and 37 controls) and excluded patients with rheumatoid arthritis or gout. The ROC curve of plasma NOx had the highest AUC, a specificity of 100%, and a sensitivity of 84.4%. The combination of IL-6 and leptin proved to be the most discriminatory, with an AUC value of 0.933, a specificity of 96.7%, and a sensitivity of 85.7%. The levels of NOx, IL-6, IL-18, and leptin in plasma were significantly correlated with their levels in SF. Leptin levels in both plasma (p = 0.036) and SF (p = 0.041) and the synovial IL-18 level (p = 0.045) were correlated with the Kellgren–Lawrence (KL) grade. Early-stage PTOA (KL 1–2) was associated with a high concentration of IL-1β in plasma before and after (OR 6.235, 95% CI 1.362 to 28.552, p = 0.018) adjusting for age, gender, and BMI.ConclusionsCirculating NOx level and a combination of IL-6 and leptin permitted the strongest discrimination of patients with PTOA from controls. PTOA severity was correlated with leptin levels in plasma and SF and with the synovial IL-18 level. Early PTOA was associated with the circulating level of IL-1β.Level of evidenceIII (case–control study).
Highlights
Osteoarthritis (OA) is a degenerative joint disease that commonly affects weight-bearing joints and is characterized by articular cartilage degradation
Analyses of Hodges–Lehmann estimators for the median differences between the groups (Table 3) yielded nearly the same pattern of significant differences as the Mann–Whitney U test or Dunn’s post hoc test (Table 2) did. The deviations from this pattern were the level of nitrite/nitrate in plasma of patients with late post-traumatic osteoarthritis (PTOA) and the TNFα level in plasma of patients with early PTOA when compared with the controls
The principal findings of this study are that some circulating biomarkers, namely nitrite/nitrate level, the combination of IL-6 and leptin, as well as IL-1β, may be used to predict the occurrence of PTOA
Summary
Osteoarthritis (OA) is a degenerative joint disease that commonly affects weight-bearing joints and is characterized by articular cartilage degradation. Recent studies have demonstrated correlations of the radiographic grading of OA with many biochemical markers in the blood, including circulating levels of IL-6 and TNF-α [5]. The identification of biomarkers of post-traumatic osteoarthritis (PTOA) progression is of clinical importance. The aims of this study were: (1) to assess the abilities of various soluble proinflammatory mediators in plasma to distinguish patients with knee PTOA from controls; (2) to determine the correlations between the mediators in plasma and those mediators in synovial fluid (SF); and (3) to explore the associations of the mediators with radiographic PTOA severity. Conclusions Circulating NOx level and a combination of IL-6 and leptin permitted the strongest discrimination of patients with PTOA from controls. PTOA severity was correlated with leptin levels in plasma and SF and with the synovial IL-18 level.
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