Can urinary CTX-II be a biomarker for knee osteoarthritis?

BACKGROUND: Early diagnosis of knee osteoarthritis (OA) remains a diagnostic challenge. Urinary C-terminal cross-linked telopeptide of type II collagen (urinary CTX-II) is one of the potential OA biomarkers. However, conclusive evidence regarding the use of this biomarker as a tool for early diagnosis is still lacking. The purposes of this study were to compare urinary CTX-II levels in patients with knee OA and in healthy controls, to evaluate the correlation between urinary CTX-II levels, radiographic severity of OA, and patient-reported outcomes and to evaluate the effect of age and gender on urinary CTX-II levels in the Asian populations. METHODS: Two groups were studied. The OA group included 78 patients with knee OA aged > 40 years who met the diagnostic criteria for knee OA described by the American College of Rheumatology (ACR). The control group consisted of 51 healthy participants age > 40 years without clinical or radiographic evidence of knee OA. Bilateral knee radiographs were taken and classified according to the Kellgren and Lawrence (KL) grading system. Urinary CTX-II was measured using a competitive ELISA test and Western Ontario and Mcmaster Universities Arthritis Index (WOMAC) was also recorded in all participants. RESULTS: Urinary CTX-II was significantly higher in the OA group than in the control group (p < 0.001). The severe knee OA group (KL grade 3 and 4) had higher urinary CTX-II levels than mild knee OA group (KL grade 2) but the difference did not reach statistical significance (p = 0.2). There was a moderate correlation between urinary CTX-II levels and KL grades (r = 0.405, p < 0.001) and a weak correlation between urinary CTX-II levels and WOMAC index scores (r = 0.367, p < 0.001). Multiple regression analysis showed that urinary CTX-II was independently associated with KL grades. Whereas age, gender, and WOMAC index had no statistically significant influence on the urinary CTX-II levels. CONCLUSIONS: Patients with knee OA had higher urinary CTX-II levels than healthy controls. Moreover, levels of urinary CTX-II were independently correlated with radiographic severity of knee OA. Age, gender, and patient-reported outcomes exerted no effect on the urinary CTX-II levels. LEVEL OF EVIDENCE: Diagnostic Level III.