C-Terminal Cross-Linked Telopeptides of Type II Collagen as Biomarker for Radiological Knee Osteoarthritis: A Meta-Analysis

Background C-terminal cross-linked telopeptides of type II collagen (CTX-II) are one of the most frequently assessed markers for osteoarthritis (OA) diagnosis. The aim of this meta-analysis was to confirm the diagnostic value of urinary CTX-II in knee OA. Materials and Methods PubMed, ScienceDirect, and EMBASE were searched for studies measured urinary CTX-II in patients with knee OA and in healthy controls. Urinary CTX-II levels were compared between knee OA patients and controls. Differences between groups were expressed as standardized mean differences (SMD) when individual outcomes were measured with different scales. Otherwise, outcomes were presented as mean differences (MD). Subgroup analyses were also conducted to compare efficiency of urinary CTX-II between Kellgren-Lawrence (KL) classification, genders, ethnicities, and study size. Results Thirteen studies involved a total of 2856 participants were included. Pooled SMD showed that urinary CTX-II levels were significantly elevated in knee OA group compared to controls (SMD 0.82; 95% CI 0.41-1.24;P< 0.0001). For KL 3 to 4 versus KL 2, higher urinary CTX-II levels were found in severe knee OA patients. Subgroup analyses revealed that urinary CTX-II performed better in females as compared with males and in European subjects as compared with Asian population. Also, study size did not influence the statistic results. Conclusion This is the largest scale meta-analysis assessing the diagnostic performance of urinary CTX-II levels as biomarker for knee OA. According to our findings, urinary CTX-II levels have a potential to distinguish knee OA patients from healthy controls which can serve as biomarker for knee OA.