Serum and Urinary CTX Levels as Biomarkers of Osteoarthritis: A Narrative Review

Abstract

Osteoarthritis (OA) is a leading progressive and disabling degenerative disorder of synovial joints, resulting in damage to cartilage tissue, characterized by pain, stiff joints, and immobility of the limb. Standard X-ray technique for detecting premature cartilage abnormality or for serial assessment is insufficiently responsive. The development of biochemical markers of cartilage turnover (particularly C-terminal crosslinked telopeptide of type II collagen [CTX-II]) to monitor cartilage catabolism and its activity as biochemical biomarkers has stimulated interest in their use for investigation. This narrative review was done to analyze existing information with the aim of finding out the status of CTX-II as a predictive, prognostic, or outcome measure of OA in either serum or urine.

Materials and Methods: A narrative review was carried out using published literature searched electronically and in published databases, original research papers, longitudinal studies, cross-sectionals, case-controls, intervention studies, animal studies, systematic reviews and meta-analyses between the years 2001 and 2025 evaluating serum/and or urinary CTX-II for OA. 22 studies that met the aims were searched and included.

Results: Collectively, the reviewed articles reported a significantly higher serum or urinary CTX-II concentration in OA compared to healthy individuals. This high CTX-II concentration was strongly correlated with radiographic severity, magnetic resonance imaging (MRI) -proven articular cartilage damage, reduced joint space, severity of pain, and limitation of function and/or activity. Longitudinal studies have shown that a greater concentration of basal CTX-II was associated with development of future loss of cartilage and progression of the disease. Finally, changes in the CTX-II concentration also correlated with the biologic response of pharmacologic or intra-articular therapy, which supports that this analyte could be used to monitor outcome. 

Conclusion: Both the serum and the urine CTX-II showed significant correlations with structural damage, disease severity and progression, and treatment response and can be valuable for the earliest diagnosis, prediction of outcome and management of OA but require further standardization and studies at a large scale.