The Role of C-Terminal Crosslinking Telopeptide of Type II Collagen (CTX-II) After Anterior Cruciate Ligament Reconstruction: A Systematic Review

Anterior cruciate ligament (ACL) injuries are known to accelerate cartilage degradation and predispose patients to early-onset osteoarthritis. C-terminal cross-linked telopeptide of type II collagen (CTX-II), a biomarker of cartilage breakdown, can be detected in various body fluids, including urine, offering a non-invasive method for evaluating cartilage degeneration. This systematic review aimed to assess existing evidence on urinary CTX-II (uCTX-II) levels following ACL reconstruction (ACLR). A systematic search of two medical databases was conducted in accordance with PRISMA guidelines. Studies were screened for inclusion based on their assessment of CTX-II in human subjects undergoing ACLR, and methodological quality was evaluated using the Modified Coleman Methodology Score (MCMS). Four studies met the inclusion criteria, with methodological quality ranging from fair to good. However, the limited number of studies and variability in time points prevented consistent analysis of uCTX-II trends postoperatively. While current evidence is insufficient to establish temporal trends or reference ranges, uCTX-II remains a promising non-invasive biomarker for monitoring cartilage degradation in ACLR patients. These findings should be interpreted cautiously due to the limited number of studies, heterogeneity in study design and postoperative time points, and the restricted database search. Further longitudinal studies are needed to validate its clinical utility.