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

**Authors:** Ali Naderi, S. Ali Ghasemi, Andrea Fabregas, Gene Shaffer, James Raphael

PMC · DOI: 10.7759/cureus.103044 · Cureus · 2026-02-05

## TL;DR

This review examines the potential of CTX-II as a non-invasive biomarker for tracking cartilage breakdown after ACL surgery, but notes the need for more research due to limited and variable data.

## Contribution

The paper systematically reviews the use of urinary CTX-II as a biomarker for cartilage degradation after ACL reconstruction.

## Key findings

- Four studies were identified, but their limited number and variability hindered consistent analysis of CTX-II trends.
- Current evidence does not support establishing clear temporal trends or reference ranges for CTX-II after ACLR.
- CTX-II remains a promising non-invasive biomarker, though further longitudinal studies are needed to confirm its clinical utility.

## Abstract

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.

## Linked entities

- **Diseases:** osteoarthritis (MONDO:0005178)

## Full-text entities

- **Genes:** IL1A (interleukin 1 alpha) [NCBI Gene 3552] {aka IL-1 alpha, IL-1A, IL1, IL1-ALPHA, IL1F1}
- **Diseases:** instability of the knee (MESH:D007718), knee OA (MESH:D020370), osteoarthritic remodelling (MESH:D020257), inflammation (MESH:D007249), orthopaedic injuries (MESH:D014947), osteoarthritic change (MESH:D009402), ACL injury (MESH:D000070598), OA (MESH:D010003), cartilage breakdown (MESH:D002357)
- **Chemicals:** CPII (-), creatinine (MESH:D003404)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

26 references — full list in the complete paper: https://tomesphere.com/paper/PMC12967235/full.md

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Source: https://tomesphere.com/paper/PMC12967235