Cartilage oligomeric matrix protein, C-terminal cross-linking telopeptide of type II collagen, and matrix metalloproteinase-3 as biomarkers for knee and hip osteoarthritis (OA) diagnosis: a systematic review and meta-analysis
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Objective This study was design to examine the diagnostic performance of cartilage oligomeric matrix protein (COMP), C-terminal cross-linking telopeptide of type II collagen (CTX-II), and matrix metalloproteinase-3 (MMP-3) as biomarker for knee and hip OA. Methods Systematic search on multiple databases was completed in January 2018 using certain keywords. COMP, CTX-II, MMP-3 levels in knee and hip OA patients and healthy individuals were collected and calculated. Differences between subgroups were expressed as standardized mean differences (SMD). Subgroup analyses were performed to compare COMP, CTX-II, and MMP-3 performance between measuring sources, genders, large and small sample size and diagnostic criteria for OA patients. Results A moderate performance of COMP in distinguishing between knee (SMD: 0.68; 95% confidence intervals (CI): 0.43-0.93; P < 0.0001) or hip (SMD: 0.25; 95% CI, 0.10, 0.40; P = 0.0008) OA patients and controls were found. CTX-II showed a moderated standardised mean differences (SMD) of 0.48 (95% CI, 0.32, 0.64; P < 0.0001) in the detection of knee OA and a large SMD of 0.76 (95% CI, 0.09, 1.42; P = 0.03) in diagnosing hip OA. A small SMD of 0.32 (95% CI, -0.03, 0.67; P = 0.07) was found for MMP-3 performance and the results did not reach statistic significance. Progression study revealed potential effectiveness of serum COMP in predicting OA progression. Subgroup analysis showed that serum COMP and urinary CTX-II performed better in male than female. Study size and diagnostic criteria did not significantly influence the pooled SMD, but they might be the sources of heterogeneity among studies. Conclusion The overall results indicates that serum COMP and urinary CTX-II can distinguish between knee or hip OA patients and control subjects. Serum COMP is effective in predicting OA progression.Further researches with rigorous study design and a larger sample size are required to validate our findings.
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CTX-II and COMP are biochemical consequences of cartilage breakdown.
“C-terminal cross-linked telopeptides of type II collagen (CTX-II) and cartilage oligomeric matrix protein (COMP) are among the many biochemical consequences of cartilage breakdown [21].”
From Biomarker-Guided Imaging and AI-Augmented Diagnosis of Degenerative Joint Disease (2025) · cites this paper as [21]
The Introduction identifies CTX-II as a byproduct of articular cartilage degradation. It describes COMP as a protein found primarily in cartilage and studied as an OA biomarker, but does not say that COMP itself is a consequence of cartilage breakdown; a reference title in the paper describes COMP fragments as markers of degradation. (LLM, conf=0.82)
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МАРКЕРИ ОБМІНУ СПОЛУЧНОЇ ТКАНИНИ У ХВОРИХ З ДІАБЕТИЧНИМИ АРТРОПАТІЯМИ
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- Authors
- Hao, H. Q., Zhang, J. F., He, Q. Q., & Wang, Z.
- Affiliations
- Shanxi University of Traditional Chinese Medicine (CN)
- Shanxi Medical University (CN)
- Corresponding author
- Zhang, J.F.
- ORCID
- Venue
- Osteoarthritis and Cartilage
- Publisher
- Elsevier BV
- Published
- 2019-05
- Volume
- 27
- Issue
- 5
- Pages
- 726-736
- ISSN
- 1063-4584 (ISSN-L)
- OpenAlex
- W2899068696
- Cited by
- 118
- References
- 88
- Citations by year
- 2026: 11 · 2025: 15 · 2024: 13 · 2023: 32 · 2022: 14 · 2021: 10 · 2020: 17 · 2019: 6
- FWCI
- 1.37
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Osteoarthritis and Cartilage (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81573245, 81102198)
- Shanxi provincial health Commission projects (2018GW09, 2014169)
- Topics
- Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
- Health Sciences › Medicine › Surgery › Hip disorders and treatments
- Health Sciences › Medicine › Pharmacology › Musculoskeletal pain and rehabilitation
- Keywords
- cartilage oligomeric matrix protein, matrix metalloproteinase-3, knee osteoarthritis, hip osteoarthritis, osteoarthritis biomarkers, osteoarthritis diagnosis, osteoarthritis progression, serum biomarkers, urinary biomarkers, diagnostic accuracy
- MeSH terms
- Humans, Peptide Fragments, Prognosis, Osteoarthritis, Hip, Biomarkers, Matrix Metalloproteinase 3, Osteoarthritis, Knee, Collagen Type II, Cartilage Oligomeric Matrix Protein
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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