Cartilage Acidic Protein 1 in Plasma Associates With Prevalent Osteoarthritis and Predicts Future Risk as Well as Progression to Joint Replacements: Results From the UK Biobank Resource
Open accessAbstract
OBJECTIVE: The level of cartilage acidic protein 1 (CRTAC1) in plasma was recently discovered to be associated with osteoarthritis (OA) risk and progression to joint replacement in Iceland. This study was undertaken to validate these findings in an independent population. METHODS: In this study, 1,462 plasma proteins were measured in 54,265 participants from the UK Biobank on the Olink Explore platform. We analyzed the association of plasma proteins with prevalent OA, incident OA, and progression to joint replacement. We assessed the specificity of OA association through comparison of associations with inflammatory joint diseases and with previous joint replacement. RESULTS: The CRTAC1 protein showed the strongest association with prevalent knee OA (odds ratio [OR] 1.34 [95% confidence interval (95% CI) 1.27, 1.41]) and was associated with hip OA (OR 1.19 [95% CI 1.11, 1.28]). It predicted incident diagnosis of OA in the knee (hazard ratio [HR] 1.40 [95% CI 1.35, 1.46]) and hip (HR 1.25 [95% CI 1.19, 1.31]), as well as progression to joint replacement (HR 1.20 [95% CI 1.08, 1.33] for the knee and HR 1.22 [95% CI 1.08, 1.38] for the hip), while no association was found with inflammatory joint diseases. Individuals in the highest quintile of risk based on CRTAC1 level, age, sex, and body mass index had a 10-fold risk of knee or hip OA within 5 years compared to those in the lowest quintile. Adding aggrecan core protein (ACAN) and neurocan core protein (NCAN) to the model improved the prediction of OA but not joint replacement. Furthermore, we replicated the association of CUB domain-containing protein 1 with prior joint replacement. CONCLUSION: Plasma CRTAC1 is a specific biomarker for OA and a predictor of OA risk and progression to joint replacement. Adding ACAN and NCAN protein levels to the CRTAC1 model improved the prediction of OA.
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CTX-II correlates with disease severity, being higher in Kellgren-Lawrence grades 3-4 than grade 2.
“correlating with disease severity (higher in Kellgren-Lawrence grades 3–4 vs. 2)”
From Biomarker-Guided Imaging and AI-Augmented Diagnosis of Degenerative Joint Disease (2025) · cites this paper as [23]
CTX-II is elevated in urine of knee OA patients.
“and is elevated in urine of knee OA patients”
From Biomarker-Guided Imaging and AI-Augmented Diagnosis of Degenerative Joint Disease (2025) · cites this paper as [23]
CTX-II is a fragment of type II collagen, which constitutes 90% of cartilage collagen, and is cleaved by collagenases.
“Specifically, CTX-II is a fragment of type II collagen (90% of cartilage collagen) cleaved by collagenases”
From Biomarker-Guided Imaging and AI-Augmented Diagnosis of Degenerative Joint Disease (2025) · cites this paper as [23]
CTX-II correlates with MRI-detected structural abnormalities: osteophytes R = 0.330, bone marrow lesions R = 0.252, and cartilage degradation R = 0.218, p < 0.05.
“and MRI-detected structural abnormalities (osteophytes R = 0.330, bone marrow lesions R = 0.252, cartilage degradation R = 0.218, p < 0.05)”
From Biomarker-Guided Imaging and AI-Augmented Diagnosis of Degenerative Joint Disease (2025) · cites this paper as [23]
Multivariate analysis highlights osteophyte load and synovitis as predictors of CTX-II, suggesting contributions from bone and synovium.
“with multivariate analysis highlighting osteophyte load and synovitis as predictors, suggesting contributions from bone and synovium [23,24,25].”
From Biomarker-Guided Imaging and AI-Augmented Diagnosis of Degenerative Joint Disease (2025) · cites this paper as [23]
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- Authors
- Styrkarsdottir, U., Lund, S. H., Thorleifsson, G., Saevarsdottir, S., Gudbjartsson, D. F., Thorsteinsdottir, U., & Stefansson, K.
- Affiliations
- deCODE genetics/Amgen Inc. Reykjavik Iceland
- deCODE genetics/Amgen Inc., Faculty of Medicine, School of Health Sciences University of Iceland, Department of Medicine, and Landspitali The National University Hospital of Iceland Reykjavik Iceland
- deCODE Genetics (Iceland) (IS)
- deCODE genetics/Amgen Inc., and Faculty of Medicine, School of Health Sciences University of Iceland Reykjavik Iceland
- Venue
- Arthritis & Rheumatology
- Publisher
- Wiley
- Published
- 2022-12-28
- Volume
- 75
- Issue
- 4
- Pages
- 544-552
- ISSN
- 2326-5191 (ISSN-L)
- 2326-5205
- OpenAlex
- W4306173676
- Cited by
- 34
- References
- 15
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 6 · 2023: 10
- FWCI
- 4.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Arthritis & Rheumatology (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Opin vísindi (Opin vísindi) (submittedVersion, cc-by-nc-sa)
- Opin vísindi (Opin vísindi) (submittedVersion, other-oa)
- Funders
- Amgen Inc.
- 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
- CRTAC1, osteoarthritis, knee osteoarthritis, hip osteoarthritis, joint replacement, plasma biomarkers, CDCP1, UK Biobank
- MeSH terms
- Calcium-Binding Proteins, Cartilage, United Kingdom, Humans, Osteoarthritis, Hip, Arthroplasty, Replacement, Osteoarthritis, Knee
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