Abstract
Objectives: The aim of this study was to identify biomarkers for radiographic OA severity and progression acting within the inflammation and metabolic pathways. Methods: For 3517 Rotterdam Study participants, 184 plasma protein levels were measured using Olink inflammation and cardiometabolic panels. We studied associations with severity and progression of knee, hip and hand OA and a composite overall OA burden score by multivariable regression models, adjusting for age, sex, cell counts and BMI. Results: We found 18 significantly associated proteins for overall OA burden, of which 5 stayed significant after multiple testing correction: circulating cartilage acidic protein 1 (CRTAC1), cartilage oligomeric matrix protein (COMP), thrombospondin 4, IL-18 receptor 1 (IL-18R1) and TNF ligand superfamily member 14. These proteins were also associated with progression of knee OA, with the exception of IL-18R1. The strongest association was found for the level of CRTAC1, with 1 s.d. increase in protein level resulting in an increase of 0.09 (95% CI 0.06, 0.12) in the overall OA Kellgren-Lawrence sum score (P = 2.9 × 10-8) in the model adjusted for age, sex, BMI and cell counts. This association was also present with the severity of OA in all three joints and progression of knee OA and was independent of BMI. We observed a stronger association for CRTAC1 with OA than for the well-known OA biomarker COMP. Conclusion: We identified several compelling biomarkers reflecting the overall OA burden and the increased risk for OA progression. CRTAC1 was the most compelling and robust biomarker for OA severity and progression. Such a biomarker may be used for disease monitoring.
| Original language | English |
|---|---|
| Pages (from-to) | 1286-1295 |
| Number of pages | 10 |
| Journal | Rheumatology (Oxford, England) |
| Volume | 62 |
| Issue number | 3 |
| Early online date | 4 Aug 2022 |
| DOIs | |
| Publication status | Published - 1 Mar 2023 |
Bibliographical note
Funding Information:Disclosure statement: S.M.A.B.-Z. declares consultancy work for Pfizer (tanezumab) and reports grants from the Netherlands Organization for Health Research and Development, the Dutch Arthritis Association and Foreum. The remaining authors declare no competing financial interests. All authors declare no non-financial conflicts of interest.
Funding Information:
Funding: This research was funded by the Netherlands Organisation for Health Research and Development (project no. 849200003). The funding source did not have any influence on study design, collection, analysis and interpretation of data, the writing of the manuscript or the decision to submit the manuscript for publication.
Funding Information:
The RS is funded by Erasmus Medical Center and Erasmus University, Rotterdam; the Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Ministry of Education, Culture and Science; the Ministry for Health, Welfare and Sports; the European Commission (DG XII) and the Municipality of Rotterdam. The authors are grateful to the study participants, the staff of the RS and the participating general practitioners and pharmacists. All authors contributed substantially to the conception and design of the article. I.A.S. and C.L.V. performed the analysis and drafted the initial manuscript. All authors critically revised it for interpretation of results and important intellectual content. All authors approved the final version of the manuscript. Patients and the General Public will be informed of the results through the dedicated website of Artrose Gezond ( https://artrosegezond.nl/ ), ZonMw ( https://zonmw.nl ) and via the Erasmus MC Rotterdam Osteoarthritis Research (ROAR) twitter account (@roar_NL).
Publisher Copyright:
© 2022 The Author(s). Published by Oxford University Press on behalf of the British Society for Rheumatology.