A M Valdes1, I Meulenbelt2, E Chassaing3, N K Arden4, S Bierma-Zeinstra5, D Hart6, A Hofman7, M Karsdal8, M Kloppenburg9, H M Kroon10, E P Slagboom2, T D Spector6, A G Uitterlinden11, J B van Meurs12, A C Bay-Jensen8. 1. Academic Rheumatology, University of Nottingham, Clinical Sciences Bld, Nottingham City Hospital, Nottingham NG5 1PB, UK; Dept of Twin Research, King's College London, London SE1 7EH, UK. Electronic address: ana.valdes@kcl.ac.uk. 2. Dept of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands. 3. Synarc Laboratory, Lyon, France. 4. NIHR Musculoskeletal Biomedical Research Unit and ARUK Centre of Excellence for Sport, Exercise and Osteoarthritis University of Oxford, UK. 5. Dept of General Practice and Dept of Orthopaedics, Erasmus MC, Rotterdam, The Netherlands. 6. Dept of Twin Research, King's College London, London SE1 7EH, UK. 7. Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands. 8. Rheumatology, Nordic Bioscience Biomarkers and Research, Herlev, Denmark. 9. Dept of Rheumatology and Dept of Clinical Epidemiology, Leiden University Medical Center, Leiden, The Netherlands. 10. Dept of Radiology, Leiden University Medical Center, Leiden, The Netherlands. 11. Department of Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands; Dept of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands. 12. Dept of Internal Medicine, Erasmus Medical Centre, Rotterdam, The Netherlands.
Abstract
OBJECTIVE: To evaluate the role of three cartilage-derived biomarkers on osteoarthritis (OA): urinary C-terminal telopeptide (uCTX-II), serum cartilage oligomeric protein (sCOMP), and serum MMP degraded type II collagen (sC2M). SUBJECTS AND METHODS: Samples from 3582 individuals from the Rotterdam Study, the Genetics osteoArthritis and Progression (GARP), the Chingford Study and the TwinsUK cohort were assayed using enzyme-linked immune sorbent assays. Log10 of concentration levels were correlated with risk of hip, hand and knee OA, hip and knee OA severity and incidence, and progression of knee OA, adjusting for age, gender and body mass index (BMI). Results were meta-analysed to assess overall significance. RESULTS: After adjusting for covariates, sCOMP was associated with knee OA and hip and knee OA incidence. Furthermore, sC2M was associated with knee OA incidence and progression. After adjustment for multiple tests (Bonferroni P < 0.002) only the association between sCOMP and knee OA remained significant (odds ratio (OR) = 3.26 (95%CI 1.63-10.1) P = 0.0008 for each standard deviation (SD) increase in biomarker levels). Levels of uCTX-II were significantly associated with risk of hand, hip and knee OA, progression and incidence of knee OA. A receiver operating characteristics (ROC) analysis showed a consistent improvement in prediction of knee OA progression from an average area under the curve (AUC) is 0.646 for age, sex and BMI alone to an AUC = 0.668 including uCTX-II for prediction. CONCLUSIONS: uCTX-II is the most informative biochemical marker for prediction of OA. Both sCOMP and C2M showed some association with OA, thus indicating that they are descriptive of disease activity.
OBJECTIVE: To evaluate the role of three cartilage-derived biomarkers on osteoarthritis (OA): urinary C-terminal telopeptide (uCTX-II), serum cartilage oligomeric protein (sCOMP), and serum MMP degraded type II collagen (sC2M). SUBJECTS AND METHODS: Samples from 3582 individuals from the Rotterdam Study, the Genetics osteoArthritis and Progression (GARP), the Chingford Study and the TwinsUK cohort were assayed using enzyme-linked immune sorbent assays. Log10 of concentration levels were correlated with risk of hip, hand and knee OA, hip and knee OA severity and incidence, and progression of knee OA, adjusting for age, gender and body mass index (BMI). Results were meta-analysed to assess overall significance. RESULTS: After adjusting for covariates, sCOMP was associated with knee OA and hip and knee OA incidence. Furthermore, sC2M was associated with knee OA incidence and progression. After adjustment for multiple tests (Bonferroni P < 0.002) only the association between sCOMP and knee OA remained significant (odds ratio (OR) = 3.26 (95%CI 1.63-10.1) P = 0.0008 for each standard deviation (SD) increase in biomarker levels). Levels of uCTX-II were significantly associated with risk of hand, hip and knee OA, progression and incidence of knee OA. A receiver operating characteristics (ROC) analysis showed a consistent improvement in prediction of knee OA progression from an average area under the curve (AUC) is 0.646 for age, sex and BMI alone to an AUC = 0.668 including uCTX-II for prediction. CONCLUSIONS: uCTX-II is the most informative biochemical marker for prediction of OA. Both sCOMP and C2M showed some association with OA, thus indicating that they are descriptive of disease activity.
Authors: Albert Hofman; Guy G O Brusselle; Sarwa Darwish Murad; Cornelia M van Duijn; Oscar H Franco; André Goedegebure; M Arfan Ikram; Caroline C W Klaver; Tamar E C Nijsten; Robin P Peeters; Bruno H Ch Stricker; Henning W Tiemeier; André G Uitterlinden; Meike W Vernooij Journal: Eur J Epidemiol Date: 2015-09-19 Impact factor: 8.082
Authors: Cesar Garriga; Maria T Sánchez-Santos; Andrew Judge; Deborah Hart; Tim Spector; Cyrus Cooper; Nigel K Arden Journal: Arthritis Care Res (Hoboken) Date: 2020-01 Impact factor: 4.794
Authors: Fatemeh Saberi Hosnijeh; Anne Sofie Siebuhr; Andre G Uitterlinden; Edwin H G Oei; Albert Hofman; Morten A Karsdal; Sita M Bierma-Zeinstra; Anne C Bay-Jensen; Joyce B J van Meurs Journal: Arthritis Res Ther Date: 2016-04-01 Impact factor: 5.156
Authors: Stefan Kluzek; Anne-Christine Bay-Jensen; Andrew Judge; Morten A Karsdal; Matthew Shorthose; Tim Spector; Deborah Hart; Julia L Newton; Nigel K Arden Journal: Biomarkers Date: 2016-02-05 Impact factor: 2.658