Identification and characterisation of osteoarthritis patients with inflammation derived tissue turnover A.S. Siebuhr, K.K. Petersen, L. Arendt-Nielsen,

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Identification and characterisation of osteoarthritis patients with inflammation derived tissue turnover A.S. Siebuhr, K.K. Petersen, L. Arendt-Nielsen, L.L. Egsgaard, T. Eskehave, C. Christiansen, O. Simonsen, H.C. Hoeck, M.A. Karsdal, A.C. Bay-Jensen Osteoarthritis and Cartilage Volume 22, Issue 1, Pages 44-50 (January 2014) DOI: 10.1016/j.joca.2013.10.020 Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 1 Biomarker level depending on grade of OA and in the group scheduled for TKR. Mild: KL 0, n = 12. Moderate: KL 1 and 2, n = 204. Severe: KL 3 and 4, n = 158. TKR: Patients referred to TKR; KL 3 and 4, n = 60. A: Systemic CRP level detected by hsCRP (μg/mL). B: MMP-derived inflammation quantified by CRPM9. C: MMP-derived degradation of type I collagen quantified by C1M18. D: MMP-derived degradation of type II collagen quantified by C2M17. E: MMP-derived degradation of type III collagen quantified by C3M16. Data is depicted as mean + 95% CI and one-way ANOVA (Tukey's multiple comparison test) was used to test for significance. Biomarker data was log-transformed before analysis. Osteoarthritis and Cartilage 2014 22, 44-50DOI: (10.1016/j.joca.2013.10.020) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 2 Likelihood plot and table of values of hsCRP and the segregation of patients based on the cut-offs of hsCRP and CRPM. A: Likelihood plot of hsCRP (μg/mL). B: Table of the highest likelihood ratios, with concomitant sensitivity, specificity and hsCRP level. C: Correlation plot of hsCRP and CRPM, with cut-off to divide patients into four categories: Q1: Low systemic and MMP-derived inflammation; Q2: Low systemic inflammation and high MMP-derived inflammation; Q3: High systemic inflammation and low MMP-derived inflammation; Q4: High systemic and MMP-derived inflammation. Filled triangles: Patients referred to TKR. Open circles: Patients not referred to TKR. CRPM: MMP-derived inflammation quantified by MMP-derived degradation of CRP. Osteoarthritis and Cartilage 2014 22, 44-50DOI: (10.1016/j.joca.2013.10.020) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions

Fig. 3 Grade of OA and destructive collagen biomarkers in the four OA populations based of systemic (hsCRP) and MMP-derived inflammation (CRPM) described in Fig. 2. A: KL level in the four quadrants. B: C1M level in the four quadrants. C: C2M level in the four quadrants. D: C3M level in the four quadrants. The quadrants refer to the quadrants in Fig. 2(C) and there are 232 patients in Q1, 45 in Q2, 41 in Q3 and 19 in Q4. Data are depicted as mean + 95% CI. One-way ANOVA (Tukey's multiple comparison test) was used to test for significance. Osteoarthritis and Cartilage 2014 22, 44-50DOI: (10.1016/j.joca.2013.10.020) Copyright © 2013 Osteoarthritis Research Society International Terms and Conditions