Cartilage collagen neoepitope C2C in urine as an integrative diagnostic marker for early knee osteoarthritis

Liisa Kuhi; Ann E Tamm; Agu O Tamm; Kalle Kisand

doi:10.1016/j.ocarto.2020.100096

Cartilage collagen neoepitope C2C in urine as an integrative diagnostic marker for early knee osteoarthritis

Osteoarthr Cartil Open. 2020 Sep 3;2(4):100096. doi: 10.1016/j.ocarto.2020.100096. eCollection 2020 Dec.

Authors

Liisa Kuhi^{1

2}, Ann E Tamm³, Agu O Tamm¹, Kalle Kisand¹

Affiliations

¹ Department of Internal Medicine, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.
² Central Laboratory, Diagnostic Clinic, East-Tallinn Central Hospital, Tallinn, Estonia.
³ Sports Medicine and Rehabilitation Clinic, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.

Abstract

Objective: To investigate the suitability of urinary collagen type-II C-terminal cleavage neoepitope (uC2C) as a marker for early knee osteoarthritis (kOA).

Design: We examined 302 Estonian subjects (mean age, 49 years): 186 subjects with and 20 control subjects without knee symptoms, and 96 patients treated by arthroscopy. For the latter, cartilage lesions were characterized using Société Francaise d'Arthroscopie (SFA) scores. Standardized radiographs of bilateral tibiofemoral (TF) and patellofemoral (PF) joints were assessed for osteoarthritis (OA) features. Osteophytes (Ophs) and joint space narrowing (JSN) were graded separately. uC2C was measured by the uC2C-HUSA assay. Logistic and linear regression models were used for data analysis.

Results: Of the kOA cases, 50% were isolated (TF or PF) grade 1; 10% were grade 2. JSN with Ophs was more frequent in females than in males (52% vs. 34%, p = 0.01). Increased uC2C level was associated with gradual increase in the risk of kOA grade of severity (odds ratio = 2.14-3.7) including grade 1 vs. 0. TF-OA and PF-OA equally predicted uC2C concentration (R ² = 0.33-0.35). uC2C prediction was better for females than for males (R ² = 0.42 vs. 0.22 by TF-OA). The best predictive model for uC2C level (R ² = 0.75) included three OA features: macroscopic cartilage lesions, TF Ophs, and PF-JSN.

Conclusions: uC2C as an integrative marker of kOA is associated with cartilage degradation and Oph formation in the PF- and TF-joints. Increased uC2C concentration could be used as an early diagnostic marker for kOA in clinical studies.

Keywords: AUC, area under the curve; BMI, body mass index; CI, confidence interval; Col1, type I collagen; Col2, type II collagen; JSN, joint space narrowing; Joint space narrowing; KL grading, Kellgren and Lawrence radiographic grading; KOOS, Knee injury and Osteoarthritis Outcome Score; Neoepitope C2C; OA, osteoarthritis; OR, odds ratio; Oph, osteophyte; Osteoarthritis; Osteophytes; PF, patellofemoral; Patellofemoral joint; SD, standard deviation; SFA score, Société Française d’Arthroscopie score; TF, tibiofemoral; Tibiofemoral joint; gOA, radiographic global grade of kOA; kOA, knee OA; lm-models, linear regression models; uC2C, Col2 cleavage neoepitopes in urine.