Correlation Analysis of C-terminal telopeptide of collagen type II and Interleukin-1β for Early Diagnosis of Knee Osteoarthritis

Abstract

Objective: To analyze the correlation between the Kellgren-Lawrence (K-L) score of knee osteoarthritis (KOA) patients with different degrees and their urine concentration of C-terminal telopeptide of collagen type II (CTX-II) and interleukin-1β (IL-1β), and to further evaluate the diagnostic value of CTX-II and IL-1β during the pathological process by producing an experimental osteoarthritis (OA) model in rabbits.

Methods: From 1 January 2017 to 31 December 2018, a total of 34 subjects (7 mild, 9 moderate, 9 severe arthritis patients, and 9 healthy individuals) comprising 16 men and 18 women were included in this study. Patients were diagnosed according to the American College of Rheumatology (ACR) criteria. The urine of all subjects was collected to detect the concentration of CTX-II and IL-1β. The rabbits in the KOA group were subjected to protease (control group with saline) injection into the articular cavity of their right knees and immobilization with gypsum. We used radiological and histological examination to identify the KOA model. ELISA was applied to investigate the concentrations of CTX-II and IL-1β in urine and serum, and Spearman's rank correlation analysis was used to analyze the correlation.

Results: There was no significant difference in the mean ages and body mass index (BMI) between groups. The mean ages of mild, moderate, and severe arthritis patients and healthy individuals were 54.29 ± 5.76, 58.44 ± 6.44, 59.89 ± 6.75, and 56.67 ± 4.18 years, respectively. The mean BMI of mild, moderate, and severe arthritis patients and healthy individuals were 23.59 ± 1.56, 23.57 ± 2.06, 24.46 ± 1.64, and 23.42 ± 1.35 kg/m² , respectively. The Kellgren-Lawrence (K-L) score was higher with the aggravation of KOA. The K-L scores of mild, moderate, and severe KOA patients were 1.14 ± 0.38, 2.56 ± 0.53, and 3.63 ± 0.52, respectively. The KOA symptoms of patients became more severe, with not only increased K-L scores but also elevated concentrations of CTX-II and IL-1β. Moreover, there was a positive correlation between CTX-II and IL-1β of all subjects (r = 0.974, P < 0.001), between K-L score and urine concentration of CTX-II (r = 0.900, P < 0.001), and between K-L score and IL-1β (r = 0.813, P < 0.001) of all subjects. Both were significantly increased in KOA group rabbits at all time points after surgery. The serum concentration of CTX-II and IL-1β was elevated as early as in the 2nd week (3.69 and 4.25 times) and reached a peak (5.41 and 7.23 times) in the 4th week after surgery. Then, until 12 weeks after surgery, the CTX-II and IL-1β concentrations in the KOA group were slightly reduced and remained around 4.5 and 6.3 times that in the control group. Moreover, there was a positive correlation between the serum concentration of IL-1β and CTX-II (r = 0.967, P < 0.001).

Conclusion: CTX-II and IL-1β, which were significantly increased during the process of KOA, can be used as biomolecular markers to provide guidelines for early diagnosis and treatment of KOA.

Keywords: C-terminal telopeptide of collagen type II; Correlation analysis; Interleukins-1β; Kellgren-Lawrence score; Knee osteoarthritis.