Prospective Association Between Inflammatory Markers and Knee Cartilage Volume Loss and Pain Trajectory

Pain Ther. 2022 Mar;11(1):107-119. doi: 10.1007/s40122-021-00341-1. Epub 2021 Nov 27.

Abstract

Introduction: Inflammation has been suggested to be involved in the pathogenesis of osteoarthritis and pain. We sought to explore the associations between inflammatory serum markers and magnetic resonance imaging-defined long-term structural change and pain trajectory.

Methods: A total of 169 randomly selected participants (mean age 63 years; 47% female) from a prospective cohort study were included in this study. Circulating levels of interleukin 6 (IL-6), tumour necrosis factor alpha (TNF-α) and high-sensitivity C-reactive protein (CRP) were measured at baseline. A knee MRI scan was performed to measure cartilage volume (CV) and bone marrow lesions (BMLs) at baseline and at 10.7 years. Knee pain at four visits was measured by the WOMAC pain questionnaire, and pain trajectories were identified using group-based trajectory modelling. Linear, log-binomial and multi-nominal logistic regression were used for the analyses.

Results: IL-6 was associated with lateral but not medial tibial CV loss (β = - 0.25% per annum, per standard deviation [SD] log pg/ml; P < 0.05) in the multivariate analysis. IL-6 was also associated with a 'Moderate pain' trajectory (relative risk ratio 1.93 per SD log pg/ml; 95% confidence interval 1.02-3.65) relative to the 'Minimal pain' trajectory group. There was no significant association of TNF-α and CRP with CV loss and pain trajectory groups with the exception of a beneficial relationship between CRP and medial tibial CV loss (β = 0.20% per annum, per SD log mg/l). No association between inflammatory markers and change in BML size was observed.

Conclusions: IL-6 was independently associated with compartment-specific CV loss and worse pain trajectory, but the other markers studied were not, suggesting that components of inflammation are implicated in the pathogenesis of cartilage loss and developing a worse pain course.

Keywords: C-reactive protein; Inflammation; Interleukin 6; Knee; MRI; Osteoarthritis; Pain; Tumor necrosis factor-alpha.