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Prospective association between inflammatory markers and knee cartilage volume loss and pain trajectory


Pan, F and Tian, J and Cicuttini, F and Jones, G, Prospective association between inflammatory markers and knee cartilage volume loss and pain trajectory, Pain and Therapy pp. 1-13. ISSN 2193-8237 (2021) [Refereed Article]

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Copyright The Author(s) 2021. This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, ( which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

DOI: doi:10.1007/s40122-021-00341-1



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.


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.


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.


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.

Item Details

Item Type:Refereed Article
Keywords:C-reactive protein, inflammation, interleukin 6, knee, MRI, osteoarthritis, pain; tumor necrosis factor-alpha
Research Division:Biomedical and Clinical Sciences
Research Group:Clinical sciences
Research Field:Pain
Objective Division:Health
Objective Group:Clinical health
Objective Field:Prevention of human diseases and conditions
UTAS Author:Pan, F (Dr Feng Pan)
UTAS Author:Tian, J (Dr Jing Tian)
UTAS Author:Jones, G (Professor Graeme Jones)
ID Code:148398
Year Published:2021
Funding Support:National Health and Medical Research Council (1157535)
Web of Science® Times Cited:2
Deposited By:Menzies Institute for Medical Research
Deposited On:2022-01-05
Last Modified:2022-02-25
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