Cross-sectional and longitudinal associations between serum inflammatory cytokines and knee bone marrow lesions in patients with knee osteoarthritis.
To describe cross-sectional and longitudinal associations between serum levels of interleukin (IL) - 6, IL-17A, IL-17F, IL-23 and knee bone marrow lesions (BMLs) in patients with knee osteoarthritis (OA).



Patients (n = 192) with symptomatic knee OA (mean 63 years, range 50-79, female 53%) were assessed at baseline and after 24 months. At each time point, serum IL-6, IL-17A, IL-17F and IL-23 were measured using Bio-Plex®Multiplex Immunoassays with Luminex xMAP technology. Knee BMLs were scored using the modified whole organ MRI score (WORMS) from T2 weighted fat-suppressed fast spin echo magnetic resonance imaging (MRI). Multivariable linear regression and log binominal regression were used to determine the associations between cytokines and BMLs.



Baseline IL-6 (quarters) were significantly associated with total knee BMLs (P < 0.01 for the trend) as well as associated with an increase in BML score (P = 0.05 for the trend), after adjustment for confounders. Baseline IL-17F and IL-23 (highest quarters vs others) was associated with an increase in BML score in females (P = 0.04 for IL-17F; P = 0.01 for IL-23), but not in males, in multivariable analyses. In contrast, IL-17A was not significantly associated with BMLs in either females or males.



IL-6 is associated with increased knee BMLs in both females and males with OA. Serum IL-17F and IL-23 predicted increased knee BML scores in females only, suggesting that inflammation is involved in BML pathogenesis in knee OA, especially in women.



ClinicalTrials.gov identifier: NCT01176344; Australian New Zealand Clinical Trials Registry: ACTRN12610000495022.
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia; Arthritis Research Institute, 1(st) Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
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Zhu
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
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Otahal
Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
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Wang
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
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Jin
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
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Laslett
Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
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Wluka
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
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Antony
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
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Han
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia; Arthritis Research Institute, 1(st) Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
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Wang
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia; Faculty of Health, University of Tasmania, Hobart, Tasmania, Australia.
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Winzenberg
Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia.
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Cicuttini
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia.
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Jones
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia; Arthritis Research Institute, 1(st) Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China; Department of Epidemiology and Preventive Medicine, Monash University, Melbourne, Victoria, Australia. Electronic address: Changhai.Ding@utas.edu.au.
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Ding
D000368:Aged; D001853:Bone Marrow / Q000000981:diagnostic imaging*; D001855:Bone Marrow Diseases / Q000000981:diagnostic imaging*; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000276:immunology*; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000276:immunology; D053759:Interleukin-23 / Q000276:immunology; D015850:Interleukin-6 / Q000276:immunology; D016014:Linear Models; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020370:Osteoarthritis, Knee / Q000000981:diagnostic imaging / Q000276:immunology*
D016207:Cytokines; C508717:IL17A protein, human; C440021:IL17F protein, human; C508600:IL6 protein, human; D020381:Interleukin-17; D053759:Interleukin-23; D015850:Interleukin-6
Bone marrow lesions; Inflammatory cytokines; Osteoarthritis