Background Low-grade inflammation may play a role in osteoarthritis (OA). Although some studies reported that inflammatory markers such as high sensitivity C-reactive protein (hs-CRP) were increased in OA, the findings for associations between hs-CRP and OA are inconsistent. The link between serum levels of hs-CRP and bone marrow lesions (BMLs) in OA patients has not been explored., Similarly, the findings for the associations between resistin and OA are controversial and little is known if resistin is associated with BMLs.
Objectives The aims of this study were, therefore, to describe the association between serum levels of hs-CRP, resistin and BMLs cross-sectionally and longitudinally in patients with knee OA.
Methods A total of 192 patients (mean 63 years, range 50-79, female 53%) with symptomatic knee OA were selected from a randomised placebo controlled clinical trial studying the effect of vitamin D supplementation on OA. Serum levels of hs-CRP and resistin were tested at baseline and 24 months later using enzyme-linked immunosorbent assay (ELISA). T2 weighted fat-supressed fast spin echo magnetic resonance imaging (MRI) was performed at baseline and 24 months to assess compartmental and total knee BMLs scores and their changes using modified Whole-Organ MRI Score system (WORMS). Linear or logistic regression analyses were used to determine the association of baseline hs-CRP and resistin with total knee BMLs as well as changes or increases in BMLs before and after adjustment for age, sex, BMI, treatment (vitamin D/placebo) and CRP/resistin as appropriate.
Results At baseline, quartiles of serum level of hs-CRP were associated with total knee bone marrow lesions in multivariable analyses (OR: 1.45 per quartile, 95% CI: 1.01, 2.09). Serum levels of resistin were associated with total knee BMLs (β: 0.04 per ng/ml, 95% CI: 0.01, 0.08). Longitudinally, quartiles of serum levels of hs-CRP predicted increases in total knee BMLs (OR: 1.51 per quartile, 95% CI: 1.08, 2.12; Figure 1), and changes in serum levels of hs-CRP were associated with changes in total knee BMLs (β: 0.09, 95% CI: 0.04, 0.34). Baseline resistin levels were not significantly associated with change in total BMLs. Change in serum levels of resistin were only associated with changes in lateral tibiofemoral BMLs (β: 0.16, 95%CI: 0.01, 0.05) and not total knee BMLs (β: 1.01, 95%CI: 0.97, 1.04).
Conclusions This is the first study to report that serum levels of hs-CRP are associated with total knee BMLs and predict worsening knee BMLs over 2 years in patients with knee OA, suggesting inflammatory involvement in the pathogenesis of BMLs. Serum resistin levels are associated with BMLs in knee OA, but the causal relationship is unknown.
Acknowledgements We especially thank the participants who made this study possible, and we gratefully acknowledge the role of the Vitamin D Effect on Osteoarthritis Study staff and volunteers in collecting the data, particularly Jodi Barling, Judy Hankin and Alice Noone.
Disclosure of Interest None declared