The association of plasma fatty acids levels with hand and knee osteoarthritis

Abstract

Purpose: Obesity is one of the most important risk factors for osteoarthritis (OA). In addition to increased mechanical loading, systemic factors also likely play a role. Nutrient excess leading to obesity may result in lipotoxicity, with increased levels of circulating fatty acids. However, our knowledge about the effect of different fatty acids on OA is sparse. Therefore, we aimed to investigate the association of plasma saturated fatty acids (SFAs), monounsaturated fatty acid (MUFAs), polyunsaturated fatty acids (PUFAs), omega (n-)3 and n-6 PUFAs on clinically defined hand and knee OA. Since we are in a postprandial state most of the day, both fasting and postprandial samples after a standardized mixed meal were used for the association analyses. Methods: In the population-based Netherlands Epidemiology of Obesity (NEO) study, a total of 6,671 middle-aged participants were recruited from the greater area of Leiden. Clinical hand and knee OA were defined by the ACR clinical classification criteria. Blood samples were obtained after an overnight fast and 150 minutes after consumption of a standardized liquid mixed meal containing 600kCal, with 16% of energy (En%) derived from protein, 50 En% from carbohydrates and 34 En% from fat. EDTA-plasma samples were used for a high-throughput proton nuclear magnetic resonance (NMR) metabolomics platform (Nightingale Health Ltd., Helsinki, Finland) to quantify 159 lipid and metabolite measures. For the present analyses the concentrations of fasting and postprandial total fatty acids, SFAs, MUFAs, PUFAs, n-6 PUFAs and n-3 PUFAs in mmol/l were used. We excluded participants who reported to have inflammatory rheumatic disease or fibromyalgia, with missing physical examination, who were non-fasting at baseline, or reported using lipid-lowering medication. Logistic regression analyses were used to investigate the association between fatty acids and clinical OA phenotypes. All analyses were stratified by sex and corrected for age, education, ethnicity and total body fat percentage. Data are presented as odds ratios (OR) with 95% confidence intervals (CI). Results: In the current analysis 5,328 NEO participants were included, with a mean age of 56 years and 58% were women. Hand OA, knee OA and concurrent hand and knee OA were defined in 8%, 10% and 4%, respectively. After correction for possible confounders, SFA, total PUFA and omega-3 PUFA levels were positively associated with clinical hand OA in men, with OR (95% CI) of 1.26 (1.00 - 1.57), 1.35 (1.00 - 1.82) and 5.27 (1.07 - 25.96) respectively. In women, these associations were not found; however, although not significant, the OR of omega-3 PUFAs and hand OA was 2.49 (0.45 - 13.72). None of the postprandial fatty acid subtypes were statistically significantly associated with knee or concurrent hand and knee OA in both men and women. In comparison, although not significant, results from the analyses with fasting fatty acids showed similar albeit slightly dampened effect estimates. Conclusions: Quantitively measured plasma postprandial SFA and omega-3 PUFA levels were significantly associated with hand OA in men. In women no significant associations were found, however the estimated effect was comparable to the results in men. Intriguingly, although SFA and omega-3 PUFAs are deemed to have opposing effects on inflammation, both were positively associated with hand OA. No significant associations were found between fatty acids and knee and concurrent hand and knee OA. Future research is warranted to replicate the association and determine whether there is a causal role for plasma fatty acid levels in hand OA.View Large Image Figure ViewerDownload Hi-res image Download (PPT)