Serum fatty acid chain length associates with prevalent symptomatic end-stage osteoarthritis, independent of BMI

J M T A Meessen,J B J Van Meurs,P E Slagboom,F Saberi-Hosnijeh,M Kloppenburg,J A Van Hilten,J G Van Der Bom,W Den Hollander,A G Uitterlinden,R G H H Nelissen,I Meulenbelt,C So-Osman,W E Van Spil,N Bomer,C M Van Duijn

doi:10.1038/s41598-020-71811-3

J M T A Meessen, J B J Van Meurs + Show 13 more

Open Access

https://doi.org/10.1038/s41598-020-71811-3

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Journal: Scientific Reports	Publication Date: Sep 22, 2020
Citations: 10	License type: open-access

Affiliation: Leiden University Medical Center, Sanquin

Abstract

Higher body mass index (BMI) is associated with osteoarthritis (OA) in both weight-bearing and non-weight-bearing joints, suggesting a link between OA and poor metabolic health beyond mechanical loading. This risk may be influenced by systemic factors accompanying BMI. Fluctuations in concentrations of metabolites may mark or even contribute to development of OA. This study explores the association of metabolites with radiographic knee/hip OA prevalence and progression. A 1H-NMR-metabolomics assay was performed on plasma samples of 1564 cases for prevalent OA and 2,125 controls collected from the Rotterdam Study, CHECK, GARP/NORREF and LUMC-arthroplasty cohorts. OA prevalence and 5 to 10 year progression was assessed by means of Kellgren-Lawrence (KL) score and the OARSI-atlas. End-stage knee/hip OA (TJA) was defined as indication for arthroplasty surgery. Controls did not have OA at baseline or follow-up. Principal component analysis of 227 metabolites demonstrated 23 factors, of which 19 remained interpretable after quality-control. Associations of factor scores with OA definitions were investigated with logistic regression. Fatty acids chain length (FALen), which was included in two factors which associated with TJA, was individually associated with both overall OA as well as TJA. Increased Fatty Acid chain Length is associated with OA.

Highlights

Higher body mass index (BMI) is associated with osteoarthritis (OA) in both weight-bearing and nonweight-bearing joints, suggesting a link between OA and poor metabolic health beyond mechanical loading
Analyses of the 227 remaining metabolites was performed in 2,125 controls and 1,556 OA cases from 4 independent studies participating in the Biobanking and BioMolecular resources Research Infrastructure consortium (BBMRI metabolomics consortium, Supplementary Table 1)
Serum metabolomic assays of hip and knee OA cases and controls were assessed by means of the Nightingale 1HNMR platform, resulting in 227 different metabolite measurements

Summary

Introduction

Higher body mass index (BMI) is associated with osteoarthritis (OA) in both weight-bearing and nonweight-bearing joints, suggesting a link between OA and poor metabolic health beyond mechanical loading. OA has been shown to associate with classical markers of poor metabolic health such as increased circulating levels of low density lipoprotein (LDL) and cholesterol[19,20] This connection remains controversial for the hip joint[21]. More studies have been performed using synovial fluid which have confirmed the some of the aforementioned amino acids, as well as identifying altered energy-, collagen-, fatty acid-, glycerolipid-, oxidative stress and nitric oxide-metabolisms[26,27,28] suggesting an altered metabolic state of the synovial fluid in OA These hallmarks of the metabolic syndrome (MS) should be present in serum as MS affects the synovium and the whole body. We aim to identify metabolic signatures of serum by including 2,125 controls and 2,372 OA cases among Dutch cohorts participating in the Biobanking and BioMolecular resources Research Infrastructure consortium (BBMRI metabolomics consortium)[29]

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