Association of urinary metabolites with radiographic progression of knee osteoarthritis in overweight and obese adults: an exploratory study

R F Loeser; W Pathmasiri; S J Sumner; S McRitchie; D Beavers; P Saxena; B J Nicklas; J Jordan; A Guermazi; D J Hunter; S P Messier

doi:10.1016/j.joca.2016.03.011

Association of urinary metabolites with radiographic progression of knee osteoarthritis in overweight and obese adults: an exploratory study

Osteoarthritis Cartilage. 2016 Aug;24(8):1479-86. doi: 10.1016/j.joca.2016.03.011. Epub 2016 Mar 21.

Authors

R F Loeser¹, W Pathmasiri², S J Sumner², S McRitchie², D Beavers³, P Saxena³, B J Nicklas³, J Jordan⁴, A Guermazi⁵, D J Hunter⁶, S P Messier⁷

Affiliations

¹ Thurston Arthritis Research Center, Division of Rheumatology, Allergy, and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA. Electronic address: richard_loeser@med.unc.edu.
² NIH Eastern Regional Comprehensive Metabolomics Resource Core, RTI International, Research Triangle Park, NC, USA.
³ Departments of Public Health Sciences and Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
⁴ Thurston Arthritis Research Center, Division of Rheumatology, Allergy, and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
⁵ Department of Radiology, Boston University School of Medicine, Boston, MA, USA.
⁶ Rheumatology Department, Royal North Shore Hospital and Institute of Bone and Joint Research, Kolling Institute, University of Sydney, Sydney, NSW, Australia.
⁷ Department of Health and Exercise Science, Wake Forest University, Winston-Salem, NC, USA.

Abstract

Introduction: Metabolic factors may contribute to osteoarthritis (OA). This study employed metabolomics analyses to determine if differences in metabolite profiles could distinguish people with knee OA who exhibited radiographic progression.

Methods: Urine samples obtained at baseline and 18 months from overweight and obese adults in the Intensive Diet and Exercise for Arthritis (IDEA) trial were selected from two subgroups (n = 22 each) for metabolomics analysis: a group that exhibited radiographic progression (≥0.7 mm decrease in joint space width, JSW) and an age, gender, and body mass index (BMI) matched group who did not progress (≤0.35 mm decrease in JSW). Multivariate analysis methods, including orthogonal partial least square discriminate analysis, were used to identify metabolite profiles that separated progressors and non-progressors. Plasma levels of IL-6 and C-reactive protein (CRP) were evaluated as inflammatory markers.

Results: Multivariate analysis of the binned metabolomics data distinguished progressors from non-progressors. Library matching revealed that glycolate, hippurate, and trigonelline were among the important metabolites for distinguishing progressors from non-progressors at baseline whereas alanine, N,N-dimethylglycine, glycolate, hippurate, histidine, and trigonelline, were among the metabolites that were important for the discrimination at 18 months. In non-progressors, IL-6 decreased from baseline to 18 months while IL-6 was unchanged in progressors; the change over time in IL-6 was significantly different between groups.

Conclusion: These findings support a role for metabolic factors in the progression of knee OA and suggest that measurement of metabolites could be useful to predict progression. Further investigation in a larger sample that would include targeted investigation of specific metabolites is warranted.

Keywords: Biomarkers; Metabolism; Osteoarthritis.

MeSH terms

Adult
Disease Progression
Humans
Knee Joint
Obesity
Osteoarthritis, Knee*
Overweight

Abstract

MeSH terms

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