title: Association of urinary metabolites with radiographic progression of knee osteoarthritis in overweight and obese adults: an exploratory study.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: 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.
authors.forename: R F
authors.initials: RF
authors.lastname: Loeser
authors.affiliation: NIH Eastern Regional Comprehensive Metabolomics Resource Core, RTI International, Research Triangle Park, NC, USA.
authors.forename: W
authors.initials: W
authors.lastname: Pathmasiri
authors.affiliation: NIH Eastern Regional Comprehensive Metabolomics Resource Core, RTI International, Research Triangle Park, NC, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Sumner
authors.affiliation: NIH Eastern Regional Comprehensive Metabolomics Resource Core, RTI International, Research Triangle Park, NC, USA.
authors.forename: S
authors.initials: S
authors.lastname: McRitchie
authors.affiliation: Departments of Public Health Sciences and Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: D
authors.initials: D
authors.lastname: Beavers
authors.affiliation: Departments of Public Health Sciences and Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: P
authors.initials: P
authors.lastname: Saxena
authors.affiliation: Departments of Public Health Sciences and Internal Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: B J
authors.initials: BJ
authors.lastname: Nicklas
authors.affiliation: Thurston Arthritis Research Center, Division of Rheumatology, Allergy, and Immunology, University of North Carolina School of Medicine, Chapel Hill, NC, USA.
authors.forename: J
authors.initials: J
authors.lastname: Jordan
authors.affiliation: Department of Radiology, Boston University School of Medicine, Boston, MA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Guermazi
authors.affiliation: Rheumatology Department, Royal North Shore Hospital and Institute of Bone and Joint Research, Kolling Institute, University of Sydney, Sydney, NSW, Australia.
authors.forename: D J
authors.initials: DJ
authors.lastname: Hunter
authors.affiliation: Department of Health and Exercise Science, Wake Forest University, Winston-Salem, NC, USA.
authors.forename: S P
authors.initials: SP
authors.lastname: Messier
mesh_terms: D000328:Adult; D018450:Disease Progression; D006801:Humans; D007719:Knee Joint; D009765:Obesity; D020370:Osteoarthritis, Knee; D050177:Overweight
keywords: Biomarkers; Metabolism; Osteoarthritis