title: Classification of osteoarthritis phenotypes by metabolomics analysis.
abstract: OBJECTIVE
  To identify metabolic markers that can classify patients with osteoarthritis (OA) into subgroups.
  
  
  METHODS
  A case-only study design was utilised.
  
  
  METHODS
  Patients were recruited from those who underwent total knee or hip replacement surgery due to primary OA between November 2011 and December 2013 in St. Clare's Mercy Hospital and Health Science Centre General Hospital in St. John's, capital of Newfoundland and Labrador (NL), Canada. 38 men and 42 women were included in the study. The mean age was 65.2±8.7 years.
  
  
  METHODS
  Synovial fluid samples were collected at the time of their joint surgeries. Metabolic profiling was performed on the synovial fluid samples by the targeted metabolomics approach, and various analytic methods were utilised to identify metabolic markers for classifying subgroups of patients with OA. Potential confounders such as age, sex, body mass index (BMI) and comorbidities were considered in the analysis.
  
  
  RESULTS
  Two distinct patient groups, A and B, were clearly identified in the 80 patients with OA. Patients in group A had a significantly higher concentration on 37 of 39 acylcarnitines, but the free carnitine was significantly lower in their synovial fluids than in those of patients in group B. The latter group was further subdivided into two subgroups, that is, B1 and B2. The corresponding metabolites that contributed to the grouping were 86 metabolites including 75 glycerophospholipids (6 lysophosphatidylcholines, 69 phosphatidylcholines), 9 sphingolipids, 1 biogenic amine and 1 acylcarnitine. The grouping was not associated with any known confounders including age, sex, BMI and comorbidities. The possible biological processes involved in these clusters are carnitine, lipid and collagen metabolism, respectively.
  
  
  CONCLUSIONS
  The study demonstrated that OA consists of metabolically distinct subgroups. Identification of these distinct subgroups will help to unravel the pathogenesis and develop targeted therapies for OA.
authors.affiliation: Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St John's, Newfoundland, Canada.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Medicine, Faculty of Medicine, Memorial University of Newfoundland, St John's, Newfoundland, Canada.
authors.forename: Sergei
authors.initials: S
authors.lastname: Likhodii
authors.affiliation: Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St John's, Newfoundland, Canada.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St John's, Newfoundland, Canada.
authors.forename: Erfan
authors.initials: E
authors.lastname: Aref-Eshghi
authors.affiliation: Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St John's, Newfoundland, Canada.
authors.forename: Patricia E
authors.initials: PE
authors.lastname: Harper
authors.affiliation: Department of Laboratory Medicine, Faculty of Medicine, Memorial University of Newfoundland, St John's, Newfoundland, Canada.
authors.forename: Edward
authors.initials: E
authors.lastname: Randell
authors.affiliation: Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St John's, Newfoundland, Canada.
authors.forename: Roger
authors.initials: R
authors.lastname: Green
authors.affiliation: Department of Surgery, Faculty of Medicine, Memorial University of Newfoundland, St John's, Newfoundland, Canada.
authors.forename: Glynn
authors.initials: G
authors.lastname: Martin
authors.affiliation: Department of Surgery, Faculty of Medicine, Memorial University of Newfoundland, St John's, Newfoundland, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Furey
authors.affiliation: Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St John's, Newfoundland, Canada.
authors.forename: Guang
authors.initials: G
authors.lastname: Sun
authors.affiliation: Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St John's, Newfoundland, Canada.
authors.forename: Proton
authors.initials: P
authors.lastname: Rahman
authors.affiliation: Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St John's, Newfoundland, Canada Department of Twin Research & Genetic Epidemiology, King's College London, London, UK.
authors.forename: Guangju
authors.initials: G
authors.lastname: Zhai
mesh_terms: D000368:Aged; D002170:Canada; D005260:Female; D006801:Humans; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism*; D010641:Phenotype; D013582:Synovial Fluid / Q000378:metabolism
keywords: EPIDEMIOLOGY; RHEUMATOLOGY