title: Lysophosphatidylcholines to phosphatidylcholines ratio predicts advanced knee osteoarthritis.
abstract: To identify novel biomarker(s) for predicting advanced knee OA.
  
  
  
  Study participants were derived from the Newfoundland Osteoarthritis Study and the Tasmania Older Adult Cohort Study. All knee OA cases were patients who underwent total knee replacement (TKR) due to primary OA. Metabolic profiling was performed on fasting plasma. Four thousand and eighteen plasma metabolite ratios that were highly correlated with that in SF in our previous study were generated as surrogates for joint metabolism.
  
  
  
  The discovery cohort included 64 TKR cases and 45 controls and the replication cohorts included a cross-sectional cohort of 72 TKR cases and 76 controls and a longitudinal cohort of 158 subjects, of whom 36 underwent TKR during the 10-year follow-up period. We confirmed the previously reported association of the branched chain amino acids to histidine ratio with advanced knee OA (P = 9.3 × 10(-7)) and identified a novel metabolic marker-the lysophosphatidylcholines (lysoPCs) to phosphatidylcholines (PCs) ratio-that was associated with advanced knee OA (P = 1.5 × 10(-7)) after adjustment for age, sex and BMI. When the subjects of the longitudinal cohort were categorized into two groups based on the optimal cut-off of the ratio of 0.09, we found the subjects with the ratio ⩾0.09 were 2.3 times more likely to undergo TKR than those with the ratio <0.09 during the 10-year follow-up (95% CI: 1.2, 4.3, P = 0.02).
  
  
  
  We identified the ratio of lysoPCs to PCs as a novel metabolic marker for predicting advanced knee OA. Further studies are required to examine whether this ratio can predict early OA change.
authors.affiliation: Discipline of Genetics.
authors.forename: Weidong
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St John's, NL, Canada.
authors.forename: Guang
authors.initials: G
authors.lastname: Sun
authors.affiliation: Musculoskeletal Unit, Menzies Institute for Medical Research, University of Tasmania, Hobart, TS, Australia.
authors.forename: Dawn
authors.initials: D
authors.lastname: Aitken
authors.affiliation: Department of Laboratory Medicine.
authors.forename: Sergei
authors.initials: S
authors.lastname: Likhodii
authors.affiliation: Discipline of Genetics.
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.affiliation: Department of Surgery, Faculty of Medicine, Memorial University of Newfoundland, St John's, NL, 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, NL, Canada.
authors.forename: Andrew
authors.initials: A
authors.lastname: Furey
authors.affiliation: Department of Laboratory Medicine.
authors.forename: Edward
authors.initials: E
authors.lastname: Randell
authors.affiliation: Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St John's, NL, Canada.
authors.forename: Proton
authors.initials: P
authors.lastname: Rahman
authors.affiliation: Musculoskeletal Unit, Menzies Institute for Medical Research, University of Tasmania, Hobart, TS, Australia.
authors.forename: Graeme
authors.initials: G
authors.lastname: Jones
authors.affiliation: Discipline of Genetics Musculoskeletal Unit, Menzies Institute for Medical Research, University of Tasmania, Hobart, TS, Australia guangju.zhai@med.mun.ca.
authors.forename: Guangju
authors.initials: G
authors.lastname: Zhai
mesh_terms: D000368:Aged; D019645:Arthroplasty, Replacement, Knee / Q000706:statistics & numerical data; D015415:Biomarkers / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008244:Lysophosphatidylcholines / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009523:Newfoundland and Labrador / Q000453:epidemiology; D020370:Osteoarthritis, Knee / Q000453:epidemiology / Q000209:etiology* / Q000601:surgery; D010713:Phosphatidylcholines / Q000378:metabolism*; D011446:Prospective Studies; D013648:Tasmania / Q000453:epidemiology
chemical_list: D015415:Biomarkers; D008244:Lysophosphatidylcholines; D010713:Phosphatidylcholines
keywords: knee osteoarthritis; metabolite ratios; metabolomics; total joint replacement