title: Identification of clinical phenotypes in knee osteoarthritis: a systematic review of the literature.
abstract: Knee Osteoarthritis (KOA) is a heterogeneous pathology characterized by a complex and multifactorial nature. It has been hypothesised that these differences are due to the existence of underlying phenotypes representing different mechanisms of the disease.
  
  
  
  The aim of this study is to identify the current evidence for the existence of groups of variables which point towards the existence of distinct clinical phenotypes in the KOA population. A systematic literature search in PubMed was conducted. Only original articles were selected if they aimed to identify phenotypes of patients aged 18 years or older with KOA. The methodological quality of the studies was independently assessed by two reviewers and qualitative synthesis of the evidence was performed. Strong evidence for existence of specific phenotypes was considered present if the phenotype was supported by at least two high-quality studies.
  
  
  
  A total of 24 studies were included. Through qualitative synthesis of evidence, six main sets of variables proposing the existence of six phenotypes were identified: 1) chronic pain in which central mechanisms (e.g. central sensitisation) are prominent; 2) inflammatory (high levels of inflammatory biomarkers); 3) metabolic syndrome (high prevalence of obesity, diabetes and other metabolic disturbances); 4) Bone and cartilage metabolism (alteration in local tissue metabolism); 5) mechanical overload characterised primarily by varus malalignment and medial compartment disease; and 6) minimal joint disease characterised as minor clinical symptoms with slow progression over time.
  
  
  
  This study identified six distinct groups of variables which should be explored in attempts to better define clinical phenotypes in the KOA population.
authors.affiliation: Institute of Applied Health Research/School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, G4 0BA, Scotland, UK. andrea.dellIsola@gcu.ac.uk.
authors.forename: A
authors.initials: A
authors.lastname: Dell'Isola
authors.affiliation: Institute of Applied Health Research/School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, G4 0BA, Scotland, UK.
authors.forename: R
authors.initials: R
authors.lastname: Allan
authors.affiliation: Institute of Applied Health Research/School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, G4 0BA, Scotland, UK.
authors.forename: S L
authors.initials: SL
authors.lastname: Smith
authors.affiliation: Institute of Applied Health Research/School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, G4 0BA, Scotland, UK.
authors.forename: S S P
authors.initials: SS
authors.lastname: Marreiros
authors.affiliation: Institute of Applied Health Research/School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, G4 0BA, Scotland, UK.
authors.forename: M
authors.initials: M
authors.lastname: Steultjens
mesh_terms: D002358:Cartilage, Articular / Q000378:metabolism; D059350:Chronic Pain; D018450:Disease Progression; D006801:Humans; D007867:Leg Bones / Q000378:metabolism; D024821:Metabolic Syndrome; D020370:Osteoarthritis, Knee / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D036301:Qualitative Research; D012307:Risk Factors
keywords: Clinical; Knee; Osteoarthritis; Phenotype; Sub-group