title: Prediction model for knee osteoarthritis incidence, including clinical, genetic and biochemical risk factors.
abstract: OBJECTIVE
  To develop and validate a prognostic model for incident knee osteoarthritis (KOA) in a general population and determine the value of different risk factor groups to prediction.
  
  
  METHODS
  The prognostic model was developed in 2628 individuals from the Rotterdam Study-I (RS-I). Univariate and multivariate analyses were performed for questionnaire/easily obtainable variables, imaging variables, genetic and biochemical markers. The extended multivariate model was tested on discrimination (receiver operating characteristic curve and area under the curve (AUC)) in two other population-based cohorts: Rotterdam Study-II and Chingford Study.
  
  
  RESULTS
  In RS-I, there was moderate predictive value for incident KOA based on the genetic score alone in subjects aged <65 years (AUC 0.65), while it was only 0.55 for subjects aged ≥65 years. The AUC for gender, age and body mass index (BMI) in prediction for KOA was 0.66. Addition of the questionnaire variables, genetic score or biochemical marker urinary C-terminal cross-linked telopeptide of type II collagen to the model did not change the AUC. However, when adding the knee baseline KL score to the model the AUC increased to 0.79. Applying external validation, similar results were observed in the Rotterdam Study-II and the Chingford Study.
  
  
  CONCLUSIONS
  Easy obtainable 'Questionnaire' variables, genetic markers, OA at other joint sites and biochemical markers add only modestly to the prediction of KOA incidence using age, gender and BMI in an elderly population. Doubtful minor radiographic degenerative features in the knee, however, are a very strong predictor of future KOA. This is an important finding, as many radiologists do not report minor degenerative changes in the knee.
authors: Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging, Rotterdam, The Netherlands.
authors: H J M
authors: HJ
authors: Kerkhof
authors: Department of General Practice, Erasmus MC, Rotterdam, The Netherlands Department of Orthopaedics, Erasmus MC, Rotterdam, The Netherlands.
authors: S M A
authors: SM
authors: Bierma-Zeinstra
authors: NIHR musculoskeletal Biomedical Research Unit, University of Oxford, Oxford, UK.
authors: N K
authors: NK
authors: Arden
authors: Department of Twin Research, King's College London, London, UK.
authors: S
authors: S
authors: Metrustry
authors: Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging, Rotterdam, The Netherlands.
authors: M
authors: M
authors: Castano-Betancourt
authors: Department of Twin Research, King's College London, London, UK.
authors: D J
authors: DJ
authors: Hart
authors: Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
authors: A
authors: A
authors: Hofman
authors: Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging, Rotterdam, The Netherlands Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
authors: F
authors: F
authors: Rivadeneira
authors: Department of Radiology, Erasmus MC, Rotterdam, The Netherlands.
authors: E H G
authors: EH
authors: Oei
authors: Department of Twin Research, King's College London, London, UK.
authors: Tim D
authors: TD
authors: Spector
authors: Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging, Rotterdam, The Netherlands Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
authors: A G
authors: AG
authors: Uitterlinden
authors: Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands.
authors: A C J W
authors: AC
authors: Janssens
authors: Department of Twin Research, King's College London, London, UK Department of Academic Rheumatology, University of Nottingham, UK.
authors: A M
authors: AM
authors: Valdes
authors: Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands The Netherlands Genomics Initiative-sponsored Netherlands Consortium for Healthy Aging, Rotterdam, The Netherlands.
authors: J B J
authors: JB
authors: van Meurs
mesh_terms: D000367:Age Factors; D000368:Aged; D019540:Area Under Curve; D015992:Body Mass Index; D024043:Collagen Type II / Q000652:urine*; D003661:Decision Support Techniques; D005260:Female; D006801:Humans; D007719:Knee Joint / Q000000981:diagnostic imaging*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009765:Obesity / Q000453:epidemiology; D020370:Osteoarthritis, Knee / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D054850:Osteophyte / Q000000981:diagnostic imaging*; D010446:Peptide Fragments / Q000652:urine*; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011859:Radiography; D012307:Risk Factors; D012737:Sex Factors; D011795:Surveys and Questionnaires
chemical_list: C000590554:C-terminal cross-linking telopeptide of type II collagen, human; D024043:Collagen Type II; D010446:Peptide Fragments
keywords: Epidemiology; Knee Osteoarthritis; Osteoarthritis