title: Prevention of knee osteoarthritis in overweight females: the first preventive randomized controlled trial in osteoarthritis.
abstract: BACKGROUND
  With accumulating knowledge on osteoarthritis development, the next step is to focus on possibilities for primary prevention.
  
  
  METHODS
  In a 2 × 2 factorial design, the effects of a diet-and-exercise program and of oral glucosamine sulfate (double blind and placebo-controlled) on the incidence of knee osteoarthritis were evaluated in a high-risk group of 407 middle-aged women with a body mass index ≥ 27 kg/m(2) without clinical signs of knee osteoarthritis at baseline (ISRCTN 42823086). Primary outcome was the incidence of knee osteoarthritis, defined as Kellgren & Lawrence grade ≥ 2, joint space narrowing of ≥ 1.0 mm, or clinical knee osteoarthritis (clinical and radiographic American College of Rheumatology criteria) after 2.5 years.
  
  
  RESULTS
  After 2.5 years, only 10% of all subjects were lost to follow-up, and 17% of all knees showed incident knee osteoarthritis. Accounting for the significant interaction between the interventions, no significant main effect of either intervention was found. Independently, both interventions alone showed indications of reduced knee osteoarthritis incidence (odds ratio [OR] 0.69; 95% CI, 0.39-1.21 for the diet-and-exercise program and OR 0.60; 95% CI, 0.31-1.12 for the glucosamine intervention). These effects were neutralized in subjects receiving both interventions (OR 0.97; 95% CI, 0.55-1.71).
  
  
  CONCLUSIONS
  No significant main effects of the diet-and-exercise program and of glucosamine sulfate were found on incident knee osteoarthritis. Nevertheless, this trial provides valuable insights for future trial design for preventive osteoarthritis studies.
authors.affiliation: Department of General Practice, Erasmus MC University Medical Center, Rotterdam, The Netherlands. Electronic address: j.runhaar@erasmusmc.nl.
authors.forename: Jos
authors.initials: J
authors.lastname: Runhaar
authors.affiliation: Department of General Practice, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Marienke
authors.initials: M
authors.lastname: van Middelkoop
authors.affiliation: Department of Orthopaedics, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Max
authors.initials: M
authors.lastname: Reijman
authors.affiliation: Department of Biostatistics, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Sten
authors.initials: S
authors.lastname: Willemsen
authors.affiliation: Department of Radiology, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Edwin H
authors.initials: EH
authors.lastname: Oei
authors.affiliation: Department of Radiology, Maasstad Hospital, Rotterdam, The Netherlands.
authors.forename: Dammis
authors.initials: D
authors.lastname: Vroegindeweij
authors.affiliation: Department of Orthopaedics, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Gerjo
authors.initials: G
authors.lastname: van Osch
authors.affiliation: Department of General Practice, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: Koes
authors.affiliation: Department of General Practice, Erasmus MC University Medical Center, Rotterdam, The Netherlands; Department of Orthopaedics, Erasmus MC University Medical Center, Rotterdam, The Netherlands.
authors.forename: Sita M A
authors.initials: SM
authors.lastname: Bierma-Zeinstra
mesh_terms: D015992:Body Mass Index; D004038:Diet, Reducing; D004311:Double-Blind Method; D005081:Exercise Therapy; D005260:Female; D005944:Glucosamine / Q000627:therapeutic use; D006801:Humans; D015994:Incidence; D057194:Intention to Treat Analysis; D007717:Knee / Q000000981:diagnostic imaging; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000150:complications* / Q000000981:diagnostic imaging / Q000517:prevention & control*; D050177:Overweight / Q000150:complications* / Q000628:therapy; D011322:Primary Prevention; D011859:Radiography; D015431:Weight Loss
chemical_list: D005944:Glucosamine
keywords: Glucosamine; Knee osteoarthritis; Overweight; Prevention; Randomized controlled trial; Weight loss