title: Evaluation of the benefit of corticosteroid injection before exercise therapy in patients with osteoarthritis of the knee: a randomized clinical trial.
abstract: OBJECTIVE
  Osteoarthritis (OA) of the knee is the most frequent form of arthritis and a cause of pain and disability. Combined nonpharmacologic and pharmacologic treatments are recommended as the optimal treatment approach, but no evidence supports the recommendation.
  
  
  OBJECTIVE
  To assess the clinical benefits of an intra-articular corticosteroid injection given before exercise therapy in patients with OA of the knee.
  
  
  METHODS
  We performed a randomized, blinded, placebo-controlled clinical trial evaluating the benefit of intra-articular corticosteroid injection vs placebo injection given before exercise therapy at an OA outpatient clinic from October 1, 2012, through April 2, 2014. The participants had radiographic confirmation of clinical OA of the knee, clinical signs of localized inflammation in the knee, and knee pain during walking (score >4 on a scale of 0 to 10).
  
  
  METHODS
  Participants were randomly allocated (1:1) to an intra-articular 1-mL injection of the knee with methylprednisolone acetate (Depo-Medrol), 40 mg/mL, dissolved in 4 mL of lidocaine hydrochloride (10 mg/mL) (corticosteroid group) or a 1-mL isotonic saline injection mixed with 4 mL of lidocaine hydrochloride (10 mg/mL) (placebo group). Two weeks after the injections, all participants started a 12-week supervised exercise program.
  
  
  METHODS
  The primary outcome was change in the Pain subscale of the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire (range, 0-100; higher scores indicate greater improvement) at week 14. Secondary outcomes included the remaining KOOS subscales and objective measures of physical function and inflammation. Outcomes were measured at baseline, week 2 (exercise start), week 14 (exercise stop), and week 26 (follow-up).
  
  
  RESULTS
  One hundred patients were randomized to the corticosteroid group (n = 50) or the placebo group (n = 50); 45 and 44 patients, respectively, completed the trial. The mean (SE) changes in the KOOS Pain subscale score at week 14 were 13.6 (1.8) and 14.8 (1.8) points in the corticosteroid and placebo groups, respectively, corresponding to a statistically insignificant mean difference of 1.2 points (95% CI, -3.8 to 6.2; P = .64). We found no statistically significant group differences in any of the secondary outcomes at any time point.
  
  
  CONCLUSIONS
  No additional benefit results from adding an intra-articular injection of 40 mg of corticosteroid before exercise in patients with painful OA of the knee. Further research is needed to establish optimal and potentially synergistic combinations of conservative treatments.
  
  
  BACKGROUND
  clinicaltrialsregister.eu Identifier: 2012-002607-18; clinicaltrials.gov Identifier: NCT01945749.
authors.affiliation: Parker Institute, Department of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, Denmark.
authors.forename: Marius
authors.initials: M
authors.lastname: Henriksen
authors.affiliation: Parker Institute, Department of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, Denmark.
authors.forename: Robin
authors.initials: R
authors.lastname: Christensen
authors.affiliation: Parker Institute, Department of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, Denmark.
authors.forename: Louise
authors.initials: L
authors.lastname: Klokker
authors.affiliation: Parker Institute, Department of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, Denmark.
authors.forename: Cecilie
authors.initials: C
authors.lastname: Bartholdy
authors.affiliation: Parker Institute, Department of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, Denmark.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Bandak
authors.affiliation: Parker Institute, Department of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, Denmark.
authors.forename: Karen
authors.initials: K
authors.lastname: Ellegaard
authors.affiliation: Parker Institute, Department of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, Denmark2Department of Radiology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, Denmark.
authors.forename: Mikael P
authors.initials: MP
authors.lastname: Boesen
authors.affiliation: Parker Institute, Department of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, Denmark2Department of Radiology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, Denmark.
authors.forename: Robert G Coumine
authors.initials: RG
authors.lastname: Riis
authors.affiliation: Parker Institute, Department of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, Denmark.
authors.forename: Else M
authors.initials: EM
authors.lastname: Bartels
authors.affiliation: Parker Institute, Department of Rheumatology, Copenhagen University Hospital at Bispebjerg and Frederiksberg, Copenhagen, Denmark.
authors.forename: Henning
authors.initials: H
authors.lastname: Bliddal
mesh_terms: D000305:Adrenal Cortex Hormones / Q000627:therapeutic use*; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D005081:Exercise Therapy; D005260:Female; D006801:Humans; D007270:Injections, Intra-Articular; D008297:Male; D008775:Methylprednisolone / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077555:Methylprednisolone Acetate; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000188:drug therapy*; D017211:Treatment Failure
chemical_list: D000305:Adrenal Cortex Hormones; D000893:Anti-Inflammatory Agents; D000077555:Methylprednisolone Acetate; D008775:Methylprednisolone