title: Chondroprotection and the prevention of osteoarthritis progression of the knee: a systematic review of treatment agents.
abstract: BACKGROUND
  Structure-modifying medications or nutraceuticals may be an effective treatment for osteoarthritis. This study identified 12 treatments that may possess chondroprotective properties: oral glucosamine; chondroitin; nonsteroidal anti-inflammatory drugs (NSAIDs); polyunsaturated fatty acids; S-adenosylmethionine; avocado and soybean unsaponifiable fractions; methylsulfonylmethane; vitamins C, D, and E; intra-articular injections of hyaluronic acid; and platelet-rich plasma (PRP).
  
  
  OBJECTIVE
  To perform a systematic review of randomized controlled trials for the effectiveness of each agent in preserving articular cartilage of the knee and delaying the progression of osteoarthritis.
  
  
  METHODS
  Systematic review; Level of evidence, 2.
  
  
  METHODS
  A literature search was performed using PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Searches were performed using "treatment," "osteoarthritis," and "knee" as keywords. Selection criteria included randomized controlled trials of ≥12 months, with a placebo control, measuring radiographic changes in joint space width, cartilage volume, or radiographic progression of osteoarthritis. The primary outcome was changes in joint integrity measures.
  
  
  RESULTS
  A total of 3514 studies were identified from the initial search, 13 of which met inclusion criteria. Treatment with chondroitin sulfate showed a significant reduction in cartilage loss in 3 of 4 studies identified compared with placebo. Two of 3 trials identified for glucosamine also reported significant structural effects relative to placebo. Intra-articular hyaluronic acid was effective in lowering the rate of cartilage loss in only 1 of 3 studies identified versus placebo. Of the 6 studies identified for NSAIDs, vitamin E, and vitamin D, none showed any structural effect compared with placebo. No studies were found that met the inclusion criteria for polyunsaturated fatty acids, S-adenosylmethionine, avocado and soybean unsaponifiable fractions, methylsulfonylmethane, vitamin C, or PRP.
  
  
  CONCLUSIONS
  For patients with or at risk for osteoarthritis, the use of glucosamine and chondroitin sulfate may serve as a nonoperative means to protect joint cartilage and delay osteoarthritis progression. Hyaluronic acid injections showed variable efficacy, while NSAIDs and vitamins E and D showed no effect on osteoarthritis progression. The other agents evaluated had no evidence in the literature to support or refute their use for chondroprotection.
authors.affiliation: Jefferson Medical College, Philadelphia, Pennsylvania, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: Gallagher
authors.affiliation: Rothman Institute, Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Fotios P
authors.initials: FP
authors.lastname: Tjoumakaris
authors.affiliation: Rothman Institute, Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Marc I
authors.initials: MI
authors.lastname: Harwood
authors.affiliation: Rothman Institute, Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Robert P
authors.initials: RP
authors.lastname: Good
authors.affiliation: Rothman Institute, Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Michael G
authors.initials: MG
authors.lastname: Ciccotti
authors.affiliation: Rothman Institute, Department of Orthopaedic Surgery, Thomas Jefferson University, Philadelphia, Pennsylvania, USA kevin.freedman@rothmaninstitute.com.
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Freedman
mesh_terms: D000284:Administration, Oral; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D018771:Arthralgia / Q000188:drug therapy; D002358:Cartilage, Articular / Q000473:pathology*; D002807:Chondroitin / Q000627:therapeutic use*; D019587:Dietary Supplements; D018450:Disease Progression; D005944:Glucosamine / Q000627:therapeutic use*; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage; D007270:Injections, Intra-Articular; D020370:Osteoarthritis, Knee / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D055675:Viscosupplements / Q000008:administration & dosage; D014815:Vitamins / Q000627:therapeutic use
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D055675:Viscosupplements; D014815:Vitamins; D006820:Hyaluronic Acid; D002807:Chondroitin; D005944:Glucosamine
keywords: articular cartilage; chondroprotection; knee; nutraceutical