title: Is Local Viscosupplementation Injection Clinically Superior to Other Therapies in the Treatment of Osteoarthritis of the Knee: A Systematic Review of Overlapping Meta-analyses.
abstract: OBJECTIVE
  To conduct a systematic review of overlapping meta-analyses comparing treatment of knee osteoarthritis (OA) with intra-articular viscosupplementation (intra-articular hyaluronic acid [IA-HA]) versus oral nonsteroidal anti-inflammatory drugs (NSAIDs), intra-articular corticosteroids (IA-corticosteroids), intra-articular platelet-rich plasma (IA-PRP), or intra-articular placebo (IA-placebo) to determine which meta-analyses provide the best current evidence and identify potential causes of discordance.
  
  
  METHODS
  Literature searches were performed for meta-analyses examining use of IA-HA versus NSAIDs, IA-corticosteroids, IA-PRP, or IA-placebo. Clinical data were extracted, and meta-analysis quality was assessed. The Jadad algorithm was applied to determine which meta-analyses provided the highest level of evidence.
  
  
  RESULTS
  Fourteen meta-analyses met the eligibility criteria and ranged in quality from Level I to IV evidence. In studies reporting patient numbers, there were a total of 20,049 patients: 13,698 receiving IA-HA, 355 receiving NSAIDs, 294 receiving IA-corticosteroids, and 5,702 receiving IA-placebo. Ten studies examined the effects of IA-HA versus IA-placebo; of these, 5 found that IA-HA improved pain and 4 found that IA-HA improved function. No clinically relevant differences in the efficacy of IA-HA versus NSAIDs regarding pain and function were found. Regarding IA-HA versus IA-PRP, IA-HA improved knee function at 2 and 6 months after injection but the effects were less robust than those of IA-PRP. Regarding IA-HA versus IA-corticosteroids, the positive effects of IA-HA were greater at 5 to 13 weeks and persisted for up to 26 weeks. After application of the Jadad algorithm, 2 concordant high-quality meta-analyses were selected and both showed that IA-HA provided clinically relevant improvements in pain and function compared with IA-placebo.
  
  
  CONCLUSIONS
  This systematic review of overlapping meta-analyses comparing IA-HA with other nonoperative treatment modalities for knee OA shows that the current highest level of evidence suggests that IA-HA is a viable option for knee OA. Its use results in improvements in knee pain and function that can persist for up to 26 weeks. IA-HA has a good safety profile, and its use should be considered in patients with early knee OA.
  
  
  METHODS
  Level IV, systematic review of Level I to IV studies.
authors.affiliation: Midwest Orthopaedics at Rush, Rush University Medical Center, Chicago, Illinois, U.S.A.. Electronic address: Kirk.anthony@gmail.com.
authors.forename: Kirk A
authors.initials: KA
authors.lastname: Campbell
authors.affiliation: Midwest Orthopaedics at Rush, Rush University Medical Center, Chicago, Illinois, U.S.A.
authors.forename: Brandon J
authors.initials: BJ
authors.lastname: Erickson
authors.affiliation: Midwest Orthopaedics at Rush, Rush University Medical Center, Chicago, Illinois, U.S.A.
authors.forename: Bryan M
authors.initials: BM
authors.lastname: Saltzman
authors.affiliation: Division of Sports Medicine, Department of Orthopaedic Surgery, The University of Texas Health Science Center at Houston, Houston, Texas, U.S.A.
authors.forename: Randy
authors.initials: R
authors.lastname: Mascarenhas
authors.affiliation: Midwest Orthopaedics at Rush, Rush University Medical Center, Chicago, Illinois, U.S.A.
authors.forename: Bernard R
authors.initials: BR
authors.lastname: Bach
authors.affiliation: Midwest Orthopaedics at Rush, Rush University Medical Center, Chicago, Illinois, U.S.A.
authors.forename: Brian J
authors.initials: BJ
authors.lastname: Cole
authors.affiliation: Midwest Orthopaedics at Rush, Rush University Medical Center, Chicago, Illinois, U.S.A.
authors.forename: Nikhil N
authors.initials: NN
authors.lastname: Verma
mesh_terms: D000305:Adrenal Cortex Hormones / Q000008:administration & dosage*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000627:therapeutic use; D018771:Arthralgia / Q000628:therapy; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage*; D007270:Injections, Intra-Articular; D007719:Knee Joint; D008297:Male; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D020370:Osteoarthritis, Knee / Q000628:therapy*; D053657:Platelet-Rich Plasma; D055676:Viscosupplementation / Q000379:methods*; D055675:Viscosupplements / Q000008:administration & dosage*
chemical_list: D000305:Adrenal Cortex Hormones; D000894:Anti-Inflammatory Agents, Non-Steroidal; D055675:Viscosupplements; D006820:Hyaluronic Acid