Systematic Review| Volume 31, ISSUE 10, P2036-2045.e14, October 2015

Is Local Viscosupplementation Injection Clinically Superior to Other Therapies in the Treatment of Osteoarthritis of the Knee: A Systematic Review of Overlapping Meta-analyses


      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.


      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.


      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.


      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.

      Level of Evidence

      Level IV, systematic review of Level I to IV studies.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Arthroscopy
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • MacDonald K.V.
        • Sanmartin C.
        • Langlois K.
        • Marshall D.A.
        Symptom onset, diagnosis and management of osteoarthritis.
        Health Rep. 2014; 25: 10-17
        • Marks R.
        Perceived health status of women with knee osteoarthritis: A cross-sectional study of the relationships of age, body mass, pain and walking limitations.
        Open Orthop J. 2014; 8: 255-263
        • Balazs E.A.
        Viscosupplementation for treatment of osteoarthritis: From initial discovery to current status and results.
        Surg Technol Int. 2004; 12: 278-289
        • Schlueter-Brust K.
        • Kugland K.
        • Stein G.
        • et al.
        Ten year survivorship after cemented and uncemented medial Uniglide unicompartmental knee arthroplasties.
        Knee. 2014; 21: 964-970
        • Gudnason A.
        • Hailer N.P.
        • W-Dahl A.
        • Sundberg M.
        • Robertsson O.
        All-polyethylene versus metal-backed tibial components—An analysis of 27,733 cruciate-retaining total knee replacements from the Swedish Knee Arthroplasty Register.
        J Bone Joint Surg Am. 2014; 96: 994-999
        • Mont M.A.
        • Pivec R.
        • Issa K.
        • Kapadia B.H.
        • Maheshwari A.
        • Harwin S.F.
        Long-term implant survivorship of cementless total knee arthroplasty: A systematic review of the literature and meta-analysis.
        J Knee Surg. 2014; 27: 369-376
        • Patil S.
        • McCauley J.C.
        • Pulido P.
        • Colwell Jr., C.W.
        How do knee implants perform past the second decade? Nineteen- to 25-year followup of the press-fit condylar design TKA.
        Clin Orthop Relat Res. 2015; 473: 135-140
        • Sabouret P.
        • Lavoie F.
        • Cloutier J.M.
        Total knee replacement with retention of both cruciate ligaments: A 22-year follow-up study.
        Bone Joint J. 2013; 95-B: 917-922
        • Weinstein A.M.
        • Rome B.N.
        • Reichmann W.M.
        • et al.
        Estimating the burden of total knee replacement in the United States.
        J Bone Joint Surg Am. 2013; 95: 385-392
        • Arrich J.
        • Piribauer F.
        • Mad P.
        • Schmid D.
        • Klaushofer K.
        • Mullner M.
        Intra-articular hyaluronic acid for the treatment of osteoarthritis of the knee: Systematic review and meta-analysis.
        CMAJ. 2005; 172: 1039-1043
        • Bannuru R.R.
        • Vaysbrot E.E.
        • Sullivan M.C.
        • McAlindon T.E.
        Relative efficacy of hyaluronic acid in comparison with NSAIDs for knee osteoarthritis: A systematic review and meta-analysis.
        Semin Arthritis Rheum. 2014; 43: 593-599
        • Moher D.
        • Cook D.J.
        • Eastwood S.
        • Olkin I.
        • Rennie D.
        • Stroup D.F.
        Improving the quality of reports of meta-analyses of randomised controlled trials: The QUOROM statement. Quality of Reporting of Meta-analyses.
        Lancet. 1999; 354: 1896-1900
        • Oxman A.D.
        • Guyatt G.H.
        Validation of an index of the quality of review articles.
        J Clin Epidemiol. 1991; 44: 1271-1278
        • Coleman B.D.
        • Khan K.M.
        • Maffulli N.
        • Cook J.L.
        • Wark J.D.
        Studies of surgical outcome after patellar tendinopathy: Clinical significance of methodological deficiencies and guidelines for future studies. Victorian Institute of Sport Tendon Study Group.
        Scand J Med Sci Sports. 2000; 10: 2-11
        • Jadad A.R.
        • Cook D.J.
        • Browman G.P.
        A guide to interpreting discordant systematic reviews.
        CMAJ. 1997; 156: 1411-1416
        • Espallargues M.
        • Pons J.M.
        Efficacy and safety of viscosupplementation with Hylan G-F 20 for the treatment of knee osteoarthritis: A systematic review.
        Int J Technol Assess Health Care. 2003; 19: 41-56
        • Strand V.
        • Conaghan P.G.
        • Lohmander L.S.
        • et al.
        An integrated analysis of five double-blind, randomized controlled trials evaluating the safety and efficacy of a hyaluronan product for intra-articular injection in osteoarthritis of the knee.
        Osteoarthritis Cartilage. 2006; 14: 859-866
        • Colen S.
        • van den Bekerom M.P.
        • Mulier M.
        • Haverkamp D.
        Hyaluronic acid in the treatment of knee osteoarthritis: A systematic review and meta-analysis with emphasis on the efficacy of different products.
        BioDrugs. 2012; 26: 257-268
        • Miller L.E.
        • Block J.E.
        US-approved intra-articular hyaluronic acid injections are safe and effective in patients with knee osteoarthritis: Systematic review and meta-analysis of randomized, saline-controlled trials.
        Clin Med Insights Arthritis Musculoskelet Disord. 2013; 6: 57-63
        • Modawal A.
        • Ferrer M.
        • Choi H.K.
        • Castle J.A.
        Hyaluronic acid injections relieve knee pain.
        J Fam Pract. 2005; 54: 758-767
        • Reichenbach S.
        • Blank S.
        • Rutjes A.W.
        • et al.
        Hylan versus hyaluronic acid for osteoarthritis of the knee: A systematic review and meta-analysis.
        Arthritis Rheum. 2007; 57: 1410-1418
        • Bellamy N.
        • Campbell J.
        • Robinson V.
        • Gee T.
        • Bourne R.
        • Wells G.
        Viscosupplementation for the treatment of osteoarthritis of the knee.
        Cochrane Database Syst Rev. 2006; : CD005321
        • Bannuru R.R.
        • Natov N.S.
        • Obadan I.E.
        • Price L.L.
        • Schmid C.H.
        • McAlindon T.E.
        Therapeutic trajectory of hyaluronic acid versus corticosteroids in the treatment of knee osteoarthritis: A systematic review and meta-analysis.
        Arthritis Rheum. 2009; 61: 1704-1711
        • Lo G.H.
        • LaValley M.
        • McAlindon T.
        • Felson D.T.
        Intra-articular hyaluronic acid in treatment of knee osteoarthritis: A meta-analysis.
        JAMA. 2003; 290: 3115-3121
        • Rutjes A.W.
        • Juni P.
        • da Costa B.R.
        • Trelle S.
        • Nuesch E.
        • Reichenbach S.
        Viscosupplementation for osteoarthritis of the knee: A systematic review and meta-analysis.
        Ann Intern Med. 2012; 157: 180-191
        • Wang C.T.
        • Lin J.
        • Chang C.J.
        • Lin Y.T.
        • Hou S.M.
        Therapeutic effects of hyaluronic acid on osteoarthritis of the knee. A meta-analysis of randomized controlled trials.
        J Bone Joint Surg Am. 2004; 86: 538-545
        • Chang K.V.
        • Hung C.Y.
        • Aliwarga F.
        • Wang T.G.
        • Han D.S.
        • Chen W.S.
        Comparative effectiveness of platelet-rich plasma injections for treating knee joint cartilage degenerative pathology: A systematic review and meta-analysis.
        Arch Phys Med Rehab. 2014; 95: 562-575
        • Cohen J.
        Statistical power analysis for the behavioral sciences.
        Lawrence Erlbaum Associates, Hillside, NJ1987
        • Jevsevar D.S.
        • Brown G.A.
        • Jones D.L.
        • et al.
        The American Academy of Orthopaedic Surgeons evidence-based guideline on: Treatment of osteoarthritis of the knee.
        J Bone Joint Surg Am. 2013; 95 (2nd edition): 1885-1886
        • Bannuru R.R.
        • Vaysbrot E.E.
        • McIntyre L.F.
        Did the American Academy of Orthopaedic Surgeons osteoarthritis guidelines miss the mark?.
        Arthroscopy. 2014; 30: 86-89