Skip to main content
SpringerLink
Log in

Hylan G-F 20 Versus Low Molecular Weight Hyaluronic Acids for Knee Osteoarthritis: A Meta-Analysis

  • Systematic Review
  • Published:
BioDrugs Aims and scope Submit manuscript

Abstract

Background

Hyaluronic acid injection has been reported to decrease pain compared with baseline levels in knee joint osteoarthritis. Hylan G-F 20 is distinguished from the other products by its chemical structure and relatively higher molecular weight. Many trials have compared hylan G-F 20 and low molecular weight hyaluronic acids (LMWHAs); however, their relative efficacy and safety are still debated.

Objective

The aim was to compare the effectiveness and safety of intra-articular injection of hylan G-F 20 and LMWHA in the treatment of knee joint osteoarthritis.

Methods

A comprehensive search of the literature up to February 2016 was performed; multiple databases were searched with ‘Synvisc’ or ‘hylan’ or ‘hyaluronan’ as free word terms. The pain-related outcomes and treatment-related adverse events from intent-to-treat analyzed studies were pooled for meta-analysis; other functional outcomes were included in the qualitative analysis.

Results

Twenty trials with a total of 3034 patients and 3153 knees were included, with a pooled dropout rate of 7.2 %. The pooled pain-related outcomes at 2 to 3 months reached a statistically significant difference in favor of hylan G-F 20 (I 2 = 88 %; random effects; P = 0.02), and the significance still existed with exclusion (in order to eliminate heterogeneity) of the three studies that most favored hylan G-F 20 (I 2 = 51 %; fixed effect; P = 0.03). No significant difference was reached for other group and subgroup analyses. No significant difference was reached in comparing the patients with treatment-related adverse events (seven trials; 2025 patients; P = 0.13) or the treatment-related adverse events (six trials; 1633 patients; P = 0.14).

Conclusion

According to the current results, limited evidence showed a superior effect favoring hylan G-F 20 over LMWHA in the period from 2 to 3 months post-injection for pain-related outcomes. There was no evidence of increased risk of treatment-related adverse events for hylan G-F 20 injections.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. WHO. The world health report: 50 facts. Geneva: World Health Organization [online]. LIRL: http://www.who.int/whr/1997/media_centre/50facts/en/. Accessed 28 Feb 2016.

  2. Brandt KD, Block JA, Michalski JP, et al. Efficacy and safety of intraarticular sodium hyaluronate in knee osteoarthritis. ORTHOVISC Study Group. Clin Orthop Relat Res. 2001;385:130–43.

    Article  PubMed  Google Scholar 

  3. Colen S, van den Bekerom MP, Mulier M, et al. Hyaluronic acid in the treatment of knee osteoarthritis: a systematic review and meta-analysis with emphasis on the efficacy of different products. BioDrugs. 2012;26:257–68.

    Article  CAS  PubMed  Google Scholar 

  4. Petrella RJ, Wakeford C. Pain relief and improved physical function in knee osteoarthritis patients receiving ongoing hylan G-F 20, a high-molecular-weight hyaluronan, versus other treatment options: data from a large real-world longitudinal cohort in Canada. Drug Des Devel Ther. 2015;9:5633–40.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Kahan A, Lleu P, Salin L. Prospective randomized study comparing the medicoeconomic benefits of hylan GF-20 vs. conventional treatment in knee osteoarthritis. Joint Bone Spine. 2003;70:276–81.

    Article  PubMed  Google Scholar 

  6. Moreland L. Intra-articular hyaluronan (hyaluronic acid) and hylans for the treatment of osteoarthritis (mechanisms of action). Arthritis Res Ther. 2003;5:54–67.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Reichenbach S, Blank S, Rutjes AW, et al. Hylan versus hyaluronic acid for osteoarthritis of the knee: a systematic review and meta-analysis. Arthritis Rheum. 2007;57:1410–8.

    Article  PubMed  Google Scholar 

  8. Atay T, Aslan A, Day N, et al. The efficacy of low- and high-molecular-weight hyaluronic acid applications after arthroscopic debridement in patients with osteoarthritis of the knee. Acta Orthop Traumatol Turc. 2008;42:228–33.

    Article  PubMed  Google Scholar 

  9. Raman R, Dutta A, Day N, et al. Efficacy of hylan G-F 20 and sodium hyaluronate in the treatment of osteoarthritis of the knee—a prospective randomized clinical trial. Knee. 2008;15:318–24.

    Article  CAS  PubMed  Google Scholar 

  10. Maheu E, Zaim M, Appelboom T, et al. Comparative efficacy and safety of two different molecular weight (MW) hyaluronans F60027 and hylan G-F20 in symptomatic osteoarthritis of the knee (KOA). Results of a non inferiority, prospective, randomized, controlled trial. Clin Exp Rheumatol. 2011;29:527–35.

    CAS  PubMed  Google Scholar 

  11. Pavelka K, Uebelhart D. Efficacy evaluation of highly purified intra-articular hyaluronic acid (Sinovial((R))) vs hylan G-F20 (Synvisc((R))) in the treatment of symptomatic knee osteoarthritis. A double-blind, controlled, randomized, parallel-group non-inferiority study. Osteoarthr Cartil. 2011;19:1294–300.

    Article  CAS  PubMed  Google Scholar 

  12. Iannitti T, Rottigni V, Palmieri B. A pilot study to compare two different hyaluronic acid compounds for treatment of knee osteoarthritis. Int J Immunopathol Pharmacol. 2012;25:1093–8.

    CAS  PubMed  Google Scholar 

  13. Khanasuk Y, Dechmaneenin T, Tanavalee A. Prospective randomized trial comparing the efficacy of single 6-ml injection of hylan G-F 20 and hyaluronic acid for primary knee arthritis: a preliminary study. J Med Assoc Thai. 2012;95(Suppl 10):S92–7.

    PubMed  Google Scholar 

  14. Petrella RJ, Emans PJ, Alleyne J, et al. Safety and performance of Hydros and Hydros-TA for knee osteoarthritis: a prospective, multicenter, randomized, double-blind feasibility trial. BMC Musculoskelet Disord. 2015;18:57–66.

    Article  Google Scholar 

  15. Jadad AR, Moore RA, Carroll D, et al. Assessing the quality of reports of randomized clinical trials: is blinding necessary? Control Clin Trials. 1996;17:1–12.

    Article  CAS  PubMed  Google Scholar 

  16. Wobig M, Bach G, Beks P, et al. The role of elastoviscosity in the efficacy of viscosupplementation for osteoarthritis of the knee: a comparison of hylan G-F 20 and a lower-molecular-weight hyaluronan. Clin Ther. 1999;21:1549–62.

    Article  CAS  PubMed  Google Scholar 

  17. Zhou G, Wang YR, Zhou ZD, et al. Comparison of two different molecular-weight of sodium hyaluronate on treatment of the osteoarthrosis. Acta Univ Med Second Shanghai. 2000;20:361–3.

    CAS  Google Scholar 

  18. Lin H, Chen X, Sun YF, et al. Viscosupplementation with sodium hyaluronate for the treatment of osteoarthritis of the knee. Chin J Clin Rehabil. 2002;6:1202–3.

    Google Scholar 

  19. Karlsson J, Sjögren LS, Lohmander LS. Comparison of two hyaluronan drugs and placebo in patients with knee osteoarthritis. A controlled, randomized, double-blind, parallel-design multicentre study. Rheumatology (Oxford). 2002;41:1240–8.

    Article  CAS  Google Scholar 

  20. Rolf CG, Engstrom B, Ohrvik J, et al. A comparative study of the efficacy and safety of hyaluronan viscosupplements and placebo in patients with symptomatic and arthroscopy-verified cartilage pathology. J Clin Res. 2005;8:183–200.

    Google Scholar 

  21. Bayramoglu M, Karatas M, Cetin N, et al. Comparison of two different cosupplements in knee osteoarthritis: a pilot study. Clin Rheumatol. 2003;22:118–22.

    Article  CAS  PubMed  Google Scholar 

  22. Karatay S, Kiziltunc A, Yildirim K, et al. Effects of different hyaluronic acid products on synovial fluid levels of intercellular adhesion molecule-1 and vascular cell adhesion molecule-1 in knee osteoarthritis. Ann Clin Lab Sci. 2004;34:330–5.

    CAS  PubMed  Google Scholar 

  23. Karatosun V, Unver B, Gocen Z, et al. Comparison of two hyaluronan drugs in patients with advanced osteoarthritis of the knee. A prospective, randomized, double-blind study with long term follow-up. Clin Exp Rheumatol. 2005;23:213–8.

    CAS  PubMed  Google Scholar 

  24. Kotevoglu N, Iyibozkurt PC, Hiz O, et al. A prospective randomised controlled clinical trial comparing the efficacy of different molecular weight hyaluronan solutions in the treatment of knee osteoarthritis. Rheumatol Int. 2006;26:325–30.

    Article  CAS  PubMed  Google Scholar 

  25. Kirchner M, Marshall D. A double-blind randomized controlled trial comparing alternate forms of high molecular weight hyaluronan for the treatment of osteoarthritis of the knee. Osteoarthr Cartil. 2006;14:154–62.

    Article  CAS  PubMed  Google Scholar 

  26. Atamaz F, Kirazli Y. Akkoc Y. A comparison of two different intra-articular hyaluronan drugs and physical therapy in the management of knee osteoarthritis. Rheumatol Int. 2006;26:873–8.

    Article  CAS  PubMed  Google Scholar 

  27. Uluçay C, Altintaş F, Ugutmen E, et al. The use of arthroscopic debridement and viscosupplementation in knee osteoarthritis. Acta Orthop Traumatol Turc. 2007;41:337–42.

    PubMed  Google Scholar 

  28. Jüni P, Reichenbach S, Trelle S, et al. Efficacy and safety of intraarticular hylan or hyaluronic acids for osteoarthritis of the knee: a randomized controlled trial. Arthritis Rheum. 2007;56:3610–9.

    Article  PubMed  Google Scholar 

  29. Waddell DD, Bricker DC. Total knee replacement delayed with hylan G-F 20 use in patients with grade IV osteoarthritis. J Manag Care Pharm. 2007;13:113–21.

    PubMed  Google Scholar 

  30. Rosen J, Sancheti P, Fierlinger A, et al. Cost-effectiveness of different forms of intra-articular injections for the treatment of osteoarthritis of the knee. Adv Ther. 2016;33(6):998–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Berenbaum F, Grifka J, Cazzaniga S, et al. A randomised, double-blind, controlled trial comparing two intra-articular hyaluronic acid preparations differing by their molecular weight in symptomatic knee osteoarthritis. Ann Rheum Dis. 2012;71:1454–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Sato E, Ando T, Ichikawa J, et al. High molecular weight hyaluronic acid increases the differentiation potential of the murine chondrocytic ATDC5 cell line. J Orthop Res. 2014;32(12):1619–27.

    Article  CAS  PubMed  Google Scholar 

  33. Conrozier T, Jerosch J, Beks P, et al. Prospective, multi-centre, randomised evaluation of the safety and efficacy of five dosing regimens of viscosupplementation with hylan G-F 20 in patients with symptomatic tibio-femoral osteoarthritis: a pilot study. Arch Orthop Trauma Surg. 2009;129:417–23.

    Article  CAS  PubMed  Google Scholar 

  34. Chevalier X, Jerosch J, Goupille P, et al. Single, intra-articular treatment with 6 ml hylan G-F 20 in patients with symptomatic primary osteoarthritis of the knee: a randomised, multicentre, double-blind, placebo. Ann Rheum Dis. 2010;69(1):113–9.

    Article  CAS  PubMed  Google Scholar 

Download references

Author Contributions

The corresponding author certifies that all authors approved the entirety of the submitted material and contributed actively to the study. ZHM conceived and designed the study; ZHM and LXJ searched the databases and identify the included articles; LHL, LY, and ZHM extracted and confirmed the protocol defined data elements; ZHM and LC wrote the manuscript; ZHM, LHL, LXJ, and LC contributed to the discussion and reviewed the manuscript. ZHM acts as guarantor for the paper. All authors saw, commented upon, and approved the final version of the paper.

Author information

Authors and Affiliations

  1. Foot and Ankle Surgery Department, Honghui Hospital, Xi’an Jiaotong University College of Medicine, Xi’an, 710054, China

    Hongmou Zhao, Hongliang Liu, Xiaojun Liang, Yi Li, Junhu Wang & Cheng Liu

Authors
  1. Hongmou Zhao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hongliang Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Xiaojun Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yi Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Junhu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Cheng Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hongmou Zhao.

Ethics declarations

Conflict of interest

ZHM, LHL, LY, LXJ, and LC declare that they have no conflicts of interest.

Funding

No source of funding was used to assist in the preparation of this study.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Zhao, H., Liu, H., Liang, X. et al. Hylan G-F 20 Versus Low Molecular Weight Hyaluronic Acids for Knee Osteoarthritis: A Meta-Analysis. BioDrugs 30, 387–396 (2016). https://doi.org/10.1007/s40259-016-0186-1

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40259-016-0186-1

Keywords

Search

Navigation