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Hyaluronic Acid in the Treatment of Knee Osteoarthritis

A Systematic Review and Meta-Analysis with Emphasis on the Efficacy of Different Products

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Abstract

Background: Although accepted as a conservative treatment option for knee osteoarthritis, the debate about the effectiveness of intra-articular treatment with hyaluronic acid (HA) is still ongoing because of contrasting outcomes in different clinical studies. Several well designed clinical studies showed a significant improvement in pain at follow-up compared with baseline but no significant improvement comparing the efficacy of HA with placebo (saline) or with other conservative treatment options. Notwithstanding the effectiveness of different types of intra-articular HA products, the question of whether one HA product is better than another is still unanswered. In this systematic review we compare the effects of intra-articularly administered HA with intra-articularly administered placebo in general and, more specifically, the effects of individual HA products with placebo. We also compare the efficacy of different HA products.

Methods: A systematic review of randomized controlled trials (RCTs) was conducted using databases including MEDLINE, Cochrane Database of Systematic Reviews, Cochrane Clinical Trial Register and EMBASE.

Results: Seventy-four RCTs were included in this systematic review. HA improves pain by approximately 40–50% compared with baseline levels. However, when compared with saline the difference in efficacy is not that large. Due to a large ‘placebo effect’ of saline (approximately 30% pain reduction, persisting for at least 3 months) we determined a weighted mean difference between the efficacy of HA and saline of just 10.20 using the visual analog scale for pain. It is debatable whether this difference reaches the minimum clinically important difference. Comparing the different HA products, which vary in the molecular weight, concentration, and volume of HA, we were not able to conclude that one brand has a better efficacy than another due to the heterogeneity of the studies and outcomes.

Discussion: In the future it will be important to determine the exact mechanism of action of placebo as this may give us an idea of how to treat osteoarthritis more efficiently. Due to the limitations of this review (follow-up of just 3 months and large heterogeneity of the included studies), it is also important to compare the different HA products to determine which product(s), or which molecular weight range, concentration, or volume of HA is the best option to treat osteoarthritis. Our recommendation is to start large (multicenter) RCTs to give us more evidence about the efficacy of the different HA products.

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Acknowledgements

In November 2010 our team received funding from TRB Chemedica AG, Haar, Germany to pay for the article processing charge for our protocol entitled “Comparison of intra-articular injections of hyaluronic acid and corticosteroid in the treatment of osteoarthritis of the hip in comparison with intra-articular injections of bupivacaine: design of a prospective, randomized, controlled study with blinding of the patients and outcome assessors”. TRB Chemedica AG had absolutely no role in the design of this review, the inclusion of articles, the analysis or interpretation of the data, the writing of the manuscript, or the decision to submit the manuscript for publication.

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  1. Department of Orthopaedic Surgery, University Hospitals Leuven, Pellenberg site, Weligerveld 1, 3212, Pellenberg, Belgium

    Sascha Colen & Michiel Mulier

  2. Department of Orthopaedic Surgery, Spaarne Hospital, Hoofddorp, the Netherlands

    Michel P. J. van den Bekerom

  3. Department of Orthopaedic Surgery, Slotervaart Hospital, Amsterdam, the Netherlands

    Daniël Haverkamp

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  1. Sascha Colen
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Correspondence to Sascha Colen.

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Colen, S., van den Bekerom, M.P.J., Mulier, M. et al. Hyaluronic Acid in the Treatment of Knee Osteoarthritis. BioDrugs 26, 257–268 (2012). https://doi.org/10.1007/BF03261884

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  • DOI: https://doi.org/10.1007/BF03261884

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