RESEARCH - Intra-articular hyaluronic acid for the treatment of OA of the knee: systemic review and meta-analysis

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CMAJ . April 12, 2005; 172 (8). doi:10.1503/cmaj.1041203.

© 2005 CMA Media Inc. or its licensors

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Review

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Intra-articular hyaluronic acid for the treatment of osteoarthritis of the

knee: systematic review and meta-analysis

Jasmin Arrich, Franz Piribauer, Philipp Mad, a Schmid, Klaus

Klaushofer and Marcus Müllner

From the Department of Emergency Medicine, Medizin Universität Wien, Vienna,

Austria (Arrich, Mad, Müllner); Hauptverband der Österreichischen

Sozialversicherungsträger, Vienna, Austria (Piribauer, Schmid, Klaushofer);

and Ludwig Boltzmann Institut für Osteologie and Medizinische Abteilung,

Hanusch Hospital, Vienna, Austria (Klaushofer, Müllner)

Abstract

Background: Osteoarthritis of the knee affects up to 10% of the elderly

population. The condition is frequently treated by intra-articular injection

of hyaluronic acid. We performed a systematic review and meta-analysis of

randomized controlled trials to assess the effectiveness of this treatment.

Methods: We searched MEDLINE, EMBASE, CINAHL, BIOSIS and the Cochrane

Controlled Trial Register from inception until April 2004 using a

combination of search terms for knee osteoarthritis and hyaluronic acid and

a filter for randomized controlled trials. We extracted data on pain at

rest, pain during or immediately after movement, joint function and adverse

events.

Results: Twenty-two trials that reported usable quantitative information on

any of the predefined end points were identified and included in the

systematic review. Even though pain at rest may be improved by hyaluronic

acid, the data available from these studies did not allow an appropriate

assessment of this end point. Patients who received the intervention

experienced a reduction in pain during movement: the mean difference on a

100-mm visual analogue scale was -3.8 mm (95% confidence interval [CI] -9.1

to 1.4 mm) after 2-6 weeks, -4.3 mm (95% CI -7.6 to -0.9 mm) after 10-14

weeks and -7.1 mm (95% CI -11.8 to -2.4 mm) after 22-30 weeks. However, this

effect was not compatible with a clinically meaningful difference (expected

to be about 15 mm on the visual analogue scale). Furthermore, the effect was

exaggerated by trials not reporting an intention-to-treat analysis. No

improvement in knee function was observed at any time point. Even so, the

effect of hyaluronic acid on knee function was more favourable when

allocation was not concealed. Adverse events occurred slightly more often

among patients who received the intervention (relative risk 1.08, 95% CI

1.01 to 1.15). Only 4 trials explicitly reported allocation concealment, had

blinded outcome assessment and presented intention-to-treat data.

Interpretation: According to the currently available evidence,

intra-articular hyaluronic acid has not been proven clinically effective and

may be associated with a greater risk of adverse events. Large trials with

clinically relevant and uniform end points are necessary to clarify the

benefit-risk ratio.

http://www.cmaj.ca/cgi/content/abstract/172/8/1039

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