Viscosupplementation for osteoarthritis of the knee: a systematic review and meta-analysis

BACKGROUND: Viscosupplementation, the intra-articular injection of hyaluronic
acid, is widely used for symptomatic knee osteoarthritis.
PURPOSE: To assess the benefits and risks of viscosupplementation for adults with
symptomatic knee osteoarthritis.
DATA SOURCES: MEDLINE (1966 to January 2012), EMBASE (1980 to January 2012), the
Cochrane Central Register of Controlled Trials (1970 to January 2012), and other
sources.
STUDY SELECTION: Randomized trials in any language that compared
viscosupplementation with sham or nonintervention control in adults with knee
osteoarthritis.
DATA EXTRACTION: Primary outcomes were pain intensity and flare-ups. Secondary
outcomes included function and serious adverse events. Reviewers used duplicate
abstractions, assessed study quality, pooled data by using a random-effects
model, examined funnel plots, and explored heterogeneity by using
meta-regression.
DATA SYNTHESIS: Eighty-nine trials involving 12 667 adults met inclusion
criteria. Sixty-eight had a sham control, 40 had a follow-up duration greater
than 3 months, and 22 used cross-linked forms of hyaluronic acid. Overall, 71
trials (9617 patients) showed that viscosupplementation moderately reduced pain
(effect size, -0.37 [95% CI, -0.46 to -0.28]). There was important between-trial
heterogeneity and an asymmetrical funnel plot: Trial size, blinded outcome
assessment, and publication status were associated with effect size. Five
unpublished trials (1149 patients) showed an effect size of -0.03 (CI, -0.14 to
0.09). Eighteen large trials with blinded outcome assessment (5094 patients)
showed a clinically irrelevant effect size of -0.11 (CI, -0.18 to -0.04). Six
trials (811 patients) showed that viscosupplementation increased, although not
statistically significantly, the risk for flare-ups (relative risk, 1.51 [CI,
0.84 to 2.72]). Fourteen trials (3667 patients) showed that viscosupplementation
increased the risk for serious adverse events (relative risk, 1.41 [CI, 1.02 to
1.97]).
LIMITATIONS: Trial quality was generally low. Safety data were often not
reported.
CONCLUSION: In patients with knee osteoarthritis, viscosupplementation is
associated with a small and clinically irrelevant benefit and an increased risk
for serious adverse events.
PRIMARY FUNDING SOURCE: Arco Foundation.