EVIDENCE-BASED ANSWER
Yes, hyaluronic acid (HA) injections relieve pain more than placebo. The effect is small but similar to results from oral nonsteroidal anti-inflammatory drugs (NSAIDs) or steroid injection (strength of recommendation ([SOR]: B, conflicting meta-analyses). The various HA products all appear to be equally effective in reducing pain (SOR: B, randomized clinical trials [RCTs]). Data concerning the effect of HA on functional ability are conflicting.
Evidence summary
A 2005 meta-analysis evaluated the effectiveness of HA injections for osteoarthritis of the knee compared with saline placebo. Researchers identified 22 studies of 8 HA products that used the common end point of pain with movement.1 (TABLE 1 lists FDA-approved HA products available in the United States.2) A decrease in pain of 15% was deemed clinically meaningful.
Compared with placebo, the mean difference in pain scores with HA products was -4% (95% confidence interval [CI], -9% to 1%) after 2 to 6 weeks; -4% (95% CI, -8% to -1%) after 10 to 14 weeks; and -7% (95% CI, -12% to -2%) after 22 to 30 weeks. The authors note that the small measured effect of HA was magnified by trials that didn’t report intention-to-treat results. The effect of HA was also larger in studies that didn’t conceal allocation. A weakness of the analysis was its inability to assess potential differences between HA products.
In this 2005 meta-analysis, HA injection didn’t improve knee function in any time interval. But in a Cochrane meta-analysis conducted the following year, HA was found to have positive results.3
TABLE 1
FDA-approved hyaluronic acid products
| TRADE NAME | COMPOSITION | MOLECULAR WEIGHT (×106 DALTONS) | COST PER INJECTION* (3-5 DOSES) | SOURCE |
|---|---|---|---|---|
| Hyalgan | Sodium hyaluronate | 0.5-0.7 | $138 | Avian |
| Supartz | Sodium hyaluronate | 0.6-1.2 | $136 | Avian |
| Euflexxa | Sodium hyaluronate | 2.4-3.6 | $133 | Bacterial |
| Orthovisc | Hyaluronin | 1.0-2.9 | $238 | Avian |
| Synvisc | Hylan G-F 20 | 6.0 | $230 | Avian |
HA relieves pain about as much as NSAIDs
The comprehensive 2006 Cochrane meta-analysis reviewed single- and double-blinded RCTs that evaluated the effect of 12 HA products on osteoarthritis of the knee.3 Studies compared HA products with placebo (40), intra-articular steroids (10), NSAIDs (6), physical therapy (3), exercise (2), and each other (15). Efficacy data for different products couldn’t be combined because the studies measured different sets of outcomes at different time points.
Overall, the authors concluded that HA injections effectively reduced pain scores, with the largest benefit occurring within 5 to 13 weeks (TABLE 2). The authors also noted that the reductions in pain with HA injections, although generally small, were comparable to oral NSAID therapy and intra-articular corticosteroids. The trials reported few adverse events.