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The Evidence Against Viscosupplementation for Symptomatic Knee Osteoarthritis

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Intra-articular hyaluronic acid injections, also known as viscosupplementation, are a common treatment option for many patients with end-stage osteoarthritis of the knee. However, the effectiveness and safety of this treatment remain subject to debate. This post comes from guest contributor Matthew Deren, MD, in response to a recent systematic review and meta-analysis in The BMJ.  


Total knee arthroplasty (TKA) provides excellent results for patients with end-stage arthritis of the knee. Prior to surgery, nonoperative management is often a course of treatment for our patients, to address pain and diminished function. Treatments include hyaluronic acid injections, also known as viscosupplementation or “gel” injections.  

In a recent BMJ report, Pereira et al. present the results of a systematic review and meta-analysis of existing randomized controlled trials on viscosupplementation. Their goal was to evaluate the evidence on the clinical benefits and safety of this treatment.  

In addition to searching Medline, Embase, and Cochrane databases, the authors included unpublished studies from trial registries as well as the grey literature. No language restrictions were imposed. They identified 169 trials with 21,163 randomized participants.   

Study Findings on Viscosupplementation 

Twenty-four placebo-controlled trials with 8,997 participants were included in the primary outcome analysis of pain intensity. Those treated with viscosupplementation experienced a small, statistically significant reduction in pain intensity compared with placebo (standardized mean difference [SMD] of −0.08; 95% confidence interval [CI], −0.15 to −0.02; p = 0.02). The authors note that the effect corresponds to a difference in pain scores of −2.00 mm (95% confidence interval [CI], −3.8 to −0.05 mm) on a 100-mm visual analogue scale.  

The secondary outcome of function was evaluated on the basis of 19 trials (6,307 patients). The analysis found a small, clinically irrelevant improvement in function levels for viscosupplementation (SMD of −0.11; p = 0001).  

Finally, the secondary outcome of serious adverse events was evaluated on the basis of 15 trials (6,462 participants). The authors found a statistically significant risk of serious adverse events compared with placebo (relative risk of 1.49; 95% CI, 1.12 to 1.98; p = 0.003).  

The authors also noted evidence of nonpublished data from industry-sponsored trials, which may be indicative of selective reporting. 

Conclusions 

As concluded by the authors: strong evidence indicates that viscosupplementation for the treatment of symptomatic knee osteoarthritis is associated with a small reduction in pain compared with placebo, but the difference is less than the minimal clinically important difference between the groups. The evidence also suggests that viscosupplementation is associated with increased risk of serious adverse events compared with placebo.  

In an evidence-based, quality-centered health-care system, the role for these injections should be narrowing. Anecdotally, I have used these injections with mixed results for nonoperative treatment prior to knee replacement in my own patients. Based on the current literature, however, I will only offer these injections to those who specifically request their use after consultation.  

Additional perspective on hyaluronic injections and the BMJ report can be found in this recent STAT article. 


Dr. Matthew Deren

Matthew Deren, MD is an Assistant Professor in the Department of Orthopaedics at Cleveland Clinic in Cleveland, Ohio. He is also a member of the JBJS Social Media Advisory Board. 

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