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J Pain Res. 2015 May 7;8:217-28. doi: 10.2147/JPR.S83076. eCollection 2015.

Safety and efficacy of US-approved viscosupplements for knee osteoarthritis: a systematic review and meta-analysis of randomized, saline-controlled trials.

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Stanford University School of Medicine, Palo Alto, CA, USA.
New York University Medical Center, White Plains, NY, USA.
Tuckahoe Orthopaedics, Richmond, VA, USA.
Miller Scientific Consulting, Inc., Asheville, NC, USA ; The Jon Block Group, San Francisco, CA, USA.
The Jon Block Group, San Francisco, CA, USA.



Intra-articular injection of hyaluronic acid is a common, yet controversial, therapeutic option for patients with knee osteoarthritis (OA). The purpose of this research was to determine the safety and efficacy of US-approved viscosupplements for symptomatic knee OA.


We searched MedLine and EMBase for randomized, sham-controlled trials evaluating safety and/or clinical efficacy of US-approved viscosupplements in patients with symptomatic knee OA. Knee pain severity and knee joint function were assessed at 4 to 13 weeks and 14 to 26 weeks. Safety outcomes included serious adverse events, treatment-related serious adverse events, patient withdrawal, and adverse event-related patient withdrawal occurring at any time during follow-up.


A total of 29 studies representing 4,866 unique patients (active: 2,673, control: 2,193) were included. All sham-controlled trials used saline injections as a control. Viscosupplementation resulted in very large treatment effects between 4 and 26 weeks for knee pain and function compared to preinjection values, with standardized mean difference values ranging from 1.07 to 1.37 (all P<0.001). Compared to controls, standardized mean difference with viscosupplementation ranged from 0.38 to 0.43 for knee pain and 0.32 to 0.34 for knee function (all P<0.001). There were no statistically significant differences between viscosupplementation and controls for any safety outcome, with absolute risk differences of 0.7% (95% confidence interval [CI]: -0.2 to 1.5%) for serious adverse events, 0% (95% CI: -0.4 to 0.4%) for treatment-related serious adverse events, 0% (95% CI: -1.6 to 1.6%) for patient withdrawal, and 0.2% (95% CI: -0.4 to 0.8%) for adverse event-related patient withdrawal.


Intra-articular injection of US-approved viscosupplements is safe and efficacious through 26 weeks in patients with symptomatic knee OA.


hyaluronic acid; intra-articular; viscosupplementation

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