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Us-Approved Intra-Articular Hyaluronic Acid Injections

are safe and effective in patients with Knee Osteoarthritis: systematic Review and Meta-Analysis of Randomized, saline-controlled Trials 

Larry E. Miller1,2 and Jon E. Block2

1Miller Scientific Consulting, Inc., Arden, NC, USA. 2The Jon Block Group, San Francisco, CA, uSA. Corresponding author email:

Abstract: We conducted a systematic review and meta-analysis of randomized saline-controlled trials to determine the safety and efficacy of US-approved intra-articular hyaluronic acid (IAHA) injections for symptomatic knee osteoarthritis. A total of 29 studies representing 4,866 unique subjects (IAHA: 2,673, saline: 2,193) were included. IAHA injection resulted in very large treatment effects between 4 and 26 weeks for knee pain and function compared to pre-injection values, with standardized mean difference (SMD) val- ues ranging from 1.07–1.37 (all P , 0.001). Compared to saline controls, SMDs with IAHA ranged from 0.38–0.43 for knee pain and 0.32–0.34 for knee function (all P , 0.001). There were no statistically significant differences between IAHA and saline controls for any safety outcome, including serious adverse events (SAEs) (P = 0.12), treatment-related SAEs (P = 1.0), study withdrawal (P = 1.0), and AE-related study withdrawal (P = 0.46). We conclude that intra-articular injection of US-approved HA products is safe and efficacious in patients with symptomatic knee osteoarthritis.

Keywords: hyaluronic acid, knee, meta-analysis, osteoarthritis, systematic review, viscosupplementation 

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