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The Benefits of Intra-Articular High Molecular Weight Hyaluronic Acid Injections Compared to Low Molecular Weight Intra-Articular Hyaluronic Acid in the Reduction of Pain, Disability, and Stiffness in Adult Patients with Osteoarthritis of the Knee

15 August 2009


Introduction: Osteoarthritis (OA) of the knee is a common disorder affecting adults and continues to be a growing concern as the current population ages. Intra-articular (IA) injections of hyaluronic acid (HA) are currently used as a viscosupplementation and have shown to provide symptomatic relief. Recently the formulation of differing molecular weight HAs have been produced to provide a further decrease in pain and stiffness, and increase physical function. The formulations include high molecular weight HA (HMW-HA) and low molecular weight HA (LMW-HA). The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) has been used as a validated tool to assess the improvements in knee OA.

Hypothesis: If pain, disability, and stiffness are affected by specific molecular weight HA, then intra-articular injections of HMW-HA will benefit patients suffering from OA of the knee.

Study Design: A systematic review of current randomized controlled trials.

Methods: An exhaustive electronic literature search was performed for relevant published, randomized controlled trials in MEDLINE, CINAHL, Evidence-Based Medicine Reviews Multifile, and PubMed from January 2002 to March 2009. Inclusion criteria included randomized controlled trials comparing the effects of intra-articular injection of high molecular weight hyaluronic acid with that of intra-articular injection of a low molecular weight to treat osteoarthritis of the knee were included in this systematic review. Outcome measures of pain, physical function, and stiffness based on the WOMAC had to be available. Exclusion criteria included trials having no randomization and no pain, disability, or stiffness (WOMAC) classification.

Results: Pooled data reveal an allocation of 1321 patients to a HMW-HA, LMW-HA, or placebo group. The average age of patients ranged from 41 to 82 years (mean 65.3 years). Of the 4 studies reviewed only one revealed a significant difference. All others reported no significant decrease in pain and stiffness, and improvement in physical function. Most studies demonstrated an improvement in all three variables from baseline, independent of the molecular weight HA used.

Conclusion: Based on this systematic review of four RCTs the use of HMW-HA does not provide an absolute clinical benefit to adult patients suffering from knee OA.


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