Knee osteoarthritis: should your patient opt for hyaluronic acid injection? A meta-analysis of hyaluronic acid's effects on pain, stiffness, and disability

Journal of Family Practice, August, 2006 by Jennifer M. Medina, Abbey Thomas, Craig R. Denegar

Statistical analysis

Homogeneity of the included studies, as determined by inclusion and exclusion criteria, allowed for meta-analysis. One meta-analysis was performed on the 3 studies that used the WOMAC scale, (16-18) 2 on the 4 studies that used the Lequesne index. (7-9,19) Most studies that used the Lequesne index reported outcomes for a variety of follow-up points (4, 5, 8, 20, 24, 26, 49, 52 weeks); however, there was not a consistent reporting timeline among these studies. We grouped the follow-up reports into "up to 6 months post-treatment" and "6 months or greater post-treatment." The first Lequesne analysis evaluated the difference between treatment and placebo groups at with data points less than 6 months post-treatment. The second Lequesne analysis examined the difference between groups at 6 months and greater post-treatment. In the study by Karlsson, (7) 2 different but similar types of hyaluronic acid were used. These groups were separated and analyzed as independent studies; 95% confidence intervals were calculated for all analyses. Effect sizes were also calculated to determine the between-group effect of the treatment and placebo.

* Results

Selection of studies

The literature search resulted in 35 potentially eligible studies, of which 7 were selected after application of the inclusion criteria. (7-9,16-19) Three of the selected studies used the WOMAC as an outcome assessment tool, (16-18) 4 used the Lequesne index. (7-9,19) The remaining 28 studies were excluded. TABLE W1 (available online at www.jfponline.com) details the rejection of studies.

Methodological quality and study characteristics

Each investigator then independently scored the methodological quality for the remaining studies by using the PEDro scale. (14) There was total agreement for all studies in regards to the PEDro score. No study received a score under 5. The average PEDro rating among the studies was 8.2 out of 10.

Homogeneity

All groups across all included studies were similar at baseline. All patients had mild to severe osteoarthritis of the knee. Mean ages of the groups were similar (treatment groups = 67.1 years, placebo = 66.7 years). Not all patients received treatment as per manufacturer's recommendations (TABLES 1 AND 2). A saline placebo was used for control groups in all studies. The volume of saline placebo for each study was equal to volume of hyaluronic acid injection plus saline vehicle used for that study. All studies used either the WOMAC scale or the Lequesne Functional Index as an outcome measurement tool. All studies included a follow-up outcome measurement; however, the range of follow-up time periods was wide (4 to 52 weeks).

Meta-analysis

The analysis for the outcome measurements on the WOMAC scale revealed no significant difference between groups in regards to pain or disability (95% confidence interval [CI] for pain, -0.6043 to 5.4755; for disability, -0.8282 to 4.8619). The outcome measurement for stiffness demonstrated a significant difference between treatment and control (95% CI for stiffness, 2.1780 to 8.7955).