Knee osteoarthritis: Should your patient opt for hyaluronic acid injection?

The Lequesne index is a 10-question interview-style survey given to patients with osteoarthritis of the knee. It has 5 questions pertaining to pain or discomfort, 1 question dealing with maximum distance walked, and 4 questions about activities of daily living. The total questionnaire is scored on a 0 to 24 scale, with lower scores meaning less functional impairment. A study by Faucher et al¹³ found the Lequesne index to be a reliable questionnaire.

Methods

Selection of studies

Two researchers (JM and AT) performed a computerized literature search of PubMed (1950–2004), CINAHL (1982–2004), and Medline (1966–2004) to identify citations concerning the efficacy of hyaluronic acid injection for management of osteoarthritis of the knee. Four separate searches were conducted. The first used the terms knee, osteoarthritis, WOMAC, and hyaluronic acid. The second used the same terms as the first, replacing WOMAC with Lequesne. The third and fourth searched WOMAC and validity and Lequesne and validity, respectively. All 4 searches were limited to human randomized clinical trials, in English-language journal reports. A hand search of the reference lists of all retrieved studies was performed to ensure that no eligible studies were excluded.

Studies were selected independently by the same 2 researchers. The search was performed independently to ensure an exhaustive review of the literature. All studies were considered eligible until disqualified based on exclusion criteria.

Studies were eligible for inclusion if they addressed hyaluronic acid injection for osteoarthritis at the knee and used the WOMAC or Lequesne indexes as outcomes measurements. It was also necessary that they provided means and standard deviations in order to perform statistical analysis. We attempted to contact authors who did not provide necessary statistics for meta-analysis; however, we received no responses.

Assessment of methodological quality and data abstraction

The methodological quality of each study was assessed independently by the reviewers using the Physiological Evidence Database (PEDro) rating scale.¹⁴ It was determined that studies must include a control group that used placebo saline injections, provide means and standard deviations at baseline for the WOMAC or Lequesne, and also means and standard deviations after the intervention for both the treatment and control groups.

All abstracted data were converted into a percentage of the total possible score for each outcome measurement using a method described by a statistical consultant and an algorithm developed by one investigator (JM) using MATLAB 7.0 (MathWorks, Inc, Natick, Mass). This allowed for comparison between results of the WOMAC and Lequesne studies. This also allowed for comparison to the results of the Wang et al¹⁵ meta-analysis.

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 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.