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

Practice recommendations

* Hyaluronic acid (HA) injection may provide short-term relief of pain and improved functionality for patients with osteoarthritis of the knee, but benefits do not last beyond 6 months.

* Examine the HA option from a cost-benefit perspective on a case-by-case basis. Based on our meta-analysis, there is no sufficient reason to recommend or not recommend HA injection for treatment of osteoarthritis of the knee.

* You may want to help select patients weigh the possible benefit of HA therapy against its cost.

Though hyaluronic acid may reduce symptoms related to osteoarthritis of the knee, the relatively small and transient response in the population studied in our analysis does not provide sufficient reason to recommend or not recommend this therapy.

Those who might want to opt for hyaluronic acid injections

With the relatively low risk of complications, some patients may still opt to try hyaluronic acid injections as opposed to other osteoarthritis management strategies. Potential candidates include those whose only other option is surgery, in the hope that HA injection might postpone having to make that decision. Also, those whose pain or stiffness have not been relieved with other therapies might want to consider HA.

* Two instruments for assessing osteoarthritis

There are many claims to the efficacy of hyaluronic acid injections for decreasing the pain associated with osteoarthritis of the knee. This meta-analysis was an attempt to collapse the data for hyaluronic acid treatment, using a reduction in score on the Western Ontario McMaster Universities Index (WOMAC) or the Lequesne index as its outcome measurement.

The WOMAC is a disease-specific, self-administered instrument for patients with osteoarthritis of the knee or hip. It has 3 separate dimensions (with 24 individual scenarios), measuring pain (5 scenarios), stiffness (2 scenarios), and physical function (17 scenarios). It may be administered using a 100 mm/10 cm visual analog scale (VAS) (where 0 = none, 100 or 10 = extreme) or a Likert scale (0 to 4, where 0 = none, 4 = extreme). These results are then scored on a 0 to 20 scale for pain, a 0 to 8 scale for stiffness, and a 0 to 68 scale for physical function. Lower scores for both scales indicate a lesser degree of pain, stiffness, or physical dysfunction. In a double-blind, randomized controlled trial, WOMAC was found to be a valid and reliable tool for determining self-reported status for osteoarthritis of the knee or hip. (12)

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 al (13) 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 al (15) meta-analysis.