Nine studies (Four RCTs and five prospective studies) were included in the review (354 participants). The quality of the studies ranged from 1 to 5 points for RCTs and 4 to 6 points for prospective studies. Follow-up duration ranged from three to 18 months. Most studies used the ankle osteoarthritis score. The overall effect size of improvement scores from baseline was 2.01 (95% CI 1.27 to 2.75; Ι²=92%). There was no significant difference in effect size when compared hyaluronic acid with reference treatments such as saline (three RCTs), exercise (one study) and arthroscopy (one study). When studies with the saline control group were pooled separately (three RCTs) to calculate the mean differences from baseline, the results showed the placebo effect of the treatment; which accounted for 87% of the observed efficacy.
Subgroup and meta-regression analyses were reported.
Fifteen percent of participants who underwent the administration of intra-articular hyaluronic acid experienced adverse effects. The reported adverse effects were transient post-injection pain (28 participants), ankle effusion (one participant), inguinal lymph node enlargement (one participant) and local pruritus (one participant). All adverse reactions resolved spontaneously without specific treatment.
Evidence of publication bias was reported.