Hyaluronic acid in ankle osteoarthritis: why evidence of efficacy is still lacking?

Intra-articular injections of hyaluronic acid (HA) are useful in the treatment of osteoarthritis (OA), as shown by studies on knee, hip, and trapezio-metacarpal joints. The positive results can be explained by several factors: the restoration of elastic and viscous properties of intra-articular fluid, the anti-inflammatory and the anti-nociceptive activity, and the normalisation of hyaluronan synthesis and inhibition of hyaluronic acid degradation. However, evidence of efficacy of hyaluronic acid in ankle osteoarthritis is still lacking: several studies have been performed without a control group, or have shown similar results to those obtained with different therapeutic procedures. The aim of this paper is to analyse the reasons which can explain the discrepancy between the sound biological background and the inconclusive clinical results. First, it must be considered that the ankle joint, from a biomechanical point of view, is more complex than other joints, and that greater stress is sustained by the articular surfaces. Second, the limited benefit can be related to the use of hyaluronic acid mostly in cases of post-traumatic osteoarthritis, where the treatment must be addressed to solve the biomechanical problems, and then to restore the rheological properties of the ankle joint. A third important explanation of the failure may be the improper technique of administration, that has been performed in all studies, but one, without imaging guidance. Indeed, it is well known that hyaluronic acid, if not delivered directly into the intra-articular space, is unlikely to be effective.