Intra-articular hyaluronan injections for the treatment of osteoarthritis: perspective for the mechanism of action

Osteoarthritis (OA) is one of the leading causes of global disability, with a tremendous individual and socioeconomic burden.1 Interest in minimally invasive methods, such as injection therapies, that may prevent or reverse the progression of cartilage disease, mostly for the treatment of early stages of OA, has grown, including the use of hyaluronic acid or hyaluronan (HA), platelet-rich plasma (PRP) and cell-based therapies.2–4 Among these approaches, intra-articular injections of HA have been one of the most frequently performed therapies. While there is an extensive body of evidence surrounding the use of HA injections, especially for the treatment of knee OA, this is composed of heterogeneous trials with conflicting conclusions.5 Even though the vast majority of the available literature covers the potential clinical effect of HA injections, considerable controversy still persists regarding its clinical effectiveness. Over several decades there have been multiple attempts to determine the ideal molecular weight and concentration of HA that would deliver the best clinical outcome, without considerable consensus. Due to the disagreement, inconsistent data and remaining debate, although HA injections may denote a safe alternative that could offer temporary reduction in pain for certain patients with knee OA, the current evidence base could not advocate its use.6,7 In this sense, it is critical to acknowledge that not all intra-articular HA products should be treated as a single group, since, for example, products with a molecular weight >3000 kDa and products derived from biological fermentation have been related to superior efficacy and safety.