Intra-articular hyaluronan (hyaluronic acid) and hylans for the treatment of osteoarthritis: mechanisms of action

Osteoarthritis (OA), the most common form of arthritis, is a chronic disease characterized by the slow degradation of cartilage, pain, and increasing disability. The disease can have an impact on several aspects of a patient's life, including functional and social activities, relationships, socioeconomic status, body image, and emotional well-being [1]. Currently available pharmacological therapies target palliation of pain and include analgesics (i.e. acetaminophen, cyclooxygenase-2-specific inhibitors, nonselective nonsteroidal anti-inflammatory drugs, tramadol, opioids), intra-articular therapies (glucocorticoids and hyaluronan [hyaluronic acid] [HA]), and topical treatments (i.e. capsaicin, methylsalicylate) [2].Intra-articular treatment with HA and hylans (see Table 1 for definitions) has recently become more widely accepted in the armamentarium of therapies for OA pain [2]. HA is responsible for the viscoelastic properties of synovial fluid. This fluid contains a lower concentration and molecular weight (MW) of HA in osteoarthritic joints than in healthy ones [3]. Thus, the goal of intra-articular therapy with HA is to help replace synovial fluid that has lost its viscoelastic properties. The efficacy and tolerability of intra-articular HA for the treatment of pain associated with OA of the knee have been demonstrated in several clinical trials [4-14]. Three (hylan G-F 20) to five (sodium hyaluronate) injections can provide relief of knee pain from OA for up to 6 months [6,7,11]. Intra-articular hylan or HA is also generally well tolerated, with a low incidence of local adverse events (from 0% to 13% of patients) [5,6,8,11,12] that was similar to that found with placebo [6,11].Because the residence time of exogenously administered HA in the joint is relatively short, HA probably has physiological effects in the joint that contribute to its effects in the joint over longer periods. The exact mechanism(s) by which intra-articular HA or hylans relieve pain is cur