Intra-articular hyaluronic acid injection for knee osteoarthritis

As one of the major causes of disability in the elderly population, knee osteoarthritis is a common degenerative joint disease. The general treatment approaches for knee osteoarthritis include physical therapy, nonsteroidal anti-inflammatory drugs (NSAIDs), intra-articular injection of steroid hormones, viscosupplementation and surgery, etc. Hyaluronic acid (HA) is a kind of macromolecule which plays pivotal roles in the articular physiology as a key component of synovial fluid and cartilage. Intra-articular injection of hyaluronic acid (IA-HA) is established as a local therapy to restore the viscoelasticity of synovial fluid and achieve physiological stability. Numerous clinical trials have demonstrated that IA-HA is effective in relieving pain and reducing structural damage in patients with knee osteoarthritis. Generally, the pain-relieving activity of IA-HA is comparable to or higher than that of NSAIDs, intra-articular corticosteroids, and physical therapy. In addition, IA-HA treatment is tolerated and is associated with less adverse events in comparison with NSAIDs, which elicits gastrointestinal bleedings and is associated with increased mortality. Studies in the mechanisms of action also revealed that HA could specifically bind to the membrane receptor (such as CD44) and adhesion molecules (ICAM-1) in cells. The connection may stimulate functional activities, including cell migration and proliferation. However, debates on whether hyaluronic acid produces significant clinical benefits still exist in the literature and different clinical practice guidelines. The variability in pharmaceutical property of different HA products, the severity of knee osteoarthritis, treatment protocol and injection technique can potentially have impacts on the outcomes of treatment of knee osteoarthritis with IA-HA.