What is hyaluronic acid?
Hyaluronic acid is a naturally occurring substance within our bodies/joints. It is increasingly recognised as an effective treatment option for osteoarthritis (mainly the mild and moderate forms of the disease). The articular cartilage is a smooth structure covering the bone surface at the joints. It is responsible for the joints' smooth and frictionless movement and is a shock absorbent. The most internal layer of the cartilage is called the “Synovial membrane”. It lines the joint capsule and produces a special fluid within the joint (synovial fluid). Synovial fluid is vital for the function of any synovial joint, as it acts as a natural lubricant. The articular cartilage, including its inner layer (the synovial membrane), has a special type of cells (called hyaluronan receptor cells). Hyaluronic acid is specifically attracted to hyaluronan receptor cells to result in the formation of a semi-permeable membrane at the surface of the articular cartilage, contributing to the joint lubricant and shock absorbent properties of the cartilage. Efficient joint lubrication depends on the viscosity of hyaluronic acid, and viscosity is directly related to its molecular weight. In other words, if the molecular weight of hyaluronic acid reduces, its viscosity also reduces. This means it will have less lubricant and shock-absorbing function, and the joint will eventually develop osteoarthritis (wear and tear changes).
In addition to the joint lubrication and shock absorbent effect of hyaluronic acid described above, it is believed that hyaluronic acid can help regulate protein synthesis and eliminate free radicals. Free radicals are usually highly reactive and unstable and can damage the joint and the articular cartilage.
Currently, Hyaluronic acid is prepared by bio-fermentation, which utilises cultures produced by certain bacteria to produce a synthetic form of hyaluronic acid.
How does intra-articular hyaluronic acid injection work?
Studies have shown that intra-articular injection of Hyaluronic acid into knee joints with osteoarthritis starts a series of reactions that result in chondral protection (protection of the articular cartilage and prevention of chondrocyte death). Also, it is found to encourage the formation of new articular cartilage and reduces joint inflammation. Furthermore, it promotes the production of proteoglycans (proteins that help build up the joint cartilage). As mentioned above, Hyaluronic acid injection will also increase the joint lubricant and shock absorbent effect of the articular cartilage (usually called viscosupplementation).
Does intra-articular hyaluronic acid injection work?
Evidence shows that hyaluronic acid injections are safe, providing more prolonged pain relief and fewer side effects when compared to NSAIDs (non-steroidal anti-inflammatories tablets), especially for the cardiovascular and gastrointestinal systems. However, research has shown that although hyaluronic acid injections result in longer-lasting pain relief compared to steroid injections, they take longer time to take effect, up to 2-5 weeks.
Are hyaluronic acid injections safe?
Increased pain (flare) is possible following hyaluronic acid injections. This can happen after a steroid injection too. Research shows that the flare-up of pain following Hyaluronic acid injections is rarer and mainly reported with repeated injections. The aetiology of post Hyaluronic acid injections pain is not clear yet. It is thought to be secondary to the accumulation of hyaluronan breakdown products within the joint, as it is mainly reported in patients who had multiple injections rather than a single one.
There is no evidence of an increased rate of local complications (infection, skin colour changes or fat atrophy) or generalised complications (anaphylaxis) when hyaluronic acid injections are compared to intra-articular steroid injections. Furthermore, there is good evidence showing that when these injections are done under ultrasound guidance, they are more accurate, with fewer complications and better outcomes when compared to non-guided injections.
What are the different types of hyaluronic acid injections?
Hyaluronic acid preparations currently available in the market are either low or high molecular weight (LMW or HMW). Example brand names for HMW preparations are Durolane and Ostenil Plus. Example brand names for the LMW preparations are Ostenil and Synvisc. The viscosity of hyaluronic acid is critical to its function as it directly affects its ability to bind to hyaluronan receptors and, therefore, its effect. Different molecular weight hyaluronic acid solutions have been shown to differ in their physiological effects. For example, LMW hyaluronic acid has been shown to have a more chondroprotective effect (protection of the cartilage) when compared to HMW hyaluronic acid. Having said that, research has shown that HMW hyaluronic acid has a more anti-inflammatory effect than LMW hyaluronic acid.
HMW and LMW hyaluronic acid preparations effectively reduce joint pain, stiffness, and function. However, LMW treatment used a prolonged course of 5 injections over five weeks. Another study showed a more favourable outcome when HMW hyaluronic acid was injected (approximately double the benefits). The Arthroscopy Association of Canada also recommends HMW hyaluronic acid for knee and hip osteoarthritis management. Most of the current evidence is based on research on the effect of Hyaluronic acid injections on knee joint osteoarthritis. Currently, there is sufficient evidence to support the use of hyaluronic acid injections to manage knee osteoarthritis. Both HMW and LMW hyaluronic acid injections can result in good outcomes. Overall, there is insufficient evidence to favour LMW or HMW regarding effectiveness in treating osteoarthritis. However, a single HMW injection is preferred and more convenient than multiple LMW hyaluronic acid injections.
What conditions is a hyaluronic acid injection useful for?
There is strong and convincing evidence regarding the effectiveness and safety of hyaluronic acid injection in managing osteoarthritis, particularly in the knee and hip.
The knee
There is abundant evidence supporting the effectiveness and safety of hyaluronic acid injections in managing knee osteoarthritis. The current and ongoing research shows that intra-articular hyaluronic acid injections are safe and efficient for controlling joint pain, reducing the need for painkiller tablets, improving function and quality of life, and delaying surgical treatment. In addition, effective pain relief from hyaluronic acid injections can last up to 6 months.
The hip
Wu et al. conducted an extensive systematic review of the usage of Hyaluronic Acid injections and hip osteoarthritis. They found that the efficacy of treatment is increased with the increase in the molecular weight of the injection. Similar to the knee results, the reduction in pain and improvement in hip joint function lasted for up to 6 months, with a very small adverse effects profile. There is also evidence that using Hyaluronic Acid injections can help reduce pain and improve function in patients diagnosed with femoroacetabular impingement in the hip. The improvement lasted up to 1 year and was maintained for up to 1 year.
The ankle
More research is required to strongly establish the effectiveness of Hyaluronic Acid injections in managing ankle osteoarthritis. The evidence suggests that the hyaluronic acid treatment has a favourable outcome in reducing pain and improving function. However, more research and analysis are required to confirm this further.
The shoulder
There is currently a small volume of published research to support the effectiveness of hyaluronic acid injections in managing shoulder osteoarthritis.
Summary
Hyaluronic acid is a naturally occurring substance within the joints essential for effective joint function and lubrication. Hyaluronic acid injections are an effective treatment choice for people diagnosed with osteoarthritis (wear and tear), particularly in the knee joint. Research has shown that Hyaluronic acid injections can result in a significant reduction of pain and improvement in joint function. The mechanisms of action of Hyaluronic Acid injections are multi-factorial, including chondral protection (protection of the cartilage) and thus increasing joint lubrication and shock absorption effect of the cartilage. It also has an anti-inflammatory effect and thus can help reduce the inflammation within joints. HMW and LMW hyaluronic acid injections can produce good results, but a single HMW injection might be preferred over multiple LMW injections.
