Is hyaluronic acid (HA) safe to use?

From the Guidelines

Hyaluronic acid is not recommended for routine use in the treatment of symptomatic osteoarthritis of the knee due to inconsistent evidence supporting its effectiveness. The use of hyaluronic acid intra-articular injections has been widely adopted, but the current evidence does not consistently support its benefits for patients with knee osteoarthritis 1. According to the AAOS clinical practice guideline summary, the recommendation against the routine use of hyaluronic acid is based on 17 high-quality and 11 moderate-quality studies that failed to demonstrate consistent benefits 1.

Key Points to Consider

• The evidence for hyaluronic acid is inconsistent, with some studies showing benefits and others showing no improvement in pain and function 1.
• The calculated number needed to treat was 17 patients, suggesting that some patients may benefit from hyaluronic acid, but the current evidence does not identify the subset of patients who benefit from it 1.
• Other treatment options, such as sustained weight loss, exercise, and oral nonsteroidal anti-inflammatory drugs (NSAIDs), have been shown to be effective in improving pain and function in patients with knee osteoarthritis 1.
• Intra-articular corticosteroid injections have considerable evidence supporting their use, with 19 high-quality and six moderate-quality studies demonstrating benefits 1.

Safety Profile

While hyaluronic acid is generally considered safe, its use as an intra-articular injection may be associated with temporary side effects such as swelling, redness, or bruising at the injection site 1. However, the safety profile of hyaluronic acid is not the primary concern, as the evidence does not consistently support its effectiveness for the treatment of symptomatic osteoarthritis of the knee. The recommendation against the routine use of hyaluronic acid is based on the lack of consistent evidence supporting its benefits, rather than safety concerns.

From the FDA Drug Label

PRINCIPAL DISPLAY PANEL - 4 mL Vial Carton Legend® (hyaluronate sodium)Injectable Solution 10 mg/mL For intravenous use in horses only The FDA drug label does not answer the question.

From the Research

Safety of Hyaluronic Acid

• Hyaluronic acid is considered safe for use in cosmetics, as stated in the safety assessment published in the International Journal of Toxicology 2.
• The study found that hyaluronic acid was not toxic, immunogenic, or a sensitizer in animal studies, and it was not a reproductive or developmental toxicant.
• Additionally, hyaluronic acid was not genotoxic, and its widespread clinical use has been free of significant adverse reactions.

Medical Applications

• Hyaluronic acid has various medical applications, including ophthalmology, rheumatology, and dermatology, due to its physico-chemical properties 3.
• In the treatment of dry eye disease, hyaluronic acid provides water retention and lubricant properties.
• For osteoarthritis, hyaluronic acid applies its lubricant and anti-inflammatory properties for treatment.
• Hyaluronic acid has also been used in dermatology and cosmetics for its benefit in revitalizing the skin.

Intra-articular Injections

• Intra-articular injections of hyaluronic acid are widely used for the treatment of knee osteoarthritis, with a systematic review of 38 randomized control trials showing its safety and efficacy 4.
• The review found that hyaluronic acid injections provide adequate pain relief and functional improvement for up to six months, with minor side effects such as local pain and swelling.
• Severe allergic reactions are extremely rare, and combination formulations with corticosteroids or platelet-rich plasma show better results than hyaluronic acid alone.

Pediatric Use

• Hyaluronic acid-based medical devices have been used in pediatric dentistry for the management of inflammatory disorders of the oral cavity and teething symptoms 5.
• The preparations of hyaluronic acid used in pediatric dentistry have anti-inflammatory and angiogenic properties, proving to be effective in therapy of oral diseases in children.
• Further clinical research is needed to confirm the effectiveness of these products and dispel doubts about any side effects.