Role of Hyaluronic Acid Injection in Knee Osteoarthritis
Hyaluronic acid injections are conditionally recommended against for knee osteoarthritis, as high-quality trials with low risk of bias show the effect size approaches zero compared to saline injections. 1
Evidence Quality and Efficacy
The 2019 American College of Rheumatology/Arthritis Foundation guidelines provide the most definitive stance on this intervention. When meta-analyses are restricted to trials with low risk of bias, hyaluronic acid injections demonstrate essentially no benefit over placebo saline injections. 1 Earlier systematic reviews that appeared to show benefit failed to account for the high risk of bias in individual studies—when only rigorous trials are considered, the apparent benefits disappear. 1
The 2022 AAOS guidelines further support this position, noting a number needed to treat of 17 patients, which reflects minimal clinical impact. 2
Clinical Context for Use
Despite the conditional recommendation against use, there is a narrow clinical scenario where hyaluronic acid may be considered:
After failure of all other conservative measures: The injection may be used only when patients have inadequate response to nonpharmacologic therapies (exercise, weight loss, physical therapy), topical NSAIDs, oral NSAIDs, and intraarticular corticosteroids. 1
Shared decision-making is essential: Patients must understand the limited evidence of benefit before proceeding. 1
Contraindications to other therapies: The ESCEO guidelines suggest consideration in patients with contraindications to NSAIDs who remain symptomatic. 1
Treatment Algorithm Position
Hyaluronic acid sits very late in the treatment hierarchy:
First-line treatments (must be attempted first):
- Land-based aerobic and resistance exercise 3
- Weight loss for overweight patients 3
- Physical therapy 3
- Topical NSAIDs (particularly for patients ≥75 years) 3
- Oral NSAIDs 3
Second-line treatments (before considering hyaluronic acid):
Last resort before surgery:
- Hyaluronic acid may be considered only after all above options have failed 1
Safety Profile
The treatment carries potential harm that contributed to the recommendation against its use. 1 Documented adverse events include:
- Local pain and swelling (most common) 4, 5
- Joint swelling and arthralgia 6
- Rare but serious: septic arthritis has been reported 7
Common Pitfalls to Avoid
Do not use hyaluronic acid in patients with:
- Complete collapse of joint space or significant bone loss—these patients show poor clinical response 7
- Hip osteoarthritis—this is a strong recommendation against (not conditional), as higher quality evidence shows lack of benefit 1
Do not delay surgical referral: Approximately 28% of patients treated with hyaluronic acid required surgery within 7 months, suggesting inadequate response. 7 Patients with severe bilateral knee pain, significant functional limitations, and failed conservative treatments should be referred for surgical evaluation rather than pursuing hyaluronic acid injections. 2
The conditional recommendation against is not intended to influence insurance coverage decisions, but clinicians should recognize that the evidence base does not support routine use. 1