What are the recommendations for using hyaluronic acid (HA) joint injections in an older adult patient with a history of osteoarthritis (OA), significant joint pain and stiffness, who has not responded to conservative treatments such as physical therapy, nonsteroidal anti-inflammatory drugs (NSAIDs), or acetaminophen?

Hyaluronic Acid Injections for Knee Osteoarthritis: Not Recommended as First-Line Therapy

Hyaluronic acid (HA) injections should not be used for this patient until after failure of intra-articular corticosteroid injections, which are the evidence-based choice for intra-articular therapy in knee OA. 1, 2

Current Guideline Recommendations

The most recent 2019 American College of Rheumatology/Arthritis Foundation guidelines provide a conditional recommendation against HA injections for knee OA, based on high-quality, low-bias trials showing effect sizes approaching zero compared to saline placebo. 1, 2 This represents a significant shift from the 2012 ACR guidelines, which made no recommendation either way. 1

• When analysis is restricted to only high-quality trials with low risk of bias, the treatment effect of HA essentially disappears—the benefit approaches zero compared to saline injections. 2, 3
• Studies showing benefit were those with higher risk of bias, while rigorous studies failed to demonstrate efficacy, suggesting positive results reflected placebo effects or methodological weaknesses rather than true therapeutic benefit. 2, 3
• The American Academy of Orthopaedic Surgeons recommends against routine use of HA due to inconsistent evidence, noting a number-needed-to-treat of 17 patients. 2

Evidence-Based Treatment Algorithm for This Patient

Step 1: Verify Core Treatments Have Been Optimized

Before considering any intra-articular injection, ensure the patient has received:

• Weight loss counseling if overweight (strongly recommended). 1
• Land-based cardiovascular and/or resistance exercise (strongly recommended). 1
• Topical NSAIDs as first-line pharmacologic therapy, especially given the patient's age (strongly recommended for patients ≥75 years over oral NSAIDs). 1
• Oral NSAIDs at lowest effective dose if topical NSAIDs insufficient. 1

Step 2: Intra-Articular Corticosteroid Injection First

If injection therapy is warranted, corticosteroid injections are strongly recommended over HA injections. 1, 2

• Corticosteroids are supported by 19 high-quality and 6 moderate-quality studies, providing effective short-term benefit typically lasting 3 months. 2
• They provide immediate symptom relief within 7 days with an effect size of 1.27. 2
• They require only a single injection versus 3-5 weekly injections for HA, making them more practical. 2
• Head-to-head comparisons show the evidence for efficacy of glucocorticoid injections is of considerably higher quality than that for HA. 1

Step 3: Consider HA Only After Corticosteroid Failure

HA injections may be considered only when the patient has failed:

• Non-pharmacologic therapies (exercise, weight loss). 2, 4
• Topical and oral NSAIDs. 2, 4
• Intra-articular corticosteroid injections. 2, 4

This requires shared decision-making acknowledging the limited evidence of benefit. 2, 4

Patient Selection Factors If HA Is Considered

If proceeding with HA after corticosteroid failure, the following factors favor better outcomes:

• Mild-to-moderate disease severity (Kellgren-Lawrence grade 1-2); severe disease shows worse response. 2, 5
• Absence of complete joint space collapse or bone loss; patients with these findings have poor clinical response. 5
• Age over 60 years with significant functional impairment. 2
• No acute effusion; corticosteroids show particular efficacy in acute flares with effusion. 2

Critical Caveats and Common Pitfalls

Avoid in Severe Disease

Do not use HA in patients with complete collapse of joint space or significant bone loss, as they demonstrate poor clinical response. 5 In one study, 28% of patients underwent surgery within 7 months of HA injection, suggesting inadequate response. 5

Slower Onset, Multiple Injections Required

• HA requires 3-5 weekly injections with delayed onset of action, whereas corticosteroids provide relief within days with a single injection. 2, 6
• Cost-effectiveness is a concern, as HA requires multiple injections with significant cost. 2

Safety Considerations

• While generally safe, adverse reactions occur in approximately 15% of patients, including local pain and swelling. 5
• Rare but serious complications include septic arthritis. 5
• One case report documents granulomatous osteitis of the proximal tibial epiphysis following HA injection. 7

Duration of Effect

• HA may provide relief for several months (up to 6 months), but with delayed onset. 2, 6
• Observational data shows no sustained symptom relief over 2 years for either HA or corticosteroid injections. 2
• Corticosteroids are effective for weeks to 3 months. 2

Alternative Pharmacologic Options

If corticosteroids are contraindicated or ineffective, consider:

• Duloxetine (conditionally recommended), which has efficacy alone or in combination with NSAIDs. 1
• Tramadol (conditionally recommended) for patients with contraindications to NSAIDs. 1

Bottom Line for This Patient

This patient should receive an intra-articular corticosteroid injection rather than HA. 1, 2 The 2019 ACR/AF guidelines explicitly state that intra-articular glucocorticoid injection is conditionally recommended over other forms of intra-articular injection, including HA preparations. 1 Only if corticosteroids fail or are contraindicated should HA be discussed, and even then, the patient must understand that high-quality evidence shows minimal benefit beyond placebo. 2, 3