What is the role of hyaluronic acid (HA) injections in the treatment of osteoarthritis (OA)?

Role of Hyaluronic Acid Injections in Osteoarthritis Treatment

Hyaluronic acid (HA) injections are not recommended as a primary treatment for osteoarthritis due to limited evidence of benefit and are conditionally recommended against in knee and first carpometacarpal joint OA, and strongly recommended against in hip OA. 1, 2

Current Guideline Recommendations

• The American College of Rheumatology/Arthritis Foundation conditionally recommends against intra-articular hyaluronic acid injections for knee and first carpometacarpal joint OA 1
• For hip OA, HA injections are strongly recommended against due to higher quality evidence showing lack of benefit 1
• The American Academy of Orthopaedic Surgeons recommends against the routine use of hyaluronic acid in patients with knee osteoarthritis due to inconsistent evidence of benefit 1

Evidence Analysis

• Meta-analyses of low-risk-of-bias trials show that the effect size of HA injections compared to saline injections approaches zero 1
• When limiting analysis to high-quality studies, benefits of HA injections are not consistently supported by evidence 1, 2
• The apparent benefits seen in some studies may be restricted to those with higher risk of bias 1
• Some real-life studies suggest potential benefits including:
  • Pain reduction and functional improvement lasting up to 6 months 3, 4
  • Possible reduction in concomitant analgesic use 3
  • Potential delay in need for total knee replacement 3

Potential Mechanisms of Action

• Mechanical viscosupplementation of the joint (providing lubrication and shock absorption) 3
• Re-establishment of joint homeostasis through induction of endogenous HA production 3

Safety Profile

• HA injections are generally considered safe with mostly minor adverse events 5, 3
• Most common side effects include local pain and swelling at the injection site 4
• Higher molecular weight cross-linked HAs may have slightly higher rates of local reactions and post-injection non-septic arthritis 3

Clinical Decision Making

• HA injections may be considered in specific clinical scenarios:
  • When patients have had inadequate response to first-line treatments (non-pharmacologic therapies, topical and oral NSAIDs, intra-articular steroids) 1, 2
  • In knee OA patients who have exhausted other treatment options 1
  • As part of shared decision-making that acknowledges the limited evidence of benefit 1

Treatment Sequence in OA Management

1. First-line: Non-pharmacologic therapies, topical and oral NSAIDs 2
2. Second-line: Intra-articular corticosteroids 2
3. Consider HA only after failure of above treatments 2

Important Caveats

• The conditional recommendation against HA is not intended to influence insurance coverage decisions 1
• Different HA products may have varying clinical effects, though this requires further investigation 3
• The number needed to treat with HA is approximately 17 patients, suggesting some patients may benefit, but current evidence cannot identify which subset of patients 1

Comparison with Other Intra-articular Therapies

• Corticosteroid injections have more substantial evidence supporting their use, though benefits typically last only about 3 months 1
• Platelet-rich plasma, stem cell injections, tumor necrosis factor inhibitors, and interleukin-1 receptor antagonists are also not recommended for routine use in OA 1