What Is Hyaluronic Acid and How Does It Work?

Hyaluronic acid is a naturally occurring glycosaminoglycan in synovial fluid, responsible for lubrication, shock absorption, and cartilage protection. In OA, the concentration and quality of HA degrade, resulting in increased joint friction and inflammation.

Intra-articular HA injections aim to restore synovial fluid properties, improve joint biomechanics, and reduce pain.

Evidence for HA Efficacy in OA

Several meta-analyses have evaluated HA’s role, particularly in knee OA:

• The Cochrane review by Bellamy et al. (2006) and updated systematic reviews (Rutjes et al., 2012) suggest that HA offers modest but clinically relevant pain relief, especially for mild-to-moderate OA.
• Higher molecular weight and cross-linked formulations appear more effective and may delay need for more invasive procedures (Altman et al., 2015).

However, the effect sizes are generally small, and guidelines vary. While the American College of Rheumatologyremains neutral, the AAOS (2013) does not currently recommend routine use, largely due to heterogeneity in study quality.

Hyaluronic Acid in New Zealand

In New Zealand, two HA products are commonly used:

• Durolane – a single-injection, high molecular weight, non-animal stabilized HA (NASHA)
• Synvisc/Synvisc-One – Hylan G-F 20, a cross-linked HA derivative administered in one to three injections

These products are not publicly funded, and patients typically pay out-of-pocket unless private insurance covers it (which is rare). This financial aspect can influence treatment decisions in clinical practice.

When Is HA a Preferred Option?

Despite the emergence of PRP, HA retains an important role, particularly in the following scenarios:

• Contraindication to PRP – Patients with active malignancy, blood disorders, or those on certain anticoagulants may not be suitable candidates for PRP. In such cases, HA remains a viable and safe option.
• Desire for short-term symptom relief – HA can be used in combination with low-dose corticosteroids for quicker onset of pain control, especially in acute exacerbations or for event-based goals (e.g., travel, family events).
• Early-stage OA (Kellgren-Lawrence Grade I–II) – HA may help delay structural progression and the need for surgical consultation.

How Does PRP Compare?

PRP, unlike HA, modulates the joint’s biology. It contains growth factors such as TGF-β, PDGF, VEGF, and IGF-1that promote chondrocyte activity, reduce inflammation, and enhance joint homeostasis.

Recent evidence favours PRP over HA in efficacy:

• A 2021 network meta-analysis (Kanchanatawan et al., 2021) found that PRP significantly improved pain and function scores compared to HA.
• Di Martino et al. (2019) followed patients over 5 years and showed sustained benefits of PRP over HA, particularly in early OA.

Synergistic Use: PRP + HA Combination Therapy

The idea of combining HA’s mechanical benefits with PRP’s biologic activity has gained traction:

• Dallari et al. (2016) demonstrated superior functional outcomes in patients receiving PRP + HA versus either alone.
• A 2021 meta-analysis (Shen et al.) showed that combination therapy offered significantly better results in VAS and WOMAC scores compared to HA or PRP monotherapy.
• Zhao et al. (2023) noted that the combination was especially effective in patients with moderate-to-severe OA(KL III).

Clinical Summary

Conclusion

While PRP is now considered the superior injectable for many OA patients, hyaluronic acid remains clinically relevant. Whether used as a safer alternative when PRP is contraindicated, or as part of a combination strategy, HA can contribute to personalised OA care. Clinicians should weigh patient goals, disease stage, comorbidities, and access when selecting therapy.

References

1. Bellamy, N., et al. (2006). Viscosupplementation for the treatment of osteoarthritis of the knee. Cochrane Database Syst Rev, (2), CD005321. https://doi.org/10.1002/14651858.CD005321.pub2
2. Rutjes, A. W., et al. (2012). Viscosupplementation for osteoarthritis of the knee: a systematic review and meta-analysis. Ann Intern Med, 157(3), 180–191. https://doi.org/10.7326/0003-4819-157-3-201208070-00473
3. Altman, R. D., et al. (2015). Hyaluronic acid injections for knee osteoarthritis: A meta-analysis. Cartilage, 6(4), 233–243. https://doi.org/10.1177/1947603515590192
4. Di Martino, A., et al. (2019). PRP vs HA for knee OA: 5-year results of an RCT. Am J Sports Med, 47(2), 347–354. https://doi.org/10.1177/0363546518814532
5. Meheux, C. J., et al. (2016). Efficacy of PRP injections in knee OA: a systematic review. Arthroscopy, 32(3), 495–505. https://doi.org/10.1016/j.arthro.2015.08.005
6. Kanchanatawan, W., et al. (2021). PRP vs HA in OA: network meta-analysis. Knee Surg Sports Traumatol Arthrosc, 29(7), 2205–2217. https://doi.org/10.1007/s00167-021-06551-w
7. Dallari, D., et al. (2016). Hyaluronic acid vs PRP with debridement for knee OA: RCT. J Bone Joint Surg Am, 98(6), 477–485. https://doi.org/10.2106/JBJS.O.00369
8. Shen, L., et al. (2021). Combination of PRP and HA for knee OA: meta-analysis of RCTs. Int Orthop, 45(3), 627–638. https://doi.org/10.1007/s00264-020-04854-1
9. Zhao, K., et al. (2023). Combination PRP and HA therapy in moderate OA. J Orthop Res, 41(1), 203–210. https://doi.org/10.1002/jor.25377