Intra-articular hyaluronic acid (viscosupplementation) for osteoarthritis: is it effective?

SUMMARY

Viscosupplementation with intra-articular hyaluronic acid derivatives and cross-linked polymers of hyaluronic acid is increasingly used to treat symptomatic osteoarthritis in the knee, hip and other joints.

Most guidelines conditionally recommend against its use to treat knee osteoarthritis, and strongly or conditionally recommend against its use for other joints, indicating a large evidence-to-practice gap.

Conclusive evidence from randomised placebo-controlled trials indicates that intra-articular hyaluronic acid provides no important benefits for people with knee (and other joints) osteoarthritis, and may have potentially serious harms including septic arthritis and severe inflammatory joint and cutaneous reactions.

Use of computed tomography scans to guide hyaluronic acid injection exposes the patient to unnecessary radiation and has an unwarranted financial and environmental cost.

When the topic arises in clinical practice, prescribers should use a shared decision-making approach that includes an explanation as to why hyaluronic acid injection is not recommended care for osteoarthritis and offer alternatives, taking into consideration the patient's values and preferences.

 

Introduction

Osteoarthritis is a chronic degenerative disease involving structural changes to the whole joint, with the knee, hip and hand joints being most affected.^1,2 It is the most common form of arthritis among adults worldwide.³ Osteoarthritis contributes to a high non-fatal disease burden and disability, and impacts on work participation and productivity.⁴

First-line management for symptomatic osteoarthritis includes provision of education about the condition; support for self-management; advice about physical activity and exercise; and weight management if appropriate. If needed, topical or oral analgesia and intra-articular corticosteroid injections may be used as adjuncts to reduce pain and enable usual activities.

Viscosupplementation, with intra-articular hyaluronic acid (HA) derivatives and cross-linked polymers of HA (hylans), is a treatment that is commonly used for symptomatic osteoarthritis in Australia, despite evidence for its lack of efficacy and recommendations against its use from various professional societies and organisations. While Australian usage data are unavailable, a US study reported that 1.09 million Medicare beneficiaries received HA for knee osteoarthritis in 2012, increasing to 1.29 million in 2018 at a cost of more than US$300 million annually, despite the 2013 American Academy of Orthopaedic Surgeons guidelines recommending against its use.⁵

In this review we explore the theoretical rationale behind the use of intra-articular HA for osteoarthritis, and provide a summary of Australian and international guidelines on its use and the evidence on its benefits and harms. We also briefly explore the evidence of benefits and harms behind other intra-articular interventions for osteoarthritis.

 

What is hyaluronic acid?

Hyaluronic acid is a nonimmunogenic glycosaminoglycan, prepared from avian-derived products such as rooster combs or non-animal sources such as bacterial fermentation. It is composed of repeating units of D-glucuronic acid and N-acetyl-D-glucosamine disaccharide.^6,7 N-acetyl-D-glucosamine is a component found in tissues, including the synovium, responsible for its viscoelastic and lubricant properties, and therefore HA is a substance that theoretically mimics the component in synovial joints.^6,7

The clinical use of viscosupplementation with HA was first trialled in the early 1970s, soon after the therapeutic effects of replenishing the viscoelasticity of the synovial hyaluronan in animal models were discovered.^8-10 It is postulated that physiologically restoring the synovial hyaluronan in arthritis results in short-term analgesic effects, and, over time, the metabolic and biomechanical properties of the joint can be restored, promoting joint healing and increasing mobility.^7,9

In Australia, HA derivatives are classed as medical devices under the Therapeutic Goods (Medical Devices) Regulations 2002. Hylan G-F 20 was the first viscosupplementation product included on the Australian Register of Therapeutic Goods in 1998. An application for Medicare Benefits Schedule (MBS) subsidy for knee osteoarthritis in 2003 was not supported,¹¹ while an application for Pharmaceutical Benefits Scheme (PBS) subsidy in 2006 was also rejected.¹²

 

Clinical use of hyaluronic acid in osteoarthritis (viscosupplementation)

Some imaging services offer image-guided (ultrasound or computed tomography [CT]) intra-articular injection of HA derivatives for symptomatic osteoarthritis of small and large synovial joints, with minimal to no out-of-pocket cost to patients. The MBS specifically precludes a benefit for consultation associated with injection of these products, while the cost of image guidance, if not borne by the patient, will be charged to Medicare.

Image guidance is not necessary for intra-articular HA injections into the knee, the most injected site, but is needed for the hip. Compared with no image guidance or ultrasound guidance, CT-guided injections are more costly, they expose the patient to unnecessary radiation, and they have a much larger carbon footprint;¹³ these costs rise with multiple injections.

Despite the increasing popularity of intra-articular HA in Australia, the Osteoarthritis of the Knee Clinical Care Standard, published by the Australian Commission on Safety and Quality in Health Care and endorsed by multiple professional organisations including the Australian Rheumatology Association, Australian Orthopaedic Association, Australian Society of Medical Imaging and Radiation Therapy, and Australasian College of Sport and Exercise Physicians, recommends against offering this treatment for knee osteoarthritis.¹⁴

Products available in Australia

There is a wide range of HA derivatives available in Australia, with different formulations and molecular weights (Table 1).¹⁵ The molecular weight of HA derivatives is regarded as the key factor in determining the frequency of injections and the interval between injections.⁹ Some products require 3 injections at weekly or fortnightly intervals, while others require only a single injection per course of treatment. Treatment courses can be repeated up to twice a year.

Table 1 Therapeutic Goods Administration–approved (Medical Device Class III) intra-articular hyaluronic acid derivative products

Product name	Compound	Intended joint(s)
Adant	Sodium hyaluronate	Knee
ArtiBest	Sodium hyaluronate	Knee
Cingal	Cross-linked hyaluronic acid with triamcinolone hexacetonide (corticosteroid)	Knee
Durolane	Sodium hyaluronate	Knee, hip, ankle, shoulder, elbow, wrist, fingers, toes
Durolane SJ	Sodium hyaluronate	Ankle, elbow, wrist, fingers, toes
Euflexxa	Sodium hyaluronate	Knee or other synovial joints
Monovisc	Cross-linked sodium hyaluronate	Knee, hip, shoulder, ankle
Synvisc	Hylan polysaccharide	Knee
Synvisc-One (hylan G-F 20)	Hylan polysaccharide	Knee
Source: Australian Register of Therapeutic Goods entries for Medical Device Class III: Synovial fluid supplementation substances containing hyaluronic acid and derivatives (as of 21 November 2025)15

Current guideline recommendations for intra-articular hyaluronic acid use in osteoarthritis

Most guidelines recommend against the use of intra-articular HA. In Australia, the 2018 Royal Australian College of General Practitioners' Guideline for the Management of Knee and Hip Osteoarthritis makes a conditional recommendation against intra-articular HA for knee osteoarthritis and a strong recommendation against it for hip osteoarthritis.¹⁶ Internationally, there are conditional recommendations both for and against use of intra-articular HA for knee osteoarthritis, while recommendations for other synovial joints are either strongly or conditionally against its use (Table 2).^16-27

Table 2 National and international guideline recommendations for intra-articular hyaluronic acid in osteoarthritis [NB1]

Guideline	Year	Recommendation(s) for intra-articular hyaluronic acid for osteoarthritis in synovial joints
		Knee	Hip	Other joints
Australian guidelines
Therapeutic Guidelines: Rheumatology17	2024	No specific recommendation but noted that evidence indicates it is not more effective than placebo and is associated with harms	-	Not more effective than placebo for carpometacarpal osteoarthritis, including thumb-based carpometacarpal osteoarthritis
The Royal Australian College of General Practitioners (RACGP)16	2018	Conditional recommendation against use	Strong recommendation against use	-
International guidelines
National Institute for Health and Care Excellence (NICE)18	2022	Not recommended ("Do not offer intra-articular hyaluronan injections to manage osteoarthritis." Rationale: "... no evidence of improved quality of life or physical function, or reduced pain, in people with knee or hip osteoarthritis")	Not recommended (same as knee; additionally, "evidence showed potential harm for hip osteoarthritis")	Not recommended ("Limited evidence for other osteoarthritis-affected joints, showing inconsistent benefits and some potential harms")
American Academy of Orthopaedic Surgeons (AAOS)19,20	2021 (knee), 2023 (hip)	Conditional recommendation against use	Strong recommendation against use	-
European Alliance of Associations for Rheumatology (EULAR)21,22	2021	"hyaluronic acid ... is probably effective in knee osteoarthritis, but the effect is relatively small, suitable patients are not well defined, and pharmacoeconomic aspects of treatment are not well established"	-	-
American College of Rheumatology/Arthritis Foundation23	2020	Conditional recommendation against use	Strong recommendation against use	Conditional recommendation against use in patients with first carpometacarpal joint osteoarthritis
US Department of Veterans Affairs/US Department of Defence24	2020	Conditional recommendation for use in patients with persistent pain inadequately relieved by other interventions	Conditional recommendation against use	-
European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO)25	2019	Conditional recommendation for use in patients who either have contraindications to NSAIDs or who remain symptomatic despite NSAIDs	-	-
Osteoarthritis Research Society International (OARSI)26	2019	Conditional recommendation for use	-	-
NSAIDs = nonsteroidal anti-inflammatory drugs NB1: Strong or conditional recommendations for or against use were made according to the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria27 where available, with additional information provided where the recommendation was restricted. Where no GRADE recommendation was made, the recommendation is reproduced verbatim to minimise misinterpretation of the intention of guideline authors. The National Institute for Health and Care Excellence (NICE) did not qualify their recommendation.

 

Evidence for efficacy and safety of hyaluronic acid in osteoarthritis

An enormous body of research of variable quality has evaluated the benefits and harms of intra-articular HA for osteoarthritis over the last 50 years, including more than 160 randomised controlled trials and numerous systematic reviews.^28-36 Nearly all evaluations were performed in people with osteoarthritis of the knee, with a smaller number in people with osteoarthritis of the hip,^37-39 carpometacarpal joint of the thumb⁴⁰ and first metatarsophalangeal joint.⁴¹

Benefits

The most up-to-date systematic review of intra-articular HA for knee osteoarthritis included 169 trials involving 21,163 participants.³⁴ Like previous reviews,^28,31,35 it found evidence of small-study effects (i.e. where smaller studies tend to show larger effect sizes than larger studies) and no published results for many adequately powered and completed large industry-funded trials, suggesting publication bias. In the pre-specified main analysis, restricted to placebo-controlled trials with at least 100 participants per group (24 trials, 8702 participants), there was conclusive evidence that HA is associated with a clinically irrelevant reduction in pain intensity compared with placebo of 2.0 mm (95% confidence interval [CI] 0.5 to 3.8 mm reduction) on a 100 mm visual analogue scale at 3 months. There was also a small clinically irrelevant improvement in function of 1.2 points (95% CI 0.6 to 2.0 points) on the 0 to 68 WOMAC function scale at 3 months (19 trials, 6108 participants). These effects were not influenced by HA structure or molecular weight.

Based on trial sequential analysis, which adds data to the pooled analysis in chronological order of publication, conclusive evidence of a lack of benefit from HA existed in 2009 and subsequent controlled trials did not alter this conclusion, highlighting research waste from continued trials.³⁴

Systematic reviews evaluating intra-articular HA in hip and thumb osteoarthritis have also found that it provides no added benefit over placebo for pain.^37,40

Harms

Pereira and colleagues reported that, based on 15 large placebo-controlled trials (6462 randomised participants with knee osteoarthritis), intra-articular HA was associated with an increased risk of serious adverse events compared with placebo (3.7% versus 2.5%; relative risk 1.49, 95% CI 1.12 to 1.98).³⁴ However, 11 of the 15 trials reported that none of the serious adverse events were treatment-related so the clinical relevance of this finding is unclear.

Adverse events that have been reported include septic arthritis, severe inflammatory reactions (mimicking septic arthritis), and severe cutaneous reactions including cellulitis, acute allergic reactions and erythema multiforme, sometimes requiring systemic or intra-articular corticosteroids, antibiotics, or both.^42-44 Common non-serious local reactions include injection-site discomfort, arthralgia and joint swelling which abate without treatment in 1 to 2 days. While HA products for intra-articular injection are registered as medical devices rather than drugs, reporting adverse events to the Therapeutic Goods Administration remains important.

Taken together, the data on efficacy and harms do not support use of HA for knee osteoarthritis, and these data are likely generalisable to its use in other joints. Low-value HA injections pose an unnecessary financial and opportunity cost to the healthcare system and unnecessary environmental cost.

How should the evidence be conveyed to patients?

Clinicians frequently receive requests from patients for intra-articular HA, often influenced by marketing. Using a shared decision-making approach, prescribers should acknowledge the patient's symptoms, along with their values and preferences, and provide an explanation as to why HA is not recommended care. In the authors' experience, most patients will then opt not to have the treatment, and other options can be discussed. Development of a decision aid to assist prescribers in these conversations would be worthwhile.

 

Other intra-articular interventions for osteoarthritis

Intra-articular platelet-rich plasma (PRP) therapy is increasingly used to treat symptomatic osteoarthritis despite evidence against its use. It is not subsidised by Medicare or the PBS. A recent Australian randomised placebo-controlled trial that included 288 participants with mild to moderate knee osteoarthritis found no clinically important benefit in symptoms or joint structure at 12 months.⁴⁵ Adverse effects were minor and transient, although more participants in the PRP group reported knee pain, swelling and stiffness after injection. A Cochrane review assessing the benefits and harms of PRP for knee osteoarthritis is underway.⁴⁶

Intra-articular stem cell therapy is another (very expensive) treatment promoted to people with osteoarthritis. A recent Cochrane review, which included 25 trials with 1341 randomised participants with knee osteoarthritis, found low-certainty evidence that stem cell therapies may provide slight improvement in pain and function, while its effects on joint structure and safety are uncertain.⁴⁷

Intra-articular corticosteroid injections are commonly used to treat symptomatic osteoarthritis. They are of proven efficacy for short-term pain relief and improvement in function (2 to 6 weeks on average).¹⁷ A 2015 Cochrane review found low-certainty evidence of small to moderate benefit for people with knee osteoarthritis (27 trials, 1767 participants).⁴⁸ More recent high-quality randomised placebo-controlled trials have confirmed these benefits.^49,50 There is also consistent evidence of benefit at other sites such as the hip.⁵¹ A recent cohort study including 163,241 knee, hand, hip and shoulder osteoarthritis patients found that intra-articular corticosteroid injections may also reduce subsequent pain medication use.⁵² Steroid-related systemic adverse effects (e.g. hyperglycaemia, flushing, impaired sleep) and local adverse effects (e.g. self-limited nonspecific musculoskeletal symptoms, skin hypopigmentation or atrophy) may occur if the corticosteroid is inadvertently injected into the subcutaneous tissue.¹⁷ Septic arthritis is a rare but potentially serious adverse event. Intra-articular corticosteroids, particularly repeated injections, have also been associated with accelerated osteoarthritis progression in both the knee⁵³ and hip,^54,55 but causation remains unproven.⁵³

 

Conclusion

There is conclusive evidence that HA provides no benefit for people with osteoarthritis of the knee (and other joints), and there are potential harms. This evidence underpins Australia's Osteoarthritis of the Knee Clinical Care Standard recommendation not to offer HA to people with knee osteoarthritis.

This article was finalised on 4 December 2025.

Conflicts of interest: Huai Leng Pisaniello and Shyan Goh declared no conflicts of interest. Rachelle Buchbinder is a member of the expert group for Therapeutic Guidelines: Rheumatology, and Chair of the Australia and New Zealand Musculoskeletal Clinical Trials Network (ANZMUSC)–Australian Rheumatology Association (ARA) Australian Living Guideline for the Pharmacological Management of Inflammatory Arthritis. Rachelle was awarded National Health and Medical Research Council (NHMRC) grants for 'Better evidence more rapidly implemented to optimise health for people with musculoskeletal conditions' (2021 to 2025), 'Wiser healthcare: better value care for all Australians' (2022 to 2026), and 'Better outcomes in inflammatory arthritis' (2022 to 2026). She received funding from the NHMRC for the Cochrane Musculoskeletal Australian Editorial Base (2020 to 2025).

This article is peer reviewed.

 

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