Hyaluronic acid and joints

by Nathan Wei, MD, FACP, FACR

Nathan Wei is a nationally known board-certified rheumatologist and author of the Second Opinion Arthritis Treatment Kit. It's available exclusively at this website... not available in stores.

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From Sanofi and Genzyme

Hyaluronic acid is a component of connective tissue.

Its function is act as a cushion and lubricant. Hyaluronan is present throughout the body Hyaluronic acid abnormalities have been seen in patients with connective tissue disorders such as mitral valve prolapse, TMJ syndrome,and osteoarthritis.

THe initial description of hyaluronic acid came from work done by Palmer and Meyer in 1934. The two investigators isolated a novel polysaccharide from the vitreous of bovine eyes. It was named “Hyaluronic Acid” due to the composition of the compound, one molecule being uronic acid, and the fact that the substance derived from hyaloid (vitreous).

The terms "Hyaluronic Acid", "Hyaluronan", and "Sodium Hyaluronate" are used inter-changeably throughout the related literature.

Hyaluronan was first marketed for human use in the early 1980s using HA derived from animal sources (rooster comb), Healon was introduced as a viscous, injectable gel for use during ophthalmic surgery. Subsequently HA has been used in many other indications, especially joint disorders.

HA can be found in a number of body tissues including skin, the ocular vitreous body, articular cartilage and synovial fluid (where it acts as a lubricant and shock absorber).

Functions of HA:

• Protecting the cartilage

o Viscous properties - Under sheer stress (surface gliding against surface), the HA molecules in the synovial fluid act as a lubricant, protecting joint surfaces from mechanical damage.

o Elastic properties - Under load bearing stress the HA in synovial fluid acts as a shock absorber, protecting the cartilage from compressive trauma.

• Cartilage Nutrition

o Small molecules such as water, electrolytes, and nutrients can diffuse to cartilage and synovium freely.

o Larger molecules such as proteins and other inflammatory mediators encounter a higher degree of difficulty in passing through the network.

• Protecting the synovium

o HA provides a protective barrier to the synovium as well as masking pain receptors.

Osteoarthritis is associated with the following characteristics:

• Inadequate lubrication due to low hyaluronic acid levels

• Painful movements due to an increased level of inflammatory substances called prostaglandins

• Reduced cartilage thickness in joint load bearing surfaces

Viscosupplementation is a treatment designed to:

• Improve the viscosity of the synovial (lubricating) fluid.

• Reduce pain and swelling within the joint.

• Increase the articular cartilage thickness (possibly) on load bearing surfaces.

Viscosupplementation can be achieved by injecting hyaluronic acid into the affected joint.

Injecting hyaluronic acid into an osteoarthritic joint has been shown to:

• Increase synovial fluid levels of hyaluronic acid improving it's viscosity

• Decrease levels of prostaglandins, improving pain

• Possibly increase the cartilage thickness on load bearing surfaces

Patient Selection

Viscosupplementation should be considered for patients with mild to moderate osteoarthritis where there has been a poor response to the following conservative treatment:

• Oral analgesia and anti-inflammatory drugs

• Topical anti-inflammatory preparations

• Physical Therapy

• Joint aspiration and intra-articular steroid injection.

Viscosupplementation does not appear to have significant beneficial effects in those patients with advanced destructive osteoarthritis.

There is clinical experience in treating other large joints (hip, shoulder, ankle).


Infection local to the injection site - to avoid taking bacteria into the joint at the time of injection.

Systemic infection with a fever - to avoid blood-borne spread of bacteria to the joint.

Allergy to birds, feathers and eggs.

Caution should be exercised in those with known coagulation defects and warfarin therapy (blood thinner) - to reduce the risk of bleeding into the joint space after injection.

There are a variety of viscosupplements. They include Hyalgan, Synvisc, Supartz, and Orthovisc.

Hyaluronic acid preparations may be injected into any synovial joint.

It’s best to inject using ultrasound or fluoroscopic guidance. This is because correct placement of the hyaluronic acid can be ascertained. If the substance is not placed inside the joint, no beneficial effect will be seen.

Knee Injection Technique

There are several ways in which the knee joint can be injected. Every physician has a favorite approach in which they were trained. The key thing is experience. Look for an experienced rheumatologist or orthopedist who uses either ultrasound or fluoroscopic guidance.

Immediate effects

Hyaluronic acid does not have an immediate pain-relieving effect

You may notice a local reaction, such as pain, warmth, and slight swelling immediately after the treatment. These symptoms generally do not last long. They appear to be more common with Synvisc than with the other viscosupplements. Applying an ice pack may help to ease the pain

For the first 48 hours after the injection, you should avoid excessive weight bearing on the leg, such as standing for long periods, jogging or heavy lifting.

Longer-term effects Over the course of the injections, you may notice that you have less pain in your knee. Most patients notice this from the 3rd treatment onwards.

Hyaluronic acid does seem to have anti-inflammatory and pain-relieving properties. The injections may also stimulate the body to produce more of its own hyaluronic acid.

Effects may last for several months.

Viscosupplementation doesn’t work for everyone. There’s no proof that it will reverse or delay the progress of osteoarthritis. In addition, it’s very expensive and clinical trials have not yet proven that it is cost-effective.

If your current course of medication and treatment is working, stay with it. However, if your arthritis isn’t responding well, or if you’re trying to delay an inevitable surgery, you may wish to discuss this option with an orthopaedic surgeon or rheumatologist.

J Biomed Mater Res. 1994 Aug;28(8):865-70.

The effect of additive hyaluronic acid on animal joints with experimentally reduced lubricating ability.

Mabuchi K, Tsukamoto Y, Obara T, Yamaguchi T.

Department of Biomedical Engineering, School of Medicine, Kitasato University, Kanagawa, Japan.

A series of in vitro experiments demonstrated a clear effect of additive hyaluronic acid (HA) on animal joints with experimentally reduced lubricating ability. Eleven canine hip joints were utilized and the experimental conditions tested were: i) intact joints, ii) after washing the joint surfaces, and iii) after adding 1% HA to them. The frictional coefficient of every joint increased after washing and subsequently decreased after adding HA. The mean values were 0.007 (SD 0.004) on the intact joints, 0.020 (SD 0.009) after washing, and 0.013 (SD 0.005) after the addition of HA. The differences between the three values of frictional coefficients were shown to be statistically significant (p < 0.01).

Rheumatology (Oxford). 1999 Jul;38(7):602-7.

Hyaluronic acid in the treatment of osteoarthritis of the knee.

Huskisson EC, Donnelly S.

Department of Rheumatology, St Bartholomew's Hospital, West Smithfield, London, UK.

OBJECTIVES: We examined the efficacy, safety and patient satisfaction of intra-articular hyaluronic acid (HA) in patients with osteoarthritis of the knee. METHODS: One hundred patients with mild to moderate osteoarthritis of the knee entered a randomized blind-observer trial of 6 months HA vs placebo. Primary efficacy criteria were pain on walking, measured with a visual analogue scale, and the Lequesne Index. RESULTS: For pain on walking, a significant difference in favour of HA was found for completed patients at week 5, the end of the course of injections, and at month 6, the end of the study (P = 0.0087 and P = 0.0049, respectively). Further analysis using the Last Observation Carried Forward (LOCF) also showed a significant benefit favouring HA at month 6 (P = 0.0010). For the Lequesne Index, a significant difference in favour of HA was found at week 5 (P = 0.030) and at month 2 (P = 0.0431), but this was only of borderline significance at month 4 (P = 0.0528). Patients' global assessment of efficacy favoured HA at month 6 (P = 0.012). Improvement in other secondary criteria was generally superior in the HA group compared to placebo both at week 5 and month 6. Adverse events, mainly local injection site reactions, occurred in both groups with equal frequency. CONCLUSIONS: The study demonstrated that five weekly intra-articular injections of sodium hyaluronate (Hyalgan) were superior to placebo and well tolerated in patients with osteoarthritis of the knee with a symptomatic benefit which persisted for 6 months.

Intra-articular Hyaluronic Acid Treatment for Golfer's Toe Keeping Older Golfers on Course

Robert J. Petrella, MD, PhD; Anthony Cogliano, MD


BACKGROUND: Osteoarthritis of the great toe can lead to a progressive decrease in range of motion (ROM) and pain at the first metatarsophalangeal (MTP) joint. This condition, observed in older golfers, results in reduced participation and enjoyment of this popular activity.

OBJECTIVE: To assess the efficacy, safety, and patient satisfaction with a series of intra-articular injections of hyaluronic acid (HA) into the first MTP joint in older patients who reported osteoarthritis-associated pain, loss of MTP joint ROM, and disability that interfered with golf participation.

METHODS: Forty-seven consecutive male golfers met the inclusion criteria and were given a weekly intra-articular HA injection for 8 weeks. Baseline measures of MTP joint ROM, pain at rest and immediately after tiptoe walking for 10 m, and global patient satisfaction (GPS) were compared with measures at 9 and 16 weeks and at presentation for a second injection series.

RESULTS: Adverse events (only local injection site pain was noted) were <0.01%. At 9 weeks, significant improvement in pain at rest, pain after tiptoe walking, ROM, and GPS were observed. These changes were maintained for all measures at 16 weeks. At presentation for the second series, GPS was significantly higher than at baseline and at 16 weeks. Pain at rest, tiptoe walking pain, and ROM were significantly improved from baseline, but tiptoe-walking pain was significantly reduced at 16 weeks.

CONCLUSION: Intra-articular HA injection significantly improved pain tolerance at rest and with activity. Patient acceptance of the treatment was high, with very few adverse events in golfers who had osteoarthritis of the first MTP joint.

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