Osteoarthritis (Degenerative Joint Disease [DJD]), the most common form of arthritis, presents with varying degrees of severity, from mild, which may respond to exercise and/or non-steroidal anti-inflammatory drugs, to severe, with bone-to-bone (denuded hyaline cartilage) contact and subsequent deformity. While arthroplasty is effective, it is not appropriate for all stages of the disease, or for all patients.

New therapies are being investigated and used. One such therapy, recently approved by the US FDA, is the intra-articular injection of hyaluronic acid. Two physicians from the University of British Columbia, Vancouver, Canada, have reviewed the status of this form of treatment.

The FDA approval was granted for the therapy as a 'device'; its possible that the standards of proof of efficacy for devices at the time of the review of viscosupplementation were slightly lower than those usually required for approval of a drug. Because of this, the evidence to date for its efficacy is imperfect.

The healthy human knee contains about 2.0 ml of synovial fluid. In DJD of the knee, the concentration of hyaluronic acid in the knee is reduced to one-half to one-third of the normal value. Furthermore, the molecular size of the hyaluronic acid is reduced and there is decreased interaction between the molecules, with lower dynamic viscous and elastic properties, and reduced barrier and filter effects.

The loss of lubrication causes increased stress forces, which further disrupt the collagen network that is essential to the integrity of the articular surface, and also reduces the nutrient availability and waste removal from the articular cartilage.

Viscosupplementation using intra-articular hyaluronic acid injections may possibly benefit the knee by the following mechanisms shown in experimental studies: anti-inflammatory, anabolic, analgesic, and chondroprotective effects, along with improved viscosity and elasticity of synovial fluid.

In the USA, Synvasc is given in a dose of 8 mg/ml at weekly intervals for 3 weeks. Hyalgan is given at a dose of 10 mg/ml at weekly intervals for 5 weeks. In Canada, Orhtovisc is given at a dose of 15 mg/ml weekly, and Neovisc at 10 mg/ml weekly, both for 3 weeks. Sterile skin prep conditions are utilized for the injections.

There have been numerous uncontrolled trials and a limited number of controlled trials using intra-articular hyaluronic acid. The placebo-controlled, randomized trials have produced conflicting results. Various outcome measures were used, including visual analog scales for pain and function, activity level, Lequesne Index, MD Global Assessment, knee function, range of motion, and the Lysholm Scale.

The overall incidence of side effects (pain, warmth, minimal local swelling) is approximately 1% per injection, and they last no more than 2 days. Higher frequencies of side effects have been reported in some series (in one study up to 8.3% of 336 patients overall). No systemic adverse effects were reported in any series.

In the US, two viscosupplements were available at the time of the article's publication: Synvisc and Hyalgan. In Canada, Orthovisc and Neovisc were available.

Cost is a significant factor in the use of viscocupplementation - over US $500 per knee for the series of injections. These costs were not shared by Medicare payments.

The authors of this review conclude that, based on available information and costs, "widespread use of these agents should be limited until more convincing data on their efficacy are available from well-designed clinical trials". Such results should help place this form of treatment for a distressing condition in the proper context.