Teaching Topic from the New England Journal of Medicine
March 12, 2015
Recent estimates suggest that knee osteoarthritis affects approximately 250 million people worldwide. Typically, knee pain limits activity and impairs quality of life. The risk of mobility disability (defined as the need for help with walking or climbing stairs) attributable to knee osteoarthritis alone is greater than that associated with any other medical condition in people 65 years of age or older.
What is the rationale for treating osteoarthritis of the knee with intraarticular injections of hyaluronic acid (viscosupplementation)?
Hyaluronate is a naturally occurring component of the cartilage and the synovial fluid. Within the normal adult knee, there is approximately 2 ml of synovial fluid, with a hyaluronate concentration of 2.5 to 4.0 mg per milliliter. Hyaluronate is responsible for the rheologic properties of synovial fluid, enabling it to act as a lubricant or shock absorber, depending on the forces exerted on it. In osteoarthritis, synovial hyaluronate is depolymerized and cleared at higher rates than normal. These changes reduce the viscoelasticity of the synovial fluid. The therapeutic goal of administration of intraarticular hyaluronate is to provide and maintain intraarticular lubrication, which increases the viscoelastic properties of synovial fluid; this form of therapy is therefore sometimes termed “viscosupplementation.”
Is there evidence that viscosupplementation is effective for osteoarthritis of the knee?
Despite numerous trials and meta-analyses, the efficacy of hyaluronate-related agents in patients with knee osteoarthritis remains debated and uncertain. Meta-analyses assessing the efficacy of this form of therapy have had discordant findings, possibly because each review used different search strategies and selection criteria to identify trials for inclusion in the analysis. There is also controversy over whether the molecular mass of hyaluronate influences efficacy. The effectiveness of intraarticular hyaluronate is at best modest and at worst, in some of the aforementioned meta-analyses, indistinguishable from that of placebo. Although there are some data suggesting that younger patients and patients with less-severe disease may have greater benefit from this treatment than do older patients and those with more advanced disease, further evidence is required to support this claim. The effect of intraarticular hyaluronate on the structural progression of osteoarthritis, especially after repeat administration over longer intervals, remains an open question, with some pilot evidence suggesting positive effects.
Morning Report Questions
Q. What side effects are associated with the procedure?
A. Minor side effects include pain at the injection site (which occurs in 1 to 33% of patients), local joint pain and swelling (in <1 to 30%), and local skin reactions (in 3 to 21%). More serious side effects can occur. Pseudoseptic reactions (occurring in 1 to 3% of patients), which are characterized by inflammation and swelling of the joint that are not caused by infection, can be severe and may require further medical treatment. These reactions usually occur after sensitization with the second or third injection of a series or with a repeat treatment course. True joint infections have also been reported, but these appear to be rare.
Q. What are the formal guidelines regarding viscosupplementation for treatment of osteoarthritis of the knee?
A. Consistent with the contradictory meta-analyses, available guidelines also have conflicting recommendations, despite being based on the same research evidence. A recent update of the evidence from the OARSI [Osteoarthritis Research Society International] suggested that the data from the more rigorous trials did not show a significant difference between the effect of hyaluronate and that of placebo; as a result, it was not recommended for the treatment of either knee or multiple-joint osteoarthritis. In the American Academy of Orthopaedic Surgeons clinical practice guideline, it was determined that the evidence was inconclusive and a recommendation could not be made for or against the use of intraarticular hyaluronate. Similarly, the 2012 American College of Rheumatology recommendations do not advocate the use of intraarticular hyaluronate for the initial management of knee osteoarthritis. However, if a patient does not have a satisfactory response to acetaminophen or nonsteroidal antiinflammatory drugs, then the use of tramadol, duloxetine, or intraarticular hyaluronate is conditionally recommended.