Introduction

Osteoarthritis (OA) is a chronic and usually progressive disease that produces pain and reduced mobility, and results in a decreased quality of life. The condition may worsen over the years, and is often more severe in people who are overweight. Various medications, usually of the aspirin type (non-steroidal anti-inflammatory drugs, or NSAIDs), physical therapy and exercise, complementary medicine (herbs, nutritional supplements), and body weight reduction programs are the main ways to try to manage OA. Many drugs have been proposed for treating osteoarthritis, but those intended to produce an effect on cartilage deserve some attention. These drugs are usually derived from constituents of the cartilage tissue itself and have shown some promises in test tubes and in animal experiments.

A group of investigators in Belgium have recently reported their findings from a 3-year clinical study of oral glucosamine sulfate (GS) in patients suffering from knee osteoarthritis.

Methods

Outpatients consulting the Bone and Cartilage Metabolism Research Unit of the University Hospital Center in Liege, Belgium were included in the study if they were older than 50 and had a diagnosis of knee osteoarthritis according to recognized clinical and X-ray criteria. They were randomly allocated to receive glucosamine sulfate (1500 mg equivalent as powder) or a placebo (dummy substance), once a day, for 3 years. Patients who had inflammation or a previous knee injury as well as those with abnormal liver or renal function tests were not allowed in the study. Pain-killers (paracetamol or non-steroidal anti-inflammatory drugs) were allowed during the whole study.

The primary purpose of the study was to measure and compare changes in the joint space on X-ray in the two treatment groups, with the expectation that GS would lessen the usual decrease in joint space seen over time in such patients. Assessment of the severity of symptoms was measured using the Western Ontario and McMaster Universities (WOMAC) index for pain, physical function and stiffness, at baseline and after 3 years.

Of the 106 patients entered into each treatment group, 71 who received placebo and 68 who received GS had a 3-year assessment. If measurements were missing, they were replaced by values from the placebo group; this may have unfortunately biased the conclusions reached by the authors.

Results

After 3 years, narrowing of the joint space was less in the GS group than in the placebo patients. The estimated difference with placebo amounted to 1/3 to ¼ mm (see below for the significance of such small changes). The total WOMAC score in the placebo group was slightly worse (10%) after 3 years than at baseline, but this worsening was not statistically significant. In other words, the disease did not seem to get measurably worse in those patients given placebo. In contrast, the WOMAC score improved by 12% in the GS group, which was statistically better than the score at the start of the study, and significantly better than the placebo group 3-year score. The use of aspirin and NSAIDs was similar in both treatment groups.

There were no differences in safety or side-effect reports between the groups. In fact, about 20% in each group withdrew from the study because of side effects, but no details were reported regarding the type of side effect leading to discontinuation. It is also unclear if other commonly-used treatments for OA which also improve WOMAC scores (e.g. physical therapy, exercise, weight control programs) were allowed or their use recorded.

Conclusions and recommendations

The authors recognize limitations of their study, such as the use of X-ray findings and what they describe as a relatively short observation period for a disease, which can evolve over decades. X-ray measurements of knee joint space, however sophisticated, depend on other factors than the thickness of the joint cartilage - for instance, displacement of the meniscus or difficulty in correct positioning due to pain.

OA is now recognized as being a disease of the entire joint, with profound changes also occurring in adjacent tissues, including the bones. The narrow focus on cartilage and its presumed influence on joint space narrowing is considered by some to be an unreliable and poor indicator of slow disease progression in the majority of patients.

However, the unexpected results concern the clinical changes reported. The improvement associated with GS would be considered as "small to moderate" using the widely-accepted WOMAC method. But, this size of improvement is clinically relevant, and at least equal to that seen with other treatments of OA.

Other clinical research results have reported similar improvements in symptoms with much shorter periods of administration of glucosamine-type substances. However, this study suggests that glucosamine-containing products may have a sustained clinical effect. More long-term placebo-controlled studies are required to document this; also, it's also not known if these results can lead to the conclusion that other pharmaceutical or nutraceutical preparations containing glucosamine sulfate are equally effective.