Glucosamine discontinuation study finds no evidence of benefit - Oct 29, 2002

New Orleans, LA - Glucosamine has become the most popular dietary supplement used in osteopathic, and several clinical trials have demonstrated a significant beneficial effect over placebo on the signs and symptoms of knee OA. But now a discontinuation trial from Canada, presented here at the American College of Hematology meeting, shows that patients who reported a benefit from glucosamine fared the same on stopping the drug as those who continued to take it. All of the patients had reported a moderate to marked subjective improvement with glucosamine and had been taking it for nearly 2 years. But in the 6-month study, the patients who continued to take it showed no difference from those who discontinued in any measure of knee OA activity, including time to disease flare. "This study provides no evidence of benefit from continued use," concluded the lead investigator, Dr Jolanda Cibere. She says the fact that the study was carried out in patients who reported benefit from glucosamine strengthens its negative conclusion: "If we can't find evidence of efficacy in these people, where will we find it?"

No difference between glucosamine and placebo on any measure. The study was conducted in 137 subjects, of whom 71 continued to take glucosamine while 66 discontinued and took a matched placebo. The 2 groups were matched in demographics with 2 exceptions there were more females in the placebo group (70% vs. 44%), while the glucosamine group had more severe knee OA as assessed radio-graphically (64% of placebo patients had grade 2 OA vs 44% in glucosamine group, and 3% placebo vs. 10% glucosamine patients had grade 4 OA). However, both groups had been taking glucosamine for a similar length of time, and both reported a similar benefit from it, as shown in the table below. They had decided themselves on the dose to use, and 64% were taking 1500-mg glucosamine per day, 29% were using 1000 mg, and 7% were using 500 mg.

Benefit from glucosamine as reported by knee OA patients upon enrolment

The primary outcome measure showed no difference between the patients who continued taking glucosamine and those who took placebo. A similar proportion in each group had a disease flare (43% and 42%, p=0.98). After adjustment for sex and OA severity as baseline, the risk of disease flare was minimally and non-significantly reduced in the glucosamine vs. placebo group (hazard ratio 0.8, 95%CI 0.5-1.4, p=0.57).

There was also no difference in time to disease flare, nor in the use of analgesics (NSAIDs and acetaminophen) (73% vs. 77% in placebo, p=0.80). And there were no significant differences in other secondary outcomes: WOMAC pain (p=0.96) and physician global assessment (p=0.43).

Cibere reported that her team performed several subgroup analyses to see if the risk of disease flare was affected by treatment, sex, site of study center, or severity of OA. "But after adjusting for these important covariants, we still found no difference between the glucosamine and placebo groups."

Divergence between industry-sponsored and independent research The presentation elicited several questions and comments. One delegate questioned the lack of a wash-out period, commenting that glucosamine is thought to linger in the joints and so the placebo group may still be experiencing benefits even though they had stopped taking the product. Cibere responded that most patients report a benefit within 2 to 3 months of taking glucosamine, so they reckoned the effect should wear off in about the same period of time, which would have been captured by the sixth month.

Dr Luciano Rovati from Rotta Research, who was instrumental in the 2 large 3-year trials (by Reginster et al and Pavelka et al) that have demonstrated significant benefit with glucosamine in knee OA, said he was rather surprised that Cibere considered this to be a negative study, as it shows that nearly 60% of patients on glucosamine didn't have a disease flare. When Cibere pointed out that 60% of the placebo patients also didn't have a flare, he also noted the lack of wash-out and short study period.

Dr Tim McAlindon (Boston University) commented that there is a divergence appearing in the glucosamine field, with industry-sponsored trials showing significant benefit (he described the Reginster trial as a "landmark study" in a Lancet editorial), while trials carried out independently tend to have negative findings and fail to find evidence of efficacy.