Glucosamine Drink Flops in Knee Osteoarthritis Trial

Janis C. Kelly

March 13, 2014

Patients with mild to moderate knee osteoarthritis (OA) who drank 1500 mg glucosamine hydrochloride dissolved in lemonade each day for 6 months had just as much pain and knee cartilage deterioration as similar patients who drank only lemonade, according to a randomized, placebo-controlled trial by C. Kent Kwoh, MD, and colleagues, published online March 10 in Arthritis & Rheumatism.

Glucosamine Not Associated With Less Cartilage Damage

Results of the study, which is notable for using 3T magnetic resonance imaging rather than plain X-ray imaging to assess worsening of cartilage damage (the primary outcome), "suggest that administration of glucosamine hydrochloride in a beverage for 24 weeks is not associated with less deterioration in knee cartilage damage, less worsening of [bone marrow lesions (BMLs), also known as "bone bruises"], improvement of BMLs in the knee, decreased urinary excretion of CTX-II [C-terminal cross-linking telopeptide of type 2 collagen, a marker of cartilage damage], and/or decreased pain and functioning in individuals from the community with chronic knee pain," the authors conclude.

"It is difficult to recommend glucosamine for patents with knee pain based on the results of our study. If a patient with knee pain asks whether glucosamine may be helpful, they may need to take it more than 6 months to derive any potential benefit more than a placebo," Dr. Kwoh, professor of medicine and medical imaging, The Charles A.L. and Suzanne M. Stephens Chair of Rheumatology, and director, University of Arizona Arthritis Center, Tucson, told Medscape Medical News.

First Study to Use MRI to Measure Glucosamine Cartilage, BML Effects

For this double-blind, placebo-controlled trial, the researchers enrolled 201 participants with mild to moderate pain in 1 or both knees, defined as a Western Ontario and McMaster Universities pain score between 25 and 100. Two thirds of patients had a Kellgren-Lawrence grade of 2 or higher in at least 1 knee on baseline radiography.

Participants were randomly assigned to receive either 24 weeks of daily treatment with 1500 mg glucosamine hydrochloride in a 16-ounce bottle of diet lemonade (n = 98) or diet lemonade placebo in an identical bottle (n = 103). The treatment drinks were prepared at the clinic using Regenasure glucosamine hydrochloride (Cargill).

The primary outcome was worsening of cartilage damage in all knees assessed using 3T magnetic resonance imaging, according to the validated Whole Organ Magnetic Resonance Imaging Score system. Secondary outcomes were change in BMLs in all knees and urinary CTX-II, which the author notes has been associated with both prevalence and progression of radiograph osteoarthritis of the knee and hip.

Glucosamine Did Not Protect Cartilage or Reduce Osteoarthritis Pain

After 24 weeks of treatment, the researchers found no difference in cartilage worsening between the 2 groups (odds ratio, 0.85; confidence interval, 0.47 - 1.54). Analysis using an adjusted logistic regression model that controlled for clustering by subregions within knees and between knees within an individual likewise showed no association between cartilage deterioration and treatment group (adjusted odds ratio, 0.938; 95% confidence interval, 0.53 - 1.67).

"We also were unable to demonstrate a benefit of glucosamine over placebo with regard to improvement in BMLs. We chose BMLs as a secondary outcome since they have been shown to be associated with subregional cartilage loss. There have been no prior studies that have examined the benefit of glucosamine on changes in BMLs," the authors add.

The researchers also found no benefit of glucosamine over placebo with regard to decreased excretion of urine CTX-II or to Western Ontario and McMaster Universities pain scores at 12 or 24 weeks.

Researchers Surprised at Glucosamine Lack of Effect in Knee OA

"Our initial hypothesis was that glucosamine would show some effectiveness. I was surprised that none of the measure indicated an effect better than placebo," Dr. Kwoh said.

Eric Matteson, MD, chair of the Division of Rheumatology at the Mayo Clinic, Rochester, Minnesota, told Medscape Medical News that the researchers adequately addressed the structural questions regarding the possible benefit of glucosamine supplementation in this form.

Dr. Matteson, who was not involved in the study, said, "I think this is an excellent study which demonstrates that oral glucosamine has no efficacy with respect to knee joint morphology. When asked, clinicians may counsel that there is no evidence that these products restore joint integrity."

Dr. Kwoh suggested that different formulations such as glucosamine sulfate or a longer treatment period might be worth further study.

According to the authors, glucosamine is the second most commonly used nonvitamin, nonmineral natural product. It is used as alternative therapy for osteoarthritis. Global sales of glucosamine supplements were more than $2.1 billion in 2010.

This trial was sponsored in part by the Beverage Institute for Health & Wellness, a project of the Coca-Cola Company, which for a time marketed Minute Maid Active orange juice containing Regenasure glucosamine HCl, and by the National Institute of Arthritis, Musculoskeletal and Skin Diseases. Dr. Kwoh has received consulting fees from Pfizer and Novartis. The other authors have disclosed no relevant financial relationships. Dr. Matteson has disclosed no relevant financial relationships.

Arthritis Rheum. Published online March 10, 2014. Abstract

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