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Would Patients Benefit from a Glucosamine/Chondroitin Supplement to Manage Knee Osteoarthritis Pain?

This Ask the Expert addresses the popular dietary supplement's use in chronic pain relief.
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An estimated 22.7% of adults in the United States have been diagnosed with some form of arthritis, of which nearly half of all cases are osteoarthritis (OA).1 The risk of arthritis increases with age and is more common among women than men. This condition represents the leading cause of disability, with one in four adults facing limitations at work.1

The goal of treatment has been to control pain, slow joint damage, and improve or maintain function and quality of life. According to the National Institute of Arthritis and Musculoskeletal Diseases, first-line treatment is acetaminophen, and then over the counter, nonsteroidal anti-inflammatory drugs (NSAIDs) (ie, ibuprofen). Some patients may turn to topical agents, injections, or prescription strength NSAIDs to avoid or postpone surgery.2

Given the drawbacks and concerns about gastrointestinal and cardiovascular risks associated with NSAIDs, many patients have become attracted to the promise of reducing or eliminating their joint pain, inflammation, and stiffness by taking a combined oral supplement of glucosamine and chondroitin.2,3

Evidence for this Popular Combined Supplement

Glucosamine is produced naturally in humans, and is used as a substrate for the biosynthesis of cartilage. It is available as a dietary supplement in the form of glucosamine hydrochloride, glucosamine sulfate, and N-acetyl glucosamine.4

Glucosamine has been evaluated for many uses, but most research has focused its efficacy in osteoarthritis.4 Table I provides a summary of the evidence for efficacy of each product, the number of available products, and how many of those products are United States Pharmacopeia (USP) verified.

The data, however, varies due to differing formulations; most often glucosamine is found together with chondroitin. Chondroitin, also found naturally in the body, is sold in supplemental form as chondroitin sulfate.4

Since existing research on efficacy of glucosamine and chondroitin has focused on knee osteoarthritis (OA), as shared below, a recommendation for its use is limited to this condition.

Efficacy of Glucosamine/Chondroitin in Knee OA

In 2015, a meta-analysis of 54 randomized controlled trials including 16,000 patients was conducted to assess the efficacy and safety of glucosamine, chondroitin, glucosamine plus chondroitin, and celecoxib.5 The primary outcomes were pain relief and functional improvement.

When compared to placebo, each treatment group showed statistically significant less pain having met criteria demonstrating a decrease of at least two points on a pain scale of 0 to 10.5 This review cited two articles offering the highest evidence, and concluded that there were sufficient findings to recommend glucosamine and chondroitin to patients with moderate-to-severe pain from knee osteoarthritis.5

The MOVES trial by Zeng et al,6 was a multicenter, phase IV, randomized, double-blind, non-inferiority study. The primary outcome was the mean decrease in the WOMAC score from baseline. Researchers assessed patients with a diagnosis of knee OA for response to severe pain (defined as a WOMAC score of at least 301) with a combination of glucosamine and chondroitin as compared to celecoxib.6 A total of 606 patients were randomized to receive either:

  • 400 mg of chondroitin and 500 mg of glucosamine hydrochloride three times a day
  • 200 mg of celecoxib every day for six months.

At the end of treatment, there were no statistically significant differences in the change in WOMAC score between the two treatment groups. Both groups decreased the WOMAC pain score by 50% and met criteria for non-inferiority with a mean difference of -1.1 (95% CI -22.0 to 9.8) between glucosamine plus chondroitin versus celecoxib.6 Also, no significant differences in adverse effects were noted between groups. The findings suggested that glucosamine plus chondroitin was non-inferior to celecoxib.

The LEGS trial,7 led by Fransen et al, was a randomized, double-blind, placebo-controlled study following patients with knee pain for more than six months. To be included, participants’ worst pain had to be at least a four (on a scale of 0 to 10) in the previous week. Patients were randomized to receive either 1500 mg of glucosamine sulfate, 800 mg of chondroitin sulfate, glucosamine plus chondroitin, or placebo.

Primary outcomes were joint space narrowing and pain relief.7 The researchers reported a marginal difference in the combination treatment group and placebo for joint space narrowing (P = 0.046, 95% CI 0.0 to 0.2) after adjusting for multiple variables.7 There were no differences noted for any of the groups with regard to pain. As such, the findings were not deemed of clinical significance. The only adverse effects reported were those that led patients to drop out. Six percent of patients withdrew possibly due to treatment, with no differences in adverse events between the groups.7 It is important to note that only 5% of patients in this study had moderate to severe disease; most were classified with mild OA.

A third key study, a multicenter, double-blind, controlled GAIT trial aimed to evaluate the safety and efficacy of glucosamine and chondroitin.8 To be included, patients had to be at least 40 years old with evidence of OA and a WOMAC score of 125 to 400. Patients were randomized to receive:

  • 500 mg of glucosamine hydrochloride three times a day
  • 400 mg of chondroitin sulfate three times a day
  • a combination of glucosamine and chondroitin three times a day
  • 200 mg of celecoxib daily
  • or placebo.

This study had specific products manufactured to ensure potency. Overall, there was no significant difference noted in pain scores across the supplement groups; a significant difference in pain was found between celecoxib and placebo.8 A subgroup analysis demonstrated a statistically significant difference between the combination of glucosamine and chondroitin and placebo, but not for celecoxib in patients with moderate to severe symptoms.8

Nearly 80% of patients in the combination treatment group achieved at least a 20% decrease in WOMAC pain score (P = 0.002), while the same effect was experienced by only 54% and 69%, respectively, in the placebo and celecoxib groups (P = 0.06).8 Only 3 of the 77 reported adverse events were related to study treatment, including heart failure (combination treatment), stroke (celecoxib), and chest pain (glucosamine). Researchers concluded that while there were no differences in treatment, there was reason to believe that patients with moderate to severe symptoms may gain some benefit from the combined therapy.8

Last updated on: January 31, 2018
Continue Reading:
Guide to Dietary Supplements Most Commonly Used in Pain Management
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