Published: Nov 12, 2014

By Pauline Anderson , Contributing Writer, MedPage Today

Taking glucosamine and chondroitin, two popular dietary supplements, doesn’t significantly relieve the pain and stiffness associated with knee osteoarthritis (OA) or modify disease progression, a new study found.

After adjusting for potential confounders, subjects who reported using glucosamine/chondroitin at three annual assessments had a 0.68 point increase (95% CI minus 0.16-1.53) on the Western Ontario and McMaster Universities Arthritis Index (WOMAC) pain scale compared with those who didn’t use the supplements (a minimally important improvement is -4.6 to -1.2), according to Shibing Yang, PhD, Division of Epidemiology, Department of Family Medicine and Population Health, Virginia Commonwealth University, Richmond, Va., and colleagues.

For stiffness and function, the differences in WOMAC measurements between those using the treatment at all assessments and never users were 0.41 (95% CI 0-0.82) and 1.28 (95% CI minus 1.23-3.79), respectively, the researchers reported inArthritis and Rheumatology.

“Our data join a growing body of evidence suggesting that glucosamine/chondroitin has no impact on relieving OA symptoms,” said the authors.

The findings support the latest guidelines which recommend against using glucosamine and chondroitin for OA treatment, they said.

OA is the most common type of arthritis and a leading cause of pain and physical disability in older adults. There are currently no effective remedies.

It is biologically plausible that glucosamine and chondroitin, both essential components of the proteoglycans in normal cartilage, would have an impact on OA. In vitro and animal studies suggest that these supplements simulate the synthesis of proteoglycans and inhibit the synthesis of proteolytic enzymes that lead to premature breakdown of cartilage.

In the U.S., glucosamine and chondroitin are typically sold in a combination pill, but studies of the combined treatment are sparse. It’s believed that the longest studies to date were 3-year trials conducted more than a decade ago in Europe.

To address this gap, researchers accessed data from the Osteoarthritis Initiative(OAI). From 2004 to 2006, four study sites in the U.S. enrolled residents who had established knee OA or were at high risk for developing the condition. Study participants had a Kellgren-Lawrence (K-L) grade of 2 or greater in at least one knee.

Use of glucosamine and chondroitin was self-reported. In separate questions, subjects were asked at baseline and annually if they had used either supplement for joint pain or arthritis.

To improve study validity, researchers used a “new-user” design; only participants not reporting use of glucosamine or chondroitin at baseline were included in the analyses. From this new-user group, researchers identified two samples: 1,625 participants for analyses of symptoms, and 1,113 for the analyses of structural changes.

The cohort was generally young (56.4% were under age 65 ) and the majority were women (58.0%) and non-Hispanic white (72.9%).

Researchers used the WOMAC to measure pain, stiffness, and physical function. Subscale scores range from 0-20 for the pain, 0-8 for stiffness, and 0-68 for the physical function domains, with larger scores representing worse symptoms or function.

To assess disease progression, researchers took regular bilateral standing knee x-rays with patients` knees flexed to 20 to 30 degrees and feet internally rotated 10 degrees. Investigators measured multiple JSWs at fixed locations along the joint.

As well, researchers gathered information on potential confounders, including: sociodemographics, general health status, body mass index (BMI), and use of conventional and alternative arthritis treatments other than glucosamine/chondroitin.

Researchers used marginal structural models (MSMs), a statistical analysis that considers time-varying confounding.

The study found that 18% of participants initiated glucosamine/chondroitin during the study period and 4% reported use at all assessments during the study period.

In addition to the results for symptoms and function, the study found that compared with never users, those who used the supplements on all assessments had on average 0.11 mm wider (95% CI minus 021 to 0.44) joint space width (JSW) (the minimally important change is 0.2 to 0.5).

“After adjustment for potential confounders with MSMs, we found that treatment with glucosamine/chondroitin for 3 years did not appear to bring about relief in symptoms or retardation of disease progression,” commented the authors.

The data on symptomatic effects are consistent with recent systematic reviews on treatment with each of these supplements alone and with independent long-term clinical trials on combination treatment. The findings for structural progression are consistent with some, but not all, previous studies.

As participants likely went on and off supplements between annual assessments, there may be misclassification of use. Another study limitation was the lack of information on supplement formulation, dosage, and purity.