Glucosamine and Chondroitin

Efficacy of Glucosamine and Chondroitin for Treatment of Osteoarthritis of the Knee

What is the problem and what is known about it so far?
Osteoarthritis (OA) is the most common form of arthritis and a cause of debilitating pain of joints such as the hands, spine, hips, and knees.  About one in four people 55 or older have had knee pain on most days of one month during the previous year.  X-ray findings are not closely associated with pain or disease severity, and only half of these people will have findings of osteoarthritis on x-ray.  Diagnosis therefore is made using symptoms and signs, while treatment is focused on relieving symptoms and slowing disease progression. 

Why did the researchers do this particular study?
Medications taken by mouth that reduce inflammation and pain such as celecoxib, ibuprofen, acetaminophen, and those given by injection into joints such as steroids and hyaluronan have variable effectiveness, can be costly and have harmful side effects.  As a result, dietary supplements such as glucosamine and chondroitin have become more popular with sales totaling $730 million in 2004.  Although these substances are thought to be safe and thus do not need FDA approval, they have only recently been tested for effectiveness.  Initial trials have been inconclusive so more research was needed.

Who was studied?
1583 people, over 39 years of age, with clinical and radiological evidence of osteoarthritis volunteered for this study.   Patients must have had six months of knee pain with pain on most days of the prior month in addition to evidence of x-ray changes.  Two thirds of the participants were women. The average age was 59 years and most were overweight (average BMI was 32).  Only patients with mild and moderate-to-severe pain associated with osteoarthritis were included.

How was the study done?
Patients from 13 national health centers were randomly assigned to receive daily doses of glucosamine hydochloride (1500mg), chondroitin sulfate (1200mg), glucosamine with chondroitin, celecoxib (200mg), or placebo.  Both subjects and providers were unaware of the assigned treatment.  Each patient’s knee pain was scored clinically and with patient surveys at 0, 4, 8, 16 and 24 weeks of the study.  Subjects in all groups were allowed to use up to 4000mg acetaminophen daily for additional pain control.  A successful response to treatment was defined as a 20% improvement in a pain score between initial and final surveys.

What did the researchers find?
Overall, the dietary supplements did not reduce knee pain when compared with placebo.  Benefit was found, however, for patients with moderate-to-severe pain at baseline that used chondroitin and glucosamine together.  No benefit was found in the subgroup with mild symptoms. Celecoxib use was associated with significant improvement in all groups at 4 and 24 weeks, as has been observed in prior studies.  Six of ten patients given a placebo reported improvement of their symptoms. 
 
What were the limitations of the study?
As it is difficult to objectively measure pain, it is hard to define a clear endpoint for "improvement", especially in patients with mild osteoarthritis.  There was a high dropout rate (20%) and thus the need to estimate what the outcome might have been for those who did not complete 24 weeks of therapy which may have made it difficult to show an effect if there was one. Although a benefit was found in the moderate-to-severe pain subgroup on combined therapy, it is unclear why improvement was not also found with celecoxib in that group. These findings cannot be applied to patients with knee pain who do not have x-ray changes. Also, glucosamine hydrochloride, not the widely available glucosamine sulfate, was used in this study. These compounds may have different effects.

What were the implications of the study?
This study suggests that people with moderate to severe osteoarthritis may benefit from combined therapy with glucosamine hydrochloride and chondroitin sulfate.  Dietary supplements are considered safe and have few side effects. Patients who desire trying glucosamine or chondroitin for osteoarthritis symptoms, especially mild pain, should be aware that there is little evidence supporting a benefit at this time.  Information about the effects of dietary supplements in slowing the progression of osteoarthritis as measured with by x-ray changes will be available next year. 

Summarized by Andrea Regan, MD, Family Medicine Resident, Fletcher Allen Health Care.
Summarized from the following three articles.
"Glucosamine, Chondroitin Sulfate, and the Two in Combination for Painful Knee Osteoarthritis."  Clegg, Daniel et al.  The New England Journal of Medicine, February 23, 2006, Volume 354(8): 795-808.
"Nutritional Supplements for Knee Osteoarthritis—Still No Resolution." Hochberg, Marc.  The New England Journal of Medicine, February 23, 2006, Volume 354(8): 858-860.
"Osteoarthritis of the Knee."  Felson, David.  The New England Journal of Medicine, February 23, 2006, Volume 354(8): 841-848.