Glucosamine is not significantly different from placebo for reducing pain-related disability or improving health-related quality of life in patients with chronic low back pain (LBP) and degenerative lumbar osteoarthritis, a new study has found.

The study results suggest the dietary supplement should not be recommended for patients with lower back pain, said the study's lead author Philip Wilkens, MChiro, from the Department of Orthopedics, Oslo University Hospital, Norway.

"Based on our findings, I don't think doctors should suggest glucosamine for low back pain," he added. "They should try to find better ways or better interventions to treat this pain."

Their results are published in the July 7 issue of the Journal of the American Medical Association.

Supplement Widely Used

Glucosamine is a precursor molecule involved in building tendons, ligaments, and cartilage. It is hypothesized to restore cartilage and to have anti-inflammatory properties, the study authors write, and, despite conflicting data on its efficacy, has become widely used as a treatment for osteoarthritis. It has also become more widely used for LBP, including degenerative lumbar osteoarthritis.

Conducted at the Oslo University Hospital Outpatient Clinic, this double-blind study included 250 patients whose primary concern was nonspecific chronic pain in the lower back, defined as the area below the 12th rib and above the gluteal folds. Patients had to be older than 25 years, have had the back pain for at least six months, and score at least 3 of 24 on the Roland Morris Disability Questionnaire (RMDQ) that measures pain-related disability.

Because glucosamine targets joint degeneration, patients also had to have a recent (within the previous year) magnetic resonance imaging scan indicating a degenerative process.

Patients were randomized to receive either a daily dose of 1500 mg of glucosamine sulfate or identical placebo administered as 3500-mg capsules. The agent used in the study — glucosamine sulfate — is relatively bioavailable. The other main type of glucosamine — glucosamine hydrochloride — is not widely used anymore, said Mr. Wilkens.

Appropriate Dose

The daily dose of 1500 mg of glucosamine was "appropriate," according to Mr. Wilkens. Studies have shown that doses below this amount do not enter the bloodstream at sufficient levels, and any amount over this dose is not absorbed, he said.

Follow-up visits were at six weeks and then at three and six months. A one-year follow-up was conducted by postal questionnaire.

During the 6-month trial, patients were allowed to use rescue medications. After six months, they were free to choose whatever therapy they preferred.

The primary outcome was the RMDQ, with a 3-point reduction in score considered a treatment response. The secondary outcome was low back and leg pain during activity and at rest as measured using an 11-point numeric pain rating scale, with 0 indicating no pain and 10 indicating the worst pain. Researchers used the Euro-Qol-5 Dimensions index to measure five quality-of-life domains.

The baseline RMDQ score was 9.2 for the glucosamine and 9.7 for the placebo groups. At the end of the study, both interventions improved functional status by about the same amount.

The six-month score was 5.0 (95% confidence interval [CI], 4.2 – 5.8) for the glucosamine and 5.0 (95% CI, 4.2 – 5.8) for the placebo group.

At the one-year follow-up, scores were 4.8 (95% CI, 3.9 – 5.6) and 5.5 (95% CI, 4.7 – 6.4), respectively.

No Difference in Quality of Life

There were no significant differences between glucosamine and placebo in terms of quality-of-life indicators or the use of concomitant medication. In the glucosamine group, 38.4% used analgesics, 53.6% used concomitant therapy, and 28.0% used both analgesics and concomitant therapy. Corresponding percentages in the placebo group were 45.6%, 53.6%, and 28.0%.

Medication adherence was also similar in the two groups as was the incidence of adverse events and rates of study withdrawal. The 86 adverse events were mild and consisted mostly of gastrointestinal and dermatologic problems.

There are several possible reasons why glucosamine was not effective in this study, the study authors speculate. The patients selected for the study may not have been responsive to the treatment, although Mr. Wilkens does not think this was a factor. "Our sample was quite representative of people with chronic low back pain and findings of degeneration in the spine," he said.

Perhaps a more likely explanation is that glucosamine may work on some joints, for example, the knee, but not the lower back. "The target molecule may differ in the different joints," said Mr. Wilkens. "There seems to be more of the (proinflammatory) target molecule for glucosamine in the knee joint. The molecule is not found much in the hip, and we don't really know the concentration of this substance in the low back."

Different Forms of Back Pain

Another factor to consider is that LBP is caused by many different conditions, some serious and others less so. "Even though you have a heterogeneous group of lower back pain patients visiting the primary care physician, they may have different forms or subcategories of low back pain," said Mr. Wilkens, adding that it is possible that glucosamine could work on some, but not all, of these conditions.

A limitation of the study was that participation was free (glucosamine is a prescription drug in Norway so its availability is controlled) and so may have attracted a certain type of patient with specific personality traits. Also, although capsule counts indicated that more than 80% of the drug was consumed, the dose response for glucosamine might require higher adherence, said the study authors.

"Well-Designed" Study

In an accompanying editorial, Andrew L Avins, MD, MPH, from the Division of Research at Northern California Kaiser-Permanente in Oakland, praised the study.

"Overall, this was a well-designed and well-conducted trial with clear eligibility criteria, adequate allocation concealment, good baseline comparability, acceptable medication adherence, few withdrawals, well-accepted outcome measures, adequate sample size specified a priori, and an appropriate intention to treat analysis," Dr. Avins writes.

He pointed out that the 95% CIs generally excluded any effect considered clinically meaningful, "suggesting the results were probably not due to insufficient statistical power."

Given the study's high quality, "the most likely explanation for the [negative] outcome is simply that glucosamine probably offers little benefit for chronic LBP with osteoarthritis beyond whatever placebo effect it may provide," said Dr. Avins.

Because this study was yet another example of a potential treatment for LBP failing to show benefit, it would be easy for clinicians to become discouraged, but the health burden of chronic LBP "cannot afford cynicism," said Dr. Avins.

There is still no effective treatment for LBP partly because no dominant organization represents the chronic LBP community, said Dr. Avins. This, he said, means treatments are often delivered in "fragmented silos" of primary care, physical therapy, surgery, interventional procedures, behavioral therapy, and complementary and alternative medicine.

LBP research is limited by "insufficient funding, misguided regulation, a heavy reliance on funding from for-profit entities, and a lack of consensus about outcome measures and clinically meaningful goals of therapy," said Dr. Avins. He added that the research community has failed to create the strong partnerships with the public that are required to build and sustain a robust clinical research agenda.

LBP is one of the most prevalent, expensive, and poorly treated conditions seen in primary care, Dr. Avins adds. The cause is often unknown, so treatment approaches are based on a relatively thin foundation of evidence, he added. Patients often turn to complementary and alternative therapies; more than 25% of patients with chronic LBP have tried glucosamine supplements.

Both the authors of the study and Dr. Avins have disclosed no relevant financial relationships.

JAMA. ;2010;304:45-52, 93-94.

Pauline Anderson • Medscape Medical News ;© ;2010 ;Medscape, LLC