Nonspecific chronic low back pain (LBP) remains one the mostprevalent, expensive, and poorly treated conditions seen byprimary care clinicians.1 The etiology of most chronic LBP isunknown; therefore, treatment approaches are often empiric andusually based on a relatively thin foundation of evidence. Mostinterventions have not been rigorously tested and many backpain studies are limited by poor design and research practice,so little is known about what treatments are or are not effectivefor patients with chronic LBP. Because patient-specific diagnosisand treatment plans cannot be rationally formulated in mostcases,2 patients frequently experiment with a variety of interventions,often turning to complementary and alternative therapies.3 - 4
Glucosamine is a precursor of the proteoglycans that make uparticular cartilage, and it is widely used orally by patientsfor treating peripheral joint osteoarthritis based on the theorythat degenerative cartilage lesions can be treated by takinghigh doses of a precursor molecule.5 However, the evidence regardingglucosamine for hip and knee osteoarthritis is inconsistentwith great variation depending on the quality of the study design,the glucosamine preparation used, and the funding source.6 - 7Similar arthritic changes often occur in the synovial facetjoints of the spine, and more than 25% of patients with chronicLBP have tried glucosamine supplements, seeking to gain relieffor their back pain.8
In this issue of JAMA, Wilkens et al9 report the results ofa randomized, double-blind clinical trial of oral glucosaminefor the treatment of patients with chronic LBP and imaging evidenceof facet joint osteoarthritis. The investigators randomized250 participants to 6 months of treatment with 1.5 g of glucosaminesulfate daily or an identical-appearing placebo. Overall, thiswas a well-designed and well-conducted trial with clear eligibilitycriteria, adequate allocation concealment, good baseline comparability,acceptable medication adherence, few withdrawals, well-acceptedoutcome measures, adequate sample size specified a priori, andan appropriate intention-to-treat analysis. The use of the sulfatesalt of glucosamine was also a wise choice given the issuessurrounding the bioavailability of this dietary supplement andthe role of sulfate in its potential efficacy.5
The results of the trial were negative: on no outcome measurewas there a statistically significant benefit of glucosamineover placebo. The 95% confidence intervals generally excludedany effect considered clinically meaningful, suggesting theresults were probably not due to insufficient statistical power.Given the high quality of the trial methods and execution, themost likely explanation for the outcome is simply that glucosamineprobably offers little benefit for chronic LBP with osteoarthritisbeyond whatever placebo effect it may provide. Importantly,there were few adverse effects associated with the use of glucosaminein this study, consistent with other literature, indicatingthat glucosamine is well tolerated and causes minimal toxicity,at least in the short term.6 Thus, the data presented by Wilkenset al9 provide no incentive for clinicians to recommend glucosaminefor patients with chronic LBP.
It would be easy for clinicians and patients to become discouragedas increasing numbers of potential chronic LBP treatments failto survive the test of clinical trials. However, the publichealth burden of chronic LBP cannot afford cynicism, and high-qualitynegative trials such as that reported by Wilkens et al9 shouldbe viewed positively as important contributions. Indeed, someimportant progress has been made as patients with back painare no longer advised to try prolonged, counterproductive bedrest and there is much greater appreciation for the complexinteractions between the psychosocial and physical aspects ofchronic LBP.10 Overall, however, care for patients with LBPremains insufficient for far too many patients. Why has suchan enormous public health problem remained so stubbornly resistantto the identification of effective treatment?
Some challenges are unique to back pain. Unlike other commonchronic illnesses, there is no dominant organization that representsthe chronic LBP community, advocating for greater attentionand funding for LBP research. It is ironic that in the UnitedStates orders of magnitude more resources are spent on treatmentsfor chronic LBP of limited or unknown value than on researchto study existing and promising new approaches that could providemore hope for patients. Moreover, the fragmented clinical silosin which chronic LBP treatments are often delivered (eg, primarycare, physical therapy, surgery, interventional procedures,behavioral therapy, complementary and alternative medicine practice)rarely align to force an objective appraisal of efficacy andcollaborate to identify optimal treatment approaches. In thecompetition for federal research dollars, back pain has notbeen allocated funding commensurate with its societal cost andquality-of-life burden. For example, as of June 2010, the NationalInstitutes of Health’s clinical trials registry ( http://clinicaltrials.gov )includes only 69 federally funded intervention studies in backpain, of which only 20 are currently recruiting patients. Fortunately,funding agencies are beginning to recognize the compelling publichealth imperative of chronic LBP as evidenced by the increasingnumbers of federally funded studies related to back pain overthe past 25 years.
The great need for more and more efficient clinical researchin chronic LBP highlights an overall clinical research environmentin the United States that operates well below its potential.Similar to other clinical conditions, LBP research is limitedby insufficient funding, misguided regulations,11 a heavy relianceon funding from for-profit entities,12 and a lack of consensusabout outcome measures and clinically meaningful goals of therapy.
Perhaps most important is that the clinical research communityhas failed to create the strong partnerships with the publicthat are required to build and sustain a robust clinical researchagenda.13 Without a fundamental change in the relationship betweenthe clinical research community and the public, clinical andtranslational research will continue to struggle with recruitmentproblems, inadequate financial and public support, and insufficientappreciation for its societal value.
The results of the high-quality clinical trial by Wilkens etal9 carefully evaluating a widely used treatment for chronicLBP were disappointing but should not be discouraging. Clearly,much more work remains before realizing the kinds of successin the treatment of chronic LBP that other conditions have experienced.With an objective and determined focus, sufficient support,greater collaboration, and a working partnership with patients,there is every reason for optimism, however cautious. The realtest will be whether the environment for this success can becreated and sustained.
Corresponding Author: Andrew L. Avins, MD, MPH, Division ofResearch, Northern California Kaiser-Permanente, 2000 Broadway,Third Floor, Oakland, CA 94612 ( email@example.com ).
Financial Disclosures: None reported.
Editorials represent the opinions of the authors and JAMA andnot those of the American Medical Association.
Author Affiliation: Division of Research, Northern California Kaiser-Permanente, Oakland. REFERENCES
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