Glucosamine supplementation demonstrates a negative effect on intervertebral disc matrix in an animal model of disc degeneration

Abstract

Study design: Laboratory based controlled in vivo study.

Objective: To determine the in vivo effects of oral glucosamine sulfate on intervertebral disc degeneration.

Summary of background data: Although glucosamine has demonstrated beneficial effect in articular cartilage, clinical benefit is uncertain. A Centers for Disease Control report from 2009 reported that many patients are using glucosamine supplementation for low back pain, without significant evidence to support its use. Because disc degeneration is a major contributor of low back pain, we explored the effects of glucosamine on disc matrix homeostasis in an animal model of disc degeneration.

Methods: Eighteen skeletally mature New Zealand White rabbits were divided into 4 groups: control, annular puncture, glucosamine, and annular puncture + glucosamine. Glucosamine treated rabbits received daily oral supplementation with 107 mg/d (weight based equivalent to human 1500 mg/d). Annular puncture surgery involved puncturing the annulus fibrosus of 3 lumbar discs with a 16-gauge needle to induce degeneration. Serial magnetic resonance images were obtained at 0, 4, 8, 12, and 20 weeks. Discs were harvested at 20 weeks for determination of glycosaminoglycan content, relative gene expression measured by real time polymerase chain reaction, and histological analyses.

Results: The magnetic resonance imaging index and nucleus pulposus area of injured discs of glucosamine treated animals with annular puncture was found to be lower than that of degenerated discs from rabbits not supplemented with glucosamine. Consistent with this, decreased glycosaminoglycan was demonstrated in glucosamine fed animals, as determined by both histological and glycosaminoglycan content. Gene expression was consistent with a detrimental effect on matrix.

Conclusion: These data demonstrate that the net effect on matrix in an animal model in vivo, as measured by gene expression, magnetic resonance imaging, histology, and total proteoglycan is antianabolic. This raises concern about this commonly used supplement, and future research is needed to establish the clinical relevance of these findings.

Figure 1

Rabbits were pre-fed glucosamine for 30 days. All animals underwent baseline MRIs immediately prior to annular puncture. Rabbits were followed with serial MRIs until sacrifice at 20wks, at which time spines were harvested and additional outcome measures were performed.

Figure 2

A. Representative mid sagittal T2 weighted MRI images of animals from each group at the 20 week timepoint. B. MRI index calculated at each timepoint. C. NP area calculated at each timepoint.

Figure 3

A. Alcian blue staining of representative discs from each group imaged at 20X. B. Safranin-O staining of representative discs from each group imaged at 20X. C. H+E staining of representative NP from each group imaged at 100X.

Figure 4

Total glycosaminoglycan per mg of tissue of glucosamine fed animals normalized to control. Non-injured discs of glucosamine treated rabbits had lower GAG content in the NP and AF compared to discs of untreated control rabbits, and these changes were statistically significant with p<0.05.