No effect of 6-month intake of glucosamine sulfate on Modic changes or high intensity zones in the lumbar spine: sub-group analysis of a randomized controlled trial

Philip Wilkens, Kjersti Storheim, Inger Scheel, Linda Berg, Ansgar Espeland, Philip Wilkens, Kjersti Storheim, Inger Scheel, Linda Berg, Ansgar Espeland

Abstract

Background: The underlying pathology and natural course of Modic changes (MC) in the vertebral body marrow and high intensity zones (HIZs) in the annulus fibrosus is not completely clarified. These findings on magnetic resonance imaging (MRI) have initiated different treatments with little or unclear effect. In a randomized trial (n=250), glucosamine sulfate (GS) had no effect on low back pain related disability. GS could still have an effect on MC and HIZ. In this sub-study, 45 patients from the trial who had MC and/or HIZ at pre-treatment underwent follow-up MRI. The aim was to examine the course of MC and HIZ and to compare this course between groups treated with 6-month intake of oral GS versus placebo.

Results: Of 141 pre-treatment MC in 42 (of 45) patients, 29 (20.6%) MC in 18 patients had altered type and 14 MC in 9 patients had altered size (decreased for 1 MC) 6-18 months later: odds ratio (OR) for type vs. size alterations 4.0; 95% confidence interval (CI) 1.2-17.7. No MC resolved. HIZ vanished from 3 of 23 discs in 3 of 21 patients with pre-treatment HIZ. Ten new MC (all type I or I/II) occurred in 8 patients and 2 new HIZs in 2 patients. The GS group (n=19) and placebo group (n=26) did not differ in proportions of MC with decreased (OR 1.6; 95% CI 0.4-6.1) or increased type I dominance at follow-up (OR placebo:GS 2.4; 95% CI 0.6-9.7), or with increased size (OR 1.0; 95% CI 0.2-4.7). HIZ vanished from 1 of 8 discs in 1 of 8 patients in the GS group vs. 2 of 15 discs in 2 of 13 patients in the placebo group (OR 0.8; 95% CI 0.02-12.2).

Conclusions: In this sub-group analysis of a placebo-controlled trial, the effect of GS on MC and HIZs was no different from the effect of the placebo intervention. MC and HIZs remained mostly unchanged during the 6-18 months study period. Some short term changes did occur and MC more often altered type than size.

Trial registration: NCT00404079 at http://www.clinicaltrial.gov.

Figures

Figure 1
Figure 1
Altered type of Modic changes. Initial (A-B) and follow-up (C-D) sagittal magnetic resonance images of one patient. Type I Modic changes (arrows; high signal on T2-weigthed image A, low signal on T1-weighted image B) alters to type II (high signal on T2- and T1-weighted images C and D; images not shown revealed alteration to type II/I).
Figure 2
Figure 2
Increased size of Modic changes. Initial (A) and follow-up (B) sagittal T2-weigthed magnetic resonance images of one patient. Modic changes at L3/L4 increase in craniocaudal extent from <1/4 to >1/2 of the vertebral body height from image A to image B (arrows).
Figure 3
Figure 3
Pre- and post-treatment craniocaudal size of Modic changes at 450 endplates in 45 patients. Arrows indicate size development. Numbers are percentages and numbers of endplates.
Figure 4
Figure 4
Resolving high intensity zone. Initial (A-B) and follow-up (C-D) T2-weighted magnetic resonance images of one patient. Image plane B is marked on A and image plane D is marked on C (stippled lines). High intensity zone in the L5/S1 disc on initial sagittal (A) and axial (B) images (arrows) is resolved on later sagittal (C) and axial (D) images.
Figure 5
Figure 5
Current sub-sample and pre-treatment findings by treatment group. Shown are numbers of Modic changes (MC) and of discs with high intensity zone (HIZ) by treatment group (glukosamine or placebo) in the current sub-sample of 45 patients with MC and / or HIZ from a trial of 250 chronic low back pain patients; n denotes number of patients.

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