In the present study, almost 80% of the MC and more than 85% of the HIZs remained stable in the 6-18 month study period. No MC resolved, but new MC, all type I or type I/II, developed at 10 of the 450 studied endplates. MC altered type at 29 and size at 14 of 141 affected endplates. HIZs resolved in 3 of 23 affected discs and occurred in 2 new discs. GS did not alter the presence or size of the MC, nor the presence of HIZ compared to placebo.
To the authors’ knowledge, this is the first trial to test the effect of GS on MC and HIZ and therefore no directly comparable data exists. Other treatments of patients with LBP and findings of MC or HIZ have been tested for clinical effect but not for effect on MC or HIZ. An uncontrolled pilot study found clinical effect of antibiotics in patients with LBP and MC type I
. Another study of 120 patients with LBP and MC type I or II indicated short-term clinical effect of intradiscal steroid injection
. LBP patients with HIZ have been treated with other interventions like intradiscal electrothermal therapy and intradiscal radiofrequency thermocoagulation without clear conclusions
Several reasons may explain the lack of difference in effect on MC and HIZ between GS- and placebo group. GS may be ineffective as modifier of the potential markers of inflammatory pain and secretion of proinflammatory mediators associated with MC and HIZ. Previous research has demonstrated the inability of GS to reduce LBP or LBP-related disability
. GS may slow down the destruction of cartilage in osteoarthritis (OA) by inhibiting the pro-inflammatory IL-1β
. IL-1β is associated with cartilage destruction in OA
. However, opposite to our assumptions, IL-1 β may not be pathologically relevant for MC or HIZ. Furthermore, 6-month glucosamine exposure may be too short time period to impact an area with limited direct blood supply. It is also possible that GS does not reach the target area because of either low concentration in the blood stream or insufficient blood supply to the lumbar vertebras and discs. However, the lack of demonstrable difference may also arise from inadequate sample size. A larger sample of MC and especially of HIZs would have made it easier to detect any smaller effect of GS on the rather slow natural course of these findings.
No MC vanished during the study period. MC are not necessarily everlasting as population research has reported resolution of MC
. However, the research is conflicting as others have found limited, or no evidence of resolution of established MC
[17, 19]. Different type of sample (general population versus LBP patients) and sample size (> 300 versus < 50 patients) may explain some of the discrepancy
[17, 19, 36].
The development of 10 new MC (in 8 of 45 patients) confirmed that MC often surface in patients with LBP
. All new MC were predominantly type I, which may support the notion that MC type I is the start point for the MC evolution
. Several MC, more type I than type II converted into a different type, indicating that MC are viable to change in as short term as 6 months to 1 year. Previous research has shown that MC may convert over 3 to 5 years after discectomy
. In addition, any type of MC may be more prone to switch between types than previously thought
Our data confirmed that MC type I is less stable than MC type II
[13, 17]. However, almost 80% of the MC did not change, which is also comparable with previous studies
. The MC size in terms of AP diameter and CC extension was more stable than the type of MC. It is noteworthy that also small MC had stable extension and did not tend to come and go. This was different from previous results that were not based on direct comparison of initial and follow-up images
. The most common places for MC to occur were at the L5-S1 and L4-L5 endplates, which is in line with previous reports
The most common locations for HIZ were also L5-S1 and L4-5, which follows previous reports
. More than 85% of the discs with HIZ remained stable throughout the study, which is also in line with earlier research
. On the other hand, HIZ was in most cases (more than 95%) present at one disc space only. The occurrence of HIZ at one level only is also comparable with past research
The present study has several strengths. It included a potentially important and distinct sub-group of LBP sufferers with MC and HIZ among the greater population of unspecific, longstanding low back pain. Two independent readers rated the MRIs using established criteria, a third independent reader resolved any disagreements, and all readers were blinded to age, gender, treatment and clinical information. Changes in MRI findings were rated by comparing initial and follow up images. This approach reflects clinical practice and is optimal for rating changes in MRI findings over time
[43, 44]. Assessment of follow-up images blinded to the initial images, may introduce unwanted variation in the rating of any alterations.
Study limitations require attention. This sub-study of the original RCT should be considered exploratory in nature. It had small sample size and was not based on a separate power calculation. The wide time range (more than 50 days) between some of the pre-treatment MRIs (10 patients) and the start of the treatment may have clouded potential alterations in MC and HIZ due to GS. Furthermore, all readers knew that all of the images were from patients with MC and/or HIZ, and this knowledge may have influenced the evaluation. However, an abundant number of normal as well as abnormal spinal levels were evaluated. Slight variability in MRI technique introduced heterogeneity, but reflects clinical practice. We focused on two MRI abnormalities only and did not address other potentially relevant degenerative findings like disc- or facet degeneration, discs bulges or disc herniations. The location of MC within the endplate was not assessed. HIZ was not confirmed using discography and we did not apply contrast enhanced T1-weighted MRI, which may be more sensitive to detect HIZ than T2-weighted MRI
[45, 46]. However, Munter et al found no increased sensitivity to detect HIZ with contrast enhancement
. New biochemical MRI methods exist for evaluating the intervertebral disc, such as T2 mapping, T2* mapping and diffusion weighted imaging
[48–50]. These methods may be more sensitive to changes under therapy than the morphological MRI techniques used in our study.