The degenerate human lumbar vertebral endplate – a mechanical, clinical and histological analysis

Marjoram, Tom (2021) The degenerate human lumbar vertebral endplate – a mechanical, clinical and histological analysis. Doctoral thesis, University of East Anglia.

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Abstract

Background
Low back pain is an increasingly common health problem. Treatment employs a range of surgical and non-surgical techniques. The adult intervertebral disc is one source of significant pain although each individual element of the functional spinal unit interacts with one another. The disc normally is largely avascular thus relying on nutritional support from the adjacent vertebral endplates. The vertebral endplate undergoes a process of degeneration alongside degeneration of the disc and has also been implicated in itself as a pain source. In a proportion of those with degeneration (but not exclusively) vertebral endplate changes can be seen on MRI imaging as described by Modic. There is little understanding of the changes in the degenerate endplate. An understanding of the changes seen at the endplate will contribute to the overall understanding of the process of degeneration in the spine.

Aims
This work aims to study the effects of degeneration of the human lumbar intervertebral disc on the endplate. The analysis incorporates the mechanical properties of indentation modulus and hardness, a clinical study exploring the translation of these mechanical properties into medical practice and a histological analysis exploring vascularity, inflammation and bone turnover.

Methods
Nano-indentation techniques have been applied to fresh, non-embedded human vertebral endplate samples taken at the time of surgery for symptomatic degenerative disc disease. Two sets of samples are included from those without degenerate discs for comparison.
Histological analysis has been performed on a representative selection of the same samples using immuno-stains for CD-3, CD-20, CD-31 and CD-56, giving unique mechanical and histological analysis of the same samples.
MRI study of each individual case had defined the clinical status of the disc and endplate. A parallel clinical analysis of post-operative lumbar interbody device subsidence at 12 months has been undertaken including patients from two independent tertiary specialist spinal surgery centres in order to bridge the basic science into clinical fields.

Results
Degeneration significantly increases the stiffness of the endplate by 26.4% (3.623GPa vs 4.581GPa) and the underlying trabecular bone by 19.8% (4.185GPa vs 5.014GPa) while also increasing the hardness of the trabeculae by 9.3% (0.150GPa vs 0.164GPa).
The presence of type 1 or type 2 Modic changes at the endplate is associated with an increase in indentation modulus and hardness at both the endplate and the underlying trabecular bone while type 3 changes showed the reverse with a decrease in indentation modulus and hardness in both regions.
Histological analysis showed degeneration to be associated with increased calcification of the cartilaginous portion of the endplate, increased vascularity in the region of the endplate and an increase in the number of CD-56 staining Osteoblast lineage cells.
Modic type 2 changes were found to be associated with an increase in endplate variability and Osteoblast lineage cells indicating a state of increased bone turnover.
Interbody fusion device subsidence was found to be highest in those with type 2 Modic changes and lowest in those with type 3 changes. This indicates that the increased hardness and stiffness in Modic 2 changes are detrimental to the mechanical stability of the device clinically.

Conclusions
Degeneration has been found to affect the mechanical properties of the human lumbar spine endplate. Modic pathology in degeneration has been shown to affect the mechanical properties which in turn (as a secondary outcome) affect the rate of clinical lumbar interbody fusion device subsidence: type 2 Modic changes have a detrimental effect and type 3 seem to offer some favourable mechanical properties. An increase in histological endplate calcification is accompanied by an increase in vascularity and markers of bone turnover, likely as a response to altered force transmission from the degenerating disc.

Item Type:	Thesis (Doctoral)
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User:	Chris White
Date Deposited:	17 Nov 2021 14:52
Last Modified:	17 Nov 2021 14:52
URI:	https://ueaeprints.uea.ac.uk/id/eprint/82153
DOI:

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