Thesis
Characterising spinal cord injury-induced osteoporosis in a rat model using micro computed-tomography and histology
- Creator
- Rights statement
- Awarding institution
- University of Strathclyde
- Date of award
- 2022
- Thesis identifier
- T16443
- Person Identifier (Local)
- 201756233
- Qualification Level
- Qualification Name
- Department, School or Faculty
- Abstract
- Severe spinal cord injury (SCI) can result in the complete or partial paralysis ofsublesional (below the level of injury) limbs. Associated with this are a large number of secondary complications which include a higher risk of bone ‘fragility fractures’ due in part to the removal of muscle-driven bone stimulation. The fractures occur most commonly in the trabecular bone-rich distal femur and proximal tibia during movements such as falls and transferring from bed to wheelchair. The occurrence of these fractures increases with time post-injury. Complications arising from these fractures decrease quality of life and increase morbidity and mortality in the affected population. This thesis aims to characterise the acute and chronic effects of complete SCI in the distal femur and proximal tibia using a rat model, through analysing the bone quantity and microarchitecture, resorption activity and blood supply using several newly developed methods to give deeper understanding of the condition. The high-resolution obtained with micro computed-tomography (microCT) is utilised to present new insights into the bone’s morphological and topological changes following SCI. Additionally, quantitative histology is employed to analyse the average number of osteoclasts (bone removing cells) and blood vessels in the affected regions. Insights from microCT and histology are combined where possible to provide a more complete picture of the progression of SCI-induced osteoporosis from the acute to chronic stages. Following SCI, rapid bone loss was found in the trabecular bone, which worsened slightly by the chronic stages. At 2 weeks post-injury (the acute stage), bone volume fraction was seen to reduce by 61% in the proximal tibia compared to age-matched, sham-operated controls. A 71% decrease was seen by 11 weeks post-injury (the chronic stage). This trend was also displayed in the average trabecular thickness (↓12/23%) and number (↓55/64%) in the two sets of rats, respectively. Only analysed at the chronic timepoint, the distal femur mirrored the proximal tibia results in trabecular bone loss. SCI also exhibited a significant effect on the rod-like/plate-like distribution of trabeculae in the distal femur, with median ellipsoid factor increasing by 163%, whereas no such change was detected at either timepoint in the proximal tibia. These results suggest that the plate-to-rod transition thought to affect osteoporotic bone occurs in a region-specific manner. The node type abundance (relative numbers of trabecular junctions of 3, 4 or 5 trabeculae) was significantly altered in both the distal femur (4N nodes) and proximal tibia (3N nodes) in chronic SCI rats, however it remained unaltered in the proximal tibia in acute SCI rats. The average angle between trabeculae was not altered in chronic SCI rats in both the distal femur and the proximal tibia, however, the in acute SCI rats, the proximal tibia exhibited a significantly reduced mean inter-trabecular angle in each of the three node types. These results suggest that the bone microarchitecture suffers in acute SCI due to an impairment in the trabecular topology; the trabeculae are less optimally aligned for mechanical load transmission due to bone remodelling effects and trabecular breakages. This impairment appears to be recovered in chronic SCI rats, with the slightly altered node type abundance ratios remaining as evidence of long term disruption in the bone remodelling balance. The cortical bone exhibited a slower response to SCI, with no change in proximal tibia cortical area in acute SCI rats, but a decrease of 18% in chronic SCI rats. Cortical bone tissue mineral density was not seen to be altered in either acute or chronic rats compared to sham controls. These results indicate that bone quality impairment due to SCI is due to morphological and topological changes in the affected bone, as opposed to a decrease in the average density of the bone mineral. Also only analysed in chronic SCI rats, the histology results helped provide a deeper understanding of the bone cell response to complete SCI. The trabecular resorption activity was not seen to be altered at the chronic stage, but the trabecular microvessel density was seen to significantly decrease by 52% compared to control in the chronic SCI distal femur. No significant change in cortical microvessel density was observed. This suggests region-specific changes in blood supply to trabecular bone, whilst cortical bone vasculature appeared to remain unaffected. The results also illustrate that the initial bone loss effects are likely due to increased resorption activity of each osteoclast, as opposed to greater numbers of the bone removing cells. Combined, the findings from the microCT and histology assessments lend weight to the idea that bone loss following SCI occurs site-specifically and at different rates throughout the sublesional long bones. They also highlight that the rapid onset of trabecular bone microarchitecture reduction is worsened by an impairment in the network’s topology and local morphometry. Additionally, the results suggest that activity of the pre-existing osteoclasts increases to produce the resorption effects following SCI, as opposed to a greater recruitment of new osteoclasts to the affected sites. Although the trabecular topology (mean inter-trabecular angle) is shown to recover the initial impairment over time, the mean local morphometry (ellipsoid factor) can display significant lasting effects due to chronic SCI. Finally, it is indicated that the blood network in trabecular bone is significantly diminished at the chronic timepoint post-injury.
- Advisor / supervisor
- Coupaud, Sylvie
- Reid, Stuart
- Williams, Jonathan A.
- Resource Type
- DOI
Relações
Itens
Miniatura | Título | Data de carga | Acesso | Ações |
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PDF of thesis T16443 | 2022-12-13 | Público | Baixar |