Characterisation of disuse-related osteoporosis in an animal model of spinal cord injury

Student thesis: Doctoral Thesis

Abstract

Injury to the spinal cord can result in paralysis below the level of injury. A secondary complication of the removal of muscle-driven bone stimulation is the development of rapid osteoporosis in the bones of the paralysed limbs. The severe deterioration of both bone quantity and quality means that spinal cord injury (SCI) patients are at a significantly higher risk of fragility fractures in the lower extremities than the able-bodied population.These fractures occur most commonly around the knee (distal femur and proximal tibia). This thesis presents a characterisation of the time-course effects a complete SCI has on the fracture-prone distal femur in a rat model. The aims are to characterise the quality and distribution of bone and to provide a uniquely detailed description of its response to SCI at various time points post-injury.Bone quality is assessed using i) ex vivo micro-Computed Tomography (┬ÁCT) for global and site-specific analysis of both trabecular and cortical bone morphometry and densitometry, and ii) three-point bending and torsional mechanical testing to provide whole-bone structural and material level properties.Evidence is presented that SCI-induced osteoporosis is site-specific within the same appendicular bone. A rapid and severe deterioration of metaphyseal trabecular bone was observed, after just 2 weeks trabecular volume fraction (BV/TV) had decreased by 59% compared to age-matched sham-operated controls. This resulted in a compromised structure composed of on average 53% fewer and 15% thinner trabeculae compared to control.At later time points post-SCI there were no further significant reductions in metaphyseal BV/TV, although significant microstructural changes did occur. On the other hand, the more distally located epiphyseal trabecular bone was structurally more resistant to SCI-induced osteoporosis. There was a 23% decrease in BV/TV at 2 weeks post-SCI compared to control, characterised by a 15% decrease in trabecular thickness, thus unlike metaphyseal trabecular structures, the epiphyseal structure's connectivity was maintained. At later time points post-SCI there was a growth-related increase in epiphyseal BV/TV.Rapid changes to cortical bone were also seen, with distal-metaphyseal regions experiencing the most severe decrease in cortical area at 2 weeks post-SCI compared to control. The varying degrees of change in the amount of both trabecular and cortical bone appears concomitant with each region's bone surface to volume ratio. Analysis of more chronic time points post-SCI (6, 10 and 16 weeks) highlights that caution must be exercised when interpreting results from rodent studies.The analysis performed here indicates that SCI-induced bone changes are a combination of bone loss and suppressed bone growth. No difference in cortical tissue mineral density was observed between SCI and control groups at any time-points assessed, indicating that the decreases in whole-bone mechanical properties observed due to SCI were primarily a result of changes to the spatial distribution of bone.Cumulatively, this thesis illustrates that SCI-induced osteoporosis has detrimentally affected the spatial distribution of both trabecular and cortical bone in site-specific ways, but the bone material itself does not appear affected.
Date of Award1 Oct 2018
LanguageEnglish
Awarding Institution
  • University Of Strathclyde
SponsorsEPSRC (Engineering and Physical Sciences Research Council)
SupervisorSylvie Coupaud (Supervisor) & James Windmill (Supervisor)

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