Global and site-specific analysis of bone in a rat model of spinal cord injury-induced osteoporosis

Jonathan A Williams,James F.C Windmill,K Elizabeth Tanner,John S Riddell,Sylvie Coupaud

doi:10.1016/j.bonr.2019.100233

Jonathan A Williams, James F.C Windmill + Show 3 more

Open Access

https://doi.org/10.1016/j.bonr.2019.100233

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Journal: Bone Reports	Publication Date: Nov 29, 2019
Citations: 10	License type: cc-by

Affiliation: University of Strathclyde, University of Glasgow

Abstract

Micro-Computed Tomography bone analysis is the gold standard method for assessing trabecular and cortical bone microarchitecture in small animal bones. This technique reports morphometric parameters as averages over selected volumes of interest (VOIs). This study proposes the introduction of an additional global 2D morphometric step into the analysis process, that provides a survey of the underlying morphometric variation present throughout both trabecular and cortical bone. The visualisation of these morphometric distributions provides a systematic approach to VOI selection that provides rationale and adds confidence to subsequent 3D morphometric analysis. To test the applicability and value of this methodological addition it was applied to the distal femur of a rat model of spinal cord injury (SCI)-induced osteoporosis. The 2D morphometric variation of both trabecular and cortical bone was quantified as a function of bone length. SCI-induced osteoporosis was localised in i) trabecular bone, where metaphyseal bone was more severely affected than epiphyseal bone, and there was a significant reduction in Distal Femoral Trabecular Extent, a new parameter defined here that quantifies how far trabecular bone penetrates in to the marrow cavity, ii) cortical bone, where diaphyseal bone underwent significant lowering of both cortical area and thickness, while distal-metaphyseal bone did not. Theses site-specific changes were validated, further elucidated and compared with follow-up conventional 3D analysis. The techniques applied here are equally applicable to other long bones (tibia, humerus, radius, ulna), other types of imaging modality and other types of experimental design including the effects of rehabilitation, aging, loading, gene knockout and pharmacological intervention.

Highlights

Micro-Computed Tomography is the gold standard technique for the assessment of trabecular and cortical bone micro-architecture, in the bones of mice and rats (Bouxsein et al, 2010)
This study used two approaches to characterise the morphometry of the distal femur in a T9 transection rat model of spinal cord injury (SCI) at 10 weeks postsurgery
A global 2D ‘slice-by-slice’ approach was developed and implemented with custom-made MATLAB scripts, where 2D morphometric parameters are expressed as a function of bone length

Summary

Introduction

Micro-Computed Tomography (μCT) is the gold standard technique for the assessment of trabecular and cortical bone micro-architecture, in the bones of mice and rats (Bouxsein et al, 2010). This pipeline most commonly consists of 6 main steps: scanning, reconstruction, orientation, segmentation, volume of interest (VOI) selection and 3D morphometric analysis. While if the size of the VOI is not appropriate it may dilute site-specific effects, for example if a trabecular VOI is very long (e.g. extending far into the diaphysis), the volume fraction of trabecular bone relative to a shorter VOI will be lower, problems occur when the VOI chosen is too small. While if the size of the VOI is not appropriate it may dilute site-specific effects, for example if a trabecular VOI is very long (e.g. extending far into the diaphysis), the volume fraction of trabecular bone relative to a shorter VOI will be lower, problems occur when the VOI chosen is too small. 3D analysis performed on VOIs provides morphometric parameters as averages, to acquire meaningful parameters, the variation of the parameter must be small enough such that

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