Changes in bone macro- and microstructure in diabetic obese mice revealed by high resolution microfocus X-ray computed tomography.

G Kerckhofs,R Vangoitsenhoven,C Marin,G Carmeliet,K Vandamme,B Van Der Schueren,M Durand,L Geris,F P Luyten

doi:10.1038/srep35517

Abstract

High resolution microfocus X-ray computed tomography (HR-microCT) was employed to characterize the structural alterations of the cortical and trabecular bone in a mouse model of obesity-driven type 2 diabetes (T2DM). C57Bl/6J mice were randomly assigned for 14 weeks to either a control diet-fed (CTRL) or a high fat diet (HFD)-fed group developing obesity, hyperglycaemia and insulin resistance. The HFD group showed an increased trabecular thickness and a decreased trabecular number compared to CTRL animals. Midshaft tibia intracortical porosity was assessed at two spatial image resolutions. At 2 μm scale, no change was observed in the intracortical structure. At 1 μm scale, a decrease in the cortical vascular porosity of the HFD bone was evidenced. The study of a group of 8 week old animals corresponding to animals at the start of the diet challenge revealed that the decreased vascular porosity was T2DM-dependant and not related to the ageing process. Our results offer an unprecedented ultra-characterization of the T2DM compromised skeletal micro-architecture and highlight an unrevealed T2DM-related decrease in the cortical vascular porosity, potentially affecting the bone health and fragility. Additionally, it provides some insights into the technical challenge facing the assessment of the rodent bone structure using HR-microCT imaging.

Highlights

Fractures are problematic because T2DM patients exhibit longer and impaired fracture healing and poorer outcomes after fracture[7]
This well-described animal model closely parallels the common course of the human disease by firstly develop obesity so as to develop diabetes. 3D-investigation of the T2DM bone structural alterations was performed by using a desktop high resolution microfocus X-ray computed tomography (HR-microCT) approach
T2DM is a complex and multifactorial disease largely resulting from a Western style diet and an excessive weight

Summary

Introduction

Fractures are problematic because T2DM patients exhibit longer and impaired fracture healing and poorer outcomes after fracture[7]. As animal models are valuable tools for the investigation of diabetic complications, the present study aimed at exploring the influence of T2DM on the bone structural properties in the high fat diet (HFD) mouse model of obesity-driven T2DM This well-described animal model closely parallels the common course of the human disease by firstly develop obesity so as to develop diabetes. 3D-investigation of the T2DM bone structural alterations was performed by using a desktop high resolution microfocus X-ray computed tomography (HR-microCT) approach This technique allows assessing the trabecular and cortical bone macrostructure, but it provides quantification of the microstructure by isolating the vascular canal porosity independently from the lacunar porosity in the cortex at high resolution in a time and cost saving way. Data gleaned from the present study provide a better characterization of the T2DM compromised skeletal macro- and micro-architecture and, highlight unrevealed T2DM-related changes in the cortical vascular porosity

Methods

Results

Conclusion