In vivo Labeling of Bone Microdamage in an Animal Model of Type 1 Diabetes Mellitus

Abstract

Type 1 diabetes mellitus (DM1) is linked to a decrease in bone strength. Bone strength entails both bone mineral density and bone quality. Limited data are available regarding diabetes-induced microdamage, which can severely influence bone quality. This study has investigated bone microdamage as a measure of bone quality in an animal model of DM1. Microdamage in the neck of the femur was labelled in vivo using multiple fluorochromes at 4, 12 and 24 weeks after the onset of DM1. Microcracks were quantified and their morphology analyzed using microscopy techniques. The mean length of microcracks at 24 weeks, and crack numerical and surface densities were significantly higher (p < 0.05) 4 weeks after the onset of DM1 when compared with control. Diffuse damage density was highest at 12 weeks after the onset of DM1. The arrangement of the collagen fibrils became progressively more irregular from 4 to 24 weeks of DM. This is the first study to analyze microdamage in vivo at different time points of DM1. DM1is associated with microcracks from the early stage, however bone microstructure shows toughening mechanisms that arrest their growth but disease progression further deteriorates bone quality resulting in longer microcracks which may increase fracture risk.

A new ex vivo model of the bone tissue response to the hyperglycemic environment – The embryonic chicken femur organotypic culture in high glucose conditions

“…Limirio et al also reported that bone biomechanical properties in diabetic rats are compromised due to the lack of proper collagen maturation, leading to loss of bone mineral content [10]. Mohsin at al referred that bone quality alterations in diabetic rats are even associated with the early stages of DM [55], being consistent with present study that establishes that the exposure to high glucose concentrations induces alteration on bone metabolism/development, even upon a short-term exposure.…”

“…Similar findings were described within in vivo studies with rodents. Mohsin et al [55], and Silva et al [56] reported, in their works, that bone structure is affected in rats with DM, with decrease bone mechanical proprieties as result of decreased matrix mineralization. Limirio et al also reported that bone biomechanical properties in diabetic rats are compromised due to the lack of proper collagen maturation, leading to loss of bone mineral content [10].…”