Research Bioengineer The University of Massachusetts Dartmouth West Bridgewater, Massachusetts, United States
Introduction: There is a rapidly escalating prevalence of Type 2 diabetes mellitus (T2D), which is a consequence of insulin resistance and is characterized by impaired insulin regulation and production. T2D leads to hyperglycemia, disrupting glucose metabolism critical for the function of numerous organ systems including the skeletal system. Despite having average or increased bone density, individuals with T2D face an increased risk of bone fractures compared to non-diabetic counterparts. As fracture risk is conventionally assessed through bone mineral density, factors beyond density may contribute to increased fragility. These factors include microvascular complications that heighten the risk of falls, changes in tissue microstructure, or alterations in bone tissue quality. Altered bone tissue quality can occur when type I collagen, the primary organic component of bone, undergoes non-enzymatic glycation and produces advanced glycation end-products (AGEs) that detrimentally impact bone's mechanical properties. There may be higher levels of AGEs in T2D given that AGEs form due to a reaction involving extracellular sugars. This project aims to determine the mechanical properties and glycation content of human cadaveric trabecular bone with and without T2D. Compression tests will be conducted to measure compressive mechanical properties and a fluorometric assay will be used to quantify AGEs. We hypothesize there will be increased AGEs and deteriorated mechanical properties in T2D trabecular bone compared to non-diabetic bone, and that AGEs and mechanical properties will be inversely correlated with each other. Overall, this research will contribute to understanding the nuanced factors influencing bone health in T2D.
Materials and
Methods: The primary objective of this research project is to evaluate the mechanical properties of trabecular bone samples obtained from human cadavers with Type 2 Diabetes (T2D) and those without T2D. To accomplish this goal, we have two specific aims, Aim 1: Determine whether mechanical properties in human trabecular bone differ between control and T2D. Human cadaveric tibial plateaus will be used to extract trabecular bone cores; samples will come from both a control group and a group that has been diagnosed with Type 2 diabetes (T2D). To assess the mechanical qualities of the extracted cores, extensive compression testing will be performed. The purpose of this method is to identify any possible differences between the control and T2D groups' trabecular bone mechanical behavior. Aim 2: Determine whether glycation content in human trabecular bone differs between control and T2D. Following the conclusion of mechanical testing, a fluorometric assay will be implemented to quantify Advanced Glycation End Products (AGEs). This process involves measuring the natural fluorescence of AGEs utilizing a spectrophotometer. The obtained measurements will be normalized to the total collagen content, providing valuable insights into the presence and concentration of AGEs in the trabecular bone samples.
Results, Conclusions, and Discussions: Results from this work may provide important new information about how Type 2 Diabetes (T2D) influences trabecular bone, specifically regarding its mechanical characteristics and molecular makeup. It is critical to comprehend the mechanical changes in trabecular bone that are linked to type 2 diabetes (T2D) because it is unclear why there is an elevated risk of fracture in T2D patients who have average bone density. Our results will help determine whether factors beyond bone density, such as the accumulation of AGEs might impact the mechanical properties of bone with a consequent effect on bone fragility in T2D. It is anticipated that increased non-enzymatic glycation of type I collagen due to the chronic hyperglycemia characteristic of T2D will cause an accumulation of AGEs in the bone matrix. Specifically, AGEs can be elevated in the bone matrix as a result of a significant increase in the binding between extracellular sugars caused by chronic hyperglycemia in T2D patients with amino acids present on the type I collagen within the bone. T2D trabecular bone is expected to have a higher glycation content than the control group, and we anticipate this will help explain the observed changes in bone mechanical properties
