Descripción del proyecto
Diabetes de tipo 2 y una estrategia novedosa para determinar el riesgo de fractura ósea
La diabetes de tipo 2 (DT2 o T2D en sus siglas inglesas) altera las propiedades materiales intrínsecas de la matriz ósea y, en consecuencia, se relaciona con una triplicación del riesgo de sufrir una fractura ósea. Las técnicas diagnósticas actuales no pueden predecir la probabilidad de sufrir una fractura con DT2. Se cree que el entrecruzamiento no enzimático de proteínas orgánicas, conocido como acumulación de productos finales de glicación avanzada, es el responsable de la fragilidad ósea en la DT2. Sin embargo, todavía no está clara la forma en que las configuraciones alteradas de las proteínas afectan a la biomecánica de todo el hueso. El proyecto MULT2D, financiado con fondos europeos, desarrolla un marco computacional que relaciona el comportamiento molecular con la estructura de todo el hueso para descubrir los mecanismos responsables de la fragilidad ósea diabética. El proyecto establecerá una estrategia novedosa para la determinación del riesgo de fractura clínica.
Objetivo
Type-2 (T2) Diabetes is associated with a 3-fold increase in bone fracture risk, despite the fact that bone volume is not reduced. This implies that T2 diabetes impairs bone quality, whereby the intrinsic material properties of the bone matrix are altered. However, current diagnostic techniques are unable to predict fracture probability in T2 diabetes as they are based on measures of bone quantity. While it is believed that non-enzymatic cross-linking of organic proteins (also known as AGE accumulation) in the bone matrix is responsible for bone fragility in T2 diabetes, there is a distinct lack of understanding how altered protein configurations impair whole-bone biomechanics. In this project, the applicant will embark on frontier research that will develop a state-of-the-art multiscale computational framework that couples behaviour from the molecular to whole-bone level, providing a basis to interrogate and elucidate the physical mechanisms that are responsible for diabetic bone fragility. A multiscale experimental framework will, for the first time, establish relationships between AGE crosslink-density and whole-bone fragility in animal and human T2 diabetic bone tissue. Together, this data will inform a probabilistic mutli-level model of hip fracture, which will be used to quantitatively evaluate the relationship between hip fracture probability, bone quantity and bone quality. The research programme will also establish a novel strategy for clinical fracture risk assessment that employs existing protocols to measure bone quantity, in combination with a surrogate measure of bone quality. The surrogate measure of bone quality proposed is a systemic measure of AGE content, which is clinically-obtainable through a blood sample and therefore widely-applicable. Overall, the project will provide a ground-breaking advance in our understanding of bone fragility, with remarkable potential to innovate novel solutions for clinical assessment of T2 diabetic bone disease.
Ámbito científico
Palabras clave
Programa(s)
Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
H91 Galway
Irlanda