Effects of unfractionated heparin on renal osteodystrophy and vascular calcification in chronic kidney disease rats.

Unfractionated heparin (UFH) is the most widely used anticoagulant in hemodialysis for chronic kidney disease (CKD) patients. Many studies have verified that UFH can induce bone loss in subjects with normal bone, but few have focused on its effect on renal osteodystrophy. We therefore investigated this issue in adenine-induced CKD rats. As CKD also impairs mineral metabolism systemically, we also studied the impacts of UFH on serum markers of CKD-mineral and bone disorder (CKD-MBD) and vascular calcification. We administered low and high doses of UFH (1U/g and 2U/g body weight, respectively) to CKD rats and compared them with CKD controls. At sacrifice, the serum markers of CKD-MBD did not significantly differ among the two UFH CKD groups and the CKD control group. The mean bone mineral densities (BMDs) of the total femur and a region of interest (ROI) constituted of trabecular and cortical bone were lower in the high-dose UFH (H-UFH) CKD group than in the CKD control group (P<0.05 and P<0.01, respectively). The BMD of the femoral ROI constituted of cortical bone did not differ between the H-UFH CKD group and the CKD control group. Histomorphometrical changes in the CKD rats indicated secondary hyperparathyroidism, and the femoral trabecular bone volume, but not cortical bone volume, significantly decreased with increasing UFH dose. The same decreasing trend was found in osteoblast parameters, and an increasing trend was found in osteoclast parameters; however, most differences were not significant. Moreover, no distinct statistical differences were found in the comparison of vascular calcium or phosphorus content among the CKD control group and the two UFH CKD groups. Therefore, we concluded that UFH could induce bone loss in CKD rats with secondary hyperparathyroidism, mainly by reducing the trabecular volume and had little effect on cortical bone volume. The underlying mechanism might involve inhibition of osteoblast activity and promotion of osteoclast activity by UFH. We did not find any effect of UFH on vascular calcification in CKD rats with secondary hyperparathyroidism.

Representación del desarrollo de la espongiosa primaria por medio de un sistema de reacción-difusión: Una hipótesis sobre el inicio de la formación de hueso inmaduro. Parte 1: Descripción del modelo / Representation of the development of the primary spongiosa by means of a reaction-diffusion system: a hypothesis on the onset of immature bone formation. Part 1: Model description

Se presenta un modelo bioquímico que predice la formación de la arquitectura de la espongiosa primaria, a partir de la interacción de 2 factores moleculares: VEGF (factor de crecimiento endotelial vascular) y MMP13 (metaloproteinasas 13). Se supone que el MMP13 regula la degradación del cartílago y el VEGF permite la vascularización y el avance del frente de osificación mediante la presencia de osteoblastos. El acople de este conjunto de moléculas se representa mediante ecuaciones de reacción-difusión con parámetros en el espacio de Turing, y se obtiene como resultado un patrón espacio-temporal estable que da paso a la formación de las trabéculas presentes en el tejido esponjoso...

A biochemical model is presented which predicts the formation of the architecture of the primary spongiosa, based on the interaction of two molecular factors: VEGF (vascular endothelial growth factor) and MMP-13 (metalloproteinases-13). It is assumed that MMP-13 regulates cartilage degradation, and VEGF allows vascularization and the advance of the ossification front through the presence of osteoblasts. The coupling of this set of molecules is represented by means of reaction-diffusion equations with Turing space parameters, and a stable spatio-temporal pattern is obtained which leads to the formation of the trabeculae present in the spongy tissue...

Representación del desarrollo de la espongiosa primaria por medio de un sistema de reacción-difusión: Una hipótesis sobre el inicio de la formación de hueso inmaduro. Parte 2: Implementación numérica / Representation of the development of the primary spongiosa by means of a reaction-diffusion system: a hypothesis on the onset of immature bone formation. Part 2: Numerical implementation

Se presenta la implementación numérica del modelo bioquímico descrito mediante el sistema de reacción-difusión de la parte 1. De los resultados obtenidos se puede concluir que la retroalimentación química de los 2 factores moleculares a través de un sistema de reacción-difusión (RD) con parámetros en el espacio de Turing, puede explicar la aparición de los patrones espacio-temporales encontrados en la arquitectura de la espongiosa primaria. Para la solución numérica fue usado el método de los elementos finitos junto con el método de Newton-Raphson para aproximar las ecuaciones diferenciales parciales lineales. Los patrones de osificación obtenidos pueden representar la formación de la espongiosa primaria durante la osificación endocondral...

A presentation is made of the numerical implementation of the biochemical model described by means of the reaction-diffusion system in Part 1. Based on the results obtained it may be concluded that the chemical feedback of the two molecular factors by means of a reaction-diffusion (RD) system with Turing space parameters may explain the appearance of the spatio-temporal patterns found in the architecture of the primary spongiosa. For the numerical solution, use was made of the finite element method in combination with the Newton-Raphson method to approximate the linear partial differential equations. The ossification patterns obtained may represent the formation of the primary spongiosa during endochondral ossification...