Author : Madge Martin
Publisher :
ISBN 13 :
Total Pages : 0 pages
Book Rating : 4.:/5 (128 download)
Book Synopsis Bone Remodeling and Mechanomics by : Madge Martin
Download or read book Bone Remodeling and Mechanomics written by Madge Martin and published by . This book was released on 2019 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Our skeleton, an essential structure for the human body, has multiple functions, among which are the regulation of metabolism and the protection of organs. We focus here on bone remodeling, a process by which the structure and chemical composition of bone evolve over time. The biochemical and structural changes of bone tissue are orchestrated by bone cells, able to synthesize bone matrix (osteoblasts), resorb mineralized bone (osteoclasts), and to regulate biochemical signaling pathways according to their mechanical environment (osteocytes). In this context, we are particularly interested in mechanomics, which is the description of the action of mechanics on biological tissues.We first study the mechanics of bone remodeling at the cellular level, where signaling pathways are essential. We therefore introduce a fine mathematical representation of bone remodeling by a system of differential equations describing the interactions between bone cells of osteoclastic and osteoblastic lineages, as well as the regulation of the biochemical environment by osteocytes. This model reproduces the bone loss in the contexts of micro-gravity during space flight and postmenopausal osteoporosis (PMO). The development of a pharmacokinetic-pharmacodynamic model coupled with biochemical dynamics makes it possible to link the dosage of an anabolic treatment of PMO (romosozumab) and the gain of bone mass, which would be beneficial for the design of a treatment specific to the patient.We also propose a macroscopic description of bone remodeling based on a generalized continuum mechanics model. First, this representation is introduced in the context of rotary remodeling of the bone microstructure. Indeed, bone is a material with a micro-architecture, composed of a mineralized collagen matrix and a fluid phase which hosts active bone cells. First, we propose an analytical identification of stable equilibrium states of rotary remodeling. This theory is then used in a 2D finite element study applied to the human femoral head. Finally, we enrich this theoretical framework by linking macroscopic mechanics to mechanobiology: the kinematics of bone remodeling is described through the evolution of macroscopic deformation, microstructural rotation, mineral fraction, porous fraction and cells concentrations. This description encompassing chemistry, biology and mechanics provides a structure for the study of interactions between these three fields in the context of remodeling. The promising results of our preliminary simulations enable an interpretation of remodeling on a small scale that can be compared with clinical data.Finally, we present in this thesis a first clinical application of our multi-scale theory with the study of bone remodeling in patients with idiopathic scoliosis of the adolescent (AIS), pathology of unknown origin characterized by a three-dimensional deviation of the spine. The analysis of the first vertebral body samples from AIS patients taken intraoperatively suggests a dependence of the properties of the material on the abnormal loading conditions due to the pathology. These observations motivate the prospect of a comparison of these results with simulations based on our mechanistic theory.In summary, we present in this thesis several bone remodeling modeling approaches, resulting in the development of a novel unifying theory whose purpose is to better understand and address the mechanisms of bone pathologies, which ultimately aim at the development of patient-specific therapeutic solutions.