Bone diseases such as osteoporosis represent one of the major health care problems in the elderly. Osteoporosis results in a severe reduction in bone mass and weakening of bone micro-structure predisposing a person to an increased risk of spontaneous fractures at a relatively late stage of the pathology. Therefore, the determination of revealing risk factors is essential to identify patients at risk and to handle the disease preventively. For the clinician, predicting fracture risk for individual patients is nearly restricted to the quantitative analysis of bone density. However, bone which is a 'living biomaterial', adapts to strains by a redistribution of trabeculae by the remodeling process. It is now fully recognized that bone strength reflects the integration of two main features: bone density and bone quality. A good estimation of bone quality has to take into account critical parameters such as trabecular and cortical microarchitecture, bone remodeling, the degree of mineral content of the collagen and other proteins bone matrix, and the amount of microdamage present. Thus, detecting the micro-structural changes and their impact in the pathogenesis of bone fragility is a crucial point to better identify the risk of fractures and improve the rationale for specific treatment of bone fragility which is at the moment mainly related on bone remodelling blockage by biphosphonates therapy. The main purpose of this research project is to develop a predicting tool for giving early, accurate and reliable diagnosis of bone quality in presence of different pathologies in order to identify persons at risk for fracture, to choose and to evaluate the efficacy of the treatment. This project, which is an interdisciplinary collaborative effort of three teams, is organized around 3 highly interrelated objectives and phases, (i) Effect of pathology and treatment on mechanical and biological properties of bone (ii) Prediction of remodelling process at the representative volume elementary (RVE) scale (iii) Development of bone adaptation model based on topology optimization They are sketched right now: 1. Effect of pathology and treatment on mechanical and biological properties of bone. This part is based on analysis of architectural (microscaner, SEM, ulstrasound), biological (Mineral content, collagen properties) and mechanical (Elastic properties) properties of bone at various levels of the structural organization. 2. Prediction of remodelling process at the RVE scale. This part is based on experimental analysis of local damage and numerical model of bone remodelling of a set of Basic Multicellular Unit for typical RVE. Experimental results will provide local criterion damage to set up signal involve in resorption phase used in numerical model. 3. Development of bone adaptation model based on topology optimization able to understand and monitor pathologic states of bone at both macroscopic and microscopic scales over time in its changing environment. The major expected result of this project is to develop a diagnostic tool of bone quality to prevent fracture risk, based on bone adaptation model validate by advanced mechanical tests to different bone samples normal, pathological or remodelled.