Computational Analysis of the Influence of Menopause and Ageing on Bone Mineral Density, Exploring the Impact of Bone Turnover and Focal Bone Balance-A Study on Overload and Underload Scenarios.

This study aims to investigate the impact of hormonal imbalances during menopause, compounded by the natural ageing process, on bone health. Specifically, it examines the effects of increased bone turnover and focal bone balance on bone mass. A three-dimensional computational bone remodeling model was employed to simulate the response of the femur to habitual loads over a 19-year period, spanning premenopause, menopause, and postmenopause. The model was calibrated using experimental bone mineral density data from the literature to ensure accurate simulations. The study reveals that individual alterations in bone turnover or focal bone balance do not fully account for the observed experimental outcomes. Instead, simultaneous changes in both factors provide a more comprehensive explanation, leading to increased porosity while maintaining the material-to-apparent density ratio. Additionally, different load scenarios were tested, demonstrating that reaching the clinical osteoporosis threshold is independent of the timing of load changes. However, underload scenarios resulted in the threshold being reached approximately 6 years earlier than overload scenarios. These findings hold significant implications for strategies aimed at delaying the onset of osteoporosis and minimizing fracture risks through targeted mechanical stimulation during the early stages of menopause.

The interplay between BMU activity linked to mechanical stress, specific surface and inhibitory theory dictate bone mass distribution: Predictions from a 3D computational model.

Bone mechanical and biological properties are closely linked to its internal tissue composition and mass distribution, which are in turn governed by the purposeful action of the basic multicellular units (BMUs). The orchestrated action of osteoclasts and osteoblasts, the resorbing and forming tissue cells respectively, in BMUs is responsible for tissue maintenance, repair and adaptation to changing load demands through the phenomenon known as remodelling. In this work, a computational mechano-biological model of bone remodelling based on the inhibitory theory and a new scheme of bone resorption introduced previously in a 2D model, is extended to a 3D model of the real external geometry of a femur under normal walking loads. Starting from a uniform apparent density (ratio of tissue local mass to total local volume) distribution, the BMU action can be shown to lead naturally to an internal density distribution similar to that of a real bone, provided that the initial density value is high enough to avoid unrealistic final mass deposition in zones of high energy density and excessive damage. Physiological internal density values are reached throughout the whole 3D geometry, and at the same time a 'boomerang'-like relationship between apparent and material density (ratio of tissue mass to tissue volume) emerges naturally under the proposed remodelling scheme. It is also shown here that bone-specific surface is a key parameter that determines the intensity of BMU action linked to the mechanical and biological requirements. Finally, by engaging in simulations of bone in disuse, we were able to confirm the appropriate selection of the model parameters. As an example, our results show good agreement with experimental measurements of bone mass on astronauts a fact that strengthens our belief in the insightful nature of our novel 3D computational model.

Influence of Chromium-Cobalt-Molybdenum Alloy (ASTM F75) on Bone Ingrowth in an Experimental Animal Model.

Cr-Co-Mo (ASTM F75) alloy has been used in the medical environment, but its use as a rigid barrier membrane for supporting bone augmentation therapies has not been extensively investigated. In the present study, Cr-Co-Mo membranes of different heights were placed in New Zealand white, male rabbit tibiae to assess the quality and volume of new bone formation, without the use of additional factors. Animals were euthanized at 20, 30, 40, and 60 days. Bone formation was observed in all of the cases, although the tibiae implanted with the standard membranes reached an augmentation of bone volume that agreed with the density values over the timecourse. In all cases, plasmatic exudate was found under the membrane and in contact with the new bone. Histological analysis indicated the presence of a large number of chondroblasts adjacent to the inner membrane surface in the first stages, and osteoblasts and osteocytes were observed under them. The bone formation was appositional. The Cr-Co-Mo alloy provides a scaffold with an adequate microenvironment for vertical bone volume augmentation, and the physical dimensions and disposition of the membrane itself influence the new bone formation.

Localized tissue mineralization regulated by bone remodelling: A computational approach.

Bone is a living tissue whose main mechanical function is to provide stiffness, strength and protection to the body. Both stiffness and strength depend on the mineralization of the organic matrix, which is constantly being remodelled by the coordinated action of the bone multicellular units (BMUs). Due to the dynamics of both remodelling and mineralization, each sample of bone is composed of structural units (osteons in cortical and packets in cancellous bone) created at different times, therefore presenting different levels of mineral content. In this work, a computational model is used to understand the feedback between the remodelling and the mineralization processes under different load conditions and bone porosities. This model considers that osteoclasts primarily resorb those parts of bone closer to the surface, which are younger and less mineralized than older inner ones. Under equilibrium loads, results show that bone volumes with both the highest and the lowest levels of porosity (cancellous and cortical respectively) tend to develop higher levels of mineral content compared to volumes with intermediate porosity, thus presenting higher material densities. In good agreement with recent experimental measurements, a boomerang-like pattern emerges when plotting apparent density at the tissue level versus material density at the bone material level. Overload and disuse states are studied too, resulting in a translation of the apparent-material density curve. Numerical results are discussed pointing to potential clinical applications.