In Silico Modeling and Simulation of Bone Biology: A Proposal

Abstract

Contemporary, computer-based mathematical modeling techniques make it possible to represent complex biological mechanisms in a manner that permits hypothesis testing in silico. This perspective shows how such approaches might be applied to bone remodeling and therapeutic research.Currently, the dominant conceptual model applied in bone research involves the dynamic balance between the continual build-up and breakdown of bone matrix by two cell types, the osteoblasts and osteoclasts, acting together as a coordinated, remodeling unit. This conceptualization has served extraordinarily well as a focal point for understanding how mutations, chemical mediators, and mechanical force, as well as external influences (e.g., drugs, diet) affect bone structure and function. However, the need remains to better understand and predict the consequences of manipulating any single factor, or combination of factors, within the context of this complex system's multiple interacting pathways. Mathematical models are a natural extension of conceptual models, providing dynamic, quantitative descriptions of the relationships among interacting components. This formalization creates the ability to simulate the natural behavior of a system, as well as its modulation by therapeutic or dietetic interventions. A number of mathematical models have been developed to study complex bone functions, but most include only a limited set of biological components needed to address a few specific questions. However, it is possible to develop larger, multiscale models that capture the dynamic interactions of many biological components and relate them to important physiological or pathological outcomes that allow broader study. Examples of such models include Entelos' PhysioLab platforms. These models simulate the dynamic, quantitative interactions among a biological system's biochemicals, cells, tissues, and organs and how they give rise to key physiologic and pathophysiologic outcomes. We propose that a similar predictive, dynamical, multiscale mathematical model of bone remodeling and metabolism would provide a better understanding of the mechanisms governing these phenomena as well as serve as an in silico platform for testing pharmaceutical and clinical interventions on metabolic bone disease.

Multiscale investigation of the functional properties of the human femur

“…The risk of fracture predicted by the probabilistic FE model over the simulated population was similar to that reported in epidemiological studies (Melton et al 1986(Melton et al , 2005. In some applications, the clinical impact of FE models has been assessed (Cody et al 1999;Defranoux et al 2005;Keyak et al 2005;Melton et al 2005). In our application, the clinical impact of the model of the femur was evaluated by implementing two distinct clinical applications: tumour and hip prostheses.…”

Identification of CXCL13 as a marker for rheumatoid arthritis outcome using an in silico model of the rheumatic joint

“…An in silico model of a prototypical articular joint in a patient with RA was created previously (RA PhysioLab platform; Entelos) (10,11). This RA PhysioLab platform represents the biology of RA with regard to synovial tissue inflammation, cartilage destruction, and bone erosion.…”

From mechanical stimulus to bone formation: A review

“…The use of conceptual and mathematical models has already proven valuable in bone research [154]. Advances in scientific knowledge, mathematical modelling, and computer technology has facilitated the integration of numerical equations into finite element models [155].…”