Osteoporosis: a multiscale modeling viewpoint

Nicola Paoletti, Pietro Liò, Emanuela Merelli, Marco Viceconti

Abstract: Our work focuses on bone remodeling with a multiscale breadth that ranges from modeling intracellular and intercellular RANK/RANKL signaling to tissue dynamics. Several important findings provide clear evidences of the multiscale properties of bone formation and of the links between RANK/RANKL and bone density in health and disease conditions. Recent studies indicate that the circulating levels of OPG and RANKL are inversely related to bone turnover and bone mineral density (BMD) and contribute to the development of osteoporosis in postmenopausal women, and thalassemia-induced osteoporosis. We make use of a spatial process algebra, the Shape Calculus, to control stochastic cell agents that are continuously remodeling the bone. We found that our description is effective for such a multiscale, multilevel process and that RANKL signaling small dynamic concentration defects are greatly amplified by the continuous alternation of absorption and formation resulting in large structural bone defects.