A mechanobiological bone remodelling model coupling bone physiology and systemic calcium and phosphorus homeostasis

  • Martinez-Reina, Javier (Universidad de Sevilla)
  • Calvo-Gallego, José Luis (Universidad de Sevilla)
  • Gutiérrez-Millán, Fernando (Universidad de Sevilla)
  • Pivonka, Peter (Queensland University of Technology)

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Bone remodelling (BR) models can be used to simulate the response of bone to various diseases such as osteoporosis (OP) and also to its treatment with drugs [1]. In the case of antiresorptive treatments, bone mass gain is mainly explained by the mineralisation of existing tissue. The process of bone mineralisation is fundamentally influenced by calcium and phosphorus concentrations in the bone marrow, which are regulated at three levels: 1) intestinal absorption, which controls the input of ions into the serum, 2) filtration in the kidney, which regulates their excretion into the urine, and 3) bone resorption, one of the phases of the BR process that constitutes a mechanism for recovery of the mineral accumulated in the bone matrix. These processes are regulated by hormones secreted by the endocrine system and by diet (mainly calcium and vitamin D intake). The concurrence of osteoporosis with endocrine and dietary disorders can aggravate the disease and compromise the effectiveness of treatments against OP, which justifies the need for a detailed study of the coupling between all processes. In this work, a mechanobiological model of BR previously developed [1] has been coupled with a physiological model of the regulation of calcium and phosphorus homeostasis [2]. The former includes a model of mechanical regulation that has allowed the analysis of the benefits of physical exercise in the treatment of OP. It also includes a model of fatigue damage accumulation in bone matrix, which has allowed the estimation of fracture risk in OP with and without treatment. The coupling with the calcium and phosphorus homeostasis model has made it possible to analyse the effect of diet and other diseases on OP and the effectiveness of drug treatments, concluding that renal insufficiency and a vitamin D deficit have a severe impact on the effectiveness of treatments.