Figure 3.

Graphical sketch, adapted from Pivonka et al. ³³, showing all mechanisms considered in the model presented in this paper, with novel contributions colored green and red: guidance of cell developments (OB_u → OB_p → OB_a and OC_p → OC_a) occurs biochemically (governed by TGF-β and the RANK-RANKL-OPG pathway, including the action of PTH) via related activator and repressor functions, π_act and π_rep, and biomechanically (the macroscopic loading Σ relates to microscopic loading σ_bm, causing microscopic deformations represented by the microscopic strain energy density Ψ_bm, the latter entering the bone cell population model); evolutions of the different cell developmental stages follows cell differentiation (considered through maximum differentiation rates , , and ), cell proliferation (considered through maximum proliferation rate ), and cell apoptosis (considered through maximum apoptosis rates and ); the mechanisms based on which the effects of PMO and denosumab administration, respectively, are depicted in the red-colored box (dotted thick lines) and in the green-colored box (dashed thick lines), respectively; see Sections 3.2–3.4 for details on related model extensions.