TABLE 6.

Methods adopted to incorporate denosumab and PTH drugs in mathematical models.

Drug	Changed parameters	Method	References
Denosumab	Activation function of preosteoclast differentiation	Adding a term reflecting denosumab–RANKL binding in the calculation of RANKL concentration.	Scheiner et al., 2014; Martínez-Reina and Pivonka, 2019
	Paracrine parameter of osteoblasts	The paracrine parameter depends on a function of denosumab concentration, this latter induce low RANKL effect on osteoclasts since the paracrine parameter is negative	Hambli et al., 2016
	Activation function of preosteoclast differentiation	RANK concentration is modified by adding denosumab occupancy term, which reflects denosumab–RANKL binding	Marathe et al., 2008
PTH	- Preosteoclasts proliferation term - Lining cells differentiation term - Osteoblast apoptosis term	- Preosteoclast proliferation and lining cell differentiation terms have been controlled by a function driven by the concentration of PTH and that depends on β-catenin concentration. - β-Catenin concentration depend on Dv1 and Axin–APC–GSK-3 complex - Axin–APC–GSK-3 complex production rate is regulated by PTH - The osteoblast apoptosis rate has been controlled by a function driven by the concentration of PTH and that depends on Bcl-2, CBEB, and Runx2 concentrations.	Trichilo et al., 2019
	Active osteoblast apoptosis rate	- The osteoblast apoptosis rate has been controlled by a function driven by the concentration of PTH and that depends on Bcl-2 concentration, which depends on PTH concentration.	Lavaill et al., 2020

RANKL, receptor activator of NFκB ligand; PTH, parathyroid hormone.