Table 2.

Values and description of the mechanical parameters.

	Description	Unit	Value	References
Denosumab
Dose	Drug dose	mg/kg	0.1, 0.3, 1.0, 3.0	33
$k_a$	Absorption rate	1/day	0.167	33
$k_{\mathit{int}}$	Drug–ligand complex internalization	1/day	$2.67\times {10}^{-2}$	33
$k_{\mathit{el}}$	Elimination rate of drug from central compartment	1/day	$2.12\times {10}^{-2}$	33
$K_D$	$K_D=k_{\mathit{off}}/k_{\mathit{on}}$	M	$3.0\times {10}^{-12}$	33
$V_C/F$	Central compartment volume	l/kg	0.114	33
$R_{\mathit{ss}}$	Steady-state free ligand concentration	nM	1.07	33
$I_{\mathit{max}}$	Maximal fractional extent of inhibition	–	0.331	33
$I{C}_{50}$	Concentration producing 50$\%$ of maximal inhibition	nM	2.64	33
$k_{\mathit{out}}$	Rate of loss of response	1/day	0.572	33
Ibandronate
Dose	Drug dose	mg	0.25, 0.5, 1.0, 2.0	8
$V_{\mathit{pl}}$	Plasma compartment volume	l	4.30	35
$V_{p1}$	Peripheral-1 compartment volume	l	2.80	35
$V_{p2}$	Peripheral-2 compartment volume	l	8.70	35
$V_b$	Bone compartment volume	l	609.00	35
$Q_{p1}$	Plasma-peripheral-1 compartmental clearances	l/day	69.43	35
$V_{p2}$	Plasma-peripheral-2 compartmental clearances	l/day	18.57	35
$V_b$	Plasma-bone compartmental clearances	l/day	51.71	35
CL	Renal clearance	l/day	57.00	35
KS	uCTX formation rate	$\mu \text{g mmol}{\text{CR}}^{-1}{\text{day}}^{-1}$	231.43	35
KD	uCTX degradation rate	1/day	0.68	35
$R_{\mathit{tar}}$	Limiting value of uCTX formation rate	$\mu \text{g mmol}{\text{CR}}^{-1}{\text{day}}^{-1}$	194.29	35
$k_{\mathit{qq}}$	Rate constant by which $R_{\mathit{tar}}$ obtained	l/day	0.0024	35
$I{C}_{50}$	Ibandronate concentration producing 50% of maximum response	$\mu g{l}^{-1}$	0.37	35
n	Hill coefficient	–	1.92	35