RANKL, a necessary chance for clinical application to osteoporosis and cancer-related bone diseases

Table 1 Comparison of features between ovariectomy and GST-RANKL bone loss models

Technique	OVX model	GST-RANKL bone loss model
Technique	OVX	Intraperitoneal injections
Term for establishment	> 4 wk	24-50 h
Term for evaluation of BP	> 4 wk	3 d
Term for evaluation of PTH	> 4 wk	14 d
Term for evaluation of SERM	> 4 wk	18 d
Term for evaluation of anti-human RANKL	No	9 d
Term for evaluation of Tec tyrosine kinase inhibitor
	NA	50 h
Evaluation of male animals	No	Yes
Term for pharmacological experiments	Several mon	Several wk/d
Advantages
	Human disease model	Rapid, easy, simple, and inducible model

GST-RANKL: Glutathione-S transferase-receptor activator of nuclear factor-κB ligand; OVX: Ovariectomy; NA: Not available; BP: Bisphosphonates; SERM: Selective estrogen receptor modulator; PTH: Parathyroid hormone.

Table 2 Comparison of serum soluble RANKL concentrations among various mouse models

Mouse model	sRANKL (ng/mL)	Phenotype
Ad-sRANKL injection (High)	1500	Severe osteoporosis/hypercalcemia
Ad-sRANKL injection (Low)	233	Severe osteoporosis/hypercalcemia
sRANKL-Tg mice	30	Severe osteoporosis
GST-RANKL injection	3.51	Osteoporosis
Wild mice	0.1	Normal

¹Serum glutathione-S transferase-receptor activator of nuclear factor-κB ligand (GST-RANKL) concentration 4 h after injection of 1 mg/kg GST-RANKL. sRANKL: Soluble RANKL; Ad-sRANKL: Harboring mouse sRANKL cDNA.