Table 2.

Drugs under development for osteoporosis with validated targets

Category	Name	Structure	Status	Mechanism of Action
Sclerostin inhibitor	Blosozumab	Monoclonal antibody	Phase II Completed	Activation of osteoblast function by direct binding to Sclerostin
	SHR-1222	Monoclonal antibody	Preparing for phase I
SERMs	Arzoxifene		Reached phase III Failed due to low efficacy	Antiresorptive action through inhibition of osteoclast activity by activation of ERα receptor and enhancement of OPG/RANKL ratio
	Lasofoxifene		Reached phase III Approval withheld by FDA due to safety concerns
RANKL inhibitor	TK006	Monoclonal antibody	Phase I	Antiresorptive action through inhibition of osteoclast activity by direct binding to RANKL
Calcium-sensing receptor antagonist	Ronacaleret		Reached phase II Failed due to low efficacy	Blocking calcium-sensing receptor that stimulates PTH release from the parathyroid glands
	Encaleret		Reached phase II Failed due to low efficacy
Cathepsin K inhibitor	Odanacatib		Reached phase III Failed due to safety issues	Inhibition of osteoclast activity by inhibition of Cathepsin K activity
	Balicatib		Phase II
	ONO-5334		Phase II
αvβ3 integrin antagonist	MK-0429		Phase I	Inhibition of osteoclast activity by selectively binding to αvβ3 integrin receptor
17β-HSD2 inhibitors	17[134]		Preclinical IC50 = 0.80μM	Controlling the availability of biologically active estrogens and androgens in the tissues
	21[135]		Preclinical IC50 = 235nM
	4[136]		Preclinical IC50 = 160nM
	15[137]		Preclinical IC50 = 2.0nM
TPH-1 inhibitor	LP 533401		Preclinical IC50 = 0.4μM	Inhibition of gut-derived serotonin synthesis and promotion of osteoblast function
	9a[138]		Preclinical. IC50 = 6.22μM