Table 3.

Present and potential near-term osteoporosis drug targets that have been linked to changes in BMD by GWAS. Table adapted from¹⁷⁸

Drug class	Drug target	Principle	Stage	Target locus identified through GWASs	Refs.
Denosumab	RANKL	Reduces bone resorption by selectively targeting RANKL	Approved for clinical use	RANKL	179
Sclerostin inhibitors (Romosozumab)	Sclerostin (SOST)	Improve the recruitment and activation of osteoblasts by targeting Wnt/β-catenin signaling pathways	Approved for clinical use in Japan, US and Europe	SOST	107
Selective estrogen receptor modulators	Estrogen receptor	Reduces bone resorption	Approved for clinical use	ESR1	180
		by targeting the OPG/RANK/RANKL pathway
Parathyroid hormone analogs	Parathyroid hormone receptor	Majorly participate in the process of bone formation	Approved for clinical use	Not identified, but the pathway has been	181,182
		by targeting the PKA pathway		highlighted through PTHLH (encodes PTHRP)
Bisphosphonates	Farnesyl pyrophosphate	Inhibition of bone resorption	Approved for clinical use	Not identified	183
Estrogen ESR1	Estrogen receptor	Reduces bone resorption	Approved for clinical use	ESR1	184
		by targeting the OPG/RANK/RANKL pathway
Cathepsin K inhibitors	Cathepsin K	Inhibition of bone resorption	Terminated	Not identified	185
		by targeting the OPG/RANK/RANKL pathway
DKK1 inhibitors	DKK1	Improve bone formation by targeting the Wnt/β-catenin signaling pathway	In the preclinical phase	DKK1	120

DKK1 dickkopf 1, ESR1 estrogen receptor 1, OPG osteoprotegerin, PKA protein kinase A, PTHLH parathyroid hormone-like hormone, PTHRP parathyroid hormone-related protein, RANK receptor activator of nuclear factor kβ, RANKL RANK ligand, SOST sclerostin, US United States