Table 3.

A summary of sclerostin-related diseases.

Sclerostin's role			Disease	Animal	Therapy		Ref.
Role	Change	Signal pathway			Drug	Phase
Maintain normal function	Sclerostin mutations (loss-of-function mutations in SOST gene)	WNT/β-Catenin	Sclerosteosis	Human	/	/	121
	Sclerostin mutations (a noncoding deletion that removes a SOST-specific regulatory element in bone)	WNT/β-Catenin	van Buchem disease	Human	/	/	121
Contributional	Sclerostin (serum) ↑	WNT/β-Catenin	POP	Mice	Scl-Ab (Romosozumab)	Approved	(FDA Press Announcements, 2019; EMA Documents, 2019)
				Rats
				Human
	Sclerostin (serum) ↑	WNT/β-Catenin	Disuse bone loss	Mice	Scl-Ab	/	111,122,123
				Rats
	Sclerostin (serum) ↑	WNT/β-Catenin	Combined POP and disuse bone loss	Rats	Scl-Ab	/	124
	Sclerostin (serum) ns	WNT/β-Catenin	Spinal cord injury (SCI)-induced bone loss	Rats	Scl-Ab	/	125
	–	WNT/β-Catenin	Fracture	Mice	Scl-Ab	Phase II	68,69
				Rats
				Monkey
				Human
	/	WNT/β-Catenin	OI	Mice	Scl-Ab (Romosozumab)	Phase I	72,73,126
				Human
	Sclerostin (serum) ↑	–	XLH	Mice	Scl-Ab (Romosozumab)	/	84
	Sclerostin (serum) ↑	WNT/β-Catenin	Age-related muscle weakness	Human	/	/	12
	Sclerostin (cancer tissue) ↑	P38/NF-κB	Cancers: triple-negative breast cancer	Mice	Scl-Ab	/	98
	Sclerostin (cancer tissue) ↑	P38/NF-κB	Breast cancer-induced muscle weakness	Mice	Scl-Ab	/	98
	Sclerostin (serum) ↑	WNT	Obesity	Mice	Scl-Ab	/	109
		BMP
	Sclerostin (serum) ↑	WNT	Diabetes	Mice	Scl-Ab	/	109
Protective	Sclerostin (serum) ↑	WNT	RA	Mice	Scl-Ab	/	127
	Sclerostin (serum) ↑	WNT	Cardiovascular diseases	Clinical trials & human genetics	Scl-Ab (Romosozumab)	/	118

/, Not applicable. –, Not available. ns: no difference.