Table 1.

Summary of osteoclast-related diseases and targeted inhibitors.

Osteoclast-related bone diseases	Osteoclast formation and function	Critical mechanisms	Current therapies and/or future targets
Osteoporosis	Excessive osteoclast formation and hyperactivated function	Estrogen deficiency, increase in RANKL levels resulting in excessive osteoclast formation and decreased bone formation	Bisphosphonates, calcitonin, estrogen replacement, SERMs, strontiumranelate, PTH peptides, RANKL antibody, sclerostin antibody
Periprosthetic osteolysis	Excessive osteoclast formation and hyperactivated function	Wear particles induce immoderate release of RANKL, resulting in excessive activation of osteoclasts	Bisphosphonates, revision surgery
Rheumatoid arthritis	Excessive osteoclast formation and hyperactivated function	Overexpression of RANKL resulting in excessive activation of osteoclastsMMP-9 and MMP-14 produced by osteoblasts	Immune inhibitors, TNF-α inhibitors, CSF-1R inhibitors, RANKL antibody
Bone tumors	Excessive osteoclast formation and hyperactivated function	Imbalance between RANKL and OPG levels in local bone tissue, resulting in excessive activation of osteoclasts	Bisphosphonates, RANKL antibody
Paget’s bone disease	Excessive osteoclast formation and hyperactivated function	High-RANKL expression leading to osteoclast hyperactivity	RANKL antibody
Osteopetrosis	Impaired osteoclast formation and function	(a)Abnormality in RANKL/RANK/OPG system (b)Mutation of M-CSF factor (c)Mutation of V-ATPase subunit (d)Loss of CLC-7 chloride channels (e)Shortage of cathepsin K (f)Lack of c-Fos protein	Hematopoietic stem cell implantation