There has been substantial progress in the management of patients with 
osteoporosis and the prevention of osteoporotic fractures. Currently available 
strong anti-resorptive agents are bisphosphonates and an anti-receptor activator 
of nuclear factor-kappa B ligand (RANKL) antibody, denosumab. Although 
bisphosphonates and denosumab both inhibit bone resorption and prevent vertebral 
and non-vertebral fractures, their mechanisms of action are different. Whereas 
bisphosphonates' effects on bone mineral density and fracture peak around 3 to 5 
years and become plateaued, those of denosumab are maintained for up to 10 
years. There are differences in the modes of action of these two drugs. 
Bisphosphonates accumulate on the mineralized bone surface and are released by 
the acid environment under osteoclastic bone resorption, whereas denosumab is 
not accumulated on bone but directly binds RANKL and inhibits its binding to the 
receptor RANK. Thus, the reduction in denosumab concentration 4 to 6 months 
after injection may enable RANK to bind to RANKL, where it is highly expressed, 
such as in damaged bone regions. As anabolic agents, only teriparatide has been 
available for a long time, but abaloparatide, a synthetic analog of PTHrP(1-34), 
is currently under development. Because of the difference in the preferential 
binding conformations of PTH1 receptor between teriparatide and abaloparatide, 
the latter shows anabolic effects with fewer bone resorptive effects. 
Romosozumab, an anti-sclerostin antibody, inhibits the action of sclerostin, a 
canonical Wnt signal inhibitor secreted from osteocytes, and enhances canonical 
Wnt signaling. Romosozumab robustly increases vertebral and proximal femoral 
bone mineral density within 12 months and inhibits vertebral and clinical 
fractures in patients with osteoporosis by enhancing bone formation and 
inhibiting bone resorption. In this review, we summarize the recent advances in 
therapeutic agents for the treatment of osteoporosis and discuss future 
prospects with their use.