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.