Abstract
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...Continue Reading
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