Increased understanding of bone biology has led to the discovery of several unique signaling pathways that regulate bone formation and resorption. The Wnt signaling pathway plays a significant role in skeletal development, adult skeletal homeostasis, and bone remodeling. Sclerostin is an inhibitor of the Wnt signaling pathway.
Romosozumab, a humanized
monoclonal antibody that binds to sclerostin, prevents sclerostin from exerting this inhibitory effect. Therefore, in the presence of
romosozumab, the Wnt signaling pathway is activated leading to bone formation and bone mineral density gain. Clinical studies of
romosozumab have shown that this agent is one of the most potent bone
anabolic agents in development to date.
Romosozumab does not act solely as an anabolic agent, but rather, it has effects on increasing bone formation as well as reducing
bone resorption. In the clinical studies, patients tolerated
romosozumab well with no major safety signals reported. In a Phase III study,
romosozumab as compared to placebo has been shown to reduce vertebral fractures by 73% after 1 year of treatment. Sequential
therapy with
romosozumab for 1 year followed by
denosumab in the second year reduced vertebral fractures by 75% as compared to the group that received placebo for 1 year and
denosumab in the second year.
Romosozumab holds significant potential, by a novel mechanism of action, to expand our ability to treat
osteoporosis. More studies are needed to determine the ideal setting in which
romosozumab may be used to optimize
osteoporosis treatment.