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.