The clinical potential of romosozumab for the prevention of fractures in postmenopausal women with osteoporosis

Abstract

The glycoprotein sclerostin inhibits activation of the canonical Wnt pathway and thereby suppresses bone formation by inhibiting the osteoblasts. Additionally, sclerostin increases bone resorption by stimulating the production of receptor activator of nuclear factor kappa-β-ligand (RANKL). Romosozumab (ROMO) is a monoclonal antibody against sclerostin. Phase III clinical trials in postmenopausal women with osteoporosis have shown that ROMO increases bone mineral density at the lumbar spine and hip and reduces the risk of vertebral and clinical fractures in comparison with placebo. In women with severe osteoporosis, ROMO reduces the risk of vertebral, nonvertebral and clinical fractures in comparison with alendronate. ROMO is the first treatment for osteoporosis with dual action, and may become a valuable tool for improving the treatment of osteoporosis. At present, the approval of ROMO by the authorities is awaiting further investigations of a potential increased risk of cardiovascular events associated with ROMO treatment.

Keywords: fracture; osteoporosis; review; romosozumab; sclerostin.

Figure 1.

The Wnt signalling pathway. Left: the Wnt pathway is activated by the interaction between LRP5/6, Wnt and Frizzled. Beta-catenin is released and enters the nucleus and activates transcription from Wnt target genes. Right: the Wnt pathway is inactivated due to sclerotin binding to LRP5/6 and beta-catenin is phosphorylated and degraded. Illustration courtesy of Alessandro Baliani© 2018. LRP5/6, low-density lipoprotein receptor protein 5 and 6; β-cat, beta-catenin; Axin, a scaffold protein; APC, adenomatous polyposis coli (tumor suppressor protein); GSK3β, glycogen synthase kinase 3 beta; P, phosphate; CK1α, casein kinase 1 alpha; DSH, disheveled (cytoplasmic protein).

Figure 2.

Romosozumab mode of action. Illustration courtesy of Alessandro Baliani© 2018. RANKL, receptor activator of nuclear factor kappa-β-ligand; Scl, sclerostin.