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.

Sclerostin Antibody Treatment Increases Bone Mass and Normalizes Circulating Phosphate Levels in Growing Hyp Mice

“…Although the current study did not evaluate vitamin D because of limited sera, increased 1,25 dihydroxyvitamin D has been noted in the sclerostin knockout mouse. (13) Scl-Ab treatment increases bone mass and, subsequently, bone strength in several preclinical animal models, including postmenopausal osteoporosis, (34) osteogenesis imperfecta, (16,35) and autosomal recessive hypophosphatemic rickets. (17) Consistent with this, we find that Scl-Ab induces gains in bone mass in Hyp animals with the largest gains in the cortical compartment.…”

Osteoanabolic and dual action drugs

“…With further experience from animal and early human studies, it became apparent that this antisclerostin agent not only stimulates bone formation, by the mechanism described above, but also leads to inhibition of bone resorption through OPG . Indeed, romosozumab lead to an increase in OPG, thus reducing the RANKL‐OPG ratio and osteoclast activity . Thus, romosozumab can be best characterized as a dual agent, serving both osteoanabolic and antiresorptive functions.…”

Could Serum Sclerostin Help in Early Assessment and Treatment of Chronic Kidney Disease – Mineral and Bone Disorder?

“…Concerning the CKD-MBD treatment a question is raised whether serum sclerostin levels should be really lowered. It is clear that blocking of sclerostin will increase bone mineral density [14] and help curing renal osteodystrophy, but the concern stays whether it influences CV risk in CKD patients promoting pathological ossification within the walls of blood vessels [15].…”