Romosozumab, a specific inhibitor of sclerostin, is a unique approach to therapy for postmenopausal osteoporosis and related disorders. The elucidation of sclerostin deficiency as the molecular defect of syndromes of high bone mass with normal quality, and the pivotal role of sclerostin as a mediator of osteoblastic activity and bone formation, provided the platform for the evaluation of inhibitors of sclerostin to activate bone formation. An extensive preclinical program and 2 large fracture endpoint trials with romosozumab, a sclerostin-binding antibody, have been completed. This review will highlight the results of those studies and describe the current status of romosozumab as a potential therapy for osteoporosis.
Female ; Humans ; Osteoblasts ; Osteogenesis ; Osteoporosis ; Osteoporosis, Postmenopausal

Denosumab, a specific inhibitor of RANK ligand, is a novel therapy for postmenopausal osteoporosis and related disorders. An extensive clinical development program has evaluated the clinical efficacy and safety of denosumab with several thousand patients being followed for up to 10 years. Combined with more than six years of postmarketing experience, these studies provide substantial confidence that denosumab is a convenient and appropriate treatment for patients, including Asians, at high risk for fracture. This review will summarize the clinical development of denosumab and lessons learned since its approval for clinical use in 2010.
Asian Continental Ancestry Group ; Denosumab* ; Female ; Humans ; Osteoporosis* ; Osteoporosis, Postmenopausal ; RANK Ligand ; Treatment Outcome

Although several effective therapies are available for the treatment of osteoporosis in postmenopausal women and older men, there remains a need for the development of even more effective and acceptable drugs. Several new drugs that are in late-stage clinical development will be discussed. Abaloparatide (recombinant parathyroid hormone related peptide [PTHrP] analogue) has anabolic activity like teriparatide. Recent data from the phase 3 fracture prevention trial demonstrate that this agent is effective in reducing fracture risk. Inhibiting cathepsin K reduces bone resorption without decreasing the numbers or activity of osteoclasts, thereby preserving or promoting osteoblast function. Progressive increases in bone mineral density (BMD) have been observed over 5 years. Early data suggest that odanacatib effectively reduces fracture risk. Lastly, inhibiting sclerostin with humanized antibodies promotes rapid, substantial but transient increases in bone formation while inhibiting bone resorption. Marked increases in BMD have been observed in phase 2 studies. Fracture prevention studies are underway. The new therapies with novel and unique mechanisms of action may, alone or in combination, provide more effective treatment options for our patients.
Antibodies, Monoclonal, Humanized ; Bone Density ; Bone Resorption ; Cathepsin K ; Female ; Humans ; Male ; Osteoblasts ; Osteoclasts ; Osteogenesis ; Osteoporosis* ; Parathyroid Hormone-Related Protein ; Teriparatide