Novel therapies for osteoporosis.
Since the identification of osteoporosis as a major health issue in aging populations and the subsequent development of the first treatment modalities for its management, considerable progress has been made in our understanding of the mechanisms controlling bone turnover and disease pathophysiology, thus enabling the pinpointing of new targets for intervention. This progress, along with advances in biotechnology, has rendered possible the development of ever more sophisticated treatments employing novel mechanisms of action. Denosumab, a monoclonal antibody against RANKL, approved for the treatment of postmenopausal and male osteoporosis, significantly and continuously increases bone mineral density (BMD) and maintains a low risk of vertebral, non-vertebral, and hip fractures for up to 8 years. Currently available combinations of estrogens with selective estrogen receptor modulators moderately increase BMD without causing the extra-skeletal adverse effects of each compound alone. The cathepsin K inhibitor odanacatib has recently been shown to decrease vertebral, non-vertebral, and hip fracture rates and is nearing approval. Romosozumab, an anti-sclerosin antibody, and abaloparatide, a PTH-related peptide analog, are at present in advanced stages of clinical evaluation, so far demonstrating efficaciousness together with a favorable safety profile. Several other agents are currently in earlier clinical and preclinical phases of development, including dickkopf-1 antagonists, activin A antagonists, β-arrestin analogs, calcilytics, and Src tyrosine kinase inhibitors.
Department of Endocrinology and Diabetes, 251 Hellenic Air Force & VA General Hospital, Athens, Greece.
Polyzois
P
Makras
Department of Endocrinology, 424 General Military Hospital, Thessaloniki, Greece.
Sideris
S
Delaroudis
Department of Endocrinology, 424 General Military Hospital, Thessaloniki, Greece. Electronic address: a.anastasilakis@gmail.com.
Athanasios D
AD
Anastasilakis
D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D017277:Drug Approval; D005260:Female; D006801:Humans; D008297:Male; D010024:Osteoporosis / Q000628:therapy*; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use; D035703:Therapies, Investigational / Q000379:methods* / Q000639:trends
D050071:Bone Density Conservation Agents; D020845:Selective Estrogen Receptor Modulators
Cathepsin K; Denosumab; Osteoporosis; Parathyroid hormone; Sclerostin