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.