Emerging pharmacologic therapies for osteoporosis.

Osteoporotic fractures are an important public health problem, contributing substantially to morbidity and mortality in an ageing world population and consuming considerable health resources. Presently available pharmacologic therapies for prevention of fragility fractures are limited in scope, efficacy and acceptability to patients. Considerable efforts are being made to develop new, more effective treatments for osteoporosis, and to refine/optimize existing therapies. These novel treatments include an expanding array of drugs that primarily inhibit osteoclastic bone resorption: estrogenic compounds, bisphosphonates, inhibitors of receptor activator of NF-kappaB ligand signaling, cathepsin K inhibitors, c-src kinase inhibitors, integrin inhibitors and chloride channel inhibitors. The advent of intermittent parathyroid hormone (PTH) therapy has provided proof-of-principle that osteoblast-targeted (anabolic) agents can effectively prevent osteoporotic fractures, and is likely to be followed by the introduction of other therapies based on PTH (orally active PTH analogs, antagonists of the calcium sensing receptor, PTH-related peptide analogs) and/or agents that induce osteoblast anabolism by means of pathways involving key, recently identified, molecular targets (wnt-low-density lipoprotein receptor-related protein 5 signaling, sclerostin and matrix extracellular phosphoglycoprotein).