Emerging and potential 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. Currently available pharmacological 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/optimise existing therapies. These novel treatments include an expanding array of drugs that primarily inhibit osteoclastic bone resorption; oestrogenic compounds, bisphosphonates, inhibitors of receptor activator of nuclear factor-kappaB ligand signalling, cathepsin K inhibitors, c-src kinase inhibitors, integrin inhibitors and chloride channel inhibitors. The advent of intermittent para-thyroid hormone (PTH) therapy has provided proof-of-principle that osteo-blast-targeted (anabolic) agents can effectively prevent osteoporotic fractures, and is likely to be followed by the introduction of other therapies based upon PTH, such as orally active PTH analogues, antagonists of the calcium sensing receptor, PTH-related peptide analogues, and/or agents that induce osteoblast anabolism via pathways involving key, recently identified, molecular targets (wnt low-density lipoprotein receptor-related protein-5 signalling, sclerostin and matrix extracellular phosphoglycoprotein).
Grey
Andrew
A
Department of Medicine, University of Auckland, Auckland, New Zealand. a.grey@auckland.ac.nz
Reid
Ian R
IR
D045930:Anabolic Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects / Q000502:physiology; D015507:Drugs, Investigational / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010024:Osteoporosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D013678:Technology, Pharmaceutical / Q000639:trends*
D045930:Anabolic Agents; D015507:Drugs, Investigational