Endocrine Abstracts

The explosion in our understanding of bone biology has resulted in a number of key targets in bone that should allow the development of new treatments. There are other important regulators of bone resorption that are being targeted and these include src kinase and the chloride channel on osteoclasts. The key enzyme in bone resorption is cathepsin K and small molecule inhibitors have been developed and these are currently in phase II and III clinical trials. These are an interesting approach to inhibiting bone resorption as there is less (or no) inhibition of bone formation. For anabolic treatments, teriparatide and PTH (1–84) are already licensed, but they are given by daily subcutaneous injection. There have been attempts to develop alternative forms of administration, such as transdermal approach. Calcilytic drugs have been developed to increase secretion of endogenous PTH, but these have not so far been successful at increasing bone mineral density. The wnt signalling pathway is a key anabolic pathway and a bone-specific regulator is sclerostin. This is a product of the osteocyte and binds to LRP-5 and it decreases wnt signalling. The current therapeutic approach is to develop an antibody to sclerostin and such trials are currently in phase II. A similar antibody approach is being taken to another inhibitory protein, Dickkopf-1, although the trials are less well advanced. The purpose of the treatment of osteoporosis is to reduce the risk of fractures. This might also be accomplished by reducing the risk of falls and so drugs that act on muscle to prevent sarcopenia are another target and these include agents such as anti-myostatin. In conclusion, we already have a number of agents that reduce the risk of fracture. However, our better understanding of bone biology will mean newer drugs being developed for this common condition.

Declaration of interest: Conflict of Interest: Consultancy with Amgen, Ono Pharma, Lilly.

Funding: No specific grant from any funding agency in the public, commercial or not-for-profit sector.