Endocrine Abstracts

Osteoporosis is characterised by bone fragility with increased susceptibility to fracture. The burden of osteoporosis already costs the NHS over £1.7 billion per annum but its prevalence is increasing. The skeleton is continually remodelled in response to endocrine, paracrine and mechanical signals by the coupled activities of osteoclasts and osteoblasts. Nevertheless, the continuous process of bone turnover results in an inexorable loss of bone because osteoblast-mediated bone formation does not completely replace the bone resorbed by osteoclasts. The few current treatments available for prevention and treatment of osteoporosis are limited by their scope and efficacy as well as by their acceptability to patients. Novel approaches are required and efforts are focused towards targeting signalling pathways that inhibit osteoclast function (anti-resorptive agents) or stimulate osteoblast activity (anabolic agents). Traditional anti-resorptive drugs include oestrogens and bisphosphonates but new osteoclast antagonists including inhibitors of receptor activator of NFκB ligand, cathepsin K, c-src kinase, integrins and chloride channels are emerging and offer considerable promise. Furthermore, development of intermittent PTH injection as an anabolic treatment has provided evidence that stimulation of osteoblastic bone formation is also an effective strategy for fracture prevention. New agents including oral PTH and PTHrP analogues and calcium sensing receptor antagonists are under development. Perhaps the most exciting advances, owever, have resulted from the elucidation of osteoblast signalling pathways that are critical for bone formation. Thus, novel anabolic agents acting via the Wnt LRP-5 pathway, sclerostin or matrix extracellular phosphoglycoprotein have great promise. These and other new approaches have the potential to revolutionise the future treatment of osteoporosis and are evidence of the considerable advances made in this rapidly changing field in recent years.