Endocrine Abstracts

There have been remarkable recent advances in bringing osteoporosis to public attention, in understanding its pathogenesis, and in improving its diagnosis and treatment.

The challenges in the next decade will include the problem of delivering the benefits of this knowledge to as many patients as possible in an efficient and cost-effective manner.

Up until now, all the major drugs used to prevent or treat osteoporosis are inhibitors of bone resorption. This includes oestrogens and oestrogen-related compounds, particularly the SERMs (Selective Estrogen Receptor Modulators), and bisphosphonates and calcitonin. The best evidence for reduction in fractures exists for bisphosphonates, particularly alendronate and risedronate, and for raloxifene.

In the future, there is likely to be an increasing emphasis on drugs that stimulate bone formation, as so-called anabolic agents, which act by enhancing the formation of new bone and therefore produce bigger changes in bone mass and strength than can be achieved with current anti-resorptive drugs. The impressive clinical results obtained with parathyroid hormone are a forerunner of other opportunities in this area.

Among other candidates, the potential anabolic effects of strontium salts and of the statins are currently under study. Experimental studies suggest many other possible approaches, including the use of proteosome inhibitors, modulators of BMP-2 synthesis and action (Bone Morphogenetic Protein-2), BMP signalling modulators, prostaglandin analogues, oestrogen-related signalling molecules, LP receptor modulators, and many others. Looking further ahead there are many other ways in which novel agents might be developed based on increasing knowledge of bone biology and the pathogenesis of osteoporosis. High throughput screening methods and combinatorial chemistry, coupled with the dramatic advances in human genetics, have vastly increased the rate at which new pharmacological candidates may be identified.