Bone Abstracts

Therapeutic glucocorticoids are still widely used for their anti-inflammatory effects. There are however significant side effects associated with their use. These include effects on bone leading to osteoporosis and fracture but also on muscle (increasing risk of falls) and systemic fuel metabolism (leading to diabetes and increased cardiovascular risk). Research over many decades has tried to develop agents which retain the anti-inflammatory effects of glucocorticoids but have reduced impact on bone, muscle, and glucose metabolism. The main approach to developing these agents was based on a model in which the glucocorticoid receptor (GR) regulated separate pathways for the anti-inflammatory and non-inflammation related effects of glucocorticoids (transrepression and transactivation respectively). However, recent work characterising the action of the GR suggests that these pathways overlap considerably and are very difficult to ‘disassociate’. A more recent approach has been to examine compounds that appear to be bone sparing and then work out which molecular properties make them useful. Using this approach interesting compounds have been identified although they do not appear safe enough for use in humans. Recent research has also highlighted how little we understand about how glucocorticoids have their effects in various diseases. In the future it is likely that anti-inflammatory bone sparing agents that work through the GR will be developed that have to be carefully matched to the underlying illness being targeted.