An Overview of the Role of Glucocorticoids in the Pathophysiology of Endocrine Disorders Glucocorticoids and Osteoporosis


GC treatment is associated with rapid bone loss, and fractures are a common side effect of long-term GC therapy.96


Bone remodelling is


dependent on the absorption of old bone matrix by osteoclasts, followed by the generation of new bone matrix by osteoblasts that subsequently enter the resorptive lacuna. GCs interfere with bone matrix formation via induction of osteoblast apoptosis via activation of caspase-3, in addition to decreasing the number of osteoblast precursor cells available for differentiation.97


Chronic GC treatment


induces the expression of macrophage colony-stimulating factor (M- CSF) and receptor activator of NF-κB ligand (RANKL), both of which are necessary for osteoclast development. GCs also increase osteoclast maturation and survival, which is classically associated with increased bone resorption and rapid loss of trabecular bone.98,99 However, recent studies suggest that osteoclasts induce a more complex effect on bone remodelling. Osteoclasts act to resorb old bone, an action that requires cytoskeletal organisation. As osteoclasts absorb the old bone matrix, they release factors that promote the movement of osteoblasts into the resorptive lacuna, which then act to synthesise new bone. Long-term GC therapy suppresses specific osteoclast functions related to cytoskeletal organisation and recruitment of osteoblasts, and therefore greatly reduces new bone formation.100


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Future Perspectives


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Anti-inflammatory and


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Animal models demonstrating tissue-specific


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