Glucocorticoid-induced osteoporosis

Glucocorticoid excess in the organism, either of endogenous (Cushing's syndrome) or exogenous iatrogenic origin, has an adverse im­ pact on both qualitative and quantitative properties of bone tissue, leading to its increased fragility. Glucocorticoid-induced osteopo­ rosis (GIOP) is one of the most common complications of systemic corticotherapy. In glucocorticoid users, the age-and sex-adjusted bone mineral density (BMD) values are lower than expected. Lower BMD correlates with the cumulative dose of corticoids. There is a predilection for the involvement of trabecular bone of the vertebral body. Corticodependent patients have higher risk of fractures of any localization, in particular vertebral compression fractures. The risk increases with the daily doses of glucocorticoids. Current or previous corticoid therapy is a predictor of fracture risk, independent of BMD values. Supraphysiological doses of glucocorticoids have a negative impact on bone tissue metabolism at many levels. They directly influence cells participating in the bone remodelling cycle and cause imbalance between bone resorption and formation. The main pathogenic mechanism is a steady decrease in new bone formation. The exception is the period immediately after glucocorticoid therapy is started, characterized by accelerated bone resorp­ tion. Glucocorticoids inhibit the differentiation of new osteoblasts, decrease the synthesis of organic bone matrix components by mature osteoblasts and stimulate osteoblast and osteocyte apoptosis. At the subcellular level, they significantly interfere with the Wnt/beta-catenin signalling pathway. Through RANKL (receptor activator of nuclear factor kappa B ligand), they promote osteoclast differentiation and maturation. Also important is their impact on the regulatory system ofbone microenvironment growth factors (IGF I, II, IGFBP). The use of glucocorticoids is related to negative calcium balance, hypogonadism and muscular atrophy. The role of pa­ rathormone in corticoid-induced bone loss is yet to be elucidated. The epidemiological and pathophysiological patterns of GIOP also influence the principles of its prevention and therapy.

Keywords: glucocorticoids, glucocorticoid-induced osteoporosis