Glucocorticoid-induced osteoporosis in children: impact of the underlying disease.
Glucocorticoids inhibit osteoblasts through multiple mechanisms, which results in significant reductions in bone formation. The growing skeleton may be especially vulnerable to adverse glucocorticoid effects on bone formation, which could possibly compromise trabecular and cortical bone accretion. Although decreased bone mineral density has been described in various pediatric disorders that require glucocorticoids, and a population-based study reported increased fracture risk in children who require >4 courses of glucocorticoids, some of the detrimental bone effects attributed to glucocorticoids may be caused by the underlying inflammatory disease. For example, inflammatory cytokines that are elevated in chronic disease, such as tumor necrosis factor alpha, suppress bone formation and promote bone resorption through mechanisms similar to glucocorticoid-induced osteoporosis. Summarized in this review are changes in bone density and dimensions during growth, the effects of glucocorticoids and cytokines on bone cells, the potential confounding effects of the underlying inflammatory-disease process, and the challenges in interpreting dual-energy x-ray absorptiometry results in children with altered growth and development in the setting of glucocorticoid therapy. Two recent studies of children treated with chronic glucocorticoids highlight the differences in the effect of underlying disease, as well as the importance of associated alterations in growth and development.
Leonard
Mary B
MB
Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA. leonard@email.chop.edu
D015502:Absorptiometry, Photon / Q000379:methods; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects / Q000276:immunology; D016723:Bone Remodeling / Q000187:drug effects; D002648:Child; D003424:Crohn Disease / Q000150:complications / Q000188:drug therapy; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects*; D006801:Humans; D008297:Male; D009404:Nephrotic Syndrome / Q000150:complications / Q000188:drug therapy; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D010024:Osteoporosis / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000276:immunology
D016207:Cytokines; D005938:Glucocorticoids