Glucocorticoid-Induced Osteoporosis in Children: Impact of the Underlying Disease

Abstract

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 Ͼ4 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 ␣, 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. S166LEONARD by guest on May 10, 2018 http://pediatrics.aappublications.org/ Downloaded from D URING CHILDHOOD AND adolescence, skeletal development is characterized by gender-, maturation-, and race-specific increases in cortical dimensions and trabecular density. The 2000 National Institutes of Health Osteoporosis Prevention, Diagnosis, and Therapy Consensus Development Conference identified bone accrual during childhood as a critical determinant of lifelong skeletal health. The authors of the resulting consensus statement 1 specifically called for research to determine the impact of chronic diseases and glucocorticoid therapy on bone accrual in children.Glucocorticoid-induced osteoporosis (GIO) is the most common cause of secondary osteoporosis in adults and is the result of profound effects of glucocorticoids on bone cells. 2 Glucocorticoids inhibit osteoblastogenesis and promote osteoblast apoptosis, which results in significant reductions in bone formation. 3 Studies in adults have demonstrated that glucocorticoids cause rapid, dose-dependent bone loss and increased fracture risk. 4 The growing skeleton may be especially vulnerable to adverse glucocorticoid effects on bone formation, which could possibly compromise trabecular and cortical bone accretion.Glucocorticoids are used in myriad pediatric diseases. Decreased bone mineral density (BMD) has been described in various pediatric disorders that require glucocorticoids, including asthma, juvenile rheumatoid arthritis, inflammatory bowel disease, systemic lupus erythematosus, and organ trans...

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