title: Glucocorticoid-induced osteoporosis in children with 21-hydroxylase deficiency.
abstract: 21-Hydroxylase deficiency (21-OHD) is the most common cause of congenital adrenal hyperplasia (CAH), resulting from deletions or mutations of the P450 21-hydroxylase gene (CYP21A2). Children with 21-OHD need chronic glucocorticoid (cGC) therapy, both to replace congenital deficit in cortisol synthesis and to reduce androgen secretion by adrenal cortex. GC-induced osteoporosis (GIO) is the most common form of secondary osteoporosis that results in an early, transient increase in bone resorption accompanied by a decrease in bone formation, maintained for the duration of GC therapy. Despite the conflicting results in the literature about the bone status on GC-treated patients with 21-OHD, many reports consider these subjects to be at risk for osteoporosis and fractures. In bone cells, at the molecular level, GCs regulate various functions including osteoblastogenesis, osteoclastogenesis, and the apoptosis of osteoblasts and osteocytes. In this paper, we focus on the physiology and biosynthesis of endogenous steroid hormones as well as on the effects of GCs on bone cells, highlighting the pathogenetic mechanism of GIO in children with 21-OHD.
authors.affiliation: Department of Biomedical Sciences and Human Oncology, University of Bari, Piazza G. Cesare 11, 70124 Bari, Italy. annav81@hotmail.it
authors.forename: Annamaria
authors.initials: A
authors.lastname: Ventura
authors.forename: Giacomina
authors.initials: G
authors.lastname: Brunetti
authors.forename: Silvia
authors.initials: S
authors.lastname: Colucci
authors.forename: Angela
authors.initials: A
authors.lastname: Oranger
authors.forename: Filomena
authors.initials: F
authors.lastname: Ladisa
authors.forename: Luciano
authors.initials: L
authors.lastname: Cavallo
authors.forename: Maria
authors.initials: M
authors.lastname: Grano
authors.forename: Maria Felicia
authors.initials: MF
authors.lastname: Faienza
mesh_terms: D000293:Adolescent; D000302:Adrenal Cortex / Q000378:metabolism / Q000473:pathology; D000312:Adrenal Hyperplasia, Congenital / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects*; D002648:Child; D002675:Child, Preschool; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010011:Osteocytes / Q000378:metabolism* / Q000473:pathology; D010024:Osteoporosis / Q000139:chemically induced* / Q000378:metabolism* / Q000473:pathology; D013255:Steroid 21-Hydroxylase
chemical_list: D005938:Glucocorticoids; C531510:CYP21A2 protein, human; D013255:Steroid 21-Hydroxylase