Bone mineral density and bone turnover in Romanian children and young adults with classical 21-hydroxylase deficiency are influenced by glucocorticoid replacement therapy

Abstract

Objective It remains controversial if glucocorticoid replacement therapy impairs bone mineral density (BMD) in young patients with 21-hydroxylase deficiency. We aimed to analyze the impact of treatment variables, phenotype and genotype on BMD and bone metabolism in these patients. Design Cross-sectional study. Measurements Twenty-eight Caucasian patients with classical 21-hydroxylase deficiency (5-39 years). Clinical parameters, hormonal status, osteocalcin (OC), C-terminal telopeptide of type I collagen (CTX), genotype and lumbar BMD (Z-scores) were assessed. Cumulative and mean hydrocortisone equivalent doses were calculated for the entire treatment period. Results Patients with severely reduced BMD Z-scores (≤-2·5 SD) had significantly higher mean/cumulative glucocorticoid doses compared to patients with moderately reduced (P = 0·003/P = 0·026) and normal Z-scores (> -1 SD) (P = 0·005/P = 0·011). Mean hydrocortisone equivalent doses > 20 mg/m2/day led to significantly lower lumbar BMD Z-scores (-2·16 ± 1·4 SD) vs. doses ≤ 20 mg/m 2/day (-0·59 ± 1·25 SD) (P = 0·008). BMD correlated negatively with mean/cumulative glucocorticoid doses and treatment duration. OC (86·45 ± 37·45 ng/ml) and CTX (1·45 ± 0·43 ng/ml) were significantly increased compared to an age- and sex-matched control group in patients with active growth; only CTX was slightly increased in patients who completed growth. Conclusions High cumulative and mean glucocorticoid doses negatively impact on BMD in children and young adults with classical 21-hydroxylase deficiency. Substitution therapy should be adapted particularly at this life period to prevent bone loss. © 2009 Blackwell Publishing Ltd.