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

P>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 center dot 5 SD) had significantly higher mean/cumulative glucocorticoid doses compared to patients with moderately reduced (P = 0 center dot 003/P = 0 center dot 026) and normal Z-scores (> -1 SD) (P = 0 center dot 005/P = 0 center dot 011). Mean hydrocortisone equivalent doses > 20 mg/m(2)/day led to significantly lower lumbar BMD Z-scores (-2 center dot 16 +/- 1 center dot 4 SD) vs. doses < 20 mg/m(2)/day (-0 center dot 59 +/- 1 center dot 25 SD) (P = 0 center dot 008). BMD correlated negatively with mean/cumulative glucocorticoid doses and treatment duration. OC (86 center dot 45 +/- 37 center dot 45 ng/ml) and CTX (1 center dot 45 +/- 0 center dot 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.