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


METHODS
Cross-sectional study.


METHODS
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 (< or = -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/m(2)/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.
Zimmermann
Anca
A
1st Medical Clinic, Department of Endocrinology and Metabolic Diseases, Johannes Gutenberg University of Mainz, Langenbeckstrasse 1, Mainz, Germany. zimmeran@uni-mainz.de
Sido
Paula Grigorescu
PG
Schulze
Egbert
E
Al Khzouz
Camelia
C
Lazea
Cecilia
C
Coldea
Cristina
C
Weber
Matthias M
MM
D000293:Adolescent; D000312:Adrenal Hyperplasia, Congenital / Q000188:drug therapy*; D000328:Adult; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D024042:Collagen Type I / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use*; D020249:Hormone Replacement Therapy / Q000009:adverse effects*; D006801:Humans; D006854:Hydrocortisone / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D015675:Osteocalcin / Q000378:metabolism; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
D024042:Collagen Type I; D005938:Glucocorticoids; D015675:Osteocalcin; D013255:Steroid 21-Hydroxylase; D006854:Hydrocortisone