Fractures and bone mineral density in adult women with 21-hydroxylase deficiency.
BACKGROUND
Patients with classical congenital adrenal hyperplasia (CAH) receive lifelong, often supraphysiological, glucocorticoid therapy. Pharmacological doses of glucocorticoids are an established risk factor for osteoporosis.


OBJECTIVE
Our objective was to evaluate bone mineral density (BMD), fracture prevalence, and markers of bone metabolism in adult females with CAH.


METHODS
This was a cross-sectional observational study.


METHODS
Tertiary care referral centers were used in this study.


METHODS
We studied 61 women, aged 18-63 yr, with genetically verified CAH due to 21-hydroxylase deficiency. They were patients with salt wasting (n = 27), simple virilizing (n = 28), and nonclassical 21-hydroxylase deficiency (n = 6). A total of 61 age-matched women were controls.


METHODS
History of fractures was recorded. Total body, lumbar spine, and femoral neck BMD were measured by dual-energy x-ray absorptiometry. The World Health Organization criteria for osteopenia and osteoporosis were used. Serum marker of bone resorption, beta-C telopeptide was studied.


RESULTS
The mean glucocorticoid dose in hydrocortisone equivalents was 16.9 +/- 0.9 mg/m2. Patients had lower BMD than controls at all measured sites (P < 0.001). In patients younger than 30 yr old, 48% were osteopenic vs. 12% in controls (P < 0.009). In patients 30 yr or older, 73% were osteopenic or osteoporotic vs. 21% in controls (P < 0.001). BMD was similar in the two classical forms and had no obvious relationship to genotypes. beta-C-telopeptide was decreased in older patients. More fractures were reported in patients than controls (P < 0.001). The number of vertebrae and wrist fractures almost reached significance (P = 0.058).


CONCLUSIONS
Women with CAH have low BMD and increased fracture risk. BMD should be monitored, adequate prophylaxis and treatment instituted, and glucocorticoid doses optimized from puberty.
Falhammar
Henrik
H
Department of Endocrinology, Metabolism and Diabetes, Karolinska University Hospital, SE-171 76 Stockholm, Sweden. henrik.falhammar@karolinska.se
Filipsson
Helena
H
Holmdahl
Gundela
G
Janson
Per-Olof
PO
Nordenskjöld
Agneta
A
Hagenfeldt
Kerstin
K
Thorén
Marja
M
D000312:Adrenal Hyperplasia, Congenital / Q000150:complications* / Q000201:enzymology / Q000453:epidemiology*; D000328:Adult; D015415:Biomarkers; D015519:Bone Density / Q000235:genetics*; D001842:Bone and Bones / Q000378:metabolism; D015331:Cohort Studies; D024042:Collagen Type I / Q000097:blood; D005260:Female; D050723:Fractures, Bone / Q000201:enzymology / Q000453:epidemiology* / Q000235:genetics*; D005838:Genotype; D005938:Glucocorticoids / Q000009:adverse effects / Q000627:therapeutic use; D006728:Hormones / Q000097:blood; D006801:Humans; D009154:Mutation / Q000502:physiology; D010024:Osteoporosis / Q000453:epidemiology / Q000235:genetics; D010281:Parathyroid Hormone / Q000097:blood; D013255:Steroid 21-Hydroxylase / Q000235:genetics*
D015415:Biomarkers; D024042:Collagen Type I; D005938:Glucocorticoids; D006728:Hormones; D010281:Parathyroid Hormone; D013255:Steroid 21-Hydroxylase