Fractures and bone mineral density in adult women with 21-hydroxylase deficiency

J Clin Endocrinol Metab. 2007 Dec;92(12):4643-9. doi: 10.1210/jc.2007-0744. Epub 2007 Sep 18.

Abstract

Context: 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.

Design: This was a cross-sectional observational study.

Setting: Tertiary care referral centers were used in this study.

Participants: 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.

Main outcome measures: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenal Hyperplasia, Congenital / complications*
  • Adrenal Hyperplasia, Congenital / enzymology
  • Adrenal Hyperplasia, Congenital / epidemiology*
  • Adult
  • Biomarkers
  • Bone Density / genetics*
  • Bone and Bones / metabolism
  • Cohort Studies
  • Collagen Type I / blood
  • Female
  • Fractures, Bone / enzymology
  • Fractures, Bone / epidemiology*
  • Fractures, Bone / genetics*
  • Genotype
  • Glucocorticoids / adverse effects
  • Glucocorticoids / therapeutic use
  • Hormones / blood
  • Humans
  • Mutation / physiology
  • Osteoporosis / epidemiology
  • Osteoporosis / genetics
  • Parathyroid Hormone / blood
  • Steroid 21-Hydroxylase / genetics*

Substances

  • Biomarkers
  • Collagen Type I
  • Glucocorticoids
  • Hormones
  • Parathyroid Hormone
  • Steroid 21-Hydroxylase