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

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/m(2). 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.