Authors: Falhammar H. Filipsson H. Holmdahl G. Janson PO. Nordenskjold A. Hagenfeldt K. Thoren M.

Institution: Department of Endocrinology, Metabolism and Diabetes, Karolinska

University Hospital, SE-171 76 Stockholm, Sweden. henrik.falhammar@karolinska.se

Title: Fractures and bone mineral density in adult women with 21-hydroxylasedeficiency.

Source: Journal of Clinical Endocrinology & Metabolism. 92(12):4643-9, 2007 Dec.

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.