The mechanisms by which glucocorticoids cause osteopenia are incompletely understood. It is generally accepted that bone formation is depressed during corticosteroid treatment, but the cause of the ongoing bone resorption is less clear. Secondary hyperparathyroidism and changes in vitamin D metabolism are thought to play a role. This is based mostly on data from cross-sectional studies in heterogeneous patient groups. We, therefore, studied longitudinally the course of biochemical parameters and the hormones influencing bone turnover in a homogeneous group of 10 euthyroid patients with Graves' ophthalmopathy, all euthyroid for at least 1 yr before, during, and after a 12-week course of prednisone. Bone formation was depressed as reflected by a fall in serum osteocalcin (3.0 ± 2.1, 1.7 ± 1.1, and 2.4 ± 1.9 μg/h at weeks 0, 4, and 12, respectively; P = 0.02) and in total alkaline phosphatase (1.15 ± 0.33, 0.83 ± 0.22, and 0.88 ± 0.40 μkat/L; P = 0.001). Parameters of bone resorption (urinary hydroxyprolire/creatinine ratio, serum acid phosphatase) and the levels of vitamin D metabolites remained unchanged. Serum intact PTH seemed to decrease slightly.

Our findings suggest that glucocorticoid induced osteopenia is caused by a depressed bone formation in the presence of an unaltered but ongoing bone resorption. Secondary hyperpara-thyroidism and changes in vitamin D metabolism are apparently not involved.