Osteoporotic fractures result in substantial morbidity after heart transplantation. To measure the acute effects of corticosteroids on bone after heart transplantation, we measured bone mineral density by dual energy x-ray absorptiometry and biochemical indexes of bone turnover in 25 patients (21 male, 4 female) at baseline, 6 months, and 12 months after transplantation. Two patients sustained vertebral fractures. Bone loss was rapid in the first 6 months, occurred in 24 of 25 (96%) patients, and was most marked from the lumbar spine (mean +/- SD, -7.4% +/- 4.5%). In the second 6 months little further bone loss was evident (lumbar spine, -7.8% total over 12 months) despite continuing moderate maintenance doses of corticosteroids. Serum osteocalcin and testosterone levels rose and urinary hydroxyproline:creatinine level ratio fell significantly by 6 months. Bone loss from the lumbar spine correlated inversely with serum osteocalcin level at 6 months. Serum osteocalcin level was the only significant predictor of lumbar spine bone loss by multiple regression analysis that included age, corticosteroid dose, cyclosporine dose, lean body mass, and body mass index. These data suggest that prophylactic therapy to prevent bone loss may only be necessary in the first 6 to 12 months after heart transplantation.