Osteopenia is a major complication of renal transplantation. Immunosuppressive regimens including cyclosporine, which permit the use of lower doses of glucocorticoids, may reduce glucocorticoid-induced osteopenia. We prospectively studied the magnitude, distribution, and mechanism of bone loss in 20 adults who received renal allografts from living related donors, who had good renal function, and who were treated with azathioprine, cyclosporine, and low doses of prednisone. We measured serum biochemical markers of bone metabolism, determined the bone mineral density of the second, third, and fourth lumbar vertebrae and the shaft of the radius, and analyzed the histomorphometric features of iliac bone at the time of transplantation and six months later. Measurements of vertebral mineral density were repeated 18 months after transplantation in 17 of the patients. After transplantation, the mean serum concentrations of parathyroid hormone, phosphorus, and alkaline phosphatase decreased and the serum calcitriol concentration increased. The mean (±SD) bone mineral density of the vertebrae had decreased 6.8±5.6 percent 6 months after transplantation (P<0.05) and 8.8±7.0 percent 18 months after transplantation. In contrast, the bone mineral density of the radius had increased six months after transplantation (P<0.05). The histomorphometric studies showed that the rate of bone formation decreased from 50.5±44.8 to 23.1±13.8 μm3 per square micrometer per year (P<0.05), and the formation period lengthened from 70±42 to 146±144 days (P<0.05). Consequently, the amount of bone replaced during a remodeling cycle diminished. Osteopenia associated with renal transplantation remains a problem in the cyclosporine era. The loss of vertebral bone in our subjects was due to an imbalance in bone remodeling consistent with a toxic effect of glucocorticoids. (N Engl J Med 1991; 325:544-50.) © 1991, Massachusetts Medical Society. All rights reserved.