Prevention of bone loss with alendronate in kidney transplant recipients.

Abstract

Bone mineral loss remains a serious problem after kidney transplantation and is most pronounced during the first few months after transplantation (1, 2). Recently, bisphosphonates have generated interest in the treatment and prevention of corticosteroid-induced osteoporosis (3). In kidney transplant patients pamidronate and clodronate were used successfully in two studies (4, 5). No data are available about the prevention of bone mineral loss with alendronate in the early posttransplant period. We analyzed two bone protecting treatments in two groups of patients with osteopenia and osteoporosis in the early posttransplant period. Group A (n=6; two men, four women; two postmenopausal) was treated with alendronate, calcium carbonate, and calcitriol, group B (n=6; three men, three women; one postmenopausal) was treated with calcium carbonate and calcitriol. Patients were aged from 22 to 60 years, no patient had diabetes mellitus, and no one was treated by specific bone protecting treatment other than calcium supplementation and vitamin D before transplantation. One patient from group A experienced an atraumatic vertebral fracture before dialysis during steroid treatment of focal glomerulosclerosis, but no patient had any fracture during the dialysis period or in the first six months after transplantation. At the introduction of preventive therapy all patients had normal serum calcium, serum creatinine below 200 μmol/l and intact PTH above 50 ng/l. No postmenopausal woman was treated with hormone replacement therapy or other drugs affecting bone metabolism. All patients were treated with cyclosporine, methylprednisolone, and azathioprine. The cyclosporine trough blood level (FPIA, monoclonal) was first held in the range from 200 to 300 ng/ml and after 3 months in the range of 100 to 200 ng/ml. The cumulative steroid dose after 6 months was 46.5±18.6 mg/kg body weight in group A and 44.2±16.1 mg/kg body weight in group B. The dose of azathioprine was 3 mg/kg and it was discontinued after 2 weeks. The daily dose of calcium carbonate was 2 g, calcitriol 0.25 μg, and alendronate 10 mg. Therapy was introduced 20.3±8.8 days (range 11–35 days) after transplantation. Patients were given ranitidine to prevent dyspepsia. Bone mineral density (BMD) was measured by dual energy x-ray absorptiometry HOLOGIC QDR 4500 (HOLOGIC INC., Waltham, MA) at the lumbar spine L2-L4. The in vivo precision error was <2%. Urine calcium was measured in a random urine specimen. Daily calcium excretion was estimated from the urine calcium-to-creatinine ratio. BMD measurement was carried out in patients within the first 3 weeks after transplantation and was repeated after 6 months of treatment. Intact PTH was measured on the day of transplantation and after 6 months. A paired t test was applied to compare changes within groups. A t test for small independent samples was applied to compare both groups at the same time of treatment. BMD and metabolic parameters at the baseline and after six months of treatment in both groups are shown in Table 1. Table 1: Bone mineral density and metabolic parameters at baseline and after six months of treatment (mean±SD){tabft}a At the introduction of treatment and after 6 months of treatment both groups did not differ significantly in BMD. b Reference value.Patients of groups A and B did not differ significantly in their mean age, body weight, the duration of dialysis treatment before transplantation and cumulative steroid dose. At the introduction of treatment and 6 months thereafter both groups did not differ significantly in BMD, serum intact parathyroid hormone (iPTH), calcium, phosphate, creatinine concentration, or the activity of serum alkaline phosphatase. After 6 months of treatment BMD increased by 6.4% in group A (P <0.05) and decreased by 9.3% in group B (P <0.05). No patient in either group showed hypercalcemia and the urinary calcium only temporarily exceeded the upper limit in four patients. No side effects of alendronate treatment were observed. It may be concluded that prevention of bone loss of the lumbar spine after kidney transplantation with alendronate, calcium, and calcitriol in patients with a well-functioning graft and very low BMD was effective and safe in the early posttransplant period. This treatment could prevent and even increase BMD in the early posttransplant period. No side effects of alendronate were observed. Treatment with calcium and calcitriol alone did not prevent bone loss in the early posttransplant period. Damjan Kovač1 Jelka Lindič Aljoša Kandus Andrej F. Bren