Effect of Teriparatide on Early Bone Loss After Kidney Transplantation
Kidney transplantation is associated with bone loss and a high risk of fractures. Prophylactic treatment of bone is therefore recommended in the early posttransplant period. As a large number of transplant recipients develop adynamic renal osteodystrophy, recombinant parathyroid hormone (rPTH) could be a promising therapeutic option.
In a 6-month double-blind, randomized trial, 26 kidney transplant recipients were treated with daily subcutaneous injections of 20 µg teriparatide (PTH 1-34) or placebo. Bone mineral density (BMD) of the femoral neck, lumbar spine and radial bone was measured at transplantation and after 6 months. Paired bone biopsies for histomorphometric analysis were obtained in six, and for measurement of bone matrix mineralization in five patients of each group. Serologic bone markers were measured at baseline and every 3 months.
A total of 24 out of 26 patients completed the study. Femoral neck BMD was stable in the teriparatide group, but decreased significantly in the placebo group. Lumbar spine and radial BMD, histomorphometric bone volume and bone matrix mineralization status remained unchanged in both groups. Serologic bone markers were similarly reduced in both groups throughout the study.
We conclude that teriparatide does not improve BMD early after kidney transplantation. Neither histological analysis nor bone markers provide evidence of improved bone turnover or mineralization.

Kidney transplantation reduces bone mineral density (BMD) and increases the risk of fracture. During the first 6 months, BMD of the lumbar spine and femoral neck is reduced by 4% and 3%, respectively. As a consequence, the incidence of fractures is several times higher than that in normal controls or hemodialysis patients. The predominant cause of posttransplant bone loss appears to be reduced bone formation and increased bone resorption by steroids or calcineurin inhibitors. Therefore, prophylactic treatment with bisphosphonates, calcitonin or active vitamin D is recommended in addition to low-dose steroid therapy.

Bone biopsies performed 6 to 12 months after transplantation demonstrated reduced bone turnover and impaired mineralization in a considerable number of patients. Thus, early posttransplant bone loss appears to be due to increased bone resorption as well as persistent or newly developed low-turnover renal osteodystrophy (ROD). In selected patients, stimulation of bone turnover by a bone anabolic agent might be more effective than inhibition of bone resorption.

Teriparatide (recombinant human parathyroid hormone 1-34) exerts anabolic effects on the skeleton when given intermittently. A 6-month course consisting of daily subcutaneous injections of 20 ug teriparatide increased the bone calcium content and reduced fracture rates in postmenopausal women with osteoporosis. Teriparatide is superior to bisphosphonates because of its anabolic effect. In steroid-induced osteoporosis, the BMD of the lumbar spine was reported to have increased by 6-11% after 1 year. Compared to the bisphosphonate alendronate, teriparatide is able to better prevent fractures in these patients. Despite its superiority to bisphosphonates, rPTH therapy has not yet been investigated in kidney transplant recipients.