Effect of kidney transplantation on bone

Abstract

A broad range of different factors aggravates renal osteodystrophy, which is present in virtually all patients with chronic kidney disease and after successful kidney transplantation. Altered hormonal status, including sex hormones and parathyroid hormone (PTH), a deficit of 1,25(OH) 2 vitamin D 3 (calcitriol), immunosuppressive therapy and post-operative immobilization contribute to a progressive loss of bone density and structure. The decrease of bone mass is particularly prominent during the first 6 months after kidney transplantation and is associated with an increased number of fractures, both compared with the normal population as well as with dialysis patients. At particular risk are patients with a history of diabetes, long duration of haemodialysis and post-menopausal women.To prevent post-transplant bone loss prescription of steroids should be minimized and withdrawn as early as possible. Additional intake of α -calcidol [25(OH) vitamin D 3 ] or calcitriol, despite normal serum levels, reduces persistent hyperparathyroidism after kidney transplantation, improves intestinal calcium absorption and activates osteoblasts. Inhibition of osteoclasts by biphosphonate therapy seems to effectively reverse bone loss during the early and late course of kidney transplantation. However, as the majority of transplant recipients have a low-turnover bone disease, inhibition of osteoclasts, through which bone turnover is impaired, might further reduce osteoblast activity and promote osteoid synthesis.Most investigations were small-scale studies with 10 -100 participants and a follow up of only 12 months. This makes conclusions on the effect of any intervention on the fracture rate impossible. Larger, randomized multicentre studies investigating bone-sparing therapy on hard end points are therefore advocated.

Micro–MR Imaging–based Computational Biomechanics Demonstrates Reduction in Cortical and Trabecular Bone Strength after Renal Transplantation

“…The present data indicate that mechanical competence of bone, measured in terms of stiffness and failure strength of cortical and trabecular compartments, deteriorates at least during the initial 6 months after renal transplantation. The mechanical weakening of cortical bone could be due to persistent secondary hyperparathyroidism, manifested as cortical thinning, intracortical resorption, and trabecularization of the endosteal cortex (23,24). Trabecular bone, on the other hand, is more susceptible to the effects of corticosteroids (3,25), especially during the initial months following transplantation, when doses are generally high enough to directly suppress bone formation.…”

“…Perturbation in cortical bone, for example, is more pronounced in patients with persistent secondary hyperparathyroidism following transplantation (23,24) and is manifested as cortical bone thinning, intracortical resorption, and trabecularization of the endosteal cortex (3,25). Trabecular bone, on the other hand, is more susceptible to the effects of glucocorticosteroids (26,27), R enal osteodystrophy is a multifactorial disorder of bone metabolism that occurs in patients with end-stage renal disease (1).…”

Effect of Teriparatide on Early Bone Loss After Kidney Transplantation

“…The difference in BMD of the lumbar spine between teriparatide-and placebo-treated patients was estimated to be 10% ± 10% after 6 months (1,8,9,(11)(12)(13)(14). Thus, a minimum of 16 [nmol/l] 29 19 44 (9,10,25 (14).…”

Cyclosporin A elicits dose-dependent biphasic effects on osteoblast differentiation and bone formation

“…This phenomenon is not only due to the underlying disease and the organ transplantation but also is thought to be a side effect of the many drugs that are administered pre-and post-transplantation, including glucocorticoids and CsA [3][4][5][6]. However, controversial evidence exists that CsA might have a bone protective effect both in human and laboratory animals [7]. Based on the literature, both in vivo and in vitro data suggest that CsA has potential biphasic effects on bone formation and osteoblast differentiation, and the seemingly contradictory reports and paradoxical results stem, in part, from the wide variation in the conditions used for these studies and in the concentrations of the immunosuppressive drugs used, ranging between 1 nM-25 μM.…”