Mechanism of transplantation-associated bone loss

Successful renal transplantation is associated with abnormalities of function of the musculoskeletal system. Some of these problems result from incomplete resolution of abnormalities of mineral metabolism associated with end-stage renal disease, such as persistent hyperparathyroidism, hypercalcemia and decreased vitamin D. However, it is now appreciated that skeletal abnormalities, especially osteopenia with subsequent fractures, develop following transplantation. Most of the new disorders of bone and mineral metabolism are secondary to the immunosuppression required to prevent rejection. Glucocorticoids can not only induce osteonecrosis, but also increase the risk for fractures by decreasing cancellous bone mass and synthesis of bone matrix, and dampen the linear growth response in pediatric recipients. Other immunosuppressive agents, especially the calcineurin-phosphate inhibitors, independently exert a negative effect on bone. Future investigation is required to develop a better understanding of the pathophysiologic mechanisms involved in post-transplant bone disease in order to develop rational approaches for prevention and treatment.