Chapter 11 - Pathogenesis of Transplantation Bone Disease: A Unifying Hypothesis

Abstract

This chapter reviews the pathogenesis and pathophysiology of bone loss after transplantation. There are three reasons why bone turnover remains elevated late after transplantation and after glucocorticoid administration has been stopped. First, a decrease in glomerular filtration rate results in an increase in osteocalcin (OC). Second, immunosuppressive agents, such as cyclosporine A may have a direct effect on the rate of bone turnover. Finally, fractures may result in an increase in bone turnover markers, reflecting fracture repair. Drugs that are used to prevent rejection appear to have an important role to play in bone loss after cardiac transplantation. This is also true for other forms of organ transplantation. The most convincing biochemical change is the increase in serum parathyroid hormone in the later post-transplant period along with the decrease in serum magnesium, which may be the cause of the increase in bone resorption. It is likely that cyclosporine A and other immunosuppressive are important determinants of the increased bone turnover, through effects on renal function and hence, on calcitriol levels and calcium absorption. Glucocorticoid therapy is a potential contributor to the fracture syndrome. The latter may be countered by bisphosphonates, such as alendronate. The decrease in calcium absorption may be countered by the administration of calcitriol, or of calcium and vitamin D.