Expression of proteins secreted by osteocytes in bone biopsies of patients with chronic kidney disease and iron overload, before and after treatment with deferoxamine.

Abstract

Individuals with CKD can develop anemia, as well as mineral and bone disorder. Anemia is treated with recombinant erythropoietin and iron supplementation, which can result iron overload in various organs. Little is known about the effects of iron overload and its treatment on bone remodeling and osteocyte expression of relevant proteins. The objective of this study was to evaluate the effects that iron overload and treatment with the iron chelator deferoxamine have on parameters of iron metabolism in bone tissue and on osteocyte protein expression. This was an observational study of individuals with CKD and iron overload who underwent bone biopsy and were treated with deferoxamine. Biochemical analysis, histomorphometry, and immunohistochemistry were performed. The results were compared with those obtained for controls. Deferoxamine treatment reduced all parameters of iron metabolism decreased calcium, increased alkaline phosphatase, and decreased (intact and c-terminal) fibroblast growth factor 23 levels. After treatment, trabecular separation increased, and osteoblast surface decreased. DFO treatment increased the expression of DMP-1, decreased the expression of DKK-1, PHEX and the RAGE proteins involved in bone remodeling and oxidative stress. Comparison of the expression of osteocyte proteins before and after DFO treatment with their expression in normal bone tissue, there was also increased expression of proteins that act in the formation of dendrites and cytoskeleton, such as E11 and CD44. In patients with CKD and iron overload, deferoxamine treatment modulates bone remodeling and expression of osteocyte proteins, which also play a role in the process.