Pleiotropic Endocrine Functions of Bone in Chronic Kidney Disease

The principal organs involved in the control of mineral homeostasis are the kidneys, parathyroid glands, intestine and bone, which interact in a finely coordinated manner to maintain calcium and phosphorus levels. Mineral balance is disrupted in the context of chronic kidney disease (CKD), triggering compensatory mechanisms that paradoxically lead to a cascade of systemic complications that affect numerous organs. Among these organs, bone has increasingly been recognized as an endocrine organ, highlighting the role of bone-derived hormones in CKD complications beyond mineral metabolism. Osteocytes play a key role in the regulation of phosphorus metabolism, mediated by Fibroblast Growth Factor 23 (FGF23), which also demonstrates pleiotropic effects. Furthermore, bone cells produce a wide range of proteins that participate in the regulation of diverse systemic functions, such as glucose metabolism, male fertility, cognitive function, inflammation, appetite and hematopoiesis, which are processes commonly impaired in patients with CKD. So far, the systemic impact of dysregulated bone homeostasis in CKD has not been addressed in detail beyond its role in calcium-phosphate metabolism. This review aims to provide an overview of the role of bone as a main endocrine organ and its potential roles in organ dysfunction in CKD.