Bone and Mineral Disorders

Abstract

Abnormal bone and mineral metabolism is a common complication of chronic kidney disease (CKD) and has been the subject of concern and controversy throughout the world [1–5]. Mounting evidence suggests that disorders of bone and mineral metabolism are associated with an increased risk for cardiovascular calcification, morbidity, and mortality [6, 7]. As kidney function declines, mineral homeostasis deteriorates leading to changes in the levels of various hormones such as parathyroid hormone (PTH), 25-hydroxyvitamin D, 1,25-dihydroxyvitamin D, other vitamin D metabolites, fibroblastic growth factor-23 (FGF23), and growth hormone. Eventually, serum and tissue concentrations of calcium and phosphorus become abnormal. The discovery of FGF23 has changed the understanding of abnormal phosphorus and vitamin D metabolism in CKD. FGF23 is a bone-derived hormone that increases phosphaturia and decreases the synthesis of 1,25-dihydroxyvitamin D (1,25(OH)2D). Increased secretion of 1,25(OH)2D and high dietary phosphorus intake are considered to be the main stimuli of FGF23 secretion [8]. FGF23 levels increase early (CKD stage 2 or 3) and steadily increase as CKD progresses. This hormone stimulates an appropriate physiologic adaptation to maintain normal phosphorus balance. It helps to augment urinary phosphate excretion, increase PTH levels, and lower 1,25(OH)2D production by decreasing phosphorus absorption from the GI tract. Over time this adaptation fails causing a progressive decline in 1,25(OH)2D levels with additional consequences such as secondary hyperparathyroidism (SHPT). High FGF23 levels have been independently linked with adverse outcomes in CKD, such as cardiovascular disease and mortality. Additionally, treatment with activated vitamin D compounds stimulates FGF23 which has reinforced the need to reconsider the risks and benefits of using activated vitamin D and to determine the optimal doses to treat CKD-mineral and bone disorder (CKD-MBD) [8].