Emerging Topics in Pediatric Bone and Mineral Disorders 2008

The calcium sensing receptor (CaSR) and fibroblast growth factor 23 (FGF-23) play central roles in the regulation of calcium and phosphorus metabolism, respectively. CaSR controls parathyroid hormone secretion and renal calcium reabsorption. Inactivating mutations of the CaSR result in conditions characterized by hypercalcemia and hypocalciuria, whereas activating lesions cause hypoparathyroidism and hypercalciuria. Calcimimetics are a group of agonists for the CaSR that have been shown to be powerful agents in the treatment of secondary hyperparathyroidism. FGF-23 acts on the kidney to inhibit the reabsorption of phosphate and the synthesis of 1,25(OH)2D. Disorders of increased FGF-23 function are associated with hypophosphatemia, inappropriately low 1,25(OH)2D levels, and either rickets or osteomalacia. Conversely, decreased FGF-23 activity results in hyperphosphatemia, increased 1,25(OH)2D levels, and abnormal soft-tissue calcification. In chronic kidney disease, increases in FGF-23 are being investigated as markers of disease progression.