Phosphate: An Anion Controlling Metabolic Functions

Phosphate accounts for about 0.6% of body weight at birth and about 1% of body weight in adults. This anion is essential for the performance of many essential human cellular processes, including energy metabolism and cell signaling; it is also a key component of the phospholipid bilayer and nucleic acids structure. In addition, phosphate is responsible for maintaining acid-base balance within the cells, functioning of the nervous system and preserving bone integrity. Normal serum phosphate levels change throughout life, varying from the neonatal period, through adolescence, and stabilizing at adult values by the end of puberty. Serum phosphate homeostasis is maintained through dietary intake, intra- and intercellular shifts, and excretion/absorption/reabsorption processes mediated by Fibroblast Growth Factor 23, parathyroid hormone, and 1,25-(OH)₂D₃. Within this homeostatic network, dietary sources and current population-based intake data highlight a widespread oversupply in modern diets that can influence chronic disease outcomes. Ultimately, alterations in serum phosphate concentrations lead to numerous pathological conditions, both congenital and acquired. These conditions may involve either hypo- or hyperphosphatemia, each characterized by a wide spectrum of clinical manifestations, some of which primarily affect the musculoskeletal system. Starting from this evidence, the primary purpose of this review is to examine the phosphate-related pathological conditions from biological-molecular and clinical perspectives, while also considering targeted nutritional and clinical strategies for managing phosphate balance. Algorithms for management and differential diagnosis are also considered, thus providing a recent overview of a medical field that is becoming increasingly important for clinicians.