Chapter 13. Regulation of Calcium, Magnesium, and Phosphate Metabolism

The mineral ion homeostatic system maintains Ca, Mg, and P (because P does not exist as free P in biological systems, it will be referred to as phosphate and abbreviated PO4) distribution and levels in the extracellular fluid and intracellular compartments while simultaneously providing sufficient absorption and retention to meet skeletal mineral requirements. Homeostasis is achieved by the coordinated interaction of the intestine, the site of net absorption; the kidney, the site of net excretion; and the skeleton, the largest repository of these ions in the body. Mineral fluxes across intestine, bone, and kidney and in and out of blood are regulated by PTH and 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], the hormonal or active form of vitamin D (also called calcitriol). There is emerging evidence that fibroblast growth factor (FGF)-23 may also be an important physiologic regulator of PO4 homeostasis. External balance may vary with the stages of the life cycle, skeletal mineral requirements, supply of the minerals in the diet, and by a variety of disorders. For example, balance is neutral in adult, nonpregnant humans who have no daily net gain or loss of body Ca, Mg, or PO4. Mineral balance becomes positive (intake and retention exceed urinary and intestinal losses) during skeletal growth during childhood and adolescence and during pregnancy and lactation. Negative balance (gastrointestinal and/or urinary losses exceed intake and retention) may occur during high rates of bone remodeling during estrogen deficiency, with aging, and with diseases such as hyperthyroidism and primary hyperparathyroidism. The adjustment or adaptation of the homeostatic system to maintain balance is mediated by PTH and 1,25(OH)2D3 through changes in intestinal and renal tubule mineral transport. In the following sections, the distributions and fluxes of Ca, Mg, and PO4 and hormonal regulations of mineral ion transport and balance are discussed.