Calcium homeostasis.

Abstract

Precise maintenance of the physiologic levels of both extracellular and intracellular ionized calcium is essential to life. Calcium and phosphate homeostasis is complex, yet three important hormones are responsible for modulating most of the extracellular control of these minerals. Parathyroid hormone acts directly on bone and kidney and indirectly on the intestine to maintain or restore the serum calcium level. The signal for increased PTH synthesis and secretion is a decrease in the serum ionized calcium concentration and a decrease in serum levels of 1,25(OH)2-D. Calcitonin is produced in parafollicular cells of the thyroid and inhibits bone resorption in pharmacologic doses. These cells recognize the calcium signal in a different way. A diminution in serum calcium decreases calcitonin production and release. The role of calcitonin in normal human physiology, however, remains in dispute. Finally, the biologically potent metabolite of vitamin D, 1,25(OH)2-D, stimulates intestinal absorption of calcium and phosphate. It also probably plays a role in the orderly mineralization and resorption of bone and has some influence on renal resorption of filtered calcium and phosphorus. A major stimulus to its production by proximal renal tubule cells is elevated PTH and decreased serum levels of calcium and phosphate. The absence of PTH as well as high serum calcium and phosphate levels can reduce its synthesis and secretion. These three hormones along with other mediators and messengers work in concert to maintain the normal calcium homeostasis. A disturbance at any level in this intricate regulatory network will result in a host of compensatory changes that may lead to clinical disease. A complete understanding of these normal mechanisms is a prerequisite to investigating the etiology and treatment of the various pathologic responses seen with many of the metabolic bone disorders.