Calcium (Ca) is required for many vital intracellular and extracellular body functions, as well as for skeletal support. About 50-60% of total Ca is in the ionized form (Ca++), which is required for a wide variety of functions, including: enzymatic reactions, membrane transport and stability, blood coagulation, nerve conduction, neuromuscular transmission, muscle contraction, vascular smooth muscle tone, hormone secretion, bone formation and resorption, control of hepatic glycogen metabolism, and cell growth and division. Abnormal serum Ca concentrations may be of diagnostic value, and may contribute to development of lesions and clinical signs of disease.

Regulation of serum Ca concentration is complex and requires the integrated actions of parathyroid hormone, vitamin D metabolites and calcitonin. Parathyroid hormone and calcitriol are the main regulators of Ca homeostasis. Parathyroid hormone is largely responsible for the minute-to-minute control of serum Ca++ concentration, whereas calcitriol maintains day-to-day control. The intestine, kidney, and bone are the major target organs affected by Ca regulatory hormones. These interactions allow conservation of Ca in the extracellular fluid volume by renal tubular reabsorption, increased intestinal transport of Ca from the diet, and internal redistribution of Ca from bone. The skeleton serves as a major supply of Ca and phosphorus when intestinal absorption and renal reabsorption are inadequate to maintain normal serum Ca concentrations. Bone Ca mobilization is important in the acute regulation of blood Ca.

Extracellular Ca++ concentration is the fraction of total Ca that is actively regulated. When blood Ca concentration falls, PTH secretion is stimulated. Parathyroid hormone exerts direct effects on bone and kidney and indirect effects on the intestine through calcitriol. PTH increases synthesis of calcitriol, which, in turn, increases Ca absorption from the intestine.

Calcitonin is a small polypeptide hormone synthesized by C-cells in the thyroid gland, and serves an important role in limiting the degree of postprandial hypercalcemia. This action, in concert with PTH, acts to maintain serum Ca++ concentration within a narrow range.

Vitamin D (calciferol) is classified as a secosteroid hormone, with several important active metabolites. The most important step in bioactivation of vitamin D occurs when the 25-hydroxyvitamin form is further hydroxylated to calcitriol in the proximal tubule of the kidney.