Calcium is the most abundant mineral in the human body. While most of the body's calcium is sequestered in the skeleton, the free, hydrated cation in solution is a key physiologic mediator in a host of metabolic and regulatory processes. The free cation concentration in the extracellular fluid, historically referred to as "ionized calcium" in clinical medicine, is frequently assayed in patients with suspected or known derangements of calcium metabolism. There is controversy in the literature as to whether direct measurement of ionized calcium, measurement of total (free plus chelated or protein-bound) calcium, or adjustment of total calcium for albumin concentration is the best or most practical clinical measure of calcium, as the three methods differ in costs and clinical sensitivities. This manuscript will review calcium biochemistry and homeostasis, compare the utilities of different methods of assessing calcium homeostasis, and discuss appropriate utilization of ionized calcium testing.
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