Calcium is a key mineral that contributes to the structural strength of the bone, but it has a myriad of other functions in the body as well, including participating in enzyme activation, nerve transmission, and muscle contraction.
In addition, it functions as an intracellular messenger and as a cofactor in the coagulation cascade. Accordingly, the precise concentration of active (ionized) calcium must be tightly regulated. Nearly all (99%) of the 1,000 g of calcium held in the body is stored within the bone in the form of a crystalline calcium phosphate called hydroxyapatite (Ca10 (PO4)6 (OH)2). Apatite crystals are 5 × 80 nm or smaller. In bone, there may be impurities of the crystal, in which other ions, such as potassium, sodium, or magnesium, replace the calcium; these substitutions can affect material properties of the bone. Only 1%of the body’s calcium is found outside the bone, primarily in the body fluids. Within cells, the concentration of ionized calcium is very low, 0.1% that of the extracellular fluid, as free calcium could form precipitates and kill the cell. In the extracellular fluid, approximately 50% of the calcium is protein bound (ie, attached primarily to albumin) or complexed to negatively charged ions, such as citrate. The other 50% is ionized. It is this ionized fraction that is biologically active. Calcium enters the body through the intestines and is reabsorbed through the renal tubule. Both processes control the level of circulating calcium ions. However, because dissolution of bone matrix can free calcium for other physiologic needs, much of the body’s minute-to-minute calcium requirements are supplied via bone resorption. Nonetheless, the intestinal absorption of dietary calcium is needed to replenish skeletal stores. In a typical 24-hour period, 500 mg of calcium are released by the bone via osteoclast resorption, and 500 mg are deposited back into the bone via osteoblast-mediated bone formation. In those 24 hours, approximately 10,000 mg of calcium are delivered to the kidneys, and nearly all of it (98%) is retained, with only 200 mg excreted in the urine. This 200-mg loss must be replaced by calcium in the diet; however, 1,000 mg must be ingested—not 200 mg—because intestinal absorption is imperfect and 800 mg are excreted in the stool. Thus, at the point of balance, 1,000 mg of calcium are ingested and 1,000 mg are excreted. The exchange between the bone and the plasma is similarly balanced (Fig. 8).