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Calcium and phosphate are the major mineral constituents of bone and are also two of the most important minerals for general cellular function. Accordingly, the body has evolved a complex set of mechanisms by which calcium and phosphate homeostasis is carefully maintained. Approximately 98% of the 1 to 2 kg of calcium and 85% of the 1 kg of phosphorus in the human adult are found in bone, the principal reservoir for these minerals. Mineral homeostasis is dynamic, with constant remodeling of bone and ready exchange of bone minerals with free ions in the extracellular fluid. Bone also serves as the principal structural support for the body and provides space for hematopoiesis in the bone marrow. Abnormalities in bone mineral homeostasis can underlie electrolyte disturbances, resulting in the clinical manifestations of muscle weakness, tetany, and coma. Dysfunction in bone mineral homeostasis can also disturb the structural support of the body in the form of osteoporosis and fractures. Hematopoietic capacity may also be reduced in conditions such as infantile osteopetrosis.

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The average American diet provides 600 to 1000 mg of calcium per day, of which a net amount of approximately 100 to 250 mg is absorbed. Absorption principally occurs in the duodenum and upper jejunum, whereas secretion principally occurs in the ileum. The amount of phosphorus in the American diet is about the same as that of calcium. However, the efficiency of phosphate absorption, which mostly occurs in the jejunum, is greater, ranging from 70 to 90%, depending on intake. The movement of calcium and phosphate across the intestinal and renal epithelia is closely regulated. At steady state, renal excretion of calcium and phosphate balances intestinal absorption. Most of the time, over 98% of filtered calcium and 85% of filtered phosphate is reabsorbed by the kidneys.

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The drugs that are used clinically to modulate bone homeostasis can be divided into endogenous molecules and exogenous substances (Figure 25–1).

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Figure 25–1.
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Drugs that modulate bone mineral homeostasis may be divided into endogenous molecules and exogenous substances. Parathyroid hormone and vitamin D are of primary importance in this regulation whereas calcitonin, glucocorticoids, and estrogens play modulatory roles. Exogenous agents such as bisphosphonates and fluoride are used to prevent or treat disorders of bone and teeth, respectively.

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Endogenous Substances

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The two hormones that serve as the principal regulators of calcium and phosphate homeostasis are parathyroid hormone (PTH), a protein, and biologically active metabolites of the steroid vitamin D (Figure 25–2). Other hormones such as calcitonin, prolactin, growth hormone, insulin, thyroid hormone, glucocorticoids, and gonadal steroids serve secondary roles in calcium and phosphate homeostasis. Several of these hormones, such as calcitonin, glucocorticoids, and estrogens, have efficacy in the treatment of bone mineral disorders. In addition, calcium, phosphate, and other ions such as sodium alter calcium and phosphate homeostasis.

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