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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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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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