Bone mineral homeostasis

Chapter 39 Adrenocorticosteroids Adrenocortical Antagonists Chapter 40 The Gonadal Hormones Inhibitors Chapter 41 Pancreatic Hormones Antidiabetic Drugs Chapter 42 Agents That Affect Bone Mineral Homeostasis... 

AccessMedicine Print Chapter 42. Agents that Affect Bone Mineral Homeostasis... 

Calcium and phosphate, the major mineral constituents of bone, 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 are carefully maintained (Figure 42-1). Approximately 98% of the 1-2 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. These functions are dynamic, with constant remodeling of bone and ready exchange of bone mineral with that in the extracellular fluid. Bone also serves as the principal structural support for the body and provides the space for hematopoiesis. Thus, abnormalities in bone mineral homeostasis can lead not only to a wide variety of cellular dysfunctions (eg, tetany, coma, muscle weakness) but also to disturbances in structural support of the body (eg, osteoporosis with fractures) and loss of hematopoietic capacity (eg, infantile osteopetrosis). 

Some mechanisms contributing to bone mineral homeostasis. Direct actions are shown and feedback may alter the net effect. Calcium (Ca) and phosphorus (P) concentrations in the serum are controlled principally by three hormones, l,25(OH)2D3 (D),... 

Calcium and phosphate enter the body from the intestine. The average American diet provides 600-1000 mg of calcium per day, of which approximately 100-250 mg is absorbed. This figure represents net absorption, because both absorption (principally in the duodenum and upper jejunum) and secretion (principally in the ileum) occur. The amount of phosphorus in the American diet is about the same as that of calcium. However, the efficiency of absorption (principally in the jejunum) is greater, ranging from 70% to 90%, depending on intake. In the steady state, renal excretion of calcium and phosphate balances intestinal absorption. In general, over 98% of filtered calcium and 85% of filtered phosphate is reabsorbed by the kidney. The movement of calcium and phosphate across the intestinal and renal epithelia is closely regulated. Intrinsic disease of the intestine (eg, nontropical sprue) or kidney (eg, chronic renal failure) disrupts bone mineral homeostasis. 

The hormonal interactions controlling bone mineral homeostasis. In the body (A), l,25(OH)2D is produced by the kidney under the... 

Principal Hormonal Regulators of Bone Mineral Homeostasis PARATHYROID HORMONE... 

A number of hormones modulate the actions of PTH, FGF23, and vitamin D in regulating bone mineral homeostasis. Compared with that of PTH, FGF23, and vitamin D, the physiologic impact of such secondary regulation on bone mineral homeostasis is minor. However, in pharmacologic amounts, a number of these hormones have actions on the bone mineral homeostatic mechanisms that can be exploited therapeutically. 

Glucocorticoid hormones alter bone mineral homeostasis by antagonizing vitamin D-stimulated intestinal calcium transport, by stimulating renal calcium excretion, and by blocking bone formation. Although these observations underscore... 

Nonhormonal Agents Affecting Bone Mineral Homeostasis BISPHOSPHONATES... 

Etidronate and the other bisphosphonates exert a variety of effects on bone mineral homeostasis. In particular, bisphosphonates are useful for the treatment of hypercalcemia associated with malignancy, for Paget s disease, and for osteoporosis (see Newer Therapies for Osteoporosis). Contrary to expectations, some of the newer bisphosphonates appear to increase bone mineral density well beyond the 2-year period predicted for a drug whose effects are limited to blocking bone resorption. The bisphosphonates exert a variety of other cellular effects, including inhibition of l,25(OH)2D... 

The major problems of chronic kidney disease that impact bone mineral homeostasis are the loss of l,25(OH)2D... 

Other Disorders of Bone Mineral Homeostasis PAGET S DISEASE OF BONE... 

SUMMARY MAJOR DRUGS USED IN DISEASES OF BONE MINERAL HOMEOSTASIS... 

PTH works with two other primary hormones— calcitonin and vitamin D—in regulating calcium homeostasis. These three hormones, as well as several other endocrine factors, are all involved in controlling calcium levels for various physiologic needs. How these hormones interact in controlling normal bone formation and resorption is of particular interest to rehabilitation specialists. Regulation of bone mineral homeostasis and the principal hormones involved in this process are presented in the following section. 

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