Regulation 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. 

Consequently, bone is a rather dynamic tissue that is constantly undergoing changes in mineral content and internal structure. The balance between bone resorption and formation is controlled by the complex interaction of local and systemic factors. In particular, several hormones regulate bone formation and help maintain adequate plasma calcium levels. The primary hormones involved in regulating bone mineral homeostasis are described below. 

Parathyroid Hormone. The role of the parathyroid gland and PTH in controlling calcium metabolism was previously discussed. A prolonged or continuous increase in the secretion of PTH increases blood calcium levels by several methods, including increased resorption of calcium from bone. High levels of PTH accelerate bone breakdown (catabolic effect) to mobilize calcium for other physiologic needs. 

However, normal or intermittent PTH release may actually enhance bone formation.70,77 That is, in- 

Vitamin D. Vitamin D is a steroidlike hormone that can be obtained from dietary sources or synthesized in the skin from cholesterol derivatives in the presence of ultraviolet light. Vitamin D produces several metabolites that are important in bone mineral homeostasis.27,31 In general, vitamin D derivatives such as 1,25 dihydroxyvitamin D3 increase serum calcium and phosphate levels by increasing intestinal calcium and phosphate absorption and by decreasing renal calcium and phosphate excretion.27,46 

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

Identify the major and minor regulators of bone mineral homeostasis. 

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. 

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 normal thyroid gland secretes sufficient amounts of the thyroid hormones—triiodothyronine (T3) and tetraiodothyronine (T4, thyroxine)—to normalize growth and development, body temperature, and energy levels. These hormones contain 59% and 65% (respectively) of iodine as an essential part of the molecule. Calcitonin, the second type of thyroid hormone, is important in the regulation of calcium metabolism and is discussed in Chapter 42 Agents That Affect Bone Mineral Homeostasis. 

VDR is a receptor of 1,25-dihydroxyvitamin D3 (DHD3 31), which is an active form of vitamin D and plays critical roles in a variety of biological activities, including regulation of calcium homeostasis, bone mineralization and control of cellular growth, differentiation, and apoptosis. VDR antagonists can be expected... 

Regulation of Calcium Homeostasis Calcium homeostasis necessitates the maintenance of a dynamic equilibrium of calcium fluxes between three different compartments which harbor the mineral ion in vastly different concentrations. Thus, homeostatic control mechanisms ought to modulate calcium fluxes between different body compartments in a way which allows the generation and maintenance of steep concentration gradients between the skeletal tissue, the extracellular fluid and the intracellular - that is, the cytoplasmic compartment. Of particular importance thereby is the rigid control of plasma free Ca " ", because even small deviations from the normal level induce profound changes in both intracellular free Ca, as well as in the amount of calcium deposited at skeletal sites, inevitably causing adverse effects on bone health (cf. Whedon 1980). 

A number of hormones interact to regulate the and phosphate concentrations. The most important are PTH and 1,25-dihydroxyvitamin D (l,25-(OH)2D caldtriol), which regulate mineral homeostasis by effects on the kidney, intestine, and bone (Figure 61-3). 

Osteomalacia is caused by deficiency of vitamin D. Vitamin D regulates calcium homeostasis in the body by facilitating absorption of calcium from the intestine and, together with PTH, by enhancing calcium mobilization from bone and by reducing excretion of calcium by the kidney. Deficiency of vitamin D leads to inadequate absorption of calcium. Low levels of calcium stimulate the release of PTH, which in turn causes release of calcium from bone and failure to mineralize newly formed bone. 

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