Intestine calcium absorption

The steroid hormone 1,25-dihydroxy vitamin D3 (calcitriol) slowly increases both intestinal calcium absorption and bone resorption, and is also stimulated through low calcium levels. In contrast, calcitonin rapidly inhibits osteoclast activity and thus decreases serum calcium levels. Calcitonin is secreted by the clear cells of the thyroid and inhibits osteoclast activity by increasing the intracellular cyclic AMP content via binding to a specific cell surface receptor, thus causing a contraction of the resorbing cell membrane. The biological relevance of calcitonin in human calcium homeostasis is not well established. 

A major regulator of bone metabolism and calcium homeostasis, parathyroid hormone (PTH) is stimulated through a decrease in plasma ionised calcium and increases plasma calcium by activating osteoclasts. PTH also increases renal tubular calcium re-absorption as well as intestinal calcium absorption. Synthetic PTH (1-34) has been successfully used for the treatment of osteoporosis, where it leads to substantial increases in bone density and a 60-70% reduction in vertebral fractures. 

Fullmer CS, Rosen JF. 1990. Effect of dietary calcium and lead status on intestinal calcium absorption. Environ Res 51 91-99. 

Supplemental vitamin D maximizes intestinal calcium absorption and has been shown to increase BMD it may also reduce fractures. 

Agnusdei, D., CiviteUi, R., Camporeale, A., Parisi, G., Gennari, L., Nardi, P., and Gennari, C. (1998). Age-related decline of bone mass and intestinal calcium absorption in normal males. Calcif. Tissue Int. 63,197-201. 

Gallagher, J. C., Riggs, B. L., Eisman, J., Hamstra, A., Arnaud, S. B., and DeLuca, H. E. (1979). Intestinal calcium absorption and serum vitamin D metabolites in normal subjects and osteoporotic patients. /. Clin. Invest. 64, 729-736. 

Krall, E. A., and Dawson-Hughes, B. (1999). Smoking increases bone loss and decreases intestinal calcium absorption. JBMR 14,215-220. 

Pattanaungkul, S., Riggs, B. L., Yergey, A. L., Vieira, N. E., O Eallon, W. M., and Khosla, S. (2000). Relationship of intestinal calcium absorption to 1,25-dihydroxyvitamin D [1,25 (0H)2D] levels in young versus elderly women Evidence for age-related intestinal resistance to l,25(OH)2D action. /. Clin. Endocrinol. Metab. 85,4023M027. 

Wasserman, R. H. (2004). Vitamin D and the dual processes of intestinal calcium absorption. /. Nutr. 134, 3137-3139. 

In the kidney, PTH stimulates the conversion of 25-(0H)D3 into 1,25-(0H)2D3. Intrarenal l,25-(OH)2D3 causes an amplification of the PTH-induced calcium reabsorption and phosphate diuresis. l,25-(OH)2D3 enhances PTH action in bone also. Once again, PTH does not directly affect intestinal calcium absorption, but it does so indirectly through induction of l,25-(OH)2D3 synthesis and enhanced enterocyte absorption. 

Vitamin Dj, through its active metabolite, 1,25-(0H)2D3, also plays an important role in maintaining calcium homeostasis by enhancing intestinal calcium absorption, PTH-induced mobilization of calcium from bone, and calcium reabsorption in the kidney. 

Cholecalciferol Regulate gene transcription via the vitamin D receptor Stimulate intestinal calcium absorption, bone resorption, renal calcium and phosphate reabsorption decrease parathyroid hormone (PTH) promote innate immunity inhibit adaptive immunity Osteoporosis, osteomalacia, renal failure, malabsorption Hypercalcemia, hypercalciuria the vitamin D preparations have much longer half-life than the metabolites and analogs... 

Bonjour, J. P., Russell, R. G. G., Morgan, D. B., Fleisch, H. A. Intestinal calcium absorption, Ca-binding protein, and Ca-ATPase in diphosphonate-treated rats. Amer. J. 

Bouillon, R., Van Cromphaut, S. and Carmeliet, G., 2003, Intestinal calcium absorption Molecular vitamin D mediated mechanisms. J Cell Biochem 88, 332-9. 

Peng, J. B., Chen, X. Z., Berger, U. V., Vassilev, P. M., Tsukaguchi, H., Brown, E. M. and Hediger, M. A., 1999, Molecular cloning and characterization of a channel-like transporter mediating intestinal calcium absorption. J Biol Chem 274, 22739—46. 

Parathyroid hormone (PTH) is an 84-amino acid peptide secreted by the parathyroid glands, and is the principal regulator of extracellular calcium levels [44, 45]. The effects of PTH on extracellular calcium are mediated directly or indirectly through effects on bone, kidney, and intestine. A decrease in extracellular calcium causes an increase in PTH secretion. As a consequence, the rise in PTH levels causes increased bone resorption and the release of calcium from bone, decreased calcium excretion by the kidney, and increased intestinal calcium absorption. The therapeutic application of PTH has centered on the bone effects as an anabolic treatment for osteoporosis. PTH increases the activity of both osteoblasts (which form bone) and osteoclasts (which mediate bone resorption). The desirable anabolic effects of PTH on osteoblasts appear to be highly dependent on dose schedule and the duration of daily exposure. 

Vitamin D-binding protein and its associated vitamin are lost in nephrotic urine. Biochemical abnormalities in nephrotic patients (children and adults) include hypocalcemia, both total (protein-bound) and ionized hypocalciuria, reduced intestinal calcium absorption and negative calcium balance reduced plasma 25-hydroxycholecalciferol and 24,25-dihydroxycholecalciferol and, surprisingly, also 1,25-dihydroxycholecalciferol and blunted response to parathormon (PTH) administration and increased PTH levels. Clinically, both osteomalacia and hyperparathyroidism have been described in nephrotic patients, more commonly in children than in adults, but bone biopsies are commonly normal, and clinically significant bone disease is very rare in nephrotic subjects. There is, however, evidence that patients with renal failure accompanied by nephrotic range proteinuria may be particularly prone to develop renal osteodystrophy. 

Both the active and passive modes of calcium transport are increased during pregnancy and lactation. This is probably due to the increase in calbindin and serum PTH and 1,25-dihydroxyvitamin D concentrations that occur during normal pregnancy. Intestinal calcium absorption is also dependent on age, with a 0.2% per year decline in absorption efficiency starting in midlife. The fractional absorption of calcium depends on the form and dietary source. Absorption rates are 29% for the calcium in cow s milk, 35% for calcium citrate, 27% for calcium carbonate, and 25% for tricalcium phosphate. Other factors that limit the bioavailability of calcium in the intestine are oxalates and phy-tates, which are found in high quantities in vegetarian diets and which chelate calcium. 

PTH also activates renal la-hydroxylase, increasing the amount of the active form of vitamin D (1,25-dihydroxyvitamin D), which in turn enhances intestinal calcium absorption. In... 

Physiological actions of PTH include regulation of bone metabolism, renal tubular reabsorption of calcium and phosphate, and intestinal calcium absorption... 

The fact that vitamin D3 toxicity results from primarily uncontrolled intestinal calcium absorption suggests that it is dietary calcium and not vitamin D3 that exacerbates the hypervitaminosis D3 toxicity effect [119]. This was tested by the interaction of excess vitamin D3 and calcium restriction [113]. Rats fed a calcium-deficient diet and given 25,000 IU of vitamin D3 three dmes/week for 2.5 weeks did not succumb to overt hypervitaminosis D3. Simple calcium restriction increased intestinal but not renal 24-OHase activity, presumably because of the absence of parathyroid hormone regulation in the intestine [113]. Coupled with vitamin D3, excess intestinal 24-OHase increased several fold more. However, when dietary calcium was adequate, vitamin D3 excess increased intestinal 24-OHase activity only slightly because of a suppressive mechanism regulated in part by increased blood calcitonin [120],... 

OH)2D3 concentrations. Low l,25-(OH)2D3 results in little to no intestinal calcium absorption for soft tissue needs. Thus, blood calcium can be low and secondary hyperparathyroidism develops. The inability to regulate renal handling of phosphate by PTH leads to phosphate-mediated repression of ionized calcium. Serious osteodystrophic lesions occur because of high PTH activity on bone resorption resulting in osteitis fibrosa and osteosclerosis. 

With the isolated perfused duodenum, there is a rapid increase in calcium transport in response to the addition of calcitriol to the perfusion medium. Isolated enterocytes and osteoblasts also show a rapid increase in calcium uptake in response to calcitriol. It is not associated with changes in mRNA or protein synthesis, but seems to be because of recruitment of membrane calcium transport proteins from intracellular vesicles to the cell surface. It is inhibited by the antimicrotubule compound colchicine. It can only be demonstrated in tissues from animals that are adequately supplied with vitamin D in vitamin D-deficient animals, the increase in intestinal calcium absorption occurs only more slowly, together with the induction of calbindin. 

Alfacalcidol and calcitriol have some advantages over calciferol, but their high potency involves a risk of hypercalcemia even after small dosage increments, because of increased intestinal calcium absorption. Because of this, constant vigilance is required to prevent hypercalcemia, especially in patients with chronic renal insufficiency and associated renal osteodystrophy. 

Because of its potent effects on parathyroid hormone, intestinal calcium absorption, and bone calcium mobilization, calcitriol can cause hypercalcemia, often precluding its use in therapeutic doses (32). Hyperphosphatemia is also a persistent problem in patients on chronic hemodialysis and can be aggravated by therapeutic doses of calcitriol. The use of large doses of calcium carbonate or acetate to control phosphate absorption can increase the risk of hypercalcemia from calcitriol (33). 

Blumsohn A, Morris B, Eastell R. Stable strontium absorption as a measure of intestinal calcium absorption comparison with the double-radiotracer calcium absorption test. Clin Science 1994 87 363-368. 

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