Mineral metabolism parathyroid hormone

R. S. Flueck, J. A. "The Interrelationships Between Vitamin D and Parathyroid Hormone in Disorders of Mineral Metabolism in Man" (Proceedings of 2nd Vitamin D Symposium), Weisbaden, West Germany, Oct., 1974, In Press. 

Bone mineral metabolism agents Parathyroid hormone Vitamin D... 

Parathyroid Hormone, Calcitonin, Vitamin D, and Other Compounds Related to Mineral Metabolism... 

Vitamin D, along with parathyroid hormone and calcitonin, plays a primary role in calcium and phosphorus homeostasis in the body. Intensive research efforts over the past several years have elucidated a role for vitamin D in many other physiological processes as well. The biological actions of this seco-steroid are mediated primarily through the action of its polar metabolite, 1,25-dihydroxy vitamin D3 (l,25(OH)2D3). There is emerging evidence that l,25(OH)2D3 has many more target tissues than those involved in its classical role in the control of mineral metabolism. In addition, some of the actions of l,25(OH)2D3 may be mediated by mechanisms other than the classical steroid-receptor interaction. In this chapter we will provide a brief overview of the multiple actions of vitamin D3 and the pleiotropic mechanisms by which these actions are accomplished. 

Schaefer L, Malchow M, Schaefer RM et al. (1996) Effects of parathyroid hormone on renal tubular proteinases. Miner Electrolyte Metabol 22 182-186 Shimizu T, Hata S, Kuroda T et al. (1999) Different roles of two types of endothelin receptors in partial ablation-induced chronic renal failure in rats. Eur J Pharmacol 381 39-49 Stockelman MG, Lorenz JN, Smith FN et al. (1998) Chronic renal failure in a mouse model of human adenine phos-phoribosyltransferase deficiency. Am J Physiol 275 Renal Physiol 44 F154-F163... 

Further evidence that C-25 and C-l hydroxylation are the activation steps of vitamin D3, and that C-24/C-23 and C-23/C-26-lactone metabolic conversions do not produce physiologically important products is with the use of side-chain fluoridated analogues of 25-OH-D3 [87, 88], Studies with these analogues were prompted by assertions that 24-hydroxylated or lactone metabolites are involved or required for such biological actions as mineralization of bone [89], suppression of parathyroid hormone secretion [90], cartilage metabolism [91], and embryonic development in the chick [92]. It is well established that plasma 24,25-(OH)2D3 concentrations (2-5 ng/ml) are approximately 50 times greater than those of l,25-(OH)2D3. Even so,... 

Q7 Calcium is present in both intracellular fluid (ICF) and ECF, but the concentration in the ECF is twice as high as that in the ICF. Calcium is found in both ionized and bound forms, and Ca2+ homeostasis is mainly controlled by parathyroid hormone, which increases absorption of calcium in the intestine and reabsorption in the nephron. Calcitonin also affects ECF calcium concentration by promoting renal excretion when there is an excess of calcium in the body. The normal kidney filters and reabsorbs most of the filtered calcium however, in renal disease this is reduced and blood calcium decreases. Calcium and phosphate imbalance can occur in patients with renal failure, leading to osteomalacia (defective mineralization of bone). Osteomalacia is mainly due to reduced production of 1,25-dihydroxycholecalciferol, an active form of vitamin D metabolized in the kidney. Deficiency of 1,25-dihydroxycholecalciferol reduces the absorption of calcium salts by the intestine. 

How does calcium work its wonders on blood pressure This gets a bit technical. The mineral reduces the concentration of parathyroid hormone in the blood that hormone regulates calcium metabolism. In turn, that might lower calcium concentrations in the body s cells and slow the calcium from entering the arteries. Calcium in the arteries affects the tone of the vessels, thus potentially leading to higher blood pressure as the arteries stiffen. 

Immunoreactive parathyroid hormone concentrations may be increased by anticonvulsants, while bone mineral content is reduced. Hypocalcemia and osteopenia can occur, despite normal serum concentrations of active vitamin D metabolites, suggesting that they may be independent of drug effects on vitamin D metabolism. Bone biopsies have shown increased osteoid but normal calcification front formation, accelerated rate of mineralization, and reduced mineralization lag time, suggesting increased skeletal turnover rather than osteomalacia (96). The risk of age-related fractures in drug-treated epileptic patients is not greatly increased (97). 

Figure 49-16 Intact PTH in assessing parathyroid function in end-stage renal disease. Dialysis patients were separated into those with early and advanced osteitis fibrosa, osteomalacia, and aplastic disease by quantitative histomorphometric analysis of undecalcified bone biopsies. (From Segre GV, Sherrard DJ, Pandian /WR, et al. Intact PTH (IRMA) II New applications to issues in parathyroid hormone and mineral metabolism. San Juan Capistrano, Calif Nichols Institute, 1989.)...

Segre GV, Sherrard DJ, Pandian MR, et al. Intact PTH (IRMA) II new applications to issues in parathyroid hormone and mineral metabolism. Nichols Institute, San Juan Capistrano, Calif, 1989. 

OLT, with roughly 20% of patients experiencing a fracture within 1 year of transplant. Poor diets, lack of physical activity, reduced serum 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D, and abnormal parathyroid hormone concentrations are all thought to contribute pretransplant. Post-OLT corticosteroid therapy will also negatively impact bone metabolism, but may not be the sole reason for continued bone loss post-OLT. Mean bone mineral density (BMD) has taken a mean of 85 months to return to pre-OLT levels. Single-dose bisphosphonate infusion did not alter bone formation or resorption in the early (30 days) post-OLT period. " It is likely that lowering steroid doses, BMD screening, preventive measures, and calciiun and vitamin D supplementation will be the mainstay treatment options for this problem. ... 

The metabolic acid-base balance affects the sensitivity of bone to parathyroid hormone (PTH) and the synthesis of 1,25-dihydroxycholecalciferol. Therefore, acknowledging this when balancing the mineral content of the diet can have an effect on the incidence of milk fever. Conditions that promote an alkalotic state (high dietary cations, Na and IC ) reduce the sensitivity of bone to PTH and can limit the release of calcium. Conversely, an acidotic state (high dietary anions, CP and S ) increases the sensitivity to PTH, increases 1,25-dihydroxycholecalciferol production and hence increases the calcium supply. Through these metabolic responses, manipulation of the acid-base balance in the diet of the pre-calving cow has been successful in reducing the incidence of milk fever. 

Hunter, D., De Lange, M., Snieder, H., et al. 2001. Genetic contribution to bone metabolism, calcium excretion, and vitamin D and parathyroid hormone regulation. J Bone Miner Res, 16 371-8. 

Various studies summarized by this author cortical and trabecular bone Bone types anatomically and metabolically factors affecting metabolism Cortical bone 80% of total, dense, compacted, mineralized trabecular bone spongy, 20% of total, with greater turnover and metabolic activity. Hormonal control is via 1,25-(OH)2-vitamin D, parathyroid hormone, calcitonin, estrogen, etc. Hernandez-Avila et al. (2002), lllich and Kerstetter (2000), Hu etal. (1998)... 

While strong evidence exists implicating cadmium as a major causative factor in itai-itai disease, other factors, such dietary deficiencies in minerals and vitamins, may have contributed to the disease (Tsuchiya 1978 Kjellstrom 1986). Serum la,25(OH)2-vitamin D concentrations were depressed in cadmium-exposed cohorts presenting with clinical nephropathy (Nogawa et al. 1987), which suggests that cadmium-induced bone effects may result from disruption of vitamin D and parathyroid hormone metabolism. Because kidney injury results from chronic cadmium exposure, a cadmium-related inhibition of the renal conversion of 25(OH)-vitamin D to la,25(OH)2 Vitamin D may lead to decreased calcium reabsorption, demineralization of bone, and eventually osteomalacia (Friberg et al. 1986). 

Vitamin D deficiency in young children causes rickets. As a child becomes vitamin D deficient, this results in a decrease in the efficiency of intestinal calcium absorption. There is a decline in blood-ionized calcium, which causes the parathyroid glands to produce and secrete more parathyroid hormone (PTH). PTH tries to conserve calcium by enhancing tubular reabsorption of calcium in the kidney. However, in the face of developing hypocalcemia, which could disturb neuromuscular function and a wide variety of metabolic and cellular processes, the body calls upon l,25(OH)2D and PTH to mobilize stem cells to become functional osteoclasts, which, in turn, mobilize calcium from the skeleton. In addition, PTH causes a loss of phosphorus into the urine causing hypophosphatemia. Thus, in early vitamin D deficiency the serum calcium is normal it is the low serum phosphorus that causes the extracellular CaXP04 to be too low for normal mineralization of... 

Calcitonin is a 32-amino-acid polypeptide hormone that was hrst purihed in 1962 by Copp and Cheney (121). It was originally thought as a product from parathyroid glands, but later it was discovered to be made by the C cells of the thyroid gland. Calcitonin participates in calcium and phosphorus metabolism, lowers plasma calcium and phosphate levels, and it has been used as a drug for bone and mineral disorders for a long time. 

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