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pubmed:abstractText |
The extracellular calcium-sensing receptor (CaR) on the parathyroid cell surface negatively regulates secretion of parathyroid hormone (PTH). Its activation by small changes in the extracellular concentration of ionized calcium (ec[Ca2+]) decreases PTH secretion and secondarily bone turnover. CaR is an ideal target for compounds that may be developed to modulate its activity - activating calcimimetics and inhibiting calcilytics. Calcimimetics can amplify the sensitivity of the CaR to ec(Ca2+), thereby suppressing PTH levels and in turn reducing blood Ca++. They dose-dependently reduce the secretion of PTH in cultured parathyroid cells, in animal models and in humans. In uremic animals, these compounds prevent parathyroid cell hyperplasia when given at the onset of the disease and stop cell proliferation if they are administered afterwards, when the hyperplasia already exists. They normalize plasma PTH levels and bone remodeling. In uremic patients undergoing hemodialysis, calcimimetics reduce plasma PTH concentrations in the short (12 weeks) and long (2 years) terms. They also reduce serum levels of calcium-phosphorus product. Calcimimetics are therefore an alternative for the treatment of secondary hyperparathyroidism, particularly in dialysis patients, when increased serum levels of calcium-phosphorus product, the attendant risk of cardiovascular calcification, and its lack of efficacy limit use of the standard treatment.
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