Calcimimetic agents and secondary hyperparathyroidism: treatment and prevention.

Calcimimetic agents are small organic molecules that act as allosteric activators of the calcium sensing receptor (CaSR) in the parathyroid glands and other tissues. They lower the threshold for CaSR activation by extracellular calcium ions and diminish parathyroid hormone (PTH) release from parathyroid cells. By targeting the molecular mechanism that modulates PTH secretion on a minute-to-minute basis, calcimimetic compounds offer a novel approach to managing excess PTH secretion in several clinical disorders w1x. Despite abundant in vitro and in vivo experimental work, experience with calcimimetic agents in humans is rather limited. Preliminary reports describe their use in small numbers of patients with primary hyperparathyroidism and in somewhat larger numbers of patients with secondary hyperparathyroidism due to end-stage renal disease w2– 4x. Although the duration of treatment in published studies has been confined to 1 or 2 weeks, calcimimetic compounds consistently and reproducibly lower plasma PTH levels when given to normal volunteers or to patients with either primary or secondary hyperparathyroidism. Results from early clinical trials in humans are consistent, therefore, with data obtained in experimental animals w5x. Apart from their effect to diminish PTH secretion, calcimimetic compounds may fundamentally influence the process of parathyroid gland hyperplasia, and their administration to experimental animals can favorably affect skeletal calcium balance. If confirmed by studies in humans, these ancillary features of calcimimetics broaden their appeal as a therapeutic approach to secondary hyperparathyroidism due to chronic renal failure.