Calcimimetics and calcilytics—fooling the calcium receptor

Abstract

Just a decade after the the calcium-sensing receptor (CaR) was identified, pharmacological manipulation of the CaR is about to enter routine practice. For hyperparathyroid states, calcimimetics, which increase activation of the CaR, have been licensed in Europe and the USA. Calcilytics, which decrease CaR function and increase secretion of parathyroid hormone (PTH), might allow the anabolic effects of PTH on bone to be harnessed for the prevention and treatment of osteoporosis. In a multicentre randomised double-blind placebo-controlled study, Munro Peacock and colleagues recently confirmed the efficacy of the oral calcimimetic cinacalcet for achieving long-term reductions in serum calcium and PTH concentrations in primary hyperparathyroidism (J Clin Endocrinol Metab 2005; 90: 135-41). The arrival of a non-surgical option for this common disorder is important. WHAT NEXT? Study in primary and uraemic secondary hyperparathyroidism will indicate whether the efficacy of calcimimetic agents extends into the longer term. The extracellular relation between the CaR and its ligands and the intracellular signalling cascades that modify PTH gene transcription and secretion need further study. Drugs acting on the CaR might treat other disorders of bone remodelling, including osteoporosis. CaR expression in tissues beyond those involved in mineral ion homoeostasis should remain an important focus of research.