Parathyroid hormone (PTH) secretion and calcium homeostasis are regulated via the calcium-sensing receptor (CaSR) on the chief cells of the parathyroid gland. When ionized serum calcium levels are elevated, the activation of the CaSR suppresses PTH secretion. Conversely, low calcium levels stimulate PTH secretion by reducing the CaSR activation. This tightly regulated feedback loop maintains the serum ionized calcium concentration within a very narrow range.
Agents that activate the CaSR are called calcimimetics. If calcimimetics do not require the presence of calcium to be effective, they are classified as type I calcimimetics. Calcimimetics that increase the sensitivity of the CaSR to calcium by inducing a conformational change are called type II calcimimetics.1 Cinacalcet, a phenylalkylamine compound, is the first-in-class type II calcimimetic agent approved for treatment of primary and secondary hyperparathyroidism (HPT) and has also been investigated for persistent (tertiary) HPT in patients after renal transplantation. Since 2004, cinacalcet has been marketed in the United States as Sensipar (Amgen Inc., Thousand Oaks, CA) and in Europe as Mimpara (Amgen Europe, Zug, Switzerland). This article summarizes the role of calcimimetics in the treatment of all three clinical forms of HPT.