Clin Osteol 2005; 10(4): 80-86

Calcimimetics - new options in the treatment of hyperparathyroidismReview articles

S. Dusilová-Sulková

Secondary hyperparathyroidism is one of the accompanying features of chronic renal failure. Secondary hyperparathyroidism occours due to impaired kidney function (phosphate retention) and decreased renal production of calcitriol. These two principal mechanisms are closely interrelated together with other contributing factors. The parathyroid activity is regulated by mechanisms involving two receptors: nuclear vitamin D receptor (VDR) and cal­ cium sensing receptor (CaR), which is localised on the cellular surface. During end-stage renal disease these mechanisms are impaired: calcitriol defi­ ciency, impaired sensitivity of CaR to calcium, increase in parathyroid hormone (PTH) production and secretion due to hyperphosphatemia. Thera­ peutic approaches in the conservative management of secondary hyperparathyroidism targeted VDR by means of active metabolites and analogues of vitamin D. Most recently, the CaR can be modulated by 2nd generation calcimimetic cinacalcet (Mimpara - EU; Sensipar - USA; produced by Am­ gen). Cinacalcet increases the sensitivity of CaR to extracellular calcium concentration. This leads to suppressed secretion of PTH. In addition, the pro­ duction of PTH is decreased together with involution of parathyroid hyperplasia. The main indications of cinacalcet therapy is secondary hyperpara­ thyroidism in end-stage kidney failure (patients on dialysis) and hypercalcemia in patients with parathyroid carcinoma. In contrast to other therapeutic procedures used in the management of hyperparathyroidism in chronic renal failure, such as the application ofvitamin D metabolites or analogues, ci­ nacalcet doesn't increase the serum concentrations of neither calcium or phosphate, as this drug doesn't lead to higher gastrointestinal absorption of calcium or phosphorus. Scarcely, hypocalcemia might occur as an adverse reaction to cinacalcet therapy. The incidence of hypocalcemia can be minimalised with vitamin D supplementation. Cinacalcet should be used orally, once-a-day in doses of 30-60 mg. 90 to 180 mg/day can be taken excep­ tionally, this with regard to the clinical state of the patient. Cinacalcet can be used in combination with other drugs affecting the calcium and phosp­ hate metabolism (phosphate binders, vitamin D analogues or metabolites).

Keywords: cinacalcet, calcium receptors, parathyroid glands, hyperparathyroidism, kidney disease.

Published: December 11, 2005  Show citation