Cinacalcet Hydrochloride Maintains Long-Term Normocalcemia in Patients with Primary Hyperparathyroidism

Abstract

Calcimimetics increase the sensitivity of parathyroid calcium-sensing receptors to extracellular calcium, thereby reducing PTH secretion. This multicenter, randomized, double-blind, placebo-controlled study assessed the ability of the oral calcimimetic cinacalcet HCl to achieve long-term reductions in serum calcium and PTH concentrations in patients with primary hyperparathyroidism (HPT). Patients (n = 78) were randomized to cinacalcet or placebo. Cinacalcet was titrated from 30-50 mg twice daily during a 12-wk dose-titration phase. Efficacy was assessed during 12-wk maintenance and 28-wk follow-up phases. The primary endpoint was the achievement of normocalcemia [serum calcium </= 10.3 mg/dl (2.57 mmol/liter)] with at least 0.5 mg/dl (0.12-mmol/liter) reduction from baseline. Plasma PTH, serum and urine biochemistry, biochemical measures of bone turnover, bone mineral density, and safety were also assessed. Seventy-three percent of cinacalcet-treated patients vs. only 5% of placebo-treated patients achieved the primary endpoint (P < 0.001). Fasting predose plasma PTH decreased 7.6% in cinacalcet patients but increased 7.7% in placebo patients (P < 0.01). Bone mineral density was unchanged by cinacalcet, but bone resorption and formation markers increased (P < 0.05). Adverse events were mild and similar between treatment groups. Cinacalcet rapidly normalizes serum calcium and reduces PTH in patients with primary HPT, and these effects are maintained with long-term treatment. Cinacalcet may be an effective, nonsurgical approach for management of primary HPT.

Serum calcium is independently associated with insulin sensitivity measured with euglycaemic–hyperinsulinaemic clamp in a community-based cohort

“…However, longitudinal intervention studies are needed in order to investigate this issue. One potential approach could be to evaluate the metabolic effects of pharmacological treatment with calcimimetics, specific parathyroid calcium receptor agonists, which decrease PTH and calcium levels, apparently without having adverse effects on other tissues [36,37].…”

Diagnosis and management of primary hyperparathyroidism: a scientific statement from the Department of Bone Metabolism, the Brazilian Society for Endocrinology and Metabolism

“…Patients initially received cinacalcet 30 mg twice daily and this dose was increased to 40-50 mg twice daily for 12 weeks. Normal serum calcium concentrations were achieved in 73% of patients during the maintenance phase, but serum PTH decreased by only 7.6% after the same period (164). Serum calcium levels remained normal and PTH remained below baseline for up to 52 weeks (A-1B).…”

MECHANISMS IN ENDOCRINOLOGY: Kidney involvement in patients with primary hyperparathyroidism: an update on clinical and molecular aspects

“…In other regions, the CASR acts to fine tune and integrate multiple stimuli that derive from sodium, pH and mineral ion metabolism, setting the sensitivity threshold for several cAMP-coupled hormones to extracellular calcium. The inhibitory effect of cinacalcet on calcium tubular reabsorption (evaluated as fasting calcium-creatinine ratio) has been supposed to be mediated by a shift in the dose-response curve of PTH on tubular calcium reabsorption or by a direct effect of cinacalcet on the CASR in the thick ascending loop (19). Calcium excretion in 24-h urine is in part determined by the intestinal calcium absorption, a component that might overcome the reduction of calcium tubular reabsorption.…”