Is therapy with cinacalcet effective and safe in patients with primary hyperparathyroidism across the spectrum of serum calcium concentrations? Is it cost-effective?
Cinacalcet is effective in lowering, and often normalizing, serum calcium and increasing serum phosphate in patients with primary hyperparathyroidism. Its effects on intact serum parathyroid hormone (PTH) concentrations are less pronounced, although marked declines can be observed in the first 2–4 hours after dose administration. Although activation of the calcium-sensing receptor in the renal tubule is expected to increase urinary calcium excretion, a significant reduction in urinary calcium excretion was often observed. This is likely due to the reduction of the filtered renal calcium load, which follows cinacalcet-induced reductions in serum calcium. In the few studies that have evaluated the effects of cinacalcet on bone turnover markers, the results have been inconsistent. No consistent effects on bone mineral density (BMD) were observed. In view of cinacalcet's clear effects to reduce the serum calcium in primary hyperparathyroidism, it should be considered in those subjects who meet criteria as set forth by the EMA and the FDA.
Is therapy with cinacalcet effective in patients with familial primary hyperparathyroidism?
Cinacalcet is effective in lowering serum calcium in patients with familial primary hyperparathyroidism and is a treatment option for patients who have persistent or recurrent hypercalcemia after parathyroidectomy. It is not recommended as initial therapy for these patients. Surgery remains the best initial approach for control of primary hyperparathyroidism associated with familial syndromes. Whether cinacalcet is effective in the control of hypercalcemia over time, given the high proliferative rate of the parathyroid cells in this disease, remains to be determined. There is, furthermore, no evidence regarding the safety of chronic systemic calcium-sensing receptor activation by cinacalcet on the growth and function of the other non-parathyroid tumors in multiple endocrine neoplasia type 1 (MEN1) and multiple endocrine neoplasia type 2A (MEN2A) and in the hyperparathyroidism-jaw tumor syndromes.
Can cinacalcet and bisphosphonate be combined in patients with primary hyperparathyroidism?
Although none of the studies of combination therapy with cinacalcet and bisphosphonate were prospective or rigorously controlled, combination therapy appears to achieve both calcium-lowering effects of cinacalcet and stabilization of BMD by bisphosphonate treatment. In subjects with low BMD and serum calcium levels in the range that is appropriate for cinacalcet use, combined therapy could be beneficial.
Sensipar® is indicated for the treatment of secondary hyperparathyroidism (SHPT) in patients with chronic kidney disease (CKD) on dialysis.
Marcocci C, Bollerslev J, Khan AA, Shoback DM. Medical management of primary hyperparathyroidism: proceedings of the fourth International Workshop on the Management of Asymptomatic Primary Hyperparathyroidism. J Clin Endocrinol Metab. 2014 Oct;99(10):3607-18.
Gerald Miller, James Davis, Edward Shatzen, Matthew Colloton, David Martin, Charles M. Henley. Cinacalcet HCl prevents development of parathyroid gland hyperplasia and reverses established parathyroid gland hyperplasia in a rodent model of CKD. Nephrol Dial Transplant. 2012 June; 27(6): 2198–2205.
Qian Zhang, Ming Li, Li You, Haiming Li, Li Ni, Yong Gu, Chuanming Hao, Jing Chen. Effects and Safety of Calcimimetics in End Stage Renal Disease Patients with Secondary Hyperparathyroidism: A Meta-Analysis.
PLoS One. 2012; 7(10): e48070.