Calcium agonists in hyperparathyroidism

Primary hyperparathyroidism (PHPT), in addition to cancer, represents an important cause of hypercalcaemia in the general population. Furthermore, hypercalcaemia, in the course of uraemic HPT, represents the late stage of chronic renal failure refractory to therapy. Neck surgery is still the only curative approach for these forms of HPT and medical treatment rarely exhibits an effective control on HPT and HPT-dependent hypercalcaemia. Moreover, some HPT patients may not undergo neck surgery due to the presence of other concomitant disorders. Therefore, more effective therapeutic approaches are needed than the commonly used 'palliative' treatments. The identification of a specific membrane receptor able to bind extracellular calcium on cells of the parathyroid and other tissues has allowed the development of new molecules acting through this receptor to reduce both parathyroid hormone secretion and the rate of parathyroid cell proliferation. Consequently, they may substantially contribute to the regulation of bloodstream calcium levels in HPT patients. Preliminary results obtained in clinical trials are encouraging, demonstrating a good efficacy and safety of such drugs. However, more in vitro and in vivo, as well as long-term clinical studies, will be necessary before they can be commonly used as therapeutical molecules in the clinical practice.