Calcitonin: physiological actions and clinical applications

Calcitonin (CT) was first reported as a hypocalcemic principle, initially thought to originate from the parathyroid gland, a view subsequently corrected to an origin from parafollicular C-cells. Human CT is a 32 amino acid peptide with an N-terminal disulphide bridge and a C-terminal prolineamide residue, shown to potently inhibit bone resorption. More recent studies have demonstrated that this may take place through a direct osteoclastic action. A number of osteoclast CT receptors have subsequently been characterized and particular receptor regions necessary for ligand binding and intracellular signaling identified. Its potent anti-resorptive effect has led to its use in treating Paget's bone disease, osteoporosis, hypercalcaemia and osteogenesis imperfecta. This review summarises some key aspects of its synthesis, structure and its actions at the cellular and molecular levels, and leads on to its therapeutic uses that have emerged since its discovery as well as possibilities for future clinical applications.