Pharmacological ActionsAll calcitonins are similar in structure, being a single chain of 32 amino acids, with the order of the seven amino acids arranged in a loop at the N-terminus varying from species to species. Salmon calcitonin is more effective and longer acting than mammalian calcitonin due to its high affinity for the receptor binding site. Salmon calcitonin inhibits osteoclast activity through its specific receptor. It reduces bone turnover to normalizable levels in conditions of increased bone resorption, such as osteoporosis. Salmon calcitonin has been shown to have analgesic effects in animal models and humans, possibly as a result of direct action on the central nervous system. A single dose of this product produces significant clinical biological effects in humans. Urinary excretion of calcium, phosphorus, and sodium (by decreasing tubular reabsorption) increases and urinary hydroxyproline excretion decreases significantly after dosing. Prolonged use of the drug (up to 5 years) resulted in a significant decrease in bone turnover markers such as serum C-terminal peptide and bone alkaline phosphate isoenzyme. Salmon Calcitonin Nasal Spray increased bone mineral density (BMD) of the lumbar spine by a statistically significant 1.0-2.0%. It was maintained for more than 5 years from the 1st year of use. BMD of the pelvis can be stabilized. Application of 200 IU/day of salmon calcitonin nasal spray resulted in a clinically and statistically significant 36% reduction in the incidence of vertebral fractures compared to vitamin D and calcium alone (placebo). In addition, it reduced the risk of multiple vertebral fractures by 35% compared to placebo. Calcitonin inhibits gastric and pancreatic secretion. Clinical Safety Information Routine long-term toxicity, reproductive effects, mutagenicity, and carcinogenicity studies have been conducted in test animals. Daily intranasal administration of placebo containing 0.01% benzalkonium chloride or high-dose calcitonin containing 0.01% benzalkonium chloride to test monkeys for up to 26 weeks proved to be well tolerated. No treatment-related respiratory changes were observed. No abnormal changes were also observed in the nasal cavity or upper respiratory tract of test dogs given daily intranasal administration of salmon calcitonin containing 0.01% benzalkonium chloride for 4 weeks. Guinea pigs and patients with metaplastic osteitis did not show any changes in the frequency of nasal cilia oscillations after 4 weeks and 6 months of treatment with salmon calcitonin nasal spray containing 0.01% benzalkonium chloride, respectively. Slight side effects of salmon calcitonin were found to be due to its pharmacologic action in toxicity tests. It is not embryotoxic and has no potential risk of teratogenicity or mutagenicity. Toxicity and carcinogenicity studies have shown an increased incidence of pituitary tumors in rats when exposed to lower than clinical doses of salmon calcitonin. However, further preclinical studies, particularly carcinogenicity studies in rats, found that the induction of pituitary tumors was rat-specific, and the dose of the drug given to rats in this test was approximately 7,000 times greater than the conventional human dose of 200 IU. No pituitary-related changes were found in the patients' 2-year paired clinical data. In addition, the number of calcitonin receptors in the human pituitary is very low or even completely absent. No adverse effects associated with pituitary tumors have been found in patients either. Thus there is good evidence that pituitary tumor induction is murine-specific and that murine pituitary tumors do not correlate in any way with the clinical use of miguelin. No alterations associated with any pituitary gland were found in the patients' 2-year paired clinical data. In addition, the number of calcitonin receptors in the human pituitary is very low or even completely absent.