The principal effects of calcitonin are to lower serum calcium and phosphate by actions on bone and kidney. Calcitonin inhibits osteoclastic bone resorption. Although bone formation is not impaired at first after calcitonin administration, with time both formation and resorption of bone are reduced. In the kidney, calcitonin reduces both calcium and phosphate reabsorption as well as reabsorption of other ions, including sodium, potassium, and magnesium. Tissues other than bone and kidney are also affected by calcitonin. Calcitonin in pharmacologic amounts decreases gastrin secretion and reduces gastric acid output while increasing secretion of sodium, potassium, chloride, and water in the gut. Pentagastrin is a potent stimulator of calcitonin secretion (as is hypercalcemia), suggesting a possible physiologic relationship between gastrin and calcitonin. In the adult human, no readily demonstrable problem develops in cases of calcitonin deficiency (thyroidectomy) or excess (medullary carcinoma of the thyroid). However, the ability of calcitonin to block bone resorption and lower serum calcium makes it a useful drug for the treatment of Paget’s disease, hypercalcemia, and osteoporosis, albeit a less efficacious drug than other available agents.
Glucocorticoid hormones alter bone mineral homeostasis by antagonizing vitamin D–stimulated intestinal calcium transport, stimulating renal calcium excretion, blocking bone formation, and at least initially stimulating bone resorption. Although these observations underscore the negative impact of glucocorticoids on bone mineral homeostasis, these hormones have proved useful in reversing the hypercalcemia associated with lymphomas and granulomatous diseases such as sarcoidosis (in which unregulated ectopic production of 1,25[OH]2D occurs) or in cases of vitamin D intoxication. Prolonged administration of glucocorticoids is a common cause of osteoporosis in adults and can cause stunted skeletal development in children (see Chapter 39).
Estrogens can prevent accelerated bone loss during the immediate postmenopausal period and at least transiently increase bone in postmenopausal women.
The prevailing hypothesis advanced to explain these observations is that estrogens reduce the bone-resorbing action of PTH. Estrogen administration leads to an increased 1,25(OH)2D level in blood, but estrogens have no direct effect on 1,25(OH)2D production in vitro. The increased 1,25(OH)2D levels in vivo following estrogen treatment may result from decreased serum calcium and phosphate and increased PTH. However, estrogens also increase DBP production by the liver, which increases the total concentrations of the vitamin D metabolites in circulation without necessarily increasing the free levels. Estrogen receptors have been found in bone, and estrogen has direct effects on bone remodeling. Case reports of men who lack the estrogen receptor or who are unable to produce estrogen because of aromatase deficiency noted marked osteopenia and failure to close epiphyses. This further substantiates the role of estrogen in bone development, even in men. The principal therapeutic application for estrogen administration in disorders of bone mineral homeostasis is the treatment or prevention of postmenopausal osteoporosis. However, long-term use of estrogen has fallen out of favor due to concern about adverse effects. Selective estrogen receptor modulators (SERMs) have been developed to retain the beneficial effects on bone while minimizing deleterious effects on breast, uterus, and the cardiovascular system (see Box: Newer Therapies for Osteoporosis and Chapter 40).