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Calcitonin
General information
Calcitonin inhibits osteoclastic bone resorption, increases the urinary excretion of calcium and phosphate, and reduces serum calcium. It is established in the treatment of disorders of high bone turnover, including Paget’s disease and postmenopausal osteoporosis, but is less effective than the bisphosphonates. Calcitonin is less effective than other therapeutic measures in the treatment of acute hypercalcemia. Long-term administration of calcitonin reduces morbidity in cases of osteogenesis imperfecta and algoneurodystrophy [ , ]. The role of calcitonin in treating acute pain due to osteoporotic crush fractures has been reviewed, but the mechanism of its analgesic effect is not known [ ].
When used continuously in high doses, the therapeutic effect of calcitonin is sustained for only a few months, probably because of down-regulation of osteoclast receptors. The duration of the response to calcitonin can be extended by periodically interrupting treatment. A number of regimens, ranging from cycles of a few days to several months, are effective both as prophylaxis in healthy postmenopausal women and in women with established osteoporosis; however, the risk of fractures is not reduced [ ]. Calcitonin also has a potent analgesic effect independent of its effect on bone, possibly mediated through endogenous opioids [ ]. It appears to be more effective when given intranasally than subcutaneously for this indication.
Salmon- and eel-derived calcitonins are more potent than the human and porcine forms. Intranasal calcitonin has a systemic availability of only 3% of the subcutaneous form but is associated with fewer adverse effects, probably because of lower systemic availability. Antibodies against calcitonin are often found after prolonged treatment, more commonly with salmon (30–69%) or eel calcitonin than with human calcitonin. Antibodies do not usually affect the clinical effect of calcitonin and have not been reported to cause any harm to the patient. Antibody-mediated resistance is exceptional.
Adverse reactions to calcitonin, although common, are usually mild. They include gastrointestinal reactions (nausea, cramps, and vomiting), dizziness and flushing, and local reactions either at the injection site (rash, pruritus) or in the nose (rhinitis, dryness, sneezing, and rarely epistaxis). In 40 patients there was nausea and dizziness in 37% of those given rectal salmon calcitonin compared with 6% of those given placebo [ ].
Drug studies
Observational studies
The usefulness of intranasally administered salmon calcitonin for 2 years has been evaluated in 44 glucocorticoid-dependent asthmatics [ ]. All were taking calcium supplements (1000 mg/day), but one group also took calcitonin 100 IU every other day. Calcitonin increased spinal bone mass during the first year of treatment, and maintained bone mass in a steady state during the second year. However, the rate of vertebral fractures was similar in the two groups. The addition of salmon calcitonin did not increase the efficacy of calcium plus vitamin D in the prevention of bone loss in 48 newly diagnosed patients taking glucocorticoids for giant cell arteritis and polymyalgia rheumatica in a double-blind, randomized, placebo-controlled trial [ ].
Comparative studies
Teriparatide (n = 34) and calcitonin 100 IU subcutaneously (n = 29) have been compared in 63 postmenopausal Asian women aged 67.5 years (range 55–85) [ ]. All received calcium 500 mg and vitamin D3 (colecalciferol) 400 IU throughout the 6-month study. Among those taking calcitonin there was one serious adverse effect, which was not documented but was not thought to be drug related. The common adverse effects of calcitonin, dizziness, vasodilatation, and vomiting, were more frequent.
Placebo-controlled studies
Salmon calcitonin nasal spray prevented bone loss in the lumbar spine of 31 patients treated with prednisone for polymyalgia rheumatica [ ]. They were randomized to salmon calcitonin nasal spray 200 IU/day or matched placebo for 1 year. Both groups were treated with calcium supplements if their dietary intake was below 800 mg/day. With calcitonin the mean bone mineral density in the lumbar spine fell by 1.3% and with placebo by 5% after 1 year. There were no differences in the hip, including the femoral neck and trochanter, or in total body bone density.
Organs and systems
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