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Calcitonin acts primarily on bone, but direct renal effects and actions on the gastrointestinal tract are also recognized. Calcitonin-salmon appears to have actions essentially identical to calcitonins of mammalian origin, but its potency per mg is greater and it has a longer duration of action. The actions of calcitonin on bone and its role in normal human bone physiology are still incompletely understood.
Single injections of calcitonin cause a marked transient inhibition of the ongoing bone resorptive process. With prolonged use, there is a persistent, smaller decrease in the rate of bone resorption. Histologically, this is associated with a decreased number of osteoclasts and an apparent decrease in their resorptive activity. Decreased osteocytic resorption may also be involved. There is some evidence that initially bone formation may be augmented by calcitonin through increased osteoblastic activity. However, calcitonin will probably not induce a long-term increase in bone formation.
Animal studies indicate that endogenous calcitonin, primarily through its action on bone, participates with parathyroid hormone in the homeostatic regulation of blood calcium. Thus, high blood calcium levels cause increased secretion of calcitonin which, in turn, inhibits bone resorption. This reduces the transfer of calcium from bone to blood and tends to return blood calcium to the normal level. The importance of this process in humans has not been determined. In normal adults, who have a relatively low rate of bone resorption, the administration of exogenous calcitonin results in only a slight decrease in serum calcium. In normal children and in patients with generalized Paget's disease, bone resorption is more rapid and decreases in serum calcium are more pronounced in response to calcitonin.
Paget's Disease of Bone (osteitis deformans)
Paget's disease is a disorder of uncertain etiology characterized by abnormal and accelerated bone formation and resorption in one or more bones. In most patients, only small areas of bone are involved and the disease is not symptomatic. In a small fraction of patients, however, the abnormal bone may lead to bone pain and bone deformity, cranial and spinal nerve entrapment, or spinal cord compression. The increased vascularity of the abnormal bone may lead to high output congestive heart failure.
Active Paget's disease involving a large mass of bone may increase the urinary hydroxyproline excretion (reflecting breakdown of collagen-containing bone matrix) and serum alkaline phosphatase (reflecting increased bone formation).
Calcitonin-salmon, presumably by an initial blocking effect on bone resorption, causes a decreased rate of bone turnover with a resultant fall in the serum alkaline phosphatase and urinary hydroxyproline excretion in approximately 2/3 of patients treated. These biochemical changes appear to correspond to changes toward more normal bone, as evidenced by a small number of documented examples of: 1) radiologic regression of Pagetic lesions, 2) improvement of impaired auditory nerve and other neurologic function, 3) decreases (measured) in abnormally elevated cardiac output. These improvements occur extremely rarely, if ever, spontaneously (elevated cardiac output may disappear over a period of years when the disease slowly enters a sclerotic phase; in the cases treated with calcitonin, however, the decreases were seen in less than one year.)
Some patients with Paget's disease, who have good biochemical and/or symptomatic responses initially, later relapse. Suggested explanations have included the formation of neutralizing antibodies and the development of secondary hyperparathyroidism, but neither suggestion appears to explain adequately the majority of relapses.
Although the parathyroid hormone levels do appear to rise transiently during each hypocalcemic response to calcitonin, most investigators have been unable to demonstrate persistent hypersecretion of parathyroid hormone in patients treated chronically with calcitonin-salmon.
Circulating antibodies to calcitonin after 2-18 months' treatment have been reported in about half of the patients with Paget's disease in whom antibody studies were done, but calcitonin treatment remained effective in many of these cases. Occasionally, patients with high antibody titers are found. These patients usually will have suffered a biochemical relapse of Paget's disease and are unresponsive to the acute hypocalcemic effects of calcitonin.
In clinical trials, calcitonin-salmon has been shown to lower the elevated serum calcium of patients with carcinoma (with or without demonstrated metastases), multiple myeloma, or primary hyperparathyroidism (lesser response). Patients with higher values for serum calcium tend to show greater reduction during calcitonin therapy. The decrease in calcium occurs about 2 hours after the first injection and lasts for about 6-8 hours. Calcitoninsalmon given every 12 hours maintained a calcium lowering effect for about 5-8 days, the time period evaluated for most patients during the clinical studies. The average reduction of 8hour post-injection serum calcium during this period was about 9%.
Calcitonin increases the excretion of filtered phosphate, calcium, and sodium by decreasing their tubular reabsorption. In some patients, the inhibition of bone resorption by calcitonin is of such magnitude that the consequent reduction of filtered calcium load more than compensates for the decrease in tubular reabsorption of calcium. The result in these patients is a decrease rather than an increase in urinary calcium.
Transient increases in sodium and water excretion may occur after the initial injection of calcitonin. In most patients, these changes return to pretreatment levels with continued therapy.
Increasing evidence indicates that calcitonin has significant actions on the gastrointestinal tract. Short-term administration results in marked transient decreases in the volume and acidity of gastric juice and in the volume and the trypsin and amylase content of pancreatic juice. Whether these effects continue to be elicited after each injection of calcitonin during chronic therapy has not been investigated.
Information from animal studies with calcitonin-salmon and from clinical studies with calcitonins of porcine and human origin suggest that calcitonin-salmon is rapidly metabolized by conversion to smaller inactive fragments, primarily in the kidneys, but also in the blood and peripheral tissues. A small amount of unchanged hormone and its inactive metabolites are excreted in the urine.
The absolute bioavailability of salmon calcitonin is approximately 66% and 71% after intramuscular (i.m.) or subcutaneous (s.c.) injection, respectively. After subcutaneous administration, peak plasma levels are reached in approximately 23 minutes. The terminal half-life is approximately 58 minutes for i.m. administration and 59 to 64 minutes for s.c. administration. The apparent volume of distribution is 0.15-0.3 L/kg.
It appears that calcitonin-salmon cannot cross the placental barrier and its passage to the cerebrospinal fluid or to breast milk has not been determined.
Last reviewed on RxList: 5/2/2012
This monograph has been modified to include the generic and brand name in many instances.
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