Drugs & Aging

, Volume 8, Issue 5, pp 378–400 | Cite as

Intranasal Salcatonin (Salmon Calcitonin)

A Review of its Pharmacological Properties and Role in the Management of Postmenopausal Osteoporosis
  • Greg L. Plosker
  • Donna McTavish
Drug Evaluation



Osteoporosis is a common problem among postmenopausal women and is associated with significant morbidity, mortality and costs primarily resulting from osteoporotic fractures.

Salcatonin (salmon calcitonin) inhibits osteoclastic bone resorption and is approximately 40 to 50 times more potent than human calcitonin. In most randomised trials in which intranasal salcatonin (usually 50 to 200 IU/day plus oral calcium supplements) was administered for 1 to 5 years to postmenopausal women for prevention of osteoporosis, bone mineral density or content of the lumbar spine increased by approximately 1 to 3% from baseline. In contrast, postmenopausal women receiving only oral calcium supplements typically had reductions in bone mineral density or content of about 3 to 6%. The difference between treatment groups was statistically significant in essentially all studies. Although changes in bone mineral density or content were broadly similar in studies of postmenopausal women with established osteoporosis to those in postmenopausal women receiving therapy for prevention of the disease, studies in women with established osteoporosis did not usually demonstrate statistically significant differences between treatment groups. Also in postmenopausal women with established osteoporosis, intranasal salcatonin reduced pain and/or analgesic consumption in some trials and, in a limited number of studies of relatively short duration (i.e. ≤2 years), the incidence of osteoporotic fractures. A large multicentre 5-year study with adequate statistical power to confirm the effect of intranasal salcatonin on reducing osteoporotic fracture rates in postmenopausal women is currently under way.

The intranasal formulation of salcatonin offers a more convenient and better tolerated alternative to the parenteral formulation of the drug which is administered by regular subcutaneous or intramuscular injections. Adverse events associated with the intranasal formulation are generally mild and transient, usually involving local reactions such as nasal discomfort, rhinorrhoea or rhinitis.

Thus, for postmenopausal women unable or unwilling to tolerate long term hormone replacement therapy, intranasal salcatonin is an attractive alternative for the management of osteoporosis.

Pharmacodynamic Properties

Salcatonin (salmon calcitonin) is approximately 40 to 50 times more potent than human calcitonin, an endogenous hormone intimately involved in calcium homeostasis. Studies in humans demonstrated that single-dose intranasal administration of salcatonin 50 to 400IU reduced bone resorption and increased urinary excretion of calcium, phosphate and sodium.

The mechanism of action of salcatonin mimics the physiological action of human calcitonin. Inhibition of bone resorption by salcatonin depends on binding of the drug to specific calcitonin receptors on osteoclasts. Once binding occurs, salcatonin reduces the recruitment and activity of these bone-resorbing cells. The effect of salcatonin on bone formation has been shown in experimental models and in clinical trials of postmenopausal women. Putative bone-forming effects may be related, in small part, to a direct anabolic action of the drug on osteoblast-line cells, although further research is needed to clarify this issue.

A number of mechanisms have been suggested to account for the analgesic action of salcatonin in patients with skeletal disorders. These include increased plasma β-endorphin levels, effects on central serotonergic or monoaminergic pathways, modification of intracellular calcium levels in the CNS and, perhaps the most likely mechanism, a direct central effect via specific receptors. The analgesic action appears to be independent of the effect on osteoclastic bone resorption.

Although antibody formation against human calcitonin is rare during long term administration of the hormone, approximately 40 to 70% of patients receiving long term therapy with intranasal or parenteral salcatonin produce antibodies specific for salcatonin. The clinical significance of these antibodies is unclear; however, clinical trials have generally shown sustained long term efficacy of intranasal salcatonin despite specific antibody formation in a significant proportion of postmenopausal women with osteoporosis.

Pharmacokinetic Properties

Peak plasma salcatonin concentrations are achieved 31 to 39 minutes after intra-nasal administration and are dose-related. Although bioavailability of intranasal salcatonin is approximately 3% of that for intramuscular salcatonin, plasma drug concentrations are typically more sustained following intranasal than parenteral administration. The intranasal formulation provides approximately 25 to 50% of the biological activity of the same parenterally administered dose. Salcatonin appears to distribute extensively into extravascular tissue sites. Elimination half-life has been calculated to be 43 minutes.

Therapeutic Use

In most randomised studies in which intranasal salcatonin (usually 50 to 200 IU/day) plus oral calcium supplements were administered for 1 to 5 years to recently postmenopausal women for prevention of osteoporosis, bone mineral density or content of the lumbar spine increased by approximately 1 to 3% from baseline compared with reductions of about 3 to 6% among women receiving oral calcium supplements only. These trials consistently demonstrated statistically significant differences between salcatonin and control treatment groups for changes in vertebral bone mineral density and, in a small number of studies, similar results were shown for changes in forearm bone mineral content. A long term evaluation of a relatively low dose intermittent intranasal salcatonin regimen (50 IU/day for 5 days/week) demonstrated a statistically significant difference in favour of salcatonin plus calcium over calcium alone in bone mineral density of lumbar vertebrae after 6 months which was maintained for the entire duration of the 5-year study. In most trials, attenuation of bone loss by salcatonin was accompanied by reductions in biochemical markers of bone résorption.

Both cyclical regimens of intranasal salcatonin 100 or 200 IU/day (which involved interruption of therapy every other month for 18 months) and continuous administration of the drug at the same dosages (all regimens with oral calcium supplements) increased bone mineral content of the lumbar spine by approximately 4 to 5% from baseline in postmenopausal women with a high rate of bone turnover. Peak increases in bone mineral content occurred somewhat earlier and tended to be slightly higher among women receiving continuous therapy.

In general, intranasal administration of salcatonin produced broadly similar effects on bone mineral density or content in postmenopausal women with established osteoporosis to those in postmenopausal women receiving the drug for prevention of the disease; however, statistically significant differences between treatment groups were usually not demonstrated. Randomised studies in postmenopausal women with established osteoporosis receiving intranasal salcatonin 50, 100 or 200 IU/day for 1 to 2 years have demonstrated a dose-related response with respect to changes in bone mineral density or content. Results of a large 2-year trial comparing intranasal salcatonin 100 IU/day with oral alendronate 10 or 20 mg/day (all with oral calcium supplements) demonstrated a somewhat greater effect of the bisphosphonate than salcatonin on increasing bone mineral density of the lumbar spine in postmenopausal women with established osteoporosis. However, the dosage of intranasal salcatonin used in the trial was only half the recommended dosage, and salcatonin was not administered under a double-blind protocol.

Importantly, both parenteral and intranasal salcatonin have been shown to decrease fracture rates in this patient population, although this has been documented in only a limited number of trials. In a study of 164 elderly postmeno-pausal women with “moderate” osteoporosis, those who received intranasal salcatonin 50, 100 or 200 IU/day plus calcium supplements for 2 years had a statistically significant reduction in fracture rate to approximately one-third that of women who received calcium supplements only. In another randomised study of 88 postmenopausal women with established osteoporosis, cyclical treatment with intranasal salcatonin 100 IU/day plus oral calcium supplements (for 2 consecutive weeks followed by 2 weeks without therapy) for 1 year resulted in a statistically significant reduction in the rate of new vertebral fractures compared with calcium alone. These studies were of relatively short duration, and the effect of long term intranasal salcatonin on osteoporotic fracture rates is currently under investigation in a much larger 5-year study of more than 1200 postmenopausal women. Intranasal salcatonin has also been associated with improvement in pain and/or reductions in analgesic consumption in some studies of postmenopausal women with established osteoporosis.


In general, adverse events associated with intranasal administration of salcatonin are relatively mild and tend to occur in less than 10% of patients. The most frequently reported adverse events are local transient reactions such as stinging or tingling of the nasal passage, sneezing, rhinitis, rhinorrhoea and nasal mucosal erythema which lead to discontinuation of therapy in about 4% of patients. In a comparative trial, primarily in patients with Paget’s disease, 10% of patients receiving subcutaneously administered salcatonin discontinued therapy because of adverse events compared with 4% of those receiving the drug by intranasal administration.

Dosage and Administration

The recommended intranasal dosage of salcatonin for the management of established osteoporosis is 200IU once daily. In clinical trials, postmenopausal women received intranasal salcatonin dosages ranging from 50 to 400 IU/day as a single daily dose or in 2 divided doses for the prevention or treatment of osteoporosis. In virtually all clinical studies with intranasal salcatonin, patients also received oral calcium supplements. It is not clear whether cyclical regimens of intranasal salcatonin plus oral calcium supplements (e.g. 1 month of therapy followed by no drug treatment for 1 month and repeated in a cyclical fashion) have any clinically significant advantages over continuous treatment.


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Copyright information

© Adis International Limited 1996

Authors and Affiliations

  • Greg L. Plosker
    • 1
  • Donna McTavish
    • 1
  1. 1.Adis International LimitedMairangi Bay, Auckland 10New Zealand

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