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Calcitonin is a 32-amino acid polypeptide hormone that is produced in humans primarily by the parafollicular (also known as C) cells of the thyroid, and in many other animals in the ultimobranchial body. It acts to reduce blood calcium (Ca2+), opposing the effects of parathyroid hormone (PTH) 
It has been found in fish, reptiles, birds, and mammals. Its importance in humans has not been as well established as its importance in other animals.
Calcitonin is formed by the proteolytic cleavage of a larger prepropeptide, which is the product of the CALC1 gene (CALCA). The CALC1 gene belongs to a superfamily of related protein hormone precursors including islet amyloid precursor protein, calcitonin gene-related peptide, and the precursor of adrenomedullin.
To be specific, calcitonin reduces blood Ca2+ levels in three ways:
Its actions, in a broad sense, are:
Calcitonin was purified in 1962 by Copp and Cheney. While it was initially considered a secretion of the parathyroid glands, it was later identified as the secretion of the C-cells of the thyroid gland.
Salmon calcitonin is used for the treatment of:
The following information is from the UK Electronic Medicines Compendium
General characteristics of the active substance
Salmon calcitonin is rapidly absorbed and eliminated. Peak plasma concentrations are attained within the first hour of administration.
Animal studies have shown that calcitonin is primarily metabolised via proteolysis in the kidney following parenteral administration. The metabolites lack the specific biological activity of calcitonin. Bioavailability following subcutaneous and intramuscular injection in humans is high and similar for the two routes of administration (71% and 66%, respectively).
Calcitonin has short absorption and elimination half-lives of 10-15 minutes and 50-80 minutes, respectively. Salmon calcitonin is primarily and almost exclusively degraded in the kidneys, forming pharmacologically-inactive fragments of the molecule. Therefore, the metabolic clearance is much lower in patients with end-stage renal failure than in healthy subjects. However, the clinical relevance of this finding is not known. Plasma protein binding is 30% to 40%.
Characteristics in patients
There is a relationship between the subcutaneous dose of calcitonin and peak plasma concentrations. Following parenteral administration of 100 IU calcitonin, peak plasma concentration lies between about 200 and 400 pg/ml. Higher blood levels may be associated with increased incidence of nausea and vomiting.
Preclinical safety data
Conventional long-term toxicity, reproduction, mutagenicity, and carcinogenicity studies have been performed in laboratory animals. Salmon calcitonin is devoid of embryotoxic, teratogenic, and mutagenic potential.
An increased incidence of pituitary adenomas has been reported in rats given synthetic salmon calcitonin for 1 year. This is considered a species-specific effect and of no clinical relevance. Salmon calcitonin does not cross the placental barrier.
In lactating animals given calcitonin, suppression of milk production has been observed. Calcitonin is secreted into the milk.
Calcitonin was extracted from the Ultimobranchial glands (thyroid-like glands) of fish, particularly salmon. Salmon calcitonin resembles human calcitonin, but is more active. At present, it is produced either by recombinant DNA technology or by chemical peptide synthesis. The pharmacological properties of the synthetic and recombinant peptides have been demonstrated to be qualitatively and quantitatively equivalent.
Use of calcitonin in osteoarthritis:
Oral calcitonin may have a chondroprotective role in osteoarthritis (OA), according to data in rats presented last month at the 10th World Congress of the Osteoarthritis Research Society International (OARSI) in Boston, Massachusetts. Although calcitonin is an established antiresorptive agent, its disease-modifying effects on chondrocytes and cartilage metabolisms have not been well established until now.
This new study, however, may help to explain how calcitonin affects osteoarthritis. “Calcitonin acts both directly on osteoclasts, resulting in inhibition of bone resorption and following attenuation of subchondral bone turnover, and directly on chondrocytes, attenuating cartilage degradation and stimulating cartilage formation,” says researcher Morten Karsdal, MSC, PhD, of the department of pharmacology at Nordic Bioscience in Herlev, Denmark. “Therefore, calcitonin may be a future efficacious drug for OA.”
Pain relief plus chondroprotection
Unlike several other potential disease-modifying OA drugs, calcitonin also has a “unique analgesic effect on bone pain, which might relieve at least in part symptoms accompanying joint disease,” says Dr. Karsdal, adding that this may be an important factor influencing future drug compliance.
Exactly how calcitonin impacts pain is not yet fully understood. However, “preclinical evidence tends to support a direct, receptor-mediated action that is independent of opioid action,” Dr. Karsdal explains. “Some evidence, however, has suggested a calcitonin interaction with opioid receptors.”
Sondergaard BC, Østergaard S, Qvist P, et al. Oral calcitonin protects against experimentally induced osteoarthritis. Presented at: 10th World Congress of the Osteoarthritis Research Society International; December 8–11, 2005; Boston, Mass. Abstract P133
PDF] Rationale for the potential use of calcitonin in osteoarthritis www.ismni.org/jmni/pdf/21/12MANICOURT.pdf
|This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Calcitonin". A list of authors is available in Wikipedia.|