Calcitonin Salmon: Overview, Physiology and Pharmacology
Mar 26,2024
General Description
Calcitonin salmon, a peptide hormone secreted by the thyroid, is widely used for the treatment of metabolic bone diseases. It has been approved in over 90 countries and has shown efficacy in postmenopausal osteoporosis and other conditions. Calcitonin salmon is available as an injectable or nasal spray, with a new oral formulation showing promise. Its physiological role is not fully understood, but it collaborates with other hormones to regulate calcium levels. Calcitonin salmon inhibits bone resorption through its action on osteoclasts and may have a potential stimulatory effect on osteoblast-mediated bone formation. Despite some uncertainties, Calcitonin salmon remains an important therapeutic option for metabolic bone diseases, with proven benefits and a favorable safety profile.
Figure 1. Calcitonin salmon
Overview
Calcitonin salmon has been widely used for over 30 years as a therapeutic agent for metabolic bone diseases. It has gained approval in more than 90 countries for the treatment of postmenopausal osteoporosis, making it a recognized and trusted option. Additionally, Calcitonin salmon has been approved for various other indications such as Paget's disease, bone-associated pain conditions, and emergency hypercalcemia (specifically for injectable salmon calcitonin). However, it is worth noting that the specific approved uses can vary from country to country. As one of the earliest antiresorptive osteoporosis therapies available, Calcitonin salmon has firmly established its efficacy and demonstrated a favorable safety profile over several decades. Recent research has provided new insights into the potential mechanisms behind its anti-fracture effectiveness, highlighting its ability to preserve bone quality, particularly trabecular microarchitecture. Calcitonin salmon is commercially available in two forms: injectable and nasal spray. Excitingly, a new oral formulation has recently been developed, and initial data from clinical trials suggest its potential usefulness not only in treating osteoporosis but also in managing osteoarthritis. With its extensive history of use and proven benefits, Calcitonin salmon remains an important therapeutic option for individuals with metabolic bone diseases. 1
Physiology and Pharmacology
Calcitonin salmon is a 32-amino-acid peptide hormone primarily secreted by the C cells of the thyroid in mammals and by the ultimobranchial glands in submammals. Its discovery in 1961 marked a significant advancement in understanding substances that lower blood calcium levels. Synthetic or recombinant calcitonins from various species, including human calcitonin, porcine calcitonin, eel calcitonin-derivative, and Calcitonin salmon, have been utilized in medical applications. Notably, Calcitonin salmon stands out as the most widely used preparation in clinical practice due to its significantly higher intrinsic potency, being 40-50 times more potent than human calcitonin, and its enhanced analgesic properties. Despite more than four decades since its discovery, the physiological role of calcitonin, including Calcitonin salmon, remains incompletely understood. It collaborates with parathyroid hormone and 1,25 dihydroxycholecalciferol to fine-tune short-term calcium homeostasis, particularly during "calcium stress" periods such as pregnancy and the postprandial state. While initial findings in calcitonin knockout mice suggested potential bone pathologies, subsequent research has not confirmed these associations in humans. In healthy individuals with normal calcium levels, Calcitonin salmon administration typically induces subtle, transient calcium-lowering effects. In hypercalcemic states, Calcitonin salmon administered at high doses via the parenteral route leads to marked, albeit primarily transient reductions in elevated calcium levels. This rapid onset of action occurs within approximately two hours and is primarily attributed to the reduction of bone resorption through the inhibition of osteoclast activity. Additionally, an increase in renal calcium excretion may contribute to the fast onset of the calcium-lowering effect of Calcitonin salmon in hypercalcemic stages. The inhibition of bone resorption by calcitonin is partially mediated by binding to osteoclast membrane receptors, with one osteoclast estimated to contain approximately one million calcitonin receptors. Exposure to calcitonin induces the flattening of osteoclast ruffled borders and withdrawal from sites of active bone resorption, with reversible effects observed. The potential stimulatory effect of calcitonin on osteoblast-mediated bone formation remains uncertain, although the existence of calcitonin receptors on osteoblasts has been suggested. Physiological down-regulation of calcitonin receptor sites has been reported, but its clinical significance is uncertain. Furthermore, the development of calcitonin antibodies in response to calcitonin administration and differences in bioavailability across preparations may result in varying therapeutic outcomes. In summary, Calcitonin salmon, with its potent calcium-lowering effects and impact on bone metabolism, plays a crucial role in managing hypercalcemic states and holds promise for further exploration in the regulation of bone resorption and formation. Though its complete physiological role and clinical implications are still being elucidated, Calcitonin salmon remains a valuable tool in medical practice, particularly in addressing conditions related to calcium homeostasis and bone health. 2
Reference
1. Chesnut CH 3rd, Azria M, Silverman S, Engelhardt M, Olson M, Mindeholm L. Salmon calcitonin: a review of current and future therapeutic indications. Osteoporos Int. 2008;19(4):479-491.
2. Henriksen K, Bay-Jensen AC, Christiansen C, Karsdal MA. Oral salmon calcitonin--pharmacology in osteoporosis. Expert Opin Biol Ther. 2010;10(11):1617-1629.
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