Role Of Calcitonin Research Articles

Role of Calcitonin and Strontium Ranelate in Osteoporosis.

Both Strontium Ranelate (SR) and Calcitonin (CT) can be used to treat osteoporosis. Calcitonin was actually one of the very initial medicines used to treat osteoporosis, especially in postmenopausal cases. However, the fracture prevention effect of Calcitonin is only proven to be in vertebrae and that too with nasal route only. When comparing Calcitonin with other conventional medications in treating osteoporosis, Calcitonin has got no additional advantages. Strontium Ranelate has got double effect, i.e., less bone resorption and more bone formation. Therefore, it can lead to an increase in bone mass significantly. Strontium Ranelate has been proven to decrease the risk of non-vertebral fractures as well as vertebral fractures. Both Calcitonin and Strontium Ranelate are used only as a second-line therapy for the treatment of osteoporosis and not as first-line therapy, mainly because of their safety concern and also because they do not provide any advantages compared to other therapy for the treatment of osteoporosis.

The Role of Calcitonin and Vitamin D in patients with Chronic Renal Failure and Arthritis

Background: Chronic kidney disease is an end stage leads to problems in bone as rheumatoid arthritis (RA) with both glomerular and tubular damage. It is often difficult to differentiate between damage due to disease activity and that due to drugs used to treat Rheumatoid Arthritis.
 The aim: To estimate the levels of Calcitonin and Vitamin D and their relationship with renal Osteodystrophy
 Methods: Calcitonin and Vitamin D were obtained from 135samples: 85 samples from patients with chronic renal failure, 25 samples with (CRF with arthritis) renal Osteodystrophy, and 25 samples apparently healthy .
 Results: A highly significant increase (p<0. 001) in the level of calcitonin in serum of patients with Chronic renal failure and renal osteodystrophy disease compared with healthy individuals. Highly significant decrease (p<0. 001) in the level of vitamin D in serum of patients with chronic renal failure and renal osteodystrophy disease compared with healthy individuals.

Lymph Node Metastases of Medullary Thyroid Cancer: Role of Calcitonin in the Washout Fluid of Fine-Needle Aspiration.

Introduction The diagnostic value of calcitonin (CT) measurement in fine-needle aspirate washout (FNA-CT) for medullary thyroid cancer (MTC) lymph node (LN) metastases remains to be determined. It may increase the diagnostic sensitivity, but data on this subject is sparse. Objective Our study aimed to evaluate the utility of FNA-CT in the diagnosis of LN metastases of MTC. Methods We retrospectively investigated, in our institutional database, 69 consecutive FNA LN cytology from 42 patients who underwent FNA cytology and CT measurement in needle washout for suspicious LN between 2012 and 2017. Results From the total of 69 FNA, 30 (43.4%) were performed in patients with personal history of MTC. MTC was detected in 19 FNA cytology (27.5%), and CT was detectable in needle washout in 23 cases (median = 2014 pg/mL; interquartile range = 490–15111 pg/mL). Based on the combined results of FNA-CT and FNA cytology, LN surgical resection was performed in 33 cases (47.8%). Histology reported MTC LN metastases in 21 lesions (63.6%). Regarding the diagnosis of MTC LN metastases, FNA cytology showed sensitivity of 81.8% and specificity of 97.9%, and FNA-CT demonstrated sensitivity of 100% and specificity of 97.9%. We determined through ROC analysis an optimal FNA-CT cut-off value of 23 pg/mL for the diagnosis of LN metastases (sensitivity 100%; specificity 100%). Conclusions FNA-CT may be a valuable diagnostic tool for detection of MTC LN metastases, along with FNA cytology, and it should be included in the clinical workup of neck adenopathies in patients with MTC or with thyroid nodules.

Calcitonin gene-related peptide (CGRP) ve kremaster kasının inmemiş testis etiyolojisindeki rolü

Calcitonin gene-related peptide (CGRP) ve kremaster kasının inmemiş testis etiyolojisindeki rolü

The Role of Calcitonin in Predicting the Extent of Surgery in Medullary Thyroid Carcinoma: A Nationwide Population-Based Study in Norway

Background: Preoperative predictors for the need of prophylactic lymph node dissection in the lateral neck have been studied in patients with medullary thyroid carcinoma (MTC). Objectives: To evaluate the ability of serum calcitonin to predict the extent of surgery needed in the lateral neck. Methods: This retrospective population-based cohort study includes data from 94 of 139 patients with MTC surgically treated in Norway from 2003 to 2016. Patients were identified in the 4 regional centers treating MTC and by the Cancer Registry of Norway, and grouped according to calcitonin levels. In 58 patients without distant metastases or disease progression to the next tumor level (NPNL), data were compared in prognostic groups (N0-NPNL), (N1a-NPNL), and (N1b-NPNL). Results: At calcitonin levels ≤500, 501–1,000, and >1,000 pmol/L, metastatic lymph nodes in the lateral neck were found in 16, 50, and 71% of the patients, respectively. In the prognostic groups, 19% of N0-NPNL patients had calcitonin >500 pmol/L and 17% of N1b-NPNL patients had calcitonin ≤500 pmol/L. In multivariate analysis, factors predicting biochemical cure and calcitonin level ≤500 pmol/L were no metastatic lymph nodes in the lateral neck (p = 0.030) and tumor diameter ≤20 mm (p < 0.001), respectively. Factors related to metastatic lymph nodes in the lateral neck were extrathyroidal extension (p = 0.007) and no biochemical cure (p = 0.028). Conclusions: Basal calcitonin cannot predict the need for prophylactic lateral lymph node dissection in patients with MTC. Further prospective, randomized studies are warranted.

CGRP and the Trigeminal System in Migraine.

ObjectiveThe goal of this narrative review is to provide an overview of migraine pathophysiology, with an emphasis on the role of calcitonin gene‐related peptide (CGRP) within the context of the trigeminovascular system.BackgroundMigraine is a prevalent and disabling neurological disease that is characterized in part by intense, throbbing, and unilateral headaches. Despite recent advances in understanding its pathophysiology, migraine still represents an unmet medical need, as it is often underrecognized and undertreated. Although CGRP has been known to play a pivotal role in migraine for the last 2 decades, this has now received more interest spurred by the early clinical successes of drugs that block CGRP signaling in the trigeminovascular system.DesignThis narrative review presents an update on the role of CGRP within the trigeminovascular system. PubMed searches were used to find recent (ie, 2016 to November 2018) published articles presenting new study results. Review articles are also included not as primary references but to bring these to the attention of the reader. Original research is referenced in describing the core of the narrative, and review articles are used to support ancillary points.ResultsThe trigeminal ganglion neurons provide the connection between the periphery, stemming from the interface between the primary afferent fibers of the trigeminal ganglion and the meningeal vasculature and the central terminals in the trigeminal nucleus caudalis. The neuropeptide CGRP is abundant in trigeminal ganglion neurons, and is released from the peripheral nerve and central nerve terminals as well as being secreted within the trigeminal ganglion. Release of CGRP from the peripheral terminals initiates a cascade of events that include increased synthesis of nitric oxide and sensitization of the trigeminal nerves. Secreted CGRP in the trigeminal ganglion interacts with adjacent neurons and satellite glial cells to perpetuate peripheral sensitization, and can drive central sensitization of the second‐order neurons. A shift in central sensitization from activity‐dependent to activity‐independent central sensitization may indicate a mechanism driving the progression of episodic migraine to chronic migraine. The pathophysiology of cluster headache is much more obscure than that of migraine, but emerging evidence suggests that it may also involve hypersensitivity of the trigeminovascular system. Ongoing clinical studies with therapies targeted at CGRP will provide additional, valuable insights into the pathophysiology of this disorder.ConclusionsCGRP plays an essential role in the pathophysiology of migraine. Treatments that interfere with the functioning of CGRP in the peripheral trigeminal system are effective against migraine. Blocking sensitization of the trigeminal nerve by attenuating CGRP activity in the periphery may be sufficient to block a migraine attack. Additionally, the potential exists that this therapeutic strategy may also alleviate cluster headache as well.

Spotlight on Anti-CGRP Monoclonal Antibodies in Migraine: The Clinical Evidence to Date.

Migraine, a common neurovascular brain disorder, represents a severe and widespread health problem; along with medication‐induced (medication‐overuse) headache, it is the third‐leading cause of disability worldwide. Currently, its therapeutic management remains unsatisfactory for several reasons; up to 40% of migraineurs are eligible for prophylactic treatment, but there are issues of efficacy, safety, and adherence. In recent years the evidence on the role of calcitonin gene‐related peptide (CGRP) in migraine pathophysiology has been consolidated, so new and promising treatments for migraine pain and its possible prevention have been developed. The following review reports the results of the clinical trials conducted so far with each of the new monoclonal antibodies targeting CGRP or its receptor, with particular reference to safety, tolerance, and efficacy in migraine prevention. Moreover, the pharmacological characterization and further developments of each monoclonal antibody are reported, based on current knowledge.

Plasma Adrenomedullin Levels In Patients With Migraine During Naturel Attack And Attack Free Period

Objective: The role of Calcitonin G related peptide (CGRP) in migraine has been demonsrated. The aim of this study was to examine the role of Adrenomedullin (AM) which is a member of the calcitonin/CGRP/amylin family in migraine patients during naturel attack and attack free period. Material and Methods: 26 migraine patients (11 with aura, 15 without aura) and 26 healty participants were involved. Blood samples were obtained from each patient in attack and attack free period, then compared with each other and control group. Results: Mean plasma AM levels were 18.95 pmol/L during migraine attacks, 26.01 pmol/L between attacks, and 33.38 pmol/L in the control group. AM levels of migraine patients were significantly lower than controls during non-attack periods (p=0.001) and more interestingly, it further decreased during attack periods (p=0.001). A comparison of the mean plasma AM levels of migraine with and without aura cases revealed the same statistically significant difference (p=0.00). Conclusion: The persistently low AM levels in migraine patients gave the impression that in physiological conditions there may be a balance between CGRP and AM and this may be changed towards to the site of CGRP in migraine pathophysiology while causing a decline in AM levels as we had found. Further studies regarding on AM involvement in migraine pathophysiology are needed to confirm these results.

Role of Calcitonin Gene-Related Peptide in Cooling-Induced Hemodynamic Perturbations in Rats: Investigation by Spectrum Analysis

Calcitonin gene-related peptide (CGRP) and its receptors are widely distributed in the nervous and cardiovascular systems as a potent vasodilator; however, the underlying mechanisms of action of CGRP on cardiovascular regulation, such as cooling-elicited hemodynamic perturbation (CEHP), are still unclear. We used spectral and crossspectral analyses to explore such questions in this study. Conscious rats were pretreated with the CGRP antagonist CGRP_(8-37)-only, or following the removal of sympathetic influences using hexamethonium (HEX) or guanethidine (GUA) and then subjected the treated rats to a stressful cooling trial (CS). Cardiovascular indices were monitored via an implanted telemetric device throughout the experiment. The analyses included measurements of blood pressure (BP), heart rate (HR), cardiovascular variabilities (BPV, HRV), coherence linkage at very-low, low and high frequency regions (VLF: 0.02 to 0.2 Hz, LF: 0.2 to 0.6 Hz, and HF: 0.6 to 3.0 Hz), and dicrotic notch (Dn). Key findings of the hemodynamic indices and spectral changes in efferent sympathetic oscillations (LF) and myogenic oscillations (VLF) in comparison with the control vehicle were demonstrated: (I) under resting condition, CGRP_(8-37)- only increased the BP, HR and powers of VLF_(BPV), LF_(BPV). In contrast, the effects of CGRP_(8-37)-only were generally diminished or further reduced when the rats were pretreated with HEX or GUA. (II) Under CS condition, CGRP_(8-37)-only increased the HR but attenuated the power of LF_(BPV), converted the negative correlation (NC) into positive correlation (PC) for VLF_(HRV) with VLF_(BPV) (VLF pair) and LF_(HRV) with LF_(BPV) (LF pair). On the other hand, when pretreated with sympathetic removals, both HEX+CGRP_(8-37) and GUA+CGRP_(8-37) generally abolished the control coolinginduced pressor and tachycardia, attenuated or further reduced the effects of CGRP_(8-37)-only on VLF_(BPV), VLF_(HRV) and LF_(BPV). In addition, HEX+CGRP_(8-37) generally persisted the CGRP_(8-37)-only effect of PC for VLF and LF pairs, but GUA reversed the PC of VLF pair back to a NC tendency. Furthermore, cross-spectral analyses indicated that throughout the experiment, CGRP8-37-only enhanced the coherence linkage between BPV and HRV at the LF region but weakened that at the HF region. HEX+CGRP_(8-37) abolished the CGRP_(8-37)-only effect on the LF region but GUA+CGRP_(8-37) persisted the CGRP_(8-37)-only effects. Taken together, our results indicate that CGRP is dependent on the status of intrinsic sympathetic tonus to exert its function on cardiovascular regulation.

The Roles of Fibroblast Growth Factor (FGF)-23, α-Klotho and Furin Protease in Calcium and Phosphate Homeostasis : A Mini-Review.

The roles of calcitonin, parathormone and calcitriol in the regulation of plasma calcium and phosphate are well-established. However, in autosomal-dominant hypophosphatemic rickety patients, studies have revealed normal plasma levels of calcium, associated with normal thyroid and parathyroid functions, but decreased levels of phosphate and calcitriol despite adequate reserves of vitamin D. Also, in tumoral calcinosis, persistent hyperphosphatemia with increased levels of 1,25(OH)2D3 have been observed. These studies indicate the involvement of factors other than the ones already known. The first decade of this century/millennium has led to the discovery of the involvement of fibroblast growth factor-23, furin protease and α-klotho in the homeostasis of calcium and phosphate, which is the subject of this mini-review.

Abstract 4218: Calcitonin receptor increases invasion of prostate cancer cells by activating cAMP-dependent protein kinase (PKA) and promoting phosphorylation of tight junction proteins

Abstract The role of calcitonin (CT) and its receptor (CTR) in epithelial cancer progression is an emerging concept with great clinical potential. Expression of CT and CTR is frequently elevated in prostate cancers (PCs) and activation of CT-CTR axis in non-invasive PC cells induces an invasive phenotype. Invasive phenotype is acquired by the EMT, a process involving the loss of cell-cell adhesion and cytoskeletal rearrangement. Tight (TJs) and adherens junctions (AJs) are shown to play an important role in this process. Present studies focused on the actions of CTR-mediated intracellular events associated with TJ functionality and the induction of EMT. We have recently identified a type 1 PDZ-binding motif in CTR-C tail, and showed that CTR-C PDZ-binding motif interacts with the PDZ3 domain of ZO-1, a critical scaffolding protein of TJs. CTR-ZO-1 interaction is critical for proinvasive actions CTR on PC cells, and deletion of either CTR-C PDZ-binding motif abolishes the ability of PC cells to form distant metastases in orthotopic xenograft model. Therefore, we first examined the kinetics of CTR-ZO-1 interaction and the effect of CTR on TJ assembly. PC3 cells expressing either CTRwt or CTRαPDZ were acutely treated with CT, and subcellular distribution of TJ proteins was examined by immunocytochemistry and immunoblotting. Since CTR is coupled to stimulatory G protein, we examined effect of PKA inhibitors on CTR actions. Next, we tested whether CTR phosphorylates TJ proteins. Finally, we generated novel peptides and delivered them intracellularly to attenuate CTR-ZO-1 interaction. The results have shown that CTR-ZO-1 interaction occurs rapidly and peaks within 30 seconds of CT stimulus; this is rapidly followed by TJ disassembly and endocytosis of TJ proteins. Endocytosis of ZO-1 occurs first, which is followed with the endocytosis of occludin and claudin 3. We then identified that CTR-mediated TJ disassembly requires PKA-mediated phosphorylation of claudin 3 and ZO-1, and this phosphorylation may cause conformational changes and lead to TJ disassembly. Next, we demonstrated that CTR-mediated PKA phosphorylation must occur within TJ complex, and this spatio-temporal specificity of PKA activation is provided by the CTR-ZO-1 interaction. Finally, we have shown that CTR-ZO-1 interaction as well as CTR-stimulated invasion of PC cells can be attenuated by novel synthetic peptides that we have generated. For the first time, we report here the chain of PKA-mediated events that lead to the disassembly of tight junctions, loss of cell-cell adhesion, induction of EMT, invasion and metastasis of PC cells. We also provide a novel translational approach to generate synthetic peptides to attenuate these events. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4218. doi:1538-7445.AM2012-4218

Association of serum calcitonin with coronary artery disease in individuals with and without chronic kidney disease

Cardiovascular disease is the leading cause of death in patients with chronic kidney disease (CKD). Recent data implicate disordered bone and mineral metabolism, including changes in serum levels of calcium, phosphate, parathyroid hormone (PTH), vitamin D, fibroblast growth factor-23 (FGF-23), and fetuin A, as novel risk factors for arterial calcification. The potential role of calcitonin, another hormonal regulator of mineral and bone metabolism, has not been studied in detail. We investigated the link between serum calcitonin and the total burden of coronary artery disease (CAD) using the validated Gensini score, in a cross-sectional study of 88 patients with estimated GFR (eGFR) between 46 and 87 ml/min/1.73 m² who underwent coronary angiography. We evaluated the associations between serum calcitonin, minerals (calcium, phosphate), calcium × phosphate product, and other factors that regulate mineral metabolism (intact PTH, 25-OH-vitamin D, FGF-23, and fetuin A) and the severity of CAD. The mean serum calcitonin was 11.5 ± 7.8 pg/ml. In univariate analysis, the Gensini CAD severity score correlated significantly with male gender, eGFR, and serum levels of 25-OH-vitamin D, iPTH, FGF-23, fetuin A, and calcitonin (R = 0.474, P = 0.001 for the latter). In multivariate analysis adjusted for calcium, phosphate, 25-OH-vitamin D, iPTH, FGF 23, fetuin A, and calcitonin, only calcitonin (β = 0.20; P = 0.03), FGF-23, fetuin A, and 25-OH-vitamin D emerged as independent predictors of Gensini score. In the second step, we adjusted for the presence of traditional risk factors, proteinuria, and GFR. After these adjustments, the FGF-23 and fetuin A remained statistically significant predictors of the Gensini score, while calcitonin did not. Our study suggests that, in addition to other well-known components of mineral metabolism, increased calcitonin levels are associated with greater severity of CAD. However, this relation was not independent of traditional and nontraditional cardiovascular risk factors. Longitudinal studies in larger populations including patients with more advanced CKD are needed.

Role of calcitonin in management of musculoskeletal pain

Calcitonin was discovered more than 40 years ago and the scientific community continues to debate the primary and secondary pharmacological actions of calcitonin. Presently calcitonin is accepted by agencies only for treatment of osteoporosis, but many studies have indicated an effect on pain in many different experimental settings both pre-clinically and clinically. The effects of calcitonin on clinical pain conditions have received increasing attention in the past decades, although a consensus on mode of action and potential indications still has to be reached. Several key advances in the pain field may enable a deeper understanding of the putative analgesic effects of calcitonin. Most studies have focused on the effect of calcitonin on musculoskeletal pain problems. Ample lines of independent evidence suggest that calcitonin exerts putative analgesic effects. Well-designed clinical trials, particularly in the field of musculoskeletal pain, are needed to validate fragmented evidence of analgesic actions. This in combination with advanced mechanism-based pain assessment tools can provide new insight into the role of calcitonin, alone or in combination with other compounds, in management of pain.

Peripheral amplification of sweating – a role for calcitonin gene‐related peptide

Neuropeptides are the mediators of neurogenic inflammation. Some pain disorders, e.g. complex regional pain syndromes, are characterized by increased neurogenic inflammation and by exaggerated sudomotor function. The aim of this study was to explore whether neuropeptides have a peripheral effect on human sweating. We investigated the effects of different concentrations of calcitonin gene-related peptide (CGRP), vasoactive intestinal peptide (VIP) and substance P (SP) on acetylcholine-induced axon reflex sweating in healthy subjects (total n = 18). All substances were applied via dermal microdialysis. The experiments were done in a parallel setting: ACh alone and ACh combined with CGRP, VIP or SP in various concentrations were applied. Acetylcholine (10(-2) m) always elicited a sweating response, neuropeptides alone did not. However, CGRP significantly enhanced ACh-induced sweating (P < 0.01). Post hoc tests revealed that CGRP in physiological concentrations of 10(-7)-10(-9) m was most effective. VIP at any concentration had no significant effect on axon reflex sweating. The duration of the sweating response (P < 0.01), but not the amount of sweat, was reduced by SP. ACh-induced skin blood flow was significantly increased by CGRP (P < 0.01), but unaltered by VIP and SP. The results indicate that CGRP amplifies axon reflex sweating in human skin.

Role of calcitonin gene-related peptide in gastric hypersensitivity in rats

Role of calcitonin gene-related peptide in gastric hypersensitivity in rats

Calcitonin and renal mineral reabsorption

Calcitonin and its receptor are well known for their ability to regulate osteoclast-mediated bone resorption. Calcitonin has been suggested to be a renal Ca(2+) and Mg(2+)-conserving hormone and may share similar signaling mechanisms with PTH. This review describes the characteristics of renal Ca(2+), Mg(2+) and Pi transport pathway and the physiological roles of calcitonin in renal mineral reabsorption.

The thyroid and the skeleton.

The relationship between the thyroid and the skeleton was first suggested in 1891 when Von Recklinghausen (1891) reported a patient with hyperthyroidism and multiple fractures. Thyroid disease is common; more than 1% of British women receive thyroxine treatment, increasing to over 3% in those over 50 years of age, and the concern is that patients with a history of hyperthyroidism or those receiving thyroxine treatment may be at increased risk of osteoporosis and fractures (Parle et al ., 1993). While the clinical consequences of overt hyperthyroidism on bone have been known for many years the molecular mechanism of action of thyroid hormone on bone has remained incompletely understood. Furthermore, earlier recognition of thyroid disease and effective treatment for clinical symptoms has meant that severe bone disease is now uncommonly seen. It is only in more recent years, with the development of more sensitive TSH assays and the recognition that even so-called subclinical thyroid disease, associated with a suppressed TSH but normal FT4 and FT3 levels, may have effects on fracture risk that there has been a renewed interest in the role of thyroid hormone in bone (Klee & Hay, 1988; Bauer et al ., 2001). The molecular actions of thyroid hormone in bone have recently been comprehensively reviewed (Harvey et al ., 2002; Bassett & Williams, 2003). This review will therefore only briefly summarize this information and instead concentrate in detail on some of the clinical aspects of thyroid hormone effects on bone growth and development in childhood and bone turnover and maintenance in adults. Tables are used to illustrate the effects of thyroid hormone suppressive therapy for thyroid cancer and thyroid hormone replacement on bone mineral density (BMD), and the effects of thyroid hormone on fracture risk. Each clinical section concludes with a summary of the salient points discussed. The role of calcitonin, a hormone also synthesized and secreted by the thyroid gland, and its effects on bone has recently been reviewed and will not be discussed further here (Inzerillo et al ., 2002). Bone biology and the skeletal consequences of thyroid disease

The role of calcitonin gene-related peptide in cutaneous immunosuppression induced by repeated subinflammatory ultraviolet irradiation exposure.

Ultraviolet (UV) light is an effective treatment for skin disorders like psoriasis in which the cutaneous neurosensory system may have a pathogenic role. In this study, we examined the possibility that UV modulation of the cutaneous neurosensory system and calcitonin gene-related peptide (CGRP) may contribute to local immunosuppression mediated by repeated subinflammatory UV irradiation. Our results indicated that exposure of hairless mice to subinflammatory UV three times weekly for 4 weeks significantly increased the number of epidermal nerve fibers (ENFs) immunoreactive for CGRP without altering the total number of ENFs. The skin content of CGRP as measured by enzyme-linked immunosorbent assay was also significantly increased after exposure to this dose of UV. These effects were most apparent 1 day after the last UV exposure and declined 1 week after UV. The role of CGRP in UV-induced immunosuppression of contact hypersensitivity was then examined. Our results indicated that UV suppression of epicutaneous 2,4-dinitro-1-fluorobenzene (DNFB) sensitization could be significantly inhibited by a systemically administered CGRP receptor antagonist. A broad-spectrum sunscreen applied before UV exposure inhibited increased cutaneous CGRP and blocked immunosuppression. These findings support a role for CGRP in the local immunosuppression caused by chronic, repeated subinflammatory UV exposure.

Calcitonin Therapy in Osteoporosis

Osteoporosis is the most prevalent metabolic bone disease and is characterized by diminished bone strength predisposing to an increased risk of fracture. Its incidence is particularly high in postmenopausal women but it can also affect other groups, such as men and patients receiving corticosteroid therapy. Calcitonin is a naturally occurring peptide which acts via specific receptors to strongly inhibit osteoclast function. It has been used in the treatment of osteoporosis for many years. Historically, calcitonin was administered as a parenteral injection, but the intranasal formulation is now the most widely used because of its improved tolerability. New approaches are currently being investigated to enhance the bioavailability and effects of calcitonin, including oral, pulmonary, and transdermal routes of administration, and novel allosteric activators of the calcitonin receptor. Several controlled trials have reported that calcitonin stabilizes and in some cases produces a short-term increase in bone density at the lumbar spine level. The most relevant clinical trial to evaluate the effect of calcitonin in the prevention of fractures was the Prevent Recurrence of Osteoporotic Fractures (PROOF) study, a 5-year double-blind, randomized, placebo-controlled trial showing that salmon calcitonin nasal spray at a dosage of 200 IU/day can reduce the risk of vertebral osteoporotic fractures by 33% (relative risk [RR] = 0.67; 95% CI 0.47, 0.97; p = 0.03). However, the 100 and 400 IU/day dosages did not significantly reduce vertebral fracture risk. Effects on nonvertebral fractures were not significant (RR = 0.80; 95% CI 0.59, 1.09; p = 0.16). There is mounting evidence to show that calcitonin diminishes bone pain in osteoporotic vertebral fractures, which may have clinical utility in vertebral crush fracture syndrome. A recent study suggests that nasal salmon calcitonin appears to be a promising therapeutic approach for the treatment of men with idiopathic osteoporosis, although long-term trials are necessary to confirm these results and evaluate fracture rate as an endpoint in men. The role of calcitonin in corticosteroid-induced osteoporosis remains controversial, hence it can only be considered a second-line agent for the treatment of patients with low bone mineral density who are receiving long-term corticosteroid therapy.

Role of calcitonin in the rapid minute-to-minute regulation of plasma Ca2+ homeostasis in the rat.

Plasma ionized calcium (Ca2+) is maintained at a very stable concentration in mammals. The hormones or factors involved in the very rapid regulation of calcium homeostasis are still debated. Thus, previous results from our laboratory have clearly shown that parathyroid hormone (PTH) and 1,25(OH)2D3 are not responsible for the rapid up-regulation of plasma Ca2+ after a brief induction of hypocalcaemia. The present investigation therefore examined in vivo the possible role of calcitonin (CT) in the very rapid, minute-to-minute regulation of plasma Ca2+ in rats. The rapid calcaemic response to acute thyroparathyroidectomy (TPTX) and to acute selective thyroidectomy (TX) (n = 10), as well as the possible effect of CT on the very rapid recovery of plasma Ca2+ after termination of a brief induction of hypocalcaemia were studied. Hypocalcaemia was induced by a 30-min EGTA infusion in ras in three different protocols: 1 h after TPTX (n = 9) compared with control TPTX rats not given EGTA (n = 13); 1 h after TX (n = 7); and 1 h after TPTX, but during supplementation with exogenous CT (n = 8) and compared with the response in TPTX rats infused with vehicle (n = 8). An immediate and significant increase of plasma Ca2+ was found after TPTX (P < 0.01) as well as after selective TX (P < 0.01) in the nonfasting rats. Significant hypercalcaemia (P < 0.05) was still present in rats fasting for 2 days before these procedures, but the increase in plasma Ca2+ was considerably less (P < 0.01). After induction of a brief period of hypocalcaemia by infusion of EGTA a significant (P < 0.01) and rapid recovery of plasma Ca2+ took place within 10 min and a further increase within the next 60 min (P < 0.01), whether or not the rats were normal, TPTX, TX or were supplemented by CT during the experiments. The plasma Ca2+ recovery curves after termination of a brief induction of hypocalcaemia all had similar appearances, indicating that presence or absence of CT had no influence on this very rapid Ca2+ recovery after induction of hypocalcaemia. Acute removal of the tonus of CT results in an acute increase in plasma Ca2+ for up to 3 h. This effect of CT is probably mainly related to the postprandial maintenance of normocalcaemia, but is also seen in fasting rats, although to a lesser degree. The very rapid calcaemic recovery after discontinuation of a brief induction of hypocalcaemia is, however, not a result of suppressed plasma calcitonin levels.