Calcitonin Treatment Research Articles

Calcitonin treatment for osteoarthritis and rheumatoid arthritis - a systematic review and meta-analysis of preclinical data.

The aim of this study was to investigate the efficacy of calcitonin (CT) in animal models of experimental osteoarthritis (OA) and rheumatoid arthritis (RA), as new stabilized CT formulations are currently being introduced. A comprehensive and systemic literature search was conducted in PubMed/MEDLINE and Embase databases to identify articles with original data on CT treatment of preclinical OA and RA. Methodological quality was assessed using the Systematic Review Centre for Laboratory Animal Experimentation's risk of bias tool for animal intervention studies. To provide summary estimates of efficacy, a meta-analysis was conducted for outcomes reported in four or more studies, using a random-effects model. Subgroup analyses were employed to correct for study specifics. Twenty-six studies were ultimately evaluated and data from 16 studies could be analyzed in the meta-analysis, which included the following outcomes: bone mineral density, bone volume, levels of cross-linked C-telopeptide of type I collagen, histopathological arthritis score, and mechanical allodynia. For all considered outcome parameters, CT-treated groups were significantly superior to control groups (P = 0.002; P = 0.01; P < 0.00001; P < 0.00001; P = 0.04). For most outcomes, effect sizes were significantly greater in OA than in RA (P ≤ 0.025). High in-between study heterogeneity was detected. There is preclinical evidence for an antioxidant, anti-inflammatory, antinociceptive, cartilage- and bone-protective effect of CT in RA and OA. Given these effects, CT presents a promising agent for the treatment of both diseases, although the potential seems to be greater in OA.

Safety and Early Results for Off-Label Use of Intranasal Calcitonin for Treatment of Nondisplaced Acromial and Scapular Spine Stress Fractures After Reverse Total Shoulder Arthroplasty.

Immobilization for acromial and scapular spine stress AU4fractures (AF/SSF) after reverse total shoulder arthroplasty (RSA) is associated with patient dissatisfaction. Our study reports the effects and safety of intranasal calcitonin alongside sling immobilization on pain and function in the treatment of AF/SSF after RSA. The treatment was regimented calcitonin (salmon) 200 unit/actuation nasal spray (1 spray/day) for 6 weeks with sling immobilization for 4 weeks. Each patient was monitored through blood work. Visual analog scale, American Shoulder and Elbow Surgeons score, and active range of motion were collected preoperatively, postoperatively, at presentation of AF/SSF, and after completion of calcitonin treatment. Two hundred eighty-two RSAs were performed by two board-certified orthopaedic surgeons, of which 18 patients sustained AF/SSF (6.4%). Ten patients met inclusion criteria (nine AFs and one SSF). After calcitonin treatment, patients demonstrated an average improvement of visual analog scale of 5.8 points, active range of motion of 46_, and American Shoulder and Elbow Surgeons score of 43.6 points at average 7.53 months after RSA. No medical complications were reported at 6-month follow-up after calcitonin treatment. The use of intranasal calcitonin was not associated withadverse events including no aberrations/signs of cancer at 6-month follow-up after administration. Calcitonin with sling immobilization markedly improved clinical and functional outcomes of patients with nondisplaced AF/SSF and may be considered by orthopaedic surgeons for symptom management.

Efficacy and Toxicity of Calcitonin Treatment in Children with Cherubism: A Single-Center Cohort Study.

Cherubism is a rare autosomal dominant disease characterized by expansile osteolytic jawbone lesions. The effect and safety of off-label calcitonin treatment during the progressive phase of the disease are not well described. In this retrospective study, we present data on the radiological response and adverse effects of subcutaneously administered calcitonin in a cohort of nine cherubism children (three female, six male). Two of the nine patients underwent two separate treatment courses with a significant off-treatment interval in between; therefore, a total of 11 treatment courses with a mean duration of 17.9 months (range <1 to 35, SD 10.8) were studied. To measure the response, the cumulative volume of cherubism lesions was calculated from available three-dimensional imaging. The primary outcome was the change in the volume of lesions during calcitonin treatment and only assessed for the eight treatment courses with a minimal duration of 6 months. A statistically significant reduction in the mean cumulative volume of lesions was seen regardless of treatment duration. Average volume reduction was highest in the first half year of treatment, with a gradual, ongoing reduction thereafter. For the secondary outcome, the change in the cumulative volume of lesions after treatment cessation was assessed for the seven treatment courses with follow-up imaging available. After six of these seven treatment courses, the cumulative volume increased again but remained undoubtedly smaller than the initial volume at the start of therapy. Adverse effects were assessed for all 11 treatment courses and occurred in 73% of them. Most adverse effects were mild and low grade, with the most severe being one grade 3 symptomatic hypocalcemia requiring hospitalization and early treatment termination. Calcitonin treatment seems effective and tolerable in treating actively progressing cherubism in children. However, further research is required to better understand the pharmacological treatment of cherubism, including also other drugs, dosing, and protocols. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

A Review of Potential Therapies to Attenuate Bone Mineral Density Loss in Obese Individuals Prior to Total Joint Replacement Surgery.

The focus of this review is to examine therapeutic interventions which may be used to increase bone mineral density (BMD), reduce bone loss, and ultimately reduce complications in obese patients prior to total joint replacement (TJR). It is recommended that obese patients lose weight prior to surgery to reduce post-surgical complications, but weight loss can also increase bone loss and fracture risk in older individuals. In this review, we investigate potential therapies to improve bone density and reduce bone loss including exercise therapy, parathyroid hormone (PTH), estrogen, bisphosphonate, and calcitonin treatment in obese patients prior to TJR. Our review of existing literature found that treatment with PTH increased total body BMD in both men and women with osteoporosis; exercise therapy in combination with weight loss prevents the weight loss-induced increase in bone turnover and attenuates the weight loss-induced decrease in BMD; and estrogen, bisphosphonate, and calcitonin reduce bone resorption.

The effects of calcitonin on quality of life in hypothyroid patients – A pilot study

IntroductionHypothyroidism is a very common endocrine disorder routinely treated with levothyroxine replacement therapy. Despite treatment to biochemical euthyroidism, some individuals continue to have hypothyroidism-related symptoms. Many individuals with hypothyroidism also have low levels of calcitonin. Our aim was to evaluate the effects of calcitonin treatment on quality of life in hypothyroid individuals treated with levothyroxine. MethodsAdult, hypothyroid individuals were treated with nasal calcitonin spray, 200 international units daily for 6 weeks. Participants completed a modified City of Hope Quality of Life questionnaire prior to initiating calcitonin and after completing 6 weeks of therapy. Perception of quality-of-life benefit with calcitonin was also assessed. ResultsImprovements in quality-of-life scores with calcitonin treatment from 184.77 to 148.44 (p = 0.342) were not statistically significant. Also, only one individual perceived any benefit with calcitonin therapy. ConclusionTreatment with nasal calcitonin spray in individuals with hypothyroidism on levothyroxine replacement therapy did not result in quality-of-life benefit.

Drp1 activates ROS/HIF-1α/EZH2 and triggers mitochondrial fragmentation to deteriorate hypercalcemia-associated neuronal injury in mouse model of chronic kidney disease

BackgroundChronic kidney disease (CKD), characterized as renal dysfunction, is regarded as a major public health problem which carries a high risk of cardiovascular diseases. The purpose of this study is to evaluate the functional significance of Drp1 in hypercalcemia-associated neuronal damage following CKD and the associated mechanism.MethodsInitially, the CKD mouse models were established. Next, RT-qPCR and Western blot analysis were performed to measure expression of Fis1 and Drp1 in CKD. Chromatin immunoprecipitation (ChIP) assay and dual-luciferase reporter gene assay were utilized to explore the relationship among Drp1, HIF-1α, EZH2, and ROS with primary cortical neurons isolated from neonatal mice. Next, CKD mice were subjected to calcitonin treatment or manipulation with adenovirus expressing sh-Drp1, so as to explore the effects of Drp1 on hypercalcemia-induced neuronal injury in CKD. TUNEL assay and immunofluorescence staining were performed to detect apoptosis and NeuN-positive cells (neurons) in prefrontal cortical tissues of CKD mice.ResultsIt was found that hypercalcemia could induce neuronal injury in CKD mice. An increase of Fis1 and Drp1 expression in cerebral cortex of CKD mice correlated with mitochondrial fragmentation. Calcitonin suppressed Drp1/Fis1-mediated mitochondrial fragmentation to attenuate hypercalcemia-induced neuronal injury after CKD. Additionally, Drp1 could increase EZH2 expression through the binding of HIF-1α to EZH2 promoter via elevating ROS generation. Furthermore, Drp1 knockdown inhibited hypercalcemia-induced neuronal injury in CKD while overexpression of EZH2 could reverse this effect in vivo.ConclusionTaken together, the key findings of the current study demonstrate the promotive role of Drp1 in mitochondrial fragmentation which contributes to hypercalcemia-induced neuronal injury in CKD.

A serological type II collagen neoepitope biomarker reflects cartilage breakdown in patients with osteoarthritis

ObjectivesThere is an unmet medical need for biomarkers in OA which can be applied in clinical drug development trials. The present study describes the development of a specific and robust assay measuring type II collagen degradation (T2CM) and discusses its potential as a noninvasive translational biomarker. MethodsA type II collagen specific neoepitope (T2CM) was identified by mass spectrometry and monoclonal antibodies were raised towards the epitope, employed in a chemiluminescence immunoassay. T2CM was assessed in bovine cartilage explants with or without MMP-13 inhibitor, and explant supernatants were analyzed by Western blot. T2CM was measured in plasma samples from one study (n ​= ​48 patients) where OA patients were referred to total knee replacement (TKR). Additionally, T2CM was quantified in serum from OA patients receiving salmon calcitonin treatment (sCT) (n ​= ​50) compared to placebo (n ​= ​57). ResultsThe T2CM assay was technically robust (13/4 ​% inter/intra-variation) and specific for the type II collagen fragment cleaved by MMP-1 and -13. The MMP-13 inhibitor reduced the T2CM release from bovine cartilage explants receiving catabolic treatment. These results were confirmed by Western blot. In human end-stage OA patients (scheduled for TKR), the T2CM levels were elevated compared to moderate OA (p<0.004). The OA patients receiving sCT had lower levels of T2CM compared to placebo group after 1, 6, and 24 months of treatment (p ​= ​0.0285, p ​= ​0.0484, p ​= ​0.0035). ConclusionsTo our knowledge, T2CM is the first technically robust serological biomarker assay which has shown biological relevance in ex vivo models and OA cohorts. This suggests that T2CM may have potential as a translational biomarker for cartilage degradation.

Evaluation of a Pharmacy-Driven Calcitonin Protocol for Treating Hypercalcemia in Hospitalized Patients: A Multisite Study

Background: The dramatic increase in the acquisition cost of injectable calcitonin led to creating a pharmacy-driven calcitonin protocol to improve the appropriate use of calcitonin and other treatment modalities for hypercalcemia. Objective: This study aimed to characterize the use of calcitonin before and after implementation of a pharmacy-driven calcitonin protocol. Methods: This was a multi-center, retrospective study of the use of injectable calcitonin in adult hospitalized patients with hypercalcemia. The study included patients treated with calcitonin from October 2014 to September 2016 and from October 2017 to September 2019. The primary outcomes were percentage of patients with a complete response, partial response, and non-responders. The secondary outcomes were time to relapse, duration of partial response, number of doses, and associated costs of calcitonin. Results: Of the 131 patients included in this study, 93 were included in a pre-protocol group and 38 were included in a post-protocol group. The primary outcome of complete response by 3 days was met in 28% of patients in the pre-protocol group and 53% of patients in the post-protocol group (P = 0.007). Calcitonin spending in dollars in the pre-protocol group was $818,956 compared to $224,320 in the post-protocol group; a difference of $594,636. Conclusion: Implementation of a pharmacy-driven calcitonin protocol effectively improved calcium levels, reduced inappropriate calcitonin use, and reduced calcitonin spending during a period of 2 fiscal years.

A novel serological pharmacodynamic biomarker assessing type II collagen degradation in osteoarthritis patients

Purpose: A major hallmark of osteoarthritis (OA) is the altered cartilage metabolism and turnover. During cartilage erosion, type II collagen is cleaved by matrix metalloproteinases (MMPs) generating new protein fragments, called neo-epitopes. These fragments are released into the circulation and may reflect disease activity, and potentially be utilized for drug development as pharmacodynamic markers. Currently, there is a lack of type II collagen biomarkers reflecting pharmacologic responses to therapeutic interventions in OA. A novel immunoassay detecting a neo-epitope fragment of type II collagen (T2CM), cleaved by MMP-1 and MMP-13, has recently been developed. The assay is shown to be technically robust and highly specific for the T2CM neo-epitope. Studies have indicated that MMP-13 plays a critical role in type II collagen degradation in articular cartilage in OA and hence, T2CM may serve as a potential pharmacodynamic biomarker candidate in OA. The aim of this study was to evaluate the pharmacodynamic property of T2CM in OA patients treated with oral salmon calcitonin compared to placebo. Methods: T2CM levels were assessed in serum samples in a subset of the SMC study, a randomized, double-blind, multi-center, placebo-controlled study where knee OA patients (n=50) received 0.8 mg oral salmon calcitonin treatment twice daily for 24 months and compared to placebo (n=57). Serum samples were collected at baseline and after 1, 6, 12, and 24 months of treatment. Study samples were collected after informed consent and approved by local ethical committee in compliance with the Helsinki declaration of 1997. The statistical analysis included two-way ANOVA with Sidak’s post hoc test for difference between multiple comparisons of T2CM levels between the OA patients receiving salmon calcitonin treatment and placebo. Data were adjusted for differences in body mass index (BMI), sex, and age. Results: The mean age of OA patients treated with oral salmon calcitonin was 63.9 years (±SD 6.9) and 34% were female, and mean age of the placebo group was 63.1 years (±SD 6.1) and 45% female. The mean BMI of the treatment group and placebo was 30.2 (SD±5.1) and 27.9 (SD±3.3), respectively. T2CM levels were significantly decreased in OA patients receiving salmon calcitonin compared to the placebo group after 1, 6, and 24 months of treatment (p=0.0285; mean -61.49 ±SD 9.10 vs -33.19 ±SD 8.50, p=0.084; mean -66.35 ±SD 8.90 vs -41.46 ±SD 8.31, p=0.0035; mean -61.73 ±SD 9.49 vs -22.19 ±SD 8.76) (Fig.1). Conclusions: The novel T2CM assay measured significantly decreased levels of T2CM in OA patients treated with salmon calcitonin compared to placebo. This suggests that T2CM may have potential as a pharmacodynamic biomarker for type II collagen degradation. Currently, no disease-modifying drugs exist in OA. A validated pharmacodynamic biomarker for type II collagen degradation could promote the development of new disease-modifying OA drugs targeting cartilage repair or degradation.

Clinical effect of intramuscular calcitonin compared with oral celecoxib in the treatment of knee bone marrow lesions: a retrospective study

BackgroundBone marrow lesions (BMLs) are a common finding in patients with osteoarthritis (OA), which are predictors of progression and pain related to cartilage damage in OA. The objective of the present research was to compare the short-term clinical effect of intramuscular calcitonin and oral celecoxib in treating knee BMLs.Patients and methodsBetween January 2016 and December 2018, the medical records of patients with knee BMLs treated by intramuscular calcitonin or oral celecoxib were reviewed. Visual analog scale (VAS) and the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) were used to assess knee pain and function, respectively. BMLs were assessed by MRI scans and were scored by the modified Whole-Organ MRI Score (WORMS). The safety of these two medications was also evaluated.ResultsA total of 123 eligible patients who received calcitonin treatment (n = 66) or celecoxib treatment (n = 57) were included. All patients were followed up clinically and radiographically for 3 months. The VAS and WOMAC scores were lower statistically in calcitonin group than celecoxib group at 4-week and 3-month follow-up. For BMLs, the WORMS scores in the calcitonin group were significantly lower than the celecoxib group. Besides, statistically higher MRI improvement rates were found in the calcitonin group compared with the celecoxib group at 4-week follow-up (21.21% vs. 7.01%; P = 0.039) and 3-month follow-up (37.88% vs. 15.79%; P = 0.006).ConclusionIntramuscular calcitonin 50 IU once daily demonstrated a better short-term effect for knee BML patients compared with oral celecoxib 200 mg twice per day.

Calcitonin inhibits intervertebral disc degeneration by regulating protein kinase C.

Intervertebral disc degeneration (IVDD) is the most critical factor that causes low back pain. Molecular biotherapy is a fundamental strategy for IVDD treatment. Calcitonin can promote the proliferation of chondrocytes, stimulate the synthesis of matrix and prevent cartilage degeneration. However, its effect and the underlying mechanism for IVDD have not been fully revealed. Chondrogenic specific matrix components’ mRNA expression of nucleus pulposus cell (NPC) was determined by qPCR. Protein expression of NPC matrix components and protein kinase C was determined by Western blotting. A rat caudal intervertebral disc degeneration model was established and tested for calcitonin in vivo. IL‐1 induced NPC change via decreasing protein kinase C (PKC)‐ε phosphorylation, while increasing PKC‐δ phosphorylation. Calcitonin treatment could prevent or reverse IL‐1‐induced cellular change on PKC signalling associated with degeneration. The positive effect of calcitonin on IVDD in vivo was verified on a rat caudal model. In summary, this study, for the first time, elucidated the important role of calcitonin in the regulation of matrix components in the nucleus of the intervertebral disc. Calcitonin can delay degeneration of the intervertebral disc nucleus by activating the PKC‐ε pathway and inhibiting the PKC‐δ pathway.

Calcitonin protects rat chondrocytes from IL-1β injury via the Wnt/β-catenin pathway.

The present study investigated whether the Wnt/β-catenin pathway was involved in the protective effect of calcitonin (CT) in interleukin-1β (IL-1β)-injured rat chondrocytes. Chondrocytes were acquired from the articular cartilage of 4-week-old rats and treated with 10 ng/ml IL-1β to stimulate an in vitro osteoarthritis model. CT (10 and 50 nM) and 5 µm IWR-1-endo (a Wnt/β-catenin inhibitor) was used for treatment. The proliferation and apoptosis of rat articular chondrocytes were measured using a cell counting kit-8 assay and Annexin V/PI staining, respectively. Expression of matrix-metalloproteinases (MMP)-13 MMP3 and MMP9 and aggrecanases [metalloproteinase thrombospondin motifs (ADAMTS4 and ADAMTS5)] were measured to assess the degradation of the cartilage extracellular matrix. The results of the present study demonstrate that CT protected rat chondrocytes from IL-1β stimulation by enhancing cell viability, suppressing apoptosis and decreasing the expression of matrix metallopeptidase (MMP) MMP13, MMP3, MMP9, ADAMTS4 and ADAMTS5. CT treatment also upregulated dickkopf-1 and downregulated β-catenin. IWR-1-endo demonstrated similar effects to that of CT treatment. The administration of CT in addition to IWR-1-endo reinforced the change trends induced by CT or IWR-1-endo in the aforementioned events, indicating that CT possibly acted via the Wnt/β-catenin pathway to exert a protective effect on IL-1β-injured rat chondrocytes.

MON-622 Can Calcitonin Replacement Improve Quality of Life in Hypothyroid Patients?

Background: Hypothyroidism is one of the most common endocrine hormone deficiencies and is associated with symptoms of cold intolerance, fatigue and weight gain. Many patients with a history of hypothyroidism continue to report persistent symptoms despite treatment with hormone replacement and normalization of Thyroid Stimulating Hormone (TSH) levels. Saravanan et al., reported that approximately 15% of the population studied reported fatigue or psychological symptoms on L-thyroxine even with normal TSH levels. This can prove challenging for physicians as there are few available options for adjunctive therapy for patients reporting significant symptoms that negatively impact their quality of life. Primary hypothyroidism is a common cause of hypothyroidism and is characterized by thyroid gland dysfunction due to radioactive ablation, surgical removal, or autoimmune Hashimoto’s thyroiditis. This dysfunction also impacts calcitonin production in the parafollicular C cells. Calcitonin treatment for persistent symptoms of hypothyroidism despite euthyroidism on replacement hormone has not been studied. However, the use of calcitonin has shown improvements in QoL in patients with osteoporosis and osteoarthritis (Shohrati et al, 2015; Esenyel et al, 2013). We proposed a pilot study in treating subjects with ongoing psychologic or metabolic symptoms and euthyroidism on thyroid hormone replacement with calcitonin. Methods: Subjects with symptomatic hypothyroidism were recruited for the study. Any patient between the age of 18-89, on levothyroxine treatment with normal TSH levels in the past 3 months qualified. Those who were considering pregnancy or had a history of PPI use, smoking, hypocalcemia, glucocorticoid use, congenital hypothyroidism, pituitary disease or thyroid cancer were excluded. Study participants filled out a Modified City of Hope Quality of Life (QoL) questionnaire that included questions about social concerns, physical health and physical well-being rated on a 10 point scale. Preliminary laboratory evaluation included calcitonin, Parathyroid Hormone panel, Phosphorus, TSH, Free T4 and Total T3. Participants were then instructed to use calcitonin nasal spray 200 International Units (IU) daily for 6 weeks. At the conclusion of the study, subjects were asked to fill out the same questionnaire to assess change in QoL. Results: We have undertaken a study to evaluate the effects of calcitonin treatment on subjects with hypothyroidism and suboptimal QoL despite thyroid hormone replacement and normal TSH.

Systemic therapy with calcitonin has positive clinical effects on systemic sclerosis in patients with cutaneous manifestations.

Calcitonin gene-related peptide (CGRP) is a vasodilatory neuropeptide that plays an important role in the blood vessels of heart and peripheral circulation, a lack of which may cause vasculopathies. In this study, the clinical course of disease, as well as the efficacy, side effects, and patient satisfaction of systemic calcitonin therapy in patients with systemic sclerosis (SSc), was evaluated. Forty-nine patients received repetitive intravenous calcitonin infusions as first-line treatment. The average number of cycles was 12.2±10.3 over a period of 30 months (each cycle: 100U/day over 10 days). Clinical examinations, laboratory tests, and organ imaging were performed before the start of, and at regular intervals during therapy in order to evaluate organ manifestations and the clinical course of the disease. In addition, patients' own experiences of the therapy, side effects, and therapy success were evaluated with standardized questionnaires. Over the course of the treatment, seven patients experienced improvements in their condition with a considerable reduction in digital ulceration and improved movement (14.3%). Pulmonary function in seven patients improved during the therapy (14.3%). With regards to side effects, nausea (41.7%), headaches (33.3%), fluctuations in blood pressure (29.2%), and flushing (29.2%) were observed. Overall, 45.8% of patients evaluated the therapy as good and 58.3% would undergo further courses of therapy with calcitonin. Systemic calcitonin treatment seems to have positive clinical effects on SSc and contributes to relieving symptoms, especially in patients with cutaneous manifestations. No severe side effects were reported during this study.

Local administration of calcitonin inhibits alveolar bone loss in an experimental periodontitis in rats

Calcitonin (CTN), a calcium regulatory hormone, promotes calcium diuresis from the kidney and suppresses bone resorption. The objective of this study was to evaluate whether the topical and intermittent application of CTN inhibits alveolar bone resorption using ligature-induced experimental periodontitis in rats. Experimental periodontitis was induced by placing a nylon ligature around maxillary molars of 8-week-old male Wistar rats for 20 days. Thirty-two rats were divided into four groups: basal sham control group, periodontitis group, periodontitis plus 0.2 U CTN (low dose), and periodontitis plus 1.0 U CTN (high dose) group. To investigate the effects of CTN on alveolar bone resorption, CTN was topically injected into the palatal gingivae every 2 days after ligature removal (day 0). Micro-computed tomography (CT) analysis was performed for linear parameter assessment of alveolar bone on day 5 and day 14. Periodontal tissues were examined histo-pathologically to assess the differences among the study groups. Micro-CT images showed that alveolar bone resorption was induced statistically around the molar of ligatured rats on day 5 and day 14. The amount of bone resorption was more severe on day 14 than that on day 5. On day 5, only high-dose CTN treatment significantly suppressed bone resorption. In addition, both doses of CTN significantly suppressed bone resorption on day 14. Histological examination clarified that there were fewer TRAP-positive cells in the CTN treatment groups than in the periodontitis group on day 5. Local administration of CTN decreased alveolar bone resorption by regulating osteoclast activation in rats with periodontitis.

Response of trabecular bone, thyroid C and follicular cells to synthetic salmon calcitonin in middle-aged orchidectomized male rats.

In contrast to studies in women, male osteoporosis is poorly understood and strictly related to advancing age. Among the first antiresorptive substances used in the prevention and treatment of osteoporosis is calcitonin (CT), a hypocalcemic hormone that potently inhibits osteoclastic bone resorption. Natural CT is produced and secreted by thyroid C-cells. The other endocrine population of thyroid cells produces thyroid hormones (TH), which also affect bone turnover. The aim of this study was to evaluate the influence of salmon CT on trabecular bone microarchitecture with special reference to effects on the structure and function of both CT- and TH-producing thyroid cells in orchidectomized (Orx) middle-aged rats. Twenty-four male Wistar rats aged 15months were randomly divided into Orx and sham-operated (SO) groups. One group of Orx animals received (s.c.) synthetic salmon CT (Orx+CT; 100IUkg-1 b.w.) subcutaneously every second day for 6 weeks. The second Orx group and SO rats were given the same volume of vehicle alone by the same schedule. Trabecular bone histomorphometrical parameters were: cancellous bone area (B.Ar), trabecular thickness (Tb.Th), trabecular number (Tb.N) and trabecular separation (Tb.Sp) were obtained with an ImageJ public-domain image-processing program. The peroxidase-antiperoxidase method was applied for localization of CT in C-cells. Anti-human CT antisera served as the primary antibodies. For immunohistochemical characterization of vascular endothelial growth factor (VEGF) in thyroid tissue, rabbit antisera against human VEGF, served as primary antibodies. CT-immunopositive thyroid C-cells, thyroid follicular epithelium, interstitium and colloid were evaluated morphometrically. Blood serum samples were analyzed for CT, osteocalcin (OC), and thyroxine (T4 ), and calcium (Ca2+ ) concentration was determined in urine samples. Salmon CT application significantly increased B.Ar, TbTh and TbN, but markedly decreased Tb.Sp. Administration of exogenous CT significantly decreased mean volume (Vc) and relative volume density (Vv) of thyroid C-cells in relation to both SO and Orx groups. The Vv of the colloid was higher, whereas the VV of the follicular epithelium was lower after CT treatment compared with Orx alone. CT treatment markedly elevated serum CT, whereas serum OC, T4 and urinary Ca2+ concentrations were lower than in the Orx group. These results indicate that salmon CT stimulates trabecular bone microarchitecture, strongly inhibits thyroid C-cells and changes the structure of the thyroid gland, indicating hypoactivity.

Calcitonin Participant in the Development of Insulin Resistance

The review contains contemporary literature data about calcitonin role in the development of insulin resistance and its potential role in the pathogenesis of carbohydrate metabolism disturbances. Analogues disturbances revealed under diabetes mellitus and under calcitonin treatment are considered. Literature data about hormone diabetogenicity are discussed. The analysis of experimental and literature data testifies that calcitonin under unfavorable conditions (age, obesity, stress) against the background of the decreasing of functional activity of insular apparatus can lead to the development of metabolic syndrome and diabetes mellitus. It is shown that calcium channel blockers inhibit calcitonin effect leads to glucose intolerance and decreases tissue insulin sensitivity. In this connection a question about direct influence on calcium mechanisms of endocrine system as possible method of drug therapy is discussed.

A Giant Pituitary Adenoma in a Patient under Salmon Calcitonin Treatment: Coincidence or a Priori Consequence

A Giant Pituitary Adenoma in a Patient under Salmon Calcitonin Treatment: Coincidence or a Priori Consequence

Central giant cell reparative granuloma of the Jaws

Central giant cell reparative granuloma (CGCRG) has been defined by The World Health Organization as a localized benign however sometimes aggressive osteolytic proliferation, consisting of fibrous tissue along with hemorrhage and hemosiderin deposits, with the presence of osteoclast-like giant cells and reactive bone formation.They are mostly localized in the maxilla and mandible , however lesions sourced from the orbit, paranasal sinuses, skull base, skull bones such as the temporal, sphenoid, ethmoid bones, and the small bones of the hands and feet have also been published.CGCRG often presents itself as a painless swelling of the face or mouth and it is divided into 2 groups according to its clinical findings, as aggressive and nonaggressive type.Nonaggressive lesions are slow-growing, mostly asymptomatic lesions which don't cause perforation of the cortical bone and root resorption. Aggressive lesions however are fast-growing; larger than 5 cm in size; cause pain and paraesthesia, root resorption and cortical perforation; and commonly show recurrence after surgery.The differential diagnosis for CGCRG includes other giant cell lesions such as the true giant cell tumor of the bone, aneurysmal bone cysts, and chondroblastoma.The traditional treatment for CGCRG is surgical abortion and this treatment is sufficient in 80% of the cases. Alternative methods to surgery are; intralesional corticosteroid therapy, calcitonin treatment, interferon alpha-2a, and imatinib treatment.

Protective effect of calcitonin on lumbar fusion-induced adjacent-segment disc degeneration in ovariectomized rat.

BackgroundIntervertebral disc (IVD) degeneration and pathological changes in the spinal cord are major causes of back pain. In addition to its well-established anti-resorptive effect on bone, calcitonin (CT) potentially exerts protective effects on IVD degeneration in ovariectomized rats. However, possible therapeutic effects of CT on lumbar fusion-induced adjacent-segment disc degeneration (ASDD) have not been investigated yet. In this study, we examined the effects of CT on IVD degeneration adjacent to a lumbar fusion in ovariectomized rats.MethodsPosterolateral lumbar fusion (PLF) at L4–5 was performed 4 weeks after ovariectomy (OVX) or sham surgery in female Sprague–Dawley rats. Following PLF + OVX, rats received either salmon CT (OVX + PLF + sCT, 16 IU/Kg/2d) or vehicle (OVX + PLF + V) treatment for 12 weeks; the remaining rats were divided into Sham + V, OVX + V, and PLF + V groups. Fusion status was analyzed by manual palpation and radiography. Adjacent segment disc was assessed by histological, histomorphometric, immunohistochemical analysis. L6 vertebrae microstructures were evaluated by micro-computed tomography.ResultsHistological analysis showed more severe ASDD occurred in OVX + PLF + V rats compared with the OVX + V or PLF + V groups. CT treatment suppressed the score for ASDD, increased disc height, and decreased the area of endplate calcification. Immunohistochemical staining demonstrated that CT decreased the expression of collagen type-I, matrix metalloproteinase-13, and a disintegrin and metalloproteinase with thrombospondin motifs-4, whereas it increased the expression of collagen type-II and aggrecan in the disc. Micro-computed tomography indicated that CT increased bone mass and improved the microstructure of the L6 vertebrae.ConclusionsThese results suggest that CT can prevent ASDD, induce beneficial changes in IVD metabolism, and inhibit deterioration of the trabecular microarchitecture of vertebrae in osteoporotic rats with lumbar fusion.