Increased Serum Calcium Research Articles

Curd paste for calcium metabolism correction

Calcium is one of critical elements influencing metabolic processes in the body. It is an essential ingredient of bone tissue. Once its amount in the blood is insufficient, bone calcium resorption occurs that leads to osteoporosis development. The goal of this publication is to demonstrate feasibility of introducing curd paste supplemented with additional source of calcium in the diet of population for improving antioxidant defense and strengthening bone tissue. This publication summarizes our previous research on developing calcium-enriched dairy products for osteoporosis prevention. It is supplemented with new data on significance of separate ingredients of curd paste, including whey protein antioxidant properties; ability of calcium and potassium salts as counterparts of strontium and cesium to reduce radionuclides absorption from gastrointestinal tract and others. Based on natural ingredients and targeted the mass consumer, Vitacalcin paste can provide a solid competition to domestic and foreign products. Formulations and technological process for curd paste Vitacalcin enriched with calcium from either eggshell powder or calcium alginate, and functional additives, such as nettle or garlic, has been developed. Products have been tested in animals and patients of Central Institute of Traumatology with primary form of osteoporosis. Bioavailability of calcium is more pronounced when consuming pastes with ESP and sulfur-containing additive. In animal model, bone mass increase has been observed after 28 days of curd paste consumption. Patients with pronounced osteoporosis consuming 200 g of curd paste daily for 30 days have demonstrated increased serum calcium level. It has been shown that the new product has a positive impact on bone tissue formation, and possesses antioxidant properties. As a result of the research, technical documentation for Vitacalcin curd paste is developed. The Institute of Nutrition recommends this product for osteoporosis prevention and correction of calcium balance.

The Vitamin D Receptor in Osteoblast-Lineage Cells Is Essential for the Proresorptive Activity of 1α,25(OH)2D3 In Vivo.

We previously reported that daily administration of a pharmacological dose of eldecalcitol, an analog of 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], increased bone mass by suppressing bone resorption. These antiresorptive effects were found to be mediated by the vitamin D receptor (VDR) in osteoblast-lineage cells. Using osteoblast-lineage-specific VDR conditional knockout (Ob-VDR-cKO) mice, we examined whether proresorptive activity induced by the high-dose 1α,25(OH)2D3 was also mediated by VDR in osteoblast-lineage cells. Administration of 1α,25(OH)2D3 (5 μg/kg body weight/day) to wild-type mice for 4 days increased the number of osteoclasts in bone and serum concentrations of C-terminal crosslinked telopeptide of type I collagen (CTX-I, a bone resorption marker). The stimulation of bone resorption was concomitant with the increase in serum calcium (Ca) and fibroblast growth factor 23 (FGF23) levels, and decrease in body weight. This suggests that a toxic dose of 1α,25(OH)2D3 can induce bone resorption and hypercalcemia. In contrast, pretreatment of wild-type mice with neutralizing anti-receptor activator of NF-κB ligand (RANKL) antibody inhibited the 1α,25(OH)2D3-induced increase of osteoclast numbers in bone, and increase of CTX-I, Ca, and FGF23 levels in serum. The pretreatment with anti-RANKL antibody also inhibited the 1α,25(OH)2D3-induced decrease in body weight. Consistent with observations in mice conditioned with anti-RANKL antibody, the high-dose administration of 1α,25(OH)2D3 to Ob-VDR-cKO mice failed to significantly increase bone osteoclast numbers, serum CTX-I, Ca, or FGF23 levels, and failed to reduce the body weight. Taken together, this study demonstrated that the proresorptive, hypercalcemic, and toxic actions of high-dose 1α,25(OH)2D3 are mediated by VDR in osteoblast-lineage cells.

Calcitonin Induces Bone Formation by Increasing Expression of Wnt10b in Osteoclasts in Ovariectomy-Induced Osteoporotic Rats.

Calcitonin is a small peptide hormone secreted from the parafollicular cells of the thyroid gland in response to an increase in serum calcium. The inhibition of osteoclastic resorption is the main mechanism by which calcitonin quickly decreases circulating calcium levels. Although calcitonin pharmacologically acts on osteoclasts to prevent bone resorption, the results of studies on genetically modified animals have shown that the physiological effect of calcitonin is in the inhibition of osteoblastic bone formation. Because the calcitonin receptor is only expressed in osteoclasts, the effect of calcitonin on osteoblasts maybe indirect and mediated via osteoclasts. Wnt ligands are involved in various aspects of skeletal biology, including bone remodeling and endochondral bone formation. Wnt10b has recently been recognized as a clastokine, and is potentially a therapeutic target for treating bone disorders. However, the extent to which Wnt signaling is involved in bone physiology and disease is not yet fully understood. We hypothesize that calcitonin indirectly increases osteoblastic bone formation by inducing Wnt10b expression in osteoclasts. Micro-CT analysis revealed reduced bone loss in calcitonin-treated ovariectomized rats. The serum of animals treated with calcitonin had decreased TRAP5b and CTX-1 but increased osteocalcin, P1NP, and Wnt10b. Immunohistochemistry staining showed that the level of Wnt10b in the femur was increased in calcitonin-treated groups as compared with control groups. Hematopoietic mononuclear cells were separated from rat femur and tibia bone marrow, and were induced into osteoclasts following treatment with M-CSF and RANKL. In these cells, immunoconfocal microscopy and Western blot analysis showed that calcitonin induced an increase in Wnt10b expression. In a culture of osteoblasts isolated from neonatal rat calvariae, the calcitonin-treated osteoclast supernatant showed an increase in mineralization, as indicated by ALP and alizarin red staining. Taken together, these results indicate that calcitonin induces bone formation by increasing the expression of Wnt10b in osteoclasts in ovariectomy-induced osteoporotic rats. The present study provides in-depth information about the effects of calcitonin on bone remodeling and will thus help in the development of future potential therapeutic strategies for postmenopausal osteoporosis.

The effect of calcium in water hardness on digoxin plasma levels in an experimental rat model.

BACKGROUNDDigoxin is a drug for ventricular rate control in atrial fibrillation (AF). The major challenge in digoxin therapy is to adjust the appropriate concentration range for this drug due to its narrow therapeutic index. Unique physiochemical properties of drinking water affect the pharmacological actions and delivery of drugs to the body whether they are administered orally, topically, or by injection. The aim of this study was to evaluate water hardness effect on digoxin therapy in an experimental rat model.METHODS48 rats weighing 200-220 g were randomly assigned to three groups that received drinking water with 50, 400, and 800 mg/l hardness degrees for 28 days. Then each group was assigned into two groups. One received digoxin 0.2 mg/kg a day orally for four days. The other group received normal saline (as control group). Continuous recording of electrocardiogram (ECG) was performed by PowerLab system (AD Instruments Company) before and day 4 of digoxin treatment. Then serum samples were collected and assessed for digoxin, sodium, potassium, calcium, magnesium, blood urea nitrogen (BUN), and creatinine levels.RESULTSWater hardness in the range of 50-800 mg/l had no effect on serum digoxin levels (P > 0.050), but consuming hard drinking water (400 and 800 mg/l) could increase serum calcium levels and then cause mortality (37.5% in both groups), following changes in ECG due to digoxin consumption.CONCLUSIONConsuming hard drinking water probably interferes with digoxin pharmacodynamics in the way of toxicity induction.

Serum Calcium Levels and Parkinson's Disease: A Mendelian Randomization Study.

BackgroundThough increasing epidemiological studies have evaluated the correlation between serum calcium contents and Parkinson’s disease (PD), the results are inconsistent. At present, whether there is a causal association between serum calcium content and PD remains undetermined.Objective and MethodsThis study was designed to explore the relationship between increased serum calcium contents and PD risk. In this present study, a Mendelian randomization trial was carried out using a large-scale serum calcium genome-wide association study (GWAS) dataset (N = 61,079, Europeans) and a large-scale PD GWAS dataset (N = 8,477, Europeans including 4,238 PD patients and 4,239 controls). Here, a total of four Mendelian randomization methods comprising weighted median, inverse-variance weighted meta-analysis (IVW), MR-Egger, and MR-PRESSO were used.ResultsOur data concluded that genetically higher serum calcium contents were not significantly related to PD.ConclusionIn conclusion, we provided genetic evidence that there was no direct causal relationship between serum calcium contents and PD. Hence, calcium supplementation may not result in reduced PD risk.

Joint replenishment of zinc and folic acid enhances the anti-depressive effect of paroxetine via increasing serum calcium and copper and decreasing serum arsenic

Insufficient zinc and folic acid levels are associated with depression and poor response to antidepressants. This study aimed to investigate the influences of combined zinc and folic acid replenishment on the anti-depressive effect of paroxetine. Male rats were randomly divided into five groups: control (C), model (M), paroxetine (MP), zinc + folic acid (MZnF), and zinc + folic acid + paroxetine (MZnFP) groups. Rats were exposed to mild unpredictable stress for 3 weeks as a depression model. The combinations of drug and supplements were applied via daily gavage for 4 weeks. The open field test was conducted to observe behavioral changes. A chemiluminescence method was used to detect folacin, and inductively coupled plasma mass spectrometry was used to detect serum elements. Supplementation of zinc and folic acid significantly improved behavior responses to paroxetine, including movement speed, total distance, and central zone frequency. In addition, higher calcium and copper levels and a lower arsenic level were found in the serum of the MZnFP group. Thus, supplementation of zinc and folacin can enhance the anti-depressive effect of paroxetine, and the mechanism is potentially related to the improved levels of calcium and copper and a reduced level of arsenic.

Early biochemical response to parathyroidectomy for primary hyperparathyroidism and its predictive value for recurrent hypercalcemia and recurrent primary hyperparathyroidism

BackgroundThe traditional definition of cure after parathyroidectomy (PTX) for primary hyperparathyroidism is normocalcemia. Our hypothesis was that early postoperative levels of serum calcium and parathyroid hormone after PTX would have predictive value for later recurrence. MethodsWe performed a retrospective study of 1,146 patients with primary hyperparathyroidism who underwent PTX and had long-term biochemical follow-up. The first postoperative serum level of calcium and parathyroid hormone values were used to categorize patients into the following four early biochemical response groups: (1) complete response (normal calcium and normal parathyroid hormone), (2) partial response with hyperparathormonemia (normal calcium and increased parathyroid hormone), (3) partial response with hypercalcemia (increased calcium and normal parathyroid hormone), and (4) non-response (increases in both calcium and parathyroid hormone). Incidences of recurrent hypercalcemia and recurrent primary hyperparathyroidism >6 months after operation were then analyzed. ResultsThe overall rate of any elevated serum levels of calcium and any increase in serum levels of parathyroid hormone during >6-month follow-up was 9.8% (112 of 1146), with 6.6% (57 of 861) for group 1, 27% (35 of 129) for group 2, and 16% (20 of 127) for group 3 (P < .02). Partial biochemical responses with either increased serum calcium or increased parathyroid hormone levels were the strongest predictors of any episode of increased serum levels of calcium after 6 months and was associated with 2.7× to 4.3× the risk of recurrent primary hyperparathyroidism, respectively. ConclusionThis study demonstrates the importance of measuring parathyroid hormone in the early postoperative period to better predict later recurrent primary hyperparathyroidism.

Hypercalcaemia in a dog with lymphoma without increases in parathyroid hormone, parathyroid hormone-related protein and vitamin D metabolites concentrations

Lymphoma is one of the most common causes of hypercalcaemia in dogs. Typically, the hypercalcaemic state is driven by ectopic production of parathyroid hormone-related protein by the malignant lymphoma cells....

Early effects of androgen deprivation on bone and mineral homeostasis in adult men: a prospective cohort study.

Long-term androgen deprivation therapy (ADT) negatively influences bone. The short-term effects on bone and mineral homeostasis are less known. Therefore, we aimed to investigate the early effects of ADT on calcium/phosphate homeostasis and bone turnover. Prospective cohort study. Eugonadal adult, male sex offenders, who were referred for ADT to the endocrine outpatient clinic, received cyproterone acetate. Changes in blood markers of calcium/phosphate homeostasis and bone turnover between baseline and first follow-up visit were studied. Of 26 screened patients, 17 were included. The median age was 44 (range 20-75) years. The median time interval between baseline and first follow-up was 13 (6-27) weeks. Compared to baseline, an 81% decrease was observed for median total testosterone (to 3.4 nmol/L (0.4-12.2); P < 0.0001) and free testosterone (to 0.06 nmol/L (0.01-0.18); P < 0.0001). Median total estradiol decreased by 71% (to 17.6 pmol/L (4.7-35.6); P < 0.0001). Increased serum calcium (P < 0.0001) and phosphate (P = 0.0016) was observed, paralleled by decreased PTH (P = 0.0156) and 1,25-dihydroxyvitamin D3 (P = 0.0134). The stable calcium isotope ratio (δ44/42Ca) decreased (P = 0.0458), indicating net calcium loss from bone. Bone-specific alkaline phosphatase and osteocalcin decreased (P < 0.0001 and P = 0.0056, respectively), periostin tended to decrease (P = 0.0500), whereas sclerostin increased (P < 0.0001), indicating suppressed bone formation. Serum bone resorption markers (TRAP, CTX) were unaltered. In adult men, calcium release from the skeleton occurs early following sex steroid deprivation, reflecting early bone resorption. The increase of sclerostin and reduction of bone formation markers, without changes in resorption markers, suggests a dominant negative effect on bone formation in the acute phase.

Bioavailability of Calcium from Chia (Salvia hispanica L.) in Ovariectomized Rats Fed a High Fat Diet

Background Skeletal abnormalities such as bone loss occur when there is an imbalance in bone matrix synthesis and bone resorption. This imbalance is also caused by hormonal changes and inflammation. Chia (Salvia hispanica L.) has a high nutritional value and is an excellent source of calcium. Evaluate the bioavailability of calcium from chia, and its effect on bone metabolism when consumed as part of a standard or high fat diet (HFD) in ovariectomized rats. Methods The study was conducted with 80 female Wistar rats that received standard diet or HFD. 40 female mice were ovariectomized (OVX) and 40 were sham-operated (SHAM). After recovery from surgery the animals received chia as a source of 20% of the calcium recommendation, calcium bioavailability was measured using the calcium balance technique. Bone strength and bone morphometry were evaluated by weight, length and microtomography measurements. Results HFD increased serum calcium and decreased calcium retention. The addition of chia to HFD did not alter bone morphology. Ovariectomy led to lower percentage of bone volume, smaller trabecular thickness, higher trabecular separation and higher porosity, when ovariectomy was associated with HFD, the final weight, waist circumference, body mass index and adiposity were increased. Conclusions Chia maintained bone health when offered as a source of 20% calcium, in a diet that met 100% of the mineral recommendation, regardless of the type of diet, in animals non-ovariectomized adults.

Women who develop ovarian cancer show an increase in serum calcium and a decrease in serum albumin. A longitudinal study in the Janus Serum Bank Cohort

BackgroundOvarian cancer is associated with high serum calcium and low serum albumin in clinical and epidemiologic studies. Whether high calcium and low albumin predispose to ovarian cancer or reflect existing cancer is unclear. ObjectiveTest the hypothesis that serum calcium increases and serum albumin decreases in women who develop ovarian cancer. MethodsTwo hundred and four women donated sera to the Janus Serum Bank in Norway pre- and post-diagnosis of ovarian cancer, donations separated by approximately 14 years. We measured calcium and albumin in these sera and calculated the albumin-corrected calcium. Sera were adjusted for patient age and storage time. ResultsPost-diagnosis, mean age- and storage-adjusted calcium increased, from 2.53 to 2.68 mmol/L (p < .001). Mean age- and storage-adjusted, albumin-corrected calcium increased from 2.3 to 2.7 mmol/L (p < .001). Conversely, mean age- and storage-adjusted albumin decreased, from a mean of 51.3 to 40.9 g/L (p < .001). Significant changes were observed in women with early stage and metastatic cancer. ConclusionsThese data support the hypothesis that calcium and albumin are serum biomarkers of extant ovarian cancer. Longitudinal changes in calcium and albumin may be useful in ovarian cancer early detection.

Intradialytic Calcium Kinetics and Cardiovascular Disease in Chronic Hemodialysis Patients

Background/Objective: Calcium loading has been associated with cardiovascular risk in hemodialysis (HD) patients. However, it remains to be elucidated whether alterations of intradialytic calcium buffering add to the increased cardiovascular disease burden in this high-risk population. Methods: Intradialytic calcium kinetics was evaluated in a cross-sectional observational study by measuring dialysate-sided ionized calcium mass balance (iCa_MB), calcium buffer capacity, and change in serum calcium levels in 40 chronic HD patients during a routine HD session. A dialysate calcium of 3.5 mEq/L was used to adequately challenge calcium buffer mechanisms. Aortic pulse wave velocity and serum osteocalcin levels were measured prior to the HD session. Presence of cardiovascular disease and diabetes was assessed. Results: The mean dialysate-sided iCa_MB, extracellular fluid ionized calcium mass gain, and buffered ionized calcium mass were 469 (±154), 111 (±49), and 358 (±145) mg/HD, respectively. The mean ionized serum calcium increase (∆iCa) was 0.42 (±0.14) mEq/L per HD. The mean intradialytic calcium buffer capacity was 73 (±18)%. Multivariate regression analysis revealed significant independent association of (1) iCa_MB with the dialysate-to-blood calcium gradient at HD start and (2) intradialytic calcium buffer capacity with undercarboxylated osteocalcin. The presence of coronary heart disease was associated with higher ∆iCa but not iCa_MB in the multivariate model. Conclusions: In line with our proof-of-concept study, we provide clinical evidence for a rapidly accessible and exchangeable calcium pool involved in intradialytic calcium regulation and for the role of osteocalcin as a potential biomarker. Our findings argue for evaluating the prognostic potential of intradialytic calcium kinetics in prospective clinical trials.

Impact of Serum Calcium Levels on Alzheimer's Disease: A Mendelian Randomization Study.

Altered calcium homeostasis is hypothesized to underlie Alzheimer's disease (AD). However, it remains unclear whether serum calcium levels are genetically associated with AD risk. To develop effective therapies, we should establish the causal link between serum calcium levels and AD. Here, we performed a Mendelian randomization study to investigate the causal association of increased serum calcium levels with AD risk using the genetic variants from a large-scale serum calcium genome-wide association study (GWAS) dataset (61,079 individuals of European descent) and a large-scale AD GWAS dataset (54,162 individuals including 17,008 AD cases and 37,154 controls of European descent). Here, we selected the inverse-variance weighted (IVW) as the main analysis method. Meanwhile, we selected other three sensitivity analysis methods to examine the robustness of the IVW estimate. IVW analysis showed that the increased serum calcium level (per 1 standard deviation (SD) increase 0.5 mg/dL) was significantly associated with a reduced AD risk (OR = 0.57, 95% CI 0.35-0.95, p = 0.031). Meanwhile, all the estimates from other sensitivity analysis methods were consistent with the IVW estimate in terms of direction and magnitude. In summary, we provided evidence that increased serum calcium levels could reduce the risk of AD. Meanwhile, randomized controlled study should be conducted to clarify whether diet calcium intake or calcium supplement, or both could reduce the risk of AD.

The clinical expression and impact of multiple endocrine neoplasia 1 during pregnancy.

Multiple endocrine neoplasia type 1 (MEN 1) is characterized by multisystem neoplasia including primary hyperparathyroidism and pituitary adenoma. Despite the adolescent onset of endocrinopathies, information regarding the impact of maternal MEN 1 on pregnancy is limited to case reports. To explore pregnancy outcomes in MEN 1 positive women. Retrospective case series of maternofoetal outcomes MEN 1 positive mothers managed at the Royal Hobart Hospital between 1967 and 2018. Data were retrieved from medical records and Australian averages calculated based on the Australian Institute of Health and Welfare data. Twenty-six women with MEN 1 were identified accounting for 96 pregnancies and 76 live born infants. Hyperparathyroidism was evident in 16 pregnancies. A significant increase in serum calcium in the second trimester (β=0.14, P<.001) occurred that was not mediated by parathyroid hormone. Hypercalcaemia was mild-moderate with parathyroidectomy or medical management required in one and four pregnancies, respectively. Compared to the Australian average, women with MEN 1 were more likely to develop gestational diabetes (56% vs 8.9%, P=.001), hypertensive disorders (25.9% vs 7.6, P=.018), have shorter gestations (38.1 vs 38.7weeks, P=.015) and have low birthweight infants (30.1% vs 6.5%, P=.001). However, emergency caesarean deliveries (63.2% vs 52.3%) and miscarriage rate (20.8% vs 20%) were not significantly different. Maternal MEN 1 is associated with an increased risk of gestational diabetes, hypertensive disorders and low neonatal birthweight, but not with an increased miscarriage rate. Whilst hypercalcaemia worsens during the second trimester, most pregnancies progressed without overt complications or requirement for intervention.

P1413EFFECT OF PULSE ORAL VERSUS INTRAMUSCULAR VITAMIN D REPLACEMENT IN HEMODIALYSIS PATIENTS WITH VITAMIN D DEFECIENCY

Abstract Background and Aims Low 25-hydroxyvitamin D (25(OH)D) level is common in patients with chronic kidney disease and hemodialysis (HD) patients . It has been associated with high bone turnover, secondary hyperparathyroidism (SHPT), and decreased bone mineral density (BMD). We aimed to investigate the efficacy of equivalent doses of pulse oral cholecalciferol (25,000 IU weekly for 12 weeks) versus single intramuscular cholecalciferol (300,000 IU) in correcting serum 25 (OH) D levels in HD patients. Method Prospective randomized open label Clinical trial. 40 prevalent HD patients with vitamin D deficiency were enrolled. Serum 25 hydroxy-vitamin D (25 (OH) D) level &amp;lt; 20 ng/m and Serum parathyroid hormone level ( iPTH) &amp;gt;100 pg/ml. Exclusion Criteria were serum calcium &amp;gt; 10 .5mg/dl, Calcium phosphorus product ≥ 55, tertiary hyperparathyroidism and Parathyroidectomy among others. Patients were randomized equally into two groups. 36 patients were compliant and completed the study. Group I :17 HD patients received oral cholecalciferol 25000 IU weekly of (Vidrop® 2800 IU/ml ) for 12 weeks. Group II: 19 HD patients received a single intramuscular injection (IM) of cholecalciferol 300,000 IU (Devarol® 200000 IU/ ampoule). Vitamin D supplements were stopped if serum calcium &amp;gt;10.5mg/dl or 25(OH) D level &amp;gt; 100 ng /ml (toxic level) during study. Serum calcium (albumin-adjusted), phosphorus, 25(OH) D by ELISA, Alkaline phosphatase (ALP) and intact parathyroid hormone (iPTH) were monitored at baseline, 6 and 12 weeks of intervention. Both groups were maintained on their regular medications used to control mineral bone disorder as: alfacalcidol, sevelamer or a calcium-based chelator. Results Significant increase in serum 25(OH) D level in group II patients who received single dose IM Cholecalciferol after 12 w. Means of 25 (OH)D levels basal and 12 w of study were (10.54±5.14 and 13.45 ±5.72) ng/ml respectively. There was a significant increase in the mean of serum calcium basal and at 12 w (8.19±0.69 and 8.42 ±0.54) mg/dl respectively. No significant reduction in the iPTH level or any significant change in the serum phosphorus level was noticed. compared to group I with oral vitamin D, there was an insignificant change in the mean of serum 25(OH) D basal and at 12 w were (11.91±6.13 and 9.30±5.29) ng/ml respectively, associated with insignificant increase in serum calcium and an insignificant change in either the level of phosphorus or iPTH level. Conclusion Cholecalciferol 300,000 IU IM single dose showed better response on serum 25 (OH) D and calcium levels as a treatment of hemodialysis patients with Vitamin D deficiency compared to weekly oral dose for 3 months.

Increased Serum Calcium Level Promotes the Risk of Lymph Node Metastasis in Endometrial Cancer.

PurposeThe early predictive values of diagnostic markers for lymph node metastasis (LNM) in endometrial cancer (EC) are still unclear at present. The purpose of this study is to explore the relationship between serum calcium and LNM in EC.MethodsWe identified all patients with EC who underwent surgery between January 2012 and December 2016. Patient characteristics and various preoperative clinicopathologic data were obtained from medical records and were reviewed retrospectively. These patients were divided into two groups according to the pathology of their lymph node. Logistic regression models analyzed the relationship between the ionized calcium and LNM of EC patients, while adjusting for the potential confounders.ResultsA total of 448 patients were assessed. Univariate analysis showed that ionized calcium, CA125 level, tumor grade, peritoneal cytology, FIGO stage, histological type, LVSI, and myometrial invasion were positively correlated with LNM (all P<0.05). The risk of LNM increased with the promotion of serum ionized calcium (P for trend <0.01). Ionized calcium level was significant before and after the adjustment of cofounders (unadjusted: OR=11.9, 95% CI: 4.8–29.6, P< 0.01; model I: OR=11.3, 95% CI: 4.5–28.8, P< 0.01; model II: OR=5.2, 95% CI: 1.6–17.2, P< 0.05). Additionally, the risk of ionized calcium was especially evident in patients whose age was older than 60, BMI<28 kg/m2, grade 3, negative peritoneal cytology and endometrioid endometrial adenocarcinoma.ConclusionIonized calcium level was highly associated with LNM in EC and acted as a potential biomarker in predicting the risk of LNM in EC.

Optimization of PTH/PTHrP Hybrid Peptides to Derive a Long-Acting PTH Analog (LA-PTH).

ABSTRACTProlonged signaling at the parathyroid hormone receptor 1 (PTHR1) correlates with the capacity of a ligand to bind to a G protein‐independent receptor conformation (R0). As long‐acting PTH (LA‐PTH) ligands hold interest as potential treatments for hypoparathyroidism (HP), we explored the structural basis in the ligand for stable R0 binding and prolonged cAMP signaling. A series of PTH/PTHrP hybrid analogs were synthesized and tested for actions in vitro and in vivo. Of the series, [Ala1,3,12,Gln10,Arg11,Trp14]‐PTH(1‐14)/PTHrP(15–36) (M‐PTH/PTHrP) bound with high affinity to R0, induced prolonged cAMP responses in UMR106 rat osteoblast‐derived cells, and induced the most prolonged increases in serum calcium (sCa) in normal rats. Daily s.c. injection of M‐PTH/PTHrP into thyroparathyroidectomized (TPTX) rats, a model of HP, normalized sCa without raising urine Ca. In contrast, oral alfacalcidol, a widely used treatment for HP, normalized sCa, but induced frank hypercalciuria. M‐PTH/PTHrP exhibited low solubility in aqueous solutions of neutral pH; however, replacement of Leu18, Phe22, and His26 with the less hydrophobic residues, Ala, Ala, and Lys, at those respective positions markedly improved solubility while maintaining bioactivity. Indeed, we recently showed that the resultant analog [Ala18,22,Lys26]‐M‐PTH/PTHrP or LA‐PTH, effectively normalizes sCa in TPTX rats and mediates prolonged actions in monkeys. These studies provide useful information for optimizing PTH and PTHrP ligand analogs for therapeutic development. © 2020 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Continuous rhPTH (1-34) treatment in chronic hypoparathyroidism.

SummaryStandard treatment of hypoparathyroidism consists of supplementation of calcium and vitamin D analogues, which does not fully restore calcium homeostasis. In some patients, hypoparathyroidism is refractory to standard treatment with persistent low serum calcium levels and associated clinical complications. Here, we report on three patients (58-year-old male, 52-year-old female, and 48-year-old female) suffering from severe treatment-refractory postsurgical hypoparathyroidism. Two patients had persistent hypocalcemia despite oral treatment with up to 4 µg calcitriol and up to 4 g calcium per day necessitating additional i.v. administration of calcium gluconate 2–3 times per week, whereas the third patient presented with high frequencies of hypocalcemic and treatment-associated hypercalcemic episodes. S.c. administration of rhPTH (1–34) twice daily (40 µg/day) or rhPTH (1–84) (100 µg/day) only temporarily increased serum calcium levels but did not lead to long-term stabilization. In all three cases, treatment with rhPTH (1–34) as continuous s.c. infusion via insulin pump was initiated. Normalization of serum calcium and serum phosphate levels was observed within 1 week at daily 1–34 parathyroid hormone doses of 15 µg to 29.4 µg. Oral vitamin D and calcium treatment could be stopped or reduced and regular i.v. calcium administration was no more necessary. Ongoing efficacy of this treatment has been documented for up to 7 years so far. Therefore, we conclude that hypoparathyroidism that is refractory to both conventional treatment and s.c. parathyroid hormone (single or twice daily) may be successfully treated with continuous parathyroid hormone administration via insulin pump.Learning points:Standard treatment of hypoparathyroidism still consists of administration of calcium and active vitamin D.Very few patients with hypoparathyroidism also do not respond sufficiently to standard treatment or administration of s.c. parathyroid hormone once or twice daily.In those cases, continuous s.c. administration of parathyroid hormone via insulin pump may represent a successful treatment alternative.

Bone metabolism in hemiplegic patients

Bone metabolism has been assessed in 36 hemiplegic patients (18-77 years), 26 with CVA and 10 with head injuries. The results show an increase of serum calcium and phosphorous levels in the first month as well as hydroxyprolinuria. The radiological examination showed signs of demineralisation, as well as single photon absorptiometry of both arms. Bone scan by 99Te demonstrated a hypercaptation in both paralysed limbs. From the 36 patients, 17 had a 47Ca kinetic study which showed an average of normal values as far as bone accretion (Vo+) is concerned. However, the two youngest patients (18 and 32 years) had a high value of this parameter. The urinary calcium excretion (Vu) and the fecal calcium excretion (Vf) was also increased in the 17 patients. The bone resorption measured by Vo- was also high at the beginning of the study and significantly decreased 12 months later. Our observations show that neurologic osteoporosis of the hemiplegic patient is related to an unbalance between the synthesis and the degradation of a bone whose metabolism is active. Related to the determination of the intramedullary pressure and intraosseous phlebography, it seems that this resorption is due to a venous stasis. This circulatory modification regime can influence cell differentiation and probably be responsible in a way for this osteoporosis.

SAT-341 Hyperparathyroid Crisis Precipitated by Rapid Correction of Symptomatic Hypercalcemia in an Occult Ectopic Parathyroid Adenoma

Background: Parathyroid adenomas (PA) are typically benign, slow-growing tumors causing gradual increase in parathyroid hormone (PTH) and serum calcium (s.Ca) levels. Hyperparathyroid crisis is a rare and potentially fatal syndrome, which occurs due to rapid elevation of PTH and s.Ca levels (s.Ca >15mg/dL). This can potentiate severe metabolic derangements, manifesting as altered mental status (AMS), renal insufficiency and cardiac arrhythmias. We present a case of hyperparathyroid crisis in the setting of an occult ectopic parathyroid adenoma.Case: 75 year old female with a medical history of osteoporosis, hypertension and Parkinson’s disease, presented to our hospital with AMS and one week history of diarrhea. She was recently hospitalized for pneumonia and treated with antibiotics. Biochemical analysis revealed corrected s.Ca 15.4mg/dL (8.2- 9.6mg/dL; 7 days prior s.Ca was 9.7mg/dL), renal insufficiency (Cr 2.26mg/dL; baseline 1.2) with normal serum phosphorus, magnesium, 25-hydroxyvitamin D and alkaline phosphatase. PTH was found to be elevated at 75pg/mL (15-65pg/mL). She was treated with aggressive intravenous hydration and calcitonin 200mg BID for 3 days. Her s.Ca appropriately trended down. However, her PTH level continued to rise: 319pg/mL 12 hours later, 591pg/mL on day 2 and peaked to 1,242pg/mL on day 3. CT angiography neck showed an incidental finding of a heterogeneous, possibly necrotic, soft tissue nodule in the left paraesophageal region. Additional work-up with technetium 99 Sestamibi scan revealed persistent activity in the upper tracheoesophageal groove consistent with an ectopic PA. She underwent parathyroid exploration with excision of an enlarged ectopic left superior parathyroid adenoma, confirmed on histopathological analysis. The remaining parathyroid glands were normal. PTH declined to 34pg/mL postoperatively. Her mental status improved significantly returning to baseline within a few days with normal PTH and s.Ca levels.Discussion: Secretion of PTH is mediated by s.Ca via the calcium sensing receptors (CaSR). Studies have shown that patients with PA have decreased expression of the CaSR leading to an autonomous rise in PTH secretion and a higher PTH-calcium set point. In our case, the patient initially presented with a mildly elevated PTH level and symptomatic hypercalcemia. The rapid correction of s.Ca levels precipitated a remarkable rise in PTH levels. We postulate that this was caused by a possible upregulation mechanism in calcium sensing by adenomatous parathyroid tissue that is responsive to acute lowering of s.Ca levels, triggering a hyperparathyroid crisis.Reference: (1) Corbetta S., et al. Calcium-sensing receptor expression and signaling in human parathyroid adenomas and primary hyperplasia. Clinical Endocrinology. 2000; 52(3):339-48.