Increased Serum Calcium Levels Research Articles

Comparative Evaluation of Bioavailability, Efficacy and Safety of MICROCORE NESC® with Calcium Carbonate and Calcium Citrate Malate in Osteopenic and Osteoporotic Patients: A Randomized Clinical Trial.

Osteoporosis is a skeletal disease characterized by loss of bone mass, reduced bone strength and increased bone fragility predisposing to fractures. This study was planned to evaluate the efficacy, safety and relative bioavailability of Microcore NESC® (Natural Egg Shell Calcium) in osteopenia and osteoporotic patients. This was a randomized, open label, parallel group interventional clinical trial which included 60 study participants with osteopenia and osteoporosis who were randomized into three groups (20 each). Group 1-Microcore NESC®, Group 2-Shelcal and Group 3-CCM with 12weeks treatment period. The participants were evaluated for relative oral bioavailability, bone mineral density (BMD), serum osteocalcin, change in VAS pain scale and quality of life-Questionnaires. There was significant improvement in the BMD T scores-post-treatment with MICROCORE NESC® and Shelcal. Higher percentage of improvement in calcium absorption as depicted by an increase in serum calcium levels (10.23%) in the MICROCORE NESC®-treated group when compared to Shelcal (7.7%) and CCM (7.2%). The relative bioavailability of MICROCORE NESC® with respect to Shelcal was 93%. MICROCORE NESC®, has shown a better oral relative bio availability of calcium (93%), better improvement of BMD T score compared to Shelcal and CCM. The general health status has improved to very good/excellent in 83% of patients in MICROCORE NESC®-treated group. Thus, MICROCORE NESC® can be considered a better and safe calcium supplement, as there are very few side effects observed without any clinically significant abnormalities in lab parameters.

Association between thymic hyperplasia and serum calcium level in Graves’ disease

BackgroundGraves' disease increases bone resorption in hyperthyroidism, leading to elevated serum calcium levels and a negative bone balance. Thymic hyperplasia is observed in some Graves' disease patients. What's more, there have been a few reports of increased serum calcium and severe osteoporosis induced by Graves’ disease with thymic hyperplasia. It remains unclear whether Graves’ disease with thymic hyperplasia is associated with higher serum calcium levels. Our study aimed to investigate the possibility of elevated serum calcium levels and aggravated bone mobilization in Graves’ disease patients with thymic hyperplasia.MethodsNewly diagnosed and untreated patients with Graves' disease (n = 96) were enrolled. They were divided into two groups based on the incidental detection of thymic hyperplasia during imaging. Albumin, alkaline phosphatase, calcium, free triiodothyronine, free thyroxine, thyroid-stimulating hormone, and thyrotrophin receptor antibody (TRAb) were measured, and a computerized tomography of the chest was obtained.ResultsPatients with Graves’ disease who had thymic hyperplasia were notably younger (P=0.018) and exhibited higher serum calcium levels (P=0.001) compared to those with Graves’ disease without thymic hyperplasia. In the multiple regression analysis, thymic hyperplasia, TRAb, and female gender were significant variables associated with elevated serum calcium levels in patients with Graves' disease, collectively accounting for 31.7% of the variation in serum calcium.ConclusionsGraves’ disease patients with thymic hyperplasia showed higher serum calcium levels. thymic hyperplasia, TRAb, and female gender were found to be correlated with increased serum calcium levels in Graves’ disease, suggesting a potential association between thymic hyperplasia and bone mobilization in Graves’ disease.

Depressive Disorder in Primary Hyperparathyroidism and Effects of Surgery in Elderly Patients: Case Series

Background: Patients with primary hyperparathyroidism (PHPT) often present nonspecific symptoms such as major depressive disorder and psychosis. Calcium plays a role in the pathogenesis of psychiatric symptoms by determining changes in monoamine metabolism in the central nervous system, thereby modifying neurotransmission and resulting in mood and cognitive alterations. Case series: This report presents a case series of 3 patients; 70-year-old, 78 year- old and 94 year-old women with PHPT and severe depression symptoms and its response to parathyroidectomy. The patients were a poor historian. Results of preoperative laboratory tests showed an increased serum calcium level (11.15mg/dL, 10.9 mg/dL and 11.4 mg/dL- reference range 8.4-10.2 mg/dL). A repeat serum calcium test confirmed hypercalcemia with concurrent elevated intact parathyroid hormone level. Two patients were undergone at parathyroidectomy. A 94 year-old patient refuse surgical approach and was efficacy treated with a single dose of zoledronic acid. Therefore, the patients underwent parathyroidectomy two months after procedure had a clinical improvement on depressive symptoms. There was any recurrent laryngeal nerve injury or recurrent PHTP. Conclusion: The presence of a long-standing depressive disorder unresponsive to medical therapy may suggest an organic disorder such as chronic hypercalcemia which may be secondary to PHPT. Surgical intervention in these selected cases can assist medical therapy in the improvement of depressive symptoms.

Relationship between Vitamin D and parathyroid hormone levels along with simvastatin effect on serum calcium levels in postmenopausal women with osteoarthritis.

Objective: To investigate the relationships between vitamin D, PTH, and Simvastatin and their effects on serum calcium levels in postmenopausal women with OA. Study Design: Cross Sectional study. Setting: Nowshera Medical College, Nowshera. Period: Six Month January to June, 2022. Material & Methods: Ethical approval was obtained, and 24 postmenopausal women with osteoarthritis (OA) were recruited. Morning blood samples were collected, processed, and stored for analysis of 25(OH) D, calcium, and PTH levels. Plasma samples were acquired 3 hours after Simvastatin administration and data analysis was performed using SPSS 17.0, with significance set at p < 0.05. Results: In this study, 24 postmenopausal women with osteoarthritis exhibited an average age of 53.4 years, with vitamin D levels at 18.7 ng/ml and consistent serum calcium levels at 9.1 mg/dl. Parathyroid hormone (PTH) levels varied widely, averaging 52.8 pg/ml. Analysis revealed that vitamin D and PTH increased serum calcium level while the combination of vitamin D with Simvastatin and PTH with Simvastatin exhibited a nuanced relationship, resulting in a moderated decrease in blood calcium levels. Conclusion: This study sheds light on the intricate interplay between vitamin D, PTH, and Simvastatin in postmenopausal women with OA, offering valuable insights for tailored treatment approaches in OA management.

The incidence of chronic diarrhea decreases with increasing serum calcium levels: a cross-sectional study based on NHANES 2005–2010

BackgroundChronic diarrhea is difficult to prevent and treat due to its complex etiology and pathogenesis. It places a huge burden on patients and public healthcare. It is known that the regulation of body homeostasis relies heavily on calcium. However, in the general population, the relationship between calcium and chronic diarrhea remains uncertain.MethodsWe assessed the association between serum calcium and diarrhea using data from the 2005–2010 National Health and Nutrition Examination Survey (NHANES). Serum calcium level was measured from collected blood samples. Diarrhea was assessed using the Bristol Stool Scale (BSFS) (types 1–7). The stability of the results was assessed using logistic regression and sensitivity analysis. The dose–response association between serum calcium and the risk of diarrhea was analyzed using a restricted cubic spline plot.ResultsThis study included 12,342 participants. In each of the five models, an increased calcium level was negatively associated with the incidence of diarrhea (OR[95%CI]:0.26 [0.13–0.53], 0.28 [0.14–0.58], 0.4 [0.19–0.82], 0.27 [0.11–0.64] and 0.24 [0.10–0.59], respectively). When serum calcium was analyzed as a categorical variable, a significant association between serum calcium and diarrhea prevalence was found. The restricted cubic spline plot showed a linear relationship between serum calcium and diarrhea. Sensitivity analysis confirmed that the results were stable.ConclusionThe results of our cross-sectional study suggest that a higher level of serum calcium may reduce the incidence of diarrhea. In the future, this finding should be further validated in a randomized controlled trial.

Evaluation of Effect of Rosmarinus officinalis L. on Ethylene Glycol Induced Kidney Stone in Rats

The present study evaluation of effect of Rosmarinus officinalis L. on ethylene glycol induced kidney stone in rats showed that the ethanolic extract of Rosmarinus officinalis possess the diuretic activity and effective in the treatment of kidney stone. The activity was evaluated against ethylene glycol (0.75%) induced kidney stone in albino rats. Animals were divided into five groups, containing six animals in each. Group I serve as normal control and received regular rat food and drinking water ad libitum. Ethylene glycol (0.75%) in drinking water was feed to Groups II to V for induction of renal calculi for 28 days. Group III received standard anti-urolithiasis drug, cystone (750mg/kg body weight) from 15th to till 35th day. Group IV and V received ethanolic extract of Rosmarinus officinalis at dose of 100mg/kg and 200mg/kg respectively from 15th to till 35th day.
 The serum creatinine level, serum urea level, urine calcium level, protein level in urine, serum uric acid was increased and serum calcium level, protein level in serum was decreased in all experimental groups except normal control group after ethylene glycol administration till day 14.
 The animals treated on the day 14th with standard drug (Cystone 750mg/kg) and Rosmarinus officinalis extract (100mg/kg and 200mg/kg), were observed significant decreased serum creatinine level, serum urea level, urine calcium level, protein level in urine and serum uric acid and increased serum calcium level, protein level in serum compared to normal control group on the day 28th and 35th.
 This indicates that the ethanolic extract of Rosmarinus officinalis (200mg/kg) have protective role against kidney stone.
 Keywords: Kidney Stone, Ethanolic extract, Rosmarinus officinalis, Ethylene glycol, uric acid, creatinine.

Increased circulating interleukin-23 level in patients with sarcoidosis

BackgroundSarcoidosis is a Th1-mediated chronic inflammatory disease characterized by non-caseating granulomas. Its pathogenesis is not yet clear, but the possible role of various proinflammatory cytokines is being discussed. AimThis study aims to determine serum cytokine (IL-6, IL-12, IL-17, and IL-23) levels in patients with sarcoidosis, and to determine a possible correlation with clinical and laboratory findings of the disease. Material and methodForty-four biopsy-proven sarcoidosis patients followed up at a single centre and 41 healthy volunteers were included in the study. Demographic, clinical, laboratory, and radiological data of all patients were recorded. Serum samples from the patients and the control group were taken and IL-6, IL-12, IL-17, IL-23 were measured by ELISA method. ResultsOf the 44 sarcoidosis patients, 13(29.5%) were male and 31(70.5%) were female. Average patient age was 47.4 years, mean disease duration was 3.2 years. Twenty-one (47.7%) patients had erythema nodosum, three (6.8%) had uveitis, 40(90.9%) had arthralgia, 23(52.3%) had ankle arthritis, 15(34.1%) had enthesitis. Laboratory evaluation showed increased serum ACE levels in 24(54.5%) patients, increased serum calcium levels in 11 (25%) patients, increased serum D3 levels in 5(11.4%) patients, increased ESR and CRP levels in 22(50%) and 23(52.3%) patients, respectively. Compared with the control group higher serum IL-23 levels were found in the patients with sarcoidosis (p=.01). Serum IL-23 was associated with ankle arthritis (p=.02). Serum IL-6, IL-12, and IL-17 levels were similar in the sarcoidosis patients and the control group (p=.128, p=.212, p=.521 respectively). ConclusionIn our study, we found increased serum IL-23 in patients with sarcoidosis, while serum IL-6, IL-12, and IL-17 were detected as normal. Although our results are somewhat contradictory to other studies in the literature, the question should still be whether sarcoidosis is a Th1/Th17 disease. Multicentre studies are needed in this regard.

Burden of ocular abnormalities in patients with beta thalassaemia: a cross-sectional study

IntroductionIn Pakistan, the reported carrier rate of thalassaemia is estimated to be 5%–8% with 5000 new patients diagnosed every year. Several known systemic complications of beta thalassaemia major have been...

Methane Reduction Potential of Hydroponic Fodders and Combination of Hydroponic Fodder Bajra with Anionic Salts in Increasing Serum Calcium Level of Transition Cows

Background: The study reported in this research is to assess the methane reduction potential of hydroponic fodders and its novel combination with anionic salts on the serum calcium level in transition cows, the period cows are prone to metabolic disorders. Methods: A growth trial of hydroponic fodders to assess the biomass yield and an in vitro gas production study was conducted to assess the methane production on inclusion of different hydroponic fodders with that of conventionally cultivated fodders along with paddy straw and concentrate feed. A feeding trial was also conducted in 16 transition cows (farm and field conditions) to assess the serum calcium level through feeding anionic salts viz., calcium sulphide and magnesium chloride along with hydroponic fodder bajra. Result: Significantly (P less than 0.05) lowest methane production was observed in paddy straw, hydroponic fodder bajra, concentrate feed group compared to other treatment groups. Anionic salts supplementation for three weeks prior to calving resulted in significant (P less than 0.05) increase in the serum calcium levels. In post supplementation, average increase in serum calcium level is 0.93 mg/dl, an increase by 10.80 per cent. Further, feeding cost of anionic salts (Calcium sulphide and magnesium chloride) for three weeks (21 days) is only INR 55.65/-.

Association of the serum calcium level with metabolic syndrome and its components among adults in Taiwan.

An increasing amount of literature indicates that the serum calcium level may be related to metabolic syndrome (MetS) and obesity. This study aimed to examine the relationship between the serum calcium level and MetS in adults in Taiwan. We conducted a crosssectional study and enrolled 1,580 participants (54.4% women; mean age, 33.28 ± 12.21 years) who underwent health examinations in northern Taiwan between 2012 and 2016. Logistic regression was performed to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) for the risk of MetS and its components in groups of patients in the tertiles of the serum calcium level. In total, 167 participants (10.6%) had MetS. The odds of high systolic blood pressure (BP), blood glucose, and triglyceride (TG) levels significantly increased as the serum calcium level increased. Compared with the participants in the lowest tertile of the serum calcium level (tertile 1), those in the second tertile (OR = 1.47, 95% CI: 0.97-2.23) and third tertile (OR = 1.63, 95% CI: 1.06-2.53) had a significantly higher risk of MetS. Further analyses revealed a significant association between MetS and an increased serum calcium level in those in the overweight and obese groups. However, there was no association between the serum calcium levels and MetS in those in the normal weight group. This study demonstrated that a higher serum calcium level is associated with an increased risk of MetS and its components in adults with overweight and obesity.

Short-Term Effects of a Therapeutic Diet on Biochemical Parameters in Hemodialysis Patients: A Randomized Crossover Trial

Although unhealthy diets exacerbate nutritional and metabolic derangements in patients with end-stage kidney disease (ESKD), how therapeutic diets that possess a variety of different dietary strategies acutely modify diverse biochemical parameters related to cardiovascular disease remains underexplored. Thirty-three adults with end-stage kidney disease undergoing thrice-weekly hemodialysis participated in a randomized crossover trial comparing a therapeutic diet with their usual diets for 7days, separated by a 4-week washout period. The therapeutic diet was characterized by adequate calorie and protein amounts, natural food ingredients with a low phosphorus-to-protein ratio, higher portions of plant-based food, and high fiber content. The primary outcome measure was the mean difference in the change-from-baseline intact fibroblast growth factor 23 (FGF23) level between the 2 diets. The other outcomes of interest included changes in mineral parameters, uremic toxins, and high-sensitivity C-reactive protein (hs-CRP) levels. Compared with the usual diet, the therapeutic diet lowered intact FGF23 levels (P=.001), decreased serum phosphate levels (P<.001), reduced intact parathyroid hormone (PTH) levels (P=.003), lowered C-terminal FGF23 levels (P=.03), increased serum calcium levels (P=.01), and tended to lower total indoxyl sulfate levels (P=.07) but had no significant effect on hs-CRP levels. Among these changes, reduction in serum phosphate level achieved in 2days, modifications of intact PTH and calcium levels in 5days, and reductions in intact and C-terminal FGF23 levels in 7days of therapeutic diet intervention. Within the 1-week intervention period, the dialysis-specific therapeutic diet rapidly reversed mineral abnormalities and tended to decrease total indoxyl sulfate levels in patients undergoing hemodialysis but had no effect on inflammation. Future studies to assess the long-term effects of such therapeutic diets are recommended.

PMON316 Novel Mutation Causing Pseudohypoaldosteronism Type 1 and Transient Hypercalcemia: A Patient Report

Abstract Background Autosomal dominant pseudohypoaldosteronism Type 1 (PHA-1) is a salt-wasting syndrome due to mutation in the renal mineralocorticoid receptor. Here, we report an infant with a novel mutation in NR3C2 causing PHA and associated with transient hypercalcemia. Clinical Case An ex-28 weeks (birth weight 1.35 kg) male infant admitted to the NICU had increased urine output of 6 mL/kg/hr on days of life (DOL) 9-10. Initial laboratory tests showed hyponatremia (121-127 mEq/L), hyperkalemia (5.4-8.4 mEq/L), hypochloremia (89-94 mEq/L), and hypercalcemia (11.2-11.6 mg/dL). Weight had decreased 4% from birth. On exam he was normotensive with no midline defect or hyperpigmentation; he had palpable testes bilaterally and 2 cm penile length. Sodium chloride (NaCl) supplementation 2.5 mEq/day was started on DOL 10. State newborn screen 17-OHP levels were normal. His family history was unremarkable. To further investigate the hyponatremia and hyperkalemia, serum ACTH, cortisol, aldosterone, and renin were obtained. ACTH and cortisol were 33 pg/mL and 11.4 mcg/dL, respectively. While awaiting the results of the aldosterone and renin assays, fludrocortisone was started with minimal improvement in serum sodium and hypercalcemia worsening to 12.0 mg/dL. Laboratory tests obtained to investigate the hypercalcemia included phosphorus 5.5 mg/dL, hypercalciuria (urine calcium to creatinine ratio 0.4), 25-OH vitamin D 21.0 ng/mL (normal 30-100 ng/mL), and PTH 29 pg/mL (normal 10-65 pg/mL). PTH was inappropriately normal, concerning for primary hyperparathyroidism. While awaiting the aldosterone level, it was therefore recommended to decrease fludrocortisone dose. Plasma renin activity resulted at 319 ng/mL/hr (normal 2-37 ng/mL/hr) and aldosterone at 612 ng/dL (normal 5-90 ng/dL), suggesting a diagnosis of PHA. Fludrocortisone was discontinued and NaCl supplementation was increased. A heterozygous pathogenic variant, c.2457C&amp;gt;A (p.Tyr819Ter), was identified in the mineralocorticoid receptor gene, NR3C2, confirming the diagnosis of autosomal dominant PHA-1. This variant has not been previously reported but meets the American College of Medical Genetics and Genomics and the Association for Molecular Pathology's criteria for pathogenicity. At his outpatient follow up at 4 months, sodium was 134 mEq/L and calcium was 10.5 mg/dL. He was continued on 1.5 grams NaCl supplementation. Conclusion We report a patient with a novel mutation in the NR3C2 gene resulting in autosomal dominant PHA-1 and associated with transient hypercalcemia. Further exacerbation of hypercalcemia was seen with addition of fludrocortisone. We suspect the etiology of the transient hypercalcemia to be secondary to excess mineralocorticoids (exogenous or endogenous) that drives PTH to increase serum calcium levels, as previously described by Vaidya et al. (1) Reference (1) Vaidya A, Brown JM, Williams JS. The renin-angiotensin-aldosterone system and calcium-regulatory hormones. J Hum Hypertens. 2015 Sep;29(9): 515-21. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Bone and mineral metabolism in patients with primary aldosteronism: A systematic review and meta-analysis.

Patients with primary aldosteronism (PA) tend to exhibit a high prevalence of osteoporosis (OP) that may vary by whether PA is unilateral or bilateral, and responsive to PA treatment. To explore relationships between bone metabolism, PA subtypes, and treatment outcomes, we performed a systematic review and meta-analysis. The PubMed, Embase, and Cochrane databases were searched for clinical studies related to PA and bone metabolism markers. Articles that met the criteria were screened and included in the systematic review; the data were extracted after evaluating their quality. R software (ver. 2022-02-16, Intel Mac OS X 11.6.4) was used for the meta-analysis. A total of 28 articles were subjected to systematic review, of which 18 were included in the meta-analysis. We found that PA patients evidenced a lower serum calcium level (mean difference [MD] = -0.06 mmol/L, 95% confidence interval [CI]: -0.10 ~ -0.01), a higher urine calcium level (MD = 1.29 mmol/24h, 95% CI: 0.81 ~ 1.78), and a higher serum parathyroid hormone (PTH) level (MD = 2.16 pmol/L, 95% CI: 1.57 ~ 2.75) than did essential hypertension (EH) subjects. After medical treatment or adrenal surgery, PA patients exhibited a markedly increased serum calcium level (MD = -0.08 mmol/L, 95% CI: -0.11 ~ -0.05), a decreased urine calcium level (MD = 1.72 mmol/24h, 95% CI: 1.00 ~ 2.44), a decreased serum PTH level (MD = 2.67 pmol/L, 95% CI: 1.73 ~ 3.62), and an increased serum 25-hydroxyvitamin D (25-OHD) level (MD = -6.32 nmol/L, 95% CI: -11.94 ~ -0.70). The meta-analysis showed that the ser um PTH level of unilateral PA patients was significantly higher than that of bilateral PA patients (MD = 0.93 pmol/L, 95% CI: 0.36 ~ 1.49) and the serum 25-OHD lower than that of bilateral PA patients (MD = -4.68 nmol/L, 95% CI: -7.58 ~ 1.77). There were, however, no significant differences between PA and EH patients of 25-OHD, or BMD of femoral neck and lumbar spine. BMDs of the femoral neck or lumbar spine did not change significantly after treatment. The meta-analytical results were confirmed via sensitivity and subgroup analyses. Excess aldosterone was associated with decreased serum calcium, elevated urinary calcium, and elevated PTH levels; these effects may be enhanced by low serum 25-OHD levels. The risks of OP and fracture might be elevated in PA patients, especially unilateral PA patients, but could be reduced after medical treatment or adrenal surgery. In view, however, of the lack of BMD changes, such hypothesis needs to be tested in further studies.

Evaluation of the Increase in Serum Calcium Levels After Unilateral Adrenalectomy.

IntroductionThis study aims to investigate the prevalence and characteristics of patients with elevated serum calcium due to adrenal insufficiency after unilateral adrenalectomy.MethodsThe study included 76 patients who underwent unilateral adrenalectomy from January 2012 to November 2021 and did not have an additional etiologic factor for hypercalcemia, During the postoperative period, the highest calcium value in six months was taken into account as the postoperative value. Calcium values were corrected according to the albumin value.ResultsOf the 76 patients included in the study, serum calcium levels were higher in six patients (7.9%) after adrenalectomy. Unlike the others, a decrease in glomerular filtration rate (GFR) and an increase in serum creatinine values were detected in the postoperative period in this patient group. In this patient group, the corrected calcium level detected an average increase of 1.3 mg/dL.ConclusionAfter unilateral adrenalectomy, hypercalcemia may occur due to adrenal insufficiency. It should also be considered that there may be a decrease in GFR and increased creatinine in these patients.

Formulation of stick laor (Eunice viridis) as an alternative food supplement for toddlers in stunting prevention

Adequate nutrition is needed as the basic capital of the child's growth and development process, especially protein. The occurrence of malnutrition conditions will affect the achievement of perfect growth. Based on this phenomenon, it is necessary to fulfill nutritional needs, especially the consumption of foods rich in energy and protein as well as micronutrients. Local food sources of energy and protein produced from Maluku Province are enbal, laor and moringa leaves. Laor (Eunice viridis) contains 29.8% protein, contains essential and non-essential amino acids, 229.26 mg calcium, 2.439 mg zinc and 3.149 mg iron per 100 grams of laor flour. The purpose of this study was to analyze the Physicochemical and sensory evaluation of stick laor (eunice viridis) as an alternative food supplement for toddlers in stunting prevention. The research method used in the first year of research was a RAL experimental design (Completely Randomized Design) which consisted of four treatments, namely the difference in comparison with the use of 5% laor flour was coded F1, for the use of 10% laor flour was coded F2 and the use of 15% laor flour coded F3. The variables measured were levels of protein, fat, carbohydrates, energy, zinc, Fe, calcium. Organoleptic test for taste, aroma, color and texture. The results showed that the highest content of energy, protein, fat, calcium, iron and zinc was F3, F2 had the best acceptability in terms of color, taste, aroma and texture. Sticks Laor increase the intake of energy, protein, and calcium for toddlers and increase serum calcium levels.&#x0D; Keywords: Sticks laor, food supplement, toddlers, stunting prevention

69-Year-Old Man With Dysuria and Right Lower Abdominal Pain

69-Year-Old Man With Dysuria and Right Lower Abdominal Pain

Vitamin D and Calcium Supplementation Accelerate Vascular Calcification in a Model of Pseudoxanthoma Elasticum.

Arterial calcification is a common feature of pseudoxanthoma elasticum (PXE), a disease characterized by ABCC6 mutations, inducing a deficiency in pyrophosphate, a key inhibitor of calcium phosphate crystallization in arteries. Methods: we analyzed whether long-term exposure of Abcc6−/− mice (a murine model of PXE) to a mild vitamin D supplementation, with or without calcium, would impact the development of vascular calcification. Eight groups of mice (including Abcc6−/− and wild-type) received vitamin D supplementation every 2 weeks, a calcium-enriched diet alone (calcium in drinking water), both vitamin D supplementation and calcium-enriched diet, or a standard diet (controls) for 6 months. Aorta and kidney artery calcification was assessed by 3D-micro-computed tomography, Optical PhotoThermal IR (OPTIR) spectroscopy, scanning electron microscopy coupled with energy-dispersive X-ray spectroscopy (SEM-EDS) and Yasue staining. Results: at 6 months, although vitamin D and/or calcium did not significantly increase serum calcium levels, vitamin D and calcium supplementation significantly worsened aorta and renal artery calcification in Abcc6−/− mice. Conclusions: vitamin D and/or calcium supplementation accelerate vascular calcification in a murine model of PXE. These results sound a warning regarding the use of these supplementations in PXE patients and, to a larger extent, patients with low systemic pyrophosphate levels.

Hypercalcemia: A complicated puzzle

This is a mini-review concerning hypercalcemia of malignancy that represents a challenging condition requiring rapid management, not only in relationship with short term complications, but also with long term mortality concerning the originating tumor approach (if feasible). Hypercalcemia on a patient with previously known or unknown cancer may be caused by dehydration, concurrent medication causing increased serum calcium levels, concomitant primary or renal hyperparathyroidism, over production of vitamin D (which may be tumor-related) or by specific circumstances that induce suppression of parathormone (PTH), so called PTH-independent mechanisms. Specific circumstances related to an active cancer means an ectopic production of parathormone, metastasis causing osteolytic lesions, tumors that produce PTHrP (parathormone related peptide) and abnormal production of 1,25-dihydroxyvitamin D by a hematologic malignancy. Parathyroid carcinoma induces an excess of PTH which is caused by a malignancy but it is not a PTH independent entity. Once a malignancy-related hypercalcemia is identified based on biological panel (mostly blood assays), the investigations are essentially continued with different imaging techniques depending on signs (if any), accessibility, etc. The approach is based on a multidisciplinary panel, on one hand, in order to restore normal levels of calcium, on the other hand, to rapidly address the underlying cause. This is essential to contribute to the outcome which typically is poor.

Genetically Predicted Lifelong Circulating 25(OH)D Levels are Associated With Serum Calcium Levels and Kidney Stone Risk.

To assess whether lifelong higher circulating 25-hydroxyvitamin D [25(OH)D] levels increase serum calcium levels and kidney stone disease (KSD) risk. Summary data for KSD were obtained from the UK biobank genome-wide association study (6536 cases and 388 508 controls). We acquired summary data for 25(OH)D from 120 618 Europeans and another large-scale analysis (443 734 Europeans) for primary and secondary analysis. Random-effect inverse-variance weighted (IVW) and 7 additional sensitivity analyses were applied. Next, multivariable Mendelian randomization (MVMR) was performed by introducing data for serum calcium levels. Genetic predisposition for a 1-SD higher 25(OH)D level was associated with increased serum calcium levels (IVW; beta, 0.014; 95% CI, 0.010-0.018; P = 7.64E-10). Genetically predicted higher circulating 25(OH)D levels were associated with increased the risk of KSD, with per 1-SD odds ratios (ORs) of 1.47 (95% CI, 1.22-1.77; P = 5.49E-05) and 1.36 (95% CI, 1.03-1.80; P = 0.029) using the IVW and MVMR-Egger methods, respectively. In secondary analysis, similar results were found: 25(OH)D was associated with an increased risk of KSD in univariate Mendelian randomization (IVW; OR 1.71; 95% CI, 1.26-2.32; P = 0.001) and MVMR (OR 1.43; 95% CI, 1.16-1.76; P < 0.001) analyses. Most sensitivity analyses were consistent with the primary results, both for the primary and secondary analyses. Our study supports that higher genetically predicted lifelong circulating 25(OH)D levels are associated with higher calcium levels and KSD risk. The effects of 25(OH)D on KSD were partially attenuated-but still significant-in MVMR.

An Updated Mendelian Randomization Analysis of the Association Between Serum Calcium Levels and the Risk of Alzheimer's Disease.

It has been a long time that the relationship between serum calcium levels and Alzheimer’s disease (AD) remains unclear. Until recently, observational studies have evaluated the association between serum calcium levels and the risk of AD, however, reported inconsistent findings. Meanwhile, a Mendelian randomization (MR) study had been conducted to test the causal association between serum calcium levels and AD risk, however, only selected 6 serum calcium SNPs as the instrumental variables. Hence, these findings should be further verified using additional more genetic variants and large-scale genome-wide association study (GWAS) dataset to increase the statistical power. Here, we conduct an updated MR analysis of the causal association between serum calcium levels and the risk of AD using a two-stage design. In discovery stage, we conducted a MR analysis using 14 SNPs from serum calcium GWAS dataset (N = 61,079), and AD GWAS dataset (N = 63,926, 21,982 cases, 41,944 cognitively normal controls). All four MR methods including IVW, weighted median, MR-Egger, and MR-PRESSO showed a reduced trend of AD risk with the increased serum calcium levels. In the replication stage, we performed a MR analysis using 166 SNPs from serum calcium GWAS dataset (N = 305,349), and AD GWAS dataset (N = 63,926, 21,982 cases, 41,944 cognitively normal controls). Only the weighted median indicated that genetically increased serum calcium level was associated with the reduced risk of AD. Hence, additional studies are required to investigate these findings.