Oral Calcium Research Articles

Abstract #1185089: Recognition of The Oral Calcium Loading Test in the Setting of Normocalcemic Hypercalcemia: A case series report

Context: Normocalcemic hyperparathyroidism is characterized by the persistence of normal serum calcium levels and elevated intact parathyroid hormone (PTH) values, after the exclusion of other secondary hyperparathyroidism causes. Patients with this condition can present with progressive complications, such as the conversion to primary hyperparathyroidism, as well as the development of osteoporosis and nephrolithiasis. The diagnosis can be challenging due to a vast number of issues including the differentiation between normocalcemic hypercalcemia and primary hyperparathyroidism, since both have similar biochemical findings.

Diagnostic and Management Problems of a Patient with Severe Life-Threatening Acute Hypocalcemia: A Case Report

Hypocalcemia is a common electrolyte disorder. Acute hypocalcemia is a life-threatening condition that needs prompt evaluation and management. We present a case of a 54-year-old woman presented to emergency room with muscle spasm and involuntary movement. Upon physical examination, the patient was disoriented and the Trousseau’s sign was bilaterally positive when the cuff was inflated. Blood test revealed severe hypocalcemia with albumin-corrected serum total calcium levels 1.77 mg/dL. Following extensive diagnostic workups, there were no alternative explanations other than vitamin D deficiency. Despite aggressive intravenous (IV) calcium correction and high-dose vitamin D supplementation the calcium levels gradually decreased and neurological symptoms relapsed. The use of phenytoin to treat neurological symptoms decreased calcium levels further. The patient was eventually discharged with oral calcium and calcitriol supplementation with minimal symptoms. This case highlights the importance of thorough diagnostic workups and judicious use of anticonvulsant drugs in hypocalcemia for optimal treatment outcome.

Unusual syncope due to silent coronary vasospasm: a case description and an overview of coronary vasospasm

Variant angina is a condition triggered by the transient vasospasm of epicardial coronary arteries, which usually causes chest pain episodes and may be associated with dangerous arrhythmias. Among patients with coronary artery vasospasm, a non-negligible subset experiences silent myocardial ischemia, defined as the objective documentation of myocardial ischemia in the absence of angina or anginal equivalents. This condition is associated with the increased cardiac mortality and incidence of acute cardiac events. Herein, we described the case of a 65-year-old man who was admitted to our Emergency Department (ED) for syncope. He reported palpitations before the event but did not complain of chest pain. Baseline electrocardiogram (ECG) showed that troponin values of biphasic T waves in V2-V6 were normal. The patient was admitted to our coronary care unit (CCU) for monitoring. Immediately after hospital admission, he developed dynamic ST segment elevation and non-sustained polymorphic ventricular tachycardia, being symptomatic only for palpitations. Both ECG abnormalities and symptoms quickly resolved after the administration of intravenous nitrates and oral calcium channel blockers. Coronary angiography showed a critical non-occlusive fixed stenosis at the proximal right coronary artery (RCA). The lesion was treated by angioplasty and stenting, and the patient was discharged on dual antiplatelet therapy, statins and oral high-dose calcium-channel antagonist.

Does Time Matter in Deficit of Calcium after Total Thyroidectomy in Subjects with Previous Bariatric Surgery?

Background: Hypoparathyroidism-related hypocalcemia is a common complication after total thyroidectomy (TT), particularly if there is a history of prior bariatric surgery. However, it is still unknown if it is the surgery timing or the type of bariatric intervention that increases the risk of developing this complication. Methods: We compared the risk of hypocalcemia (serum calcium levels < 8 mg/dL) and hypoparathyroidism (both transient and permanent) between patients with restrictive procedures (LSG and GB) and patients without a history of obesity surgery in the immediate post-operative period and after 12 months. Hypoparathyroidism was considered permanent if the plasma parathyroid hormone (PTH) levels at 6 months were less than 15 pg/mL and the patient still required oral calcium (calcium carbonate) and vitamin D supplementation, in addition to the supplements that were taken routinely before thyroidectomy. Results: From the 96 patients who underwent TT, 50% had a history of bariatric surgery: 36 LSG and 12 GB. The risk of hypocalcemia was similar in patients with a history of restrictive procedures (31.35%) and in controls (25%) (p = 0.49). Furthermore, hypocalcemia risk was similar between patients with a history of LSG (30.5%) and GB (33%) (p = 0.85). The prevalences of transient and permanent hypoparathyroidism were similar between patients with a history of restrictive procedures and in controls; similarly, no differences were detected between subjects undergoing LSG and GB. Conclusions: Restrictive bariatric surgery (LSG and GB) is not a risk factor for post-thyroidectomy hypocalcemia and hypoparathyroidism and thus did not require a different perioperative supplementation protocol compared to subjects without history of bariatric surgery undergoing TT.

Supplemental calcium and vitamin D and long-term mortality in aortic stenosis

ObjectiveCalcium metabolism has long been implicated in aortic stenosis (AS). Studies assessing the long-term safety of oral calcium and/or vitamin D in AS are scarce yet imperative given the rising...

Multicenter retro-prospective observational study on chronic hypoparathyroidism and rhPTH (1–84) treatment

PurposeThe main purpose of this study was to investigate the effects of 12 months of rhPTH (1–84) (Natpar®) treatment in a cohort of patients selected according to the indications of hypoparathyroidism guidelines. The use of recombinant human PTH (1–84) [rhPTH (1–84)] is approved as hormonal replacement therapy in patients with hypoparathyroidism not adequately controlled with conventional therapy.MethodsIt is a multicenter, observational, retro-prospective, open label study. Eleven Italian Endocrinological centers, members of Hypoparathyroidism Working Group of the Italian Society of Endocrinology (HypoparaNET) were involved. Main outcome measures were serum and urinary calcium and phosphate concentration, calcium-phosphate product, renal function, oral calcium and vitamin D doses, and clinical manifestations.ResultsFourteen adult subjects, affected by chronic hypoparathyroidism, were treated with rhPTH (1–84) for 12 months. At 12 months of rhPTH (1–84) treatment, 61.5% of patients discontinued calcium supplement and 69.2% calcitriol. Mean albumin-adjusted total serum calcium levels quickly normalized after initiation of rhPTH (1–84) treatment compared to baseline (p = 0.009), remaining in the normal range until 12 months. Rare hypo-hypercalcemia episodes were reported. Renal function was maintained normal and no renal complications were reported. Serum and urinary phosphate and urinary calcium were maintained in the normal range. Mean phosphatemia levels linearly decreased from 3 months up to 12 months compared to baseline (p = 0.014). No severe adverse events were described.ConclusionsBiochemical and clinical results confirm the efficacy and safety of rhPTH (1–84) therapy, which represents an important option for hypoparathyroid patients unresponsive to conventional therapy.

P138 Real-world incidence and management of hypocalcaemia after denosumab administration in patients with chronic kidney disease: a UK secondary-care based audit

Abstract Background/Aims Hypocalcaemia is a recognized complication of denosumab therapy in patients with renal impairment. Our local protocol states that patients with creatinine clearance (CrCl) &amp;lt;35ml/min should have blood tests for calcium and renal function weekly for 4 weeks after each denosumab injection. This audit aimed to assess whether such patients underwent appropriate blood monitoring, and to evaluate the incidence, severity and management of hypocalcaemia in this patient population. Methods Patients who commenced denosumab between 2011 and March 2020 were eligible for inclusion if they had CrCl &amp;lt;35ml/min. Data collection was undertaken through retrospective review of clinical records and pathology systems. Results 53 patients fitting the above criteria were identified. One further patient with eGFR 32ml/min was also included, giving 54 patients in total for analysis. The age range of the patients was 76-97, 9/54 (17%) were male. None were on renal replacement therapy. 29/52 patients (56%) missed one or more post-injection blood tests (incomplete data n = 2). The most commonly missed blood tests were the 1st and 4th weekly checks. 18/54 (33%) developed hypocalcaemia at some point after starting denosumab. In 8/18 this was a one-off episode, but 10/18 experienced recurrent hypocalcaemia. Lowest values for adjusted calcium varied from 1.83-2.18mmol/l. Only 3 patients had a value &amp;lt;2.0mmol/l. Patients who did and did not develop hypocalcaemia had a mean (SD) CrCl of 27.3 (5.03) and 27.8 (5.19) respectively. There was no significant difference in CrCl between these two groups (unpaired t-test, p value 0.7338). Comparing those with &amp;gt;1 episode of hypocalcaemia with the rest of the group, again the mean CrCl was not significantly different (26.6 vs. 27.9, p = 0.47). The three patients who developed more severe hypocalcaemia (adjusted calcium &amp;lt;2.00mmol/l) had CrCl values of 33.2, 24.0 and 21.0ml/min. 17/18 patients who developed hypocalcaemia were on combined calcium and vitamin D supplementation. One patient was on vitamin D3 alone due to intolerance of calcium supplements - they developed mild hypocalcaemia only (nadir 2.13mmol/l) and had CrCl 27ml/min. One patient with CrCl 21ml/min became hypercalcaemic on combined supplementation which was later switched to alfacalcidol by the renal team. Hypocalcaemia was most commonly observed 1-week post-injection, but delayed onset of hypocalcaemia 4-6 weeks post-injection was observed in a few cases. Most episodes resolved within 1-2 weeks, almost all within 4 weeks. One patient died 2 weeks after their 2nd denosumab dose from an unrelated cause - adjusted calcium was 2.16 just prior to death. Additional oral calcium was given in two patients; in one of these, hypocalcaemia recurred after a subsequent injection despite additional supplements, and denosumab was discontinued. Conclusion In a real-world setting, hypocalcaemia after denosumab in patients with reduced renal function (not on renal replacement therapy) is generally mild and rarely requires treatment. Disclosure S.A. Hardcastle: Other; S.H. received conference fee funding from Lilly (UK) in 2018. R. Alshakh: None. J. Webb: None. S. Warren: None. T. Ahmed: None.

Hungry bone syndrome in delay diagnosed primary hyperparathyroidism with fi brocystic osteitis: A case report

Fibrocystic osteitis is a rare but severe primary hyperparathyroidism (PHPT) complication. We describe a 66-year-old female presented with fi brocystic osteitis and nephrocalcinosis with eGFR reduction to CKD stage 4 due to primary hyperparathyroidism. Delayed diagnosis of long-term hypercalcemia, high parathyroid hormone level, unsubstituted 25(OH)D defi ciency, and the use of bisphosphonates in high doses caused development of «hungry bones» syndrome in early postoperative period. Severe hypocalcemia required prescription of active and native vitamin D metabolites, oral calcium supplements as well as intravenous calcium. Delay in diagnosis of PHPT with fi brocystic osteitis formation led to lower well-being, reduced quality of life and also provoked sever postoperative hypocalcemia («hungry bone» syndrome).

Epidemiology, natural course, and preventive measures of osteoporotic vertebral fractures: WFNS Spine Committee Recommendations.

This review aims to search for up-to-date information on epidemiology, natural course, and preventive measures of osteoporotic spine fractures. We reviewed the literature of the last ten years using keywords "natural course and osteoporotic vertebral fractures," "epidemiology and osteoporotic vertebral fractures" and "prevention and osteoporotic vertebral fractures." We then discussed the search results to reach an agreement in two consensus meetings on January and February 2021 of the World Federation of Neurosurgical Societies (WFNS) Spine Committee. Finally, we utilized the Delphi method to administer the questionnaire to preserve a high degree of validity. We summarized seven papers on the natural course, 15 articles on epidemiology, and 84 papers on preventing osteoporotic vertebral fractures. Finally, the consensus results after voting are presented. Natural course of acute osteoporotic vertebral fractures is benign; many patients may have sufficient pain relief during the first three months with conservative treatment. At the end of one year of conservative treatment, 40% may still have pain with VAS-scores ≥4. Since the populations are aging, the incidence of OVF continues to rise. Although the prevalence varies across the globe, the highest rates are from North America and some countries of Asia. Preventive treatment of OVF must involve an active lifestyle, adequate nutrition, prevention of immobilization with physical therapy, and pharmacological therapy. Oral calcium and vitamin D are first-line interventions to prevent the bone mass loss, especially in postmenopausal women. There are many pharmacological treatment options; the decision must be made by fracture risk assessment (clinical factors + BMD + BMI) alone or along with DXA (dual-energy X-ray absorptiometry) or history of previous fragility fractures. The indication of one respect to the others is based on patient preference, compliance, and risk of discontinuation related to adverse events and administration method. The incidence of osteoporotic vertebral fractures increases with age and other factors. The natural course shows that most patients benefit from conservative therapy without any surgical intervention during the first three months. Preventive measures must include active lifestyle, adequate nutrition, prevention of immobilization with physical therapy, oral calcium, and vitamin D intake, and pharmacological therapy after fracture risk assessment.

Abstract 37: Adolescent primary hyperparathyroidism masquerading as rickets

Introduction: Primary hyperparathyroidism (PHPT), is a rare disorder in pediatric age-group, with an estimated incidence of 2–5 cases in 100,000 live births. Around 80% children are symptomatic with renal or gastrointestinal manifestations. Presentation with skeletal symptoms is rare with less than 30 reported cases with most cases being misdiagnosed and treated as rickets.Case Synopsis: 14 year old boy presented with pain in both the legs and knock knees for 1 year. He was treated as nutritional rickets with oral calcium and vitamin D supplements for 1 month. He subsequently developed abdominal pain and recurrent vomiting. He was diagnosed to have abdominal tuberculosis and was started on empirical Anti- tubercular treatment. He continued to worsen symptomatically and was send to Endocrinology for evaluation of worsening leg deformity- ? Resistant RicketsOn examination his weight was <3rd centile, height 3-10th centile, waddling gait with genu valgum. Other systemic examination was normal.Investigations showed, corrected S. Calcium of 14.9 mg/dl, Phosphorus -2.9 mg/dl, ALP- 1277 IU/L, iPTH- 1900 pg/ml, 25(OH)D – 17 ng/dl, S. Creatinine -0.4 mg/dl and Hb-9.7 gm/dl. Ultrasound neck showed a 30 x19 x13 mm left parathyroid lesion with concordance in the Tc 99 Sestamibi scan. A clinical Exome sequencing for young onset PHPT was negative. He underwent a Left inferior parathyroidectomy and histopathology showed parathyroid adenoma. 4 months post-surgery, his S. calcium is 9.1 mg/dl on oral Calcium 500 mg twice a day. He gained 8 kilos and his bone pain and proximal myopathy has improved with persistent genu- valgum.

Abstract 60: Rickets in congenital bullous ichthyosiform erythroderma

Introduction: Congenital ichthyosiform erythroderma (CIE), also known as bullous congenitalichthyosiform erythroderma is a rare type of the ichthyosis family of skin diseases which occurs in 1 in 200,000 to 300,000 births. CIE comes under the umbrella term autosomal recessive congenital ichthyosis (ARCI), which include non-syndromic congenital ichthyosis such as harlequinichthyosis and lamellar ichthyosis. Ichthyosiform erythroderma due to keratinizing disordersmaysuppress cutaneous vitamin D synthesis, leading to vitamin D deficiency and rickets.Description: A 8 year 10 months old female child presented with poor height gain from 5 years and inward bending of knees from 5 years. h/o hyperpigmented hyperkeratotic scaly dry skinfrombirth. She was diagnosed with Bullous ichythosiform erythroderma and was prescribed emollients by a dermatologist. She is born out of non-consangienous marriage, second in birth order has an elder and youngersibling who are apparently normal. Ichythyosis present from birth more during winter season. h/o delayed dentition present. No h/o constipation or weight gain. h/o delayed motor milestones present. Language and social skills normal. o/e height is 78 cms @ < -10.8 SDS; height age <2 years weight 10 kg @ < - 6 SDS ; weight age < 2 years inward bending of knees + ; forward bending of tibia + ; ichthyosis over lower limbs, abdomen and upper limb. Her labs showed low Vit D levels of 8.7 ng/ml; calcium of 7.5 mg/dl (8- 10 mg/dl); phosphorus 2.6 mg/ml (2.5-4.8 mg/dl); elevated serum Alkaline phosphatase of 1450 IU/L; serum PTH of 181 pg/ml; normal thyroid and renal profile. She was started on oral vitamin D3 supplements and calcium supplements.Discussion: Ichthyosiform erythroderma is of two types, one inherited as an autosomal dominant and the other as an autosomal recessive trait. The recessive form is nonbullous and is associated with growth retardation, oligophrenia, spastic paralysis, genital hypoplasia, hypotrichia and shortened life expectancy. In the autosomal dominant or bullous form, however, life expectancy is not shortened, and the associated symptoms include only seborrhoea of the head an probably polydipsia. Both types begin at birth and are localized mostly on the flexor surfaces. Nonbullous congenital ichthyosiform erythroderma is characterized by prominent erythroderma and fine white, superficial semiadherent scales. The majority of affected individuals are present at birth as collodion babies. Skin histology shows hyperkeratosis, an increase in stratum corneum thickness, a normal or prominent granular layer and increased mitoses. Development of skeletal features in this condition can be explained by the fact that the maintenance of healthy skeleton requires vitamin D, the main source of which is biosynthesis in the skin. Epidermal hyperproliferation disturbs this synthesis and results in rickets.

Abstract 155: Vitamin D dependent rickets type II: Our experience and systematic review

Background: Hereditary vitamin D resistant rickets, is a rare autosomal recessive disease caused by variants affecting VDR gene. We aimed to describe our experience and systematically review the world literature.Objective: To evaluate the phenotypic and genotypic spectrum of VDDR2.Methods: The clinical and genetic spectrum of VDDR2 were analyzed.Results: Six patients of VDDR 2 were included. The mean age at the development of rachitic changes was 12±3.79 months. Baseline biochemistry revealed hypocalcemia (6.67±1.5 mg/dl), hypophosphatemia (3±1.5 mg/dl) with elevated serum alkaline phosphatase (3579±845 IU/ml) and PTH (372±183 pg/ml). Three novels variants in VDR gene were detected (p.N444D=1, p.I268T=1, p.H85R=1, p.H355TfsTer7=1). A systematic review (probands 112) revealed alopecia in majority of patients (81.2%). Complete response to oral therapy with supra-physiological dose of calcitriol and high dose of oral calcium was observed in 32.5% of cases. Recurrent variants specific to geographical locations were p.Lys45Glu (Africa); p.Cys41Tyr, p.Gln152Ter (Asia); p.Gln356Ter (Europe); p.Gln259Glu (Latino). Patients with variants in ligand binding domain (LBD) had better response to oral therapy compared to cases with DBD variants.Conclusion: Patients with VDDR2 presents in infancy with alopecia. Higher complete response rate to oral therapy can be anticipated in cases with variants affecting LBD.

Effects of vitamin D with or without calcium on pathological ossification: A retrospective clinical study.

Vitamin D protects against the development and severity of several rheumatic diseases. However, the effect of vitamin D on the pathological ossification associated with rheumatic diseases remains unknown. The present retrospective study analyzed the clinical outcomes of vitamin D without calcium compared with vitamin D with calcium on pathological ossification in joints and ligaments. Data were collected from patients who were diagnosed with osteoarthritis, rheumatoid arthritis or spondylarthritis, and the presence of pathological ossification in joints or ligaments was confirmed by X-ray, computed tomography or magnetic resonance imaging examination. A total of 2,965 patients aged 18-75 years old were included, among who, 1,725 were included in the vitamin D alone group and 1,240 in the vitamin D with calcium group. Vitamin D was administered intramuscularly (300,000 IU) once every 7-10 days, 4-6 times in total. Patients who ingested an oral calcium supplement (1,000 mg/day; ≥5 days/week) were considered the vitamin D with calcium group. The clinical outcome was evaluated based on the imaging changes of pathological ossification, which were classified as alleviation, aggravation and unchanged. The bone mineral density (BMD) was determined, and the calcium concentration in the serum and urine was measured. The results revealed that vitamin D alone alleviated pathological ossification, while vitamin D combined with calcium aggravated pathological ossification in the majority of patients (P<0.0001) independent of disease type and patient age. BMD measurements demonstrated a decreasing trend in the vitamin D alone group, whereas they exhibited an increasing trend in the vitamin D combined with calcium group. The urine calcium concentration increased after vitamin D treatment alone. Therefore, it was concluded that vitamin D exerted both pro-resorptive and anti-resorptive actions on pathological ossification. The bidirectional action of vitamin D on bone metabolism may depend on exogenous calcium supplementation.

Abstract P2-08-10: First results of the randomized window of opportunity clinical trial D-Biomark: Immunomodulatory effect of denosumab in early breast cancer

Abstract Background: Most breast cancers (BC) exhibit low immune infiltration and are unresponsive to immunotherapy. Inhibitors of the Receptor Activator of NFkB (RANK) pathway, such as denosumab, used for the treatment of bone metastasis, have been shown to prevent BC, reducing tumor cell proliferation and survival. Our recent data supports that RANK pathway inhibition in BC cells enhances anti-tumor immune response. However, the population of BC patients who may benefit from denosumab remains to be identified. The aim of the study is to evaluate the antiproliferative, proapoptotic and/or immunomodulatory activity of denosumab in early BC and to identify biomarkers of response. Methods: Patients with early stage HER2-negative BC, candidates to tumor excision as first therapeutic approach were included. Patients were randomized 2: 1 to denosumab (two doses of 120mg/Kg subcutaneous denosumab, days 1 and 8 plus oral calcium 1000 mg daily for a month) and control arm (no treatment). Blood and tumor samples were collected at baseline and at surgery (2-4 weeks later). Putative changes in tumor cell proliferation by Ki67 immunohistochemistry (IHC), survival by Cleaved caspase-3 IHC and tumor infiltrating lymphocytes (TILs) quantified in H&amp;E were evaluated between initial biopsy and surgery. RANK and RANKL expression will be analysed by IHC and the infiltrating immune populations will be characterized by specific antibodies (CD3, CD4, CD8, CD20, FoxP3, CD68, PDL1, PD1). We will analyse denosumab driven gene expression changes in tumor samples and tools such as CIBERSORT will be used to characterize the immune infiltrate. To assess the increase in TILs and the variation in Ki 67 and Cleaved caspase-3, the T-test for paired samples was used. A value of p less than 0.05 was defined as statistically significant. Result: We present results from the initial 45 patients enrolled out of 60, 31 cases in the experimental arm and 13 in the control arm. Mean age was 55,97 (range 37-88) years. 38 women with luminal breast cancer were analysed and 7 cases of triple negative BC (5 in experimental arm and 2 in control arm). Clinical and tumor characteristics were well balanced between both groups. No relevant toxicities were reported. There was no reduction of Ki67 in either of the two arms and no changes in Cleaved caspase-3 were observed. Interestingly, a statistically significant increase in TILs was observed in the denosumab treated group (p=0.0092, Paired t test) but not in the control group (p=0.68). 29.03% of patients treated with denosumab showed a ≥10% increase in TILs vs 7.14% in the control group (p=0.13). Denosumab was associated with an effective systemic inhibition of RANKL. No relationship was found between serum RANKL levels at baseline and response to denosumab. RNAseq analysis and immunophenotyping is still in progress. Conclusion: Short term neoadjuvant denosumab induces an immunomodulatory effect with an increase in stromal TILs in early BC. ClinicalTrials.gov Identifier: NCT03691311 Table 1.ResultsBiopsySurgeryKi 67 (mean frequency) Control24.5729.57Ki 67 (mean frequency) Experimental22.3927.90Cleaved caspase 3 (mean area) Control0.260.58Cleaved caspase 3 (mean area) Experimental0.350.42TILs (mean percentage) Control9.3410.29TILs (mean percentage) Experimental8.2913.54TILs incrementControl p=0.68 vs. Experimental p=0.009 Citation Format: Andrea Vethencourt, Eva M Trinidad, Anna Petit, María T Soler-Monsó, Clara Gómez Aleza, Ander Urruticochea, Amparo García-Tejedor, Anna Gumà Martinez, Veronica Obadia, Silvia Vazquez, Rafael Villanueva, Adela Fernánez, Monica Cejuela, Sabela Recalde Penabad, Agostina Stradella, Miguel Gil-Gil, Sonia Pernas, Eva Gonzalez-Suarez, Catalina Falo. First results of the randomized window of opportunity clinical trial D-Biomark: Immunomodulatory effect of denosumab in early breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-08-10.

Blood calcium dynamics in cows receiving an aqueous calcium suspension for voluntary consumption or a calcium bolus following parturition.

The form of oral calcium (Ca) supplement and the Ca source influence Ca absorption dynamics resulting in different postpartum calcemia. The objective of this study was to investigate whether an oral Ca supplement (mainly CaCO3) offered for voluntary consumption would maintain or increase postpartum blood Ca to the same degree as a Ca bolus (mainly CaCl2) providing an equivalent dose of a Ca. A total of 72 Holstein cows were blocked by expected parturition date and parity. Within each block of 3 animals, cows were randomly assigned to one of three treatments, including an oral Ca supplement offered for voluntary consumption (Ca-drink, n = 23), an oral Ca bolus (Ca-bolus, n = 24), or an untreated group (CON, n = 25). Treatments were administered once within 15 min postpartum. The Ca-drink provided 45 g of Ca (CaCO3 source) and was mixed in 20 L of lukewarm water and offered to cows for 30 min. The Ca-bolus provided 43 g of Ca (71% from CaCl2 and 29% from CaSO4) and was administered once. Both Ca-bolus and CON cows received 20-l of lukewarm water at parturition to standardize the volume of fluids (Ca-drink or 20-l lukewarm water) offered at parturition. Dairy cows offered Ca-drink had a 28% higher fluid consumption than Ca-bolus and CON cows. Milk yield and milk composition expressed in percentage protein, fat, lactose, and urea did not differ, whilst there was a small but significant increase in DMI in cows receiving the Ca-drink compared to CON, while Ca-bolus did not differ from other groups. This was consistent with reduced BW losses between week 1 and 3 in cows receiving the Ca-drink suspension. Treatment by time interactions were present for blood Ca, glucose, and urea concentrations. Blood Ca was relatively stable in Ca-drink cows, while higher fluctuations were observed in Ca-bolus cows. In Ca-bolus cows, blood Ca increased from 15 min to 6 h, decreased from 6 to 24 h, and finally increased again from 24 to 48 h. At 24 h post administration, blood Ca was greater in cows receiving the Ca-drink than cows receiving the Ca-bolus. Blood glucose was greater in Ca-bolus cows at 15 min after treatment administration compared with Ca-bolus and CON, while blood urea was higher in CON than Ca-drink and Ca-bolus throughout the sampling period. These results indicate that voluntary oral Ca resulted in a relatively stable calcemia, whereas higher fluctuations were observed in cows receiving the Ca-bolus. Due to a lack of differences between Ca-drink and Ca-bolus compared with CON, it is not possible to conclude regarding the efficacy in maintaining postpartum blood Ca.

Assessment of calcium and vitamin D medications adherence in patients with hypoparathyroidism after thyroidectomy.

In this study, we aimed to evaluate adherence to active vitamin D and calcium replacement in patients with post-surgical hypoparathyroidism. To elucidate the medication adherence, we performed a questionnaire survey using the six-item "Medication adherence questionnaire"(MAQ). The first, second, and sixth questions reflect the motivation status of the patients whereas the third, fourth, and fifth questions reflect the knowledge about the medication that is received. The responses are scored and patients are classified regarding their motivation to and knowledge about the particular drug. Totally, 64 patients (male: 12/female: 52; mean age 48.6±11.6 years) who had post-operative hypoparathyroidism were included in our study. Median disease durance was 60 months (min-max: 12-295 months). We found that motivation score of calcium usage was significantly lower compared to vitamin D usage (p<0.001). The calcium motivation score was reversely correlated with disease duration (r= -0.256 and p=0.046). The most common worry about calcium usage was nephrotoxicity, and the most common worries about calcitriol treatment were kidney damage and polyuria. One-third of the patients were taking oral calcium and calcitriol less than the recommended dose. One-third of patients lack motivation to use calcium whereas half of the patients experiences anxiety about drug-related side effects. This is a preliminary study showing that vital calcium and active vitamin D intake may be interrupted due to side effect anxiety.

Clinical Study of High Dose Calcium to Prevent Pregnancy Specific Hypertensive Disorders, Their Severity, Still A Research Agenda!

Background: Worldwide hypertensive disorders of pregnancy (HDsP) continue to be leading causes of maternal, perinatal severe morbidity mortality, long term disabilities. Prevention of HDsP, their severity through high dose calcium supplementation is being suggested. However, whether calcium really helps is still not established. So, research continues. Objectives: Present study was carried out to know the efficacy of high dose daily calcium from midpregnancy on reduction in occurrence of HDsP, their severity and perinatal outcome. Material Methodology: Study was done with 1200 women, (600 cases, 600 controls) of 18-39 years with, 20 + 2 weeks pregnancy, no obvious medical disorders in mothers, no ultra sonographically diagnosed anomaly in fetus at entry to study. Study cases (S) received 2 gms oral calcium daily, similar controls (C) were not given calcium. Research assistant was not part of the care providers, but kept track of everything. Women got antenatal care, clinicians not knowing which women got extra calcium. Desired information, pregnancy outcome, complications during pregnancy, birth weight, neonatal outcome, admission of baby to neonatal intensive care unit and compliance to calcium tablets in study subjects was collected by research assistant using pretested tool. Results: HDsP occurred in 7.5% S cases, 7.33% C group. Amongst group S9.43% Primigravida, 4.3% Multigravida developed HDsP (gestational hypertension 6%, preeclampsia 1.16%, eclampsia 0.33%). In group C 8.04% primigravida, 3.08% multigravida developed HDsP, (6%GH, 1% preeclampsia, 0.33% eclampsia), Total 8.8% perinatal deaths occurred in S cases who had HDsP, 2.27% in C, with HDsP and no maternal death. Conclusion: No benefit was found with high dose calcium. On the contrary, perinatal outcome was poorer. More research is needed about high dose calcium for HDsP, their severity, perinatal outcome. Keywords: Hypertensive Disorders of Pregnancy; Occurrence; Severity; Perinantal outcome

Thyroidectomy and uncontrolled graves' disease - Multidisciplinary approach prevents unnecessary cancellation.

Dear Editor, Thyroidectomy is the definitive treatment for thyrotoxicosis for patients resistant to medical treatment and performed preferably when the patient is euthyroid.[1] Sometimes it may not be possible to render a patient euthyroid for various reasons leading to postponement or deferment of surgery.[2] A 35-year-old woman, was suffering from Graves’ disease, confirmed by a low thyroid-stimulating hormone (<0.005 miliunits/L), markedly elevated free thyroxine (>100 nanograms/dL), and positive thyroid receptor antibodies. Thionamide (carbimazole) therapy was started to lower the circulating thyroid hormone levels and beta-blockers added to reduce her hyper-adrenergic symptoms. She developed adverse drug effects resulting in agranulocytosis which necessitated discontinuing thionamide therapy. A multidisciplinary team consisting of an endocrinologist, endocrine surgeon, and anaesthetist was convened and a consensus view emerged for urgent total thyroidectomy. In preparation for surgery Lugol’s iodine and oral propranolol 20 mg 8 hourly administered to control tachycardia. Intravenous hydrocortisone 100 mg 8 hourly was started 1 week prior to planned operation to reduce peripheral conversion of free thyroxine to free triiodothyronine. General anaesthesia was administered with target-controlled infusion (TCI) of propofol and remifentanil with intubating dose of atracurium. Neural integrity monitor (NIM) electromyogram tracheal tube was used for intraoperative recurrent laryngeal nerve function monitoring. No further dose of atracurium was used. Anaesthesia was maintained with total intravenous anaesthesia (TIVA) using TCI devices and depth of anaesthesia was monitored with bispectral index (BIS monitor). Total thyroidectomy with parathyroid preservation was uneventful. After a brief observation in the post-anaesthesia recovery unit, she was transferred to the high dependency unit for monitoring. The postoperative course was complicated by severe hypocalcaemia (0.82 mg/dL) due to transient postsurgical hypoparathyroidism. This was confirmed by inappropriately normal parathyroid hormone levels post-surgery despite severe hypocalcaemia. Prolonged and severe stimulation of thyroid hormone is known to induce a high bone turnover state described as thyrotoxic osteodystrophy.[34] The high incidence of hypocalcaemia after thyroidectomy in thyrotoxic patients suggests that rapid loss and sudden removal of T3 and T4 hormone stimulation and inadequate parathyroid hormone response resulting in transient post-thyroidectomy hypocalcaemia. The calcium levels stabilized over the next 3 days with intravenous calcium replacement; subsequently, she was discharged with oral calcium and vitamin D supplements. Thyroidectomy may be the last option in some patients with Graves’ thyrotoxicosis refractory to medical treatment who cannot be optimized by medical treatment. A multidisciplinary team approach may help in appropriate preparation of patients prior to thyroidectomy avoiding unnecessary cancellation or postponement of surgery. Close postoperative monitoring of serum-ionized calcium is also recommended. Declaration of patient consent The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

Association of Salivary Statherin, Calcium, and Proline-Rich Proteins: A Potential Predictive Marker of Dental Caries.

Background: Salivary factors modulate the balanced dynamic mineralization process of the dental enamel. Salivary proteins such as statherin and acidic proline-rich proteins (PRPs) protect oral surfaces by regulating oral calcium homeostasis and remineralization of enamel. Thus, they possibly play vital roles in dental caries. Aim: The present study aims to find the association of salivary statherin, proline-rich protein, and calcium levels with dental caries. Methods: A descriptive, cross-sectional study was conducted among 188 healthy participants (age between 18 and 50 years), from dental clinic of MAHSA University, Malaysia. Dental caries was measured using standard WHO criteria. Stimulated whole mouth saliva was collected, and salivary statherin, acidic PRP (aPRP), and calcium levels were estimated using ELISA Kit and calorimetric assay kit, respectively. Data were analyzed using Spearman's rho and Pearson's correlation coefficient (SPSS statistical package-version 25.0) to find correlation of salivary statherin, calcium, and proline-rich protein levels with dental caries.Results: A statistically significant (P < 0.001) moderate negative correlation (r = −0.500) was found between salivary statherin and proline-rich protein levels. There was no statistically significant association of dental caries with salivary statherin, calcium, and aPRP levels.Conclusion: Salivary statherin and aPRP levels appear to perform mutually complementing functions and thus may have potential role in the maintenance of tooth integrity.

Acute catabolic bone metabolism response to exercise in young and older adults: A narrative review.

Exercise is recommended for cardiometabolic benefits and to preserve or improve bone health, especially for older adults at increased risk of fracture. However, exercise interventions have modest benefits on areal bone mineral density (aBMD), and exercise can lead to bone loss in young athletes under certain conditions. In this narrative review, we discuss evidence for a disruption in calcium homeostasis during exercise that may diminish the skeletal benefits of exercise. Topics include 1) a general overview of the effects of exercise on aBMD; 2) discussion of the exercise-induced disruption in calcium homeostasis; 3) factors that influence the magnitude of the exercise-induced disruption in calcium homeostasis, including age, sex, and exercise mode, intensity, and duration; 4) oral calcium supplementation to minimize the exercise-induced disruption in calcium homeostasis; and 5) potential for exercise-induced increase in parathyroid hormone to be both catabolic and anabolic to bone.