Effects Of Hypocalcemia Research Articles

Hypocalcemia in trauma patients: A narrative review

Hypothermia, acidosis, and coagulopathy together make up the trauma triad of death, which has been acknowledged as a key factor in the demise of trauma patients. Hypocalcemia has recently been added as the fourth element of the "diamond of death" in trauma. However, the effects of hypocalcemia in trauma patients have received insufficient attention from systematic reviews. The primary focus of this review will be the impact of hypocalcemia on the mortality rates among trauma victims. Regardless of a large transfusion, hypocalcemia can occur in trauma patients; this condition is known as "trauma-induced hypocalcemia". Hypocalcemia driven by trauma is multifaceted and linked to the fatal triad, which may worsen or even result in death. Our review showed an association between hypocalcemia and increased mortality. Recent data have introduced hypocalcemia integrated with the trauma lethal triad for predicting the prognosis and mortality of critically traumatized patients. However, the benefit of prophylactic calcium supplementation requires further study to support it.

The effects of hypocalcemia in severely injured pediatric trauma patients.

The role of calcium is ubiquitous in human physiology. Emerging evidence suggests that the lethal triad be revised to include hypocalcemia (hypoCa) and thus be known as the lethal diamond . There are data showing that traumatic injury may result in hypoCa independent from the mechanism of calcium chelation by citrate-based blood preservatives. Minimal literature exists analyzing the role of hypoCa in pediatric trauma patients. We hypothesize that there is an independent association of hypoCa with increased blood product requirements and mortality. A retrospective cohort study of severely injured pediatric trauma patients was conducted. Trauma registry data were collected from January 2016 to August 2021. Ionized calcium (iCa) levels were obtained from arrival blood draws. Subjects were categorized into two groups by a threshold iCa level of 1.00 mmol/L and compared. Shock Index Pediatric Adjusted scores were used to adjust for age-specific differences in vital signs. A total of 142 patients were compared, of which 46.5% were hypocalcemic (iCa <1.00 mmol/L). Patients were well matched in terms of demographics and injury severity. The hypocalcemic group had lower systolic blood pressure and a higher percentage of Shock Index Pediatric Adjusted-positive patients. Weight-adjusted transfusion volumes were significantly higher in the hypocalcemic group at both the 4-hour and 24-hour time points without a difference in prehospital transfusion requirements. There was no observed difference in early or in-hospital mortality. This study contributes to the body of literature regarding the association between hypoCa and traumatic injury in the pediatric population. Hypocalcemia was associated with increased blood product requirements without a difference in prehospital transfusion requirements, suggesting a possible independent association. Further prospective studies are needed to better understand this relationship. Therapeutic/Care Management; Level IV.

Being an Expert Does Not Mean You Know Everything

Being an Expert Does Not Mean You Know Everything

The effect of hypocalcemia on motor symptoms of Parkinson’s disease

BackgroundThe disabling nature of Parkinson’s disease (PD) impairs functional mobility and worsens quality of life. Calcium imbalances are thought to have a significant role in the progression of PD.ObjectiveTo evaluate the relation between calcium deficiency and deterioration of PD motor symptoms.MethodsA total of 28 idiopathic PD patients were subjected to motor symptoms evaluation using the modified Hoehn–Yahr scale (H–Y), Unified Parkinson’s Disease Rating Scale (UPDRS) Part II and III and Schwab and England Activities of Daily Living Scale (S–E ADL). Total and ionized serum calcium levels were measured for the PD patients and the 30 healthy control subjects.ResultsThe level of ionized calcium was significantly lower among PD patients (4.19 mg/dl ± 0.53) than in control subjects (4.8 mg/dl ± 0.35) (p < 0.0001). The PD patients with hypocalcemia showed marked deterioration of motor symptoms and significant impairment of daily life activities when compared to PD patients with normal calcium levels regarding their scores on the modified H–Y scale (p = 0.001), UPDRS-III (p = 0.001), UPDRS-II (p = 0.001), and S–E ADL scale (p = 0.001). Ionized calcium correlated significantly with PD patients’ scores on the modified H–Y scale (p = 0.019), UPDRS-Part II (p = 0.001), UPDRS-Part III (p = 0.001) and S–E ADL scale (p = 0.001). The significant cutoff point of the ionized calcium for detection of the deteriorated PD patients that presented with stages more than grade 2 of the modified H–Y scale was < 3.99 (p = 0.037) with a sensitivity of 80% and specificity of 95%.ConclusionsOur findings conclude that calcium deficiency could contribute to the deterioration of PD motor symptoms.

Association of hypocalcemia with in-hospital mortality and complications in patients with acute pulmonary embolism: results from the 2017 Nationwide Inpatient Sample

BackgroundAcute pulmonary embolism (PE) is a common cause for hospitalization associated with significant mortality and morbidity. Disorders of calcium metabolism are a frequently encountered medical problem. The effect of hypocalcemia is not well defined on the outcomes of patients with PE. We aimed to identify the prognostic value of hypocalcemia in hospitalized PE patients utilizing the 2017 Nationwide Inpatient Sample (NIS).MethodsIn this retrospective study, we selected patients with a primary diagnosis of Acute PE using ICD 10 codes. They were further stratified based on the presence of hypocalcemia. We primarily aimed to compare in-hospital mortality for PE patients with and without hypocalcemia. We performed multivariate logistic regression analysis to adjust for potential confounders. We also used propensity‐matched cohort of patients to compare mortality.ResultsIn the 2017 NIS, 187,989 patients had a principal diagnosis of acute PE. Among the above study group, 1565 (0.8%) had an additional diagnosis of hypocalcemia. 12.4% of PE patients with hypocalcemia died in the hospital in comparison to 2.95% without hypocalcemia. On multivariate regression analysis, PE and hypocalcemia patients had 4 times higher odds (aOR-4.03, 95% CI 2.78–5.84, p < 0.001) of in-hospital mortality compared to those with only PE. We observed a similarly high odds of mortality (aOR = 4.4) on 1:1 propensity-matched analysis. The incidence of acute kidney injury (aOR = 2.62, CI 1.95–3.52, p < 0.001), acute respiratory failure (a0R = 1.84, CI 1.42–2.38, p < 0.001), sepsis (aOR = 4.99, CI 3.08–8.11, p < 0.001) and arrhythmias (aOR = 2.63, CI 1.99–3.48, p < 0.001) were also higher for PE patients with hypocalcemia.ConclusionPE patients with hypocalcemia have higher in-hospital mortality than those without hypocalcemia. The in-hospital complications were also higher, along with longer length of stay.

Relationship between the extent of central node dissection and parathyroid function preservation in thyroid cancer surgery.

The risk and effect of hypocalcemia following surgery of different magnitudes remains unclear. Thus, we assessed whether different extents of central lymph node dissection (CLND) and status of preserved parathyroid glands can influence parathyroid function in differentiated thyroid carcinoma (DTC) patients with initial surgical resection. Participants were categorized into 6 groups based on the extent of the surgical procedures, number of parathyroid glands preserved in situ, and parathyroid autotransplantation. The frequencies of hypocalcemia, serum calcium (Ca) levels, and parathyroid hormone (PTH) levels among the different groups were analyzed. The prevalence of hypocalcemia, number and status of parathyroid glands preserved in situ, and parathyroid autotransplantation were inversely related to extensive CLND (r=-0.18; P<0.05). The decrease of serum Ca and PTH was most severe on postoperative days (POD) 1-7. The incidence of hypocalcemia was higher in Group C than in Group B and A (P<0.05). The average postoperative serum Ca and PTH levels in Group C were significantly lower than group A on POD 1-7 (P<0.05). The incidence of hypocalcemia was obviously increased in Group D compared to Groups E and F (P<0.05). The mean serum Ca and PTH levels in Group D were significantly lower than in Group F (P<0.05), and the same results could be observed between Groups D and E (P<0.05). However, through parathyroid autotransplantation, there was no significant difference that could be found between Groups E and F on POD 1-7 (P>0.05). With the expansion of CLND scope, postoperative parathyroid function will be affected, increasing the risk of postoperative hypocalcemia. When at least 1-2 parathyroid glands were reserved in situ plus at least 1 parathyroid gland autotransplantation, there was little effect on postoperative parathyroid function.

Serum calcium slope is a predictor of post-thyroidectomy hypocalcemia

Background: Hypocalcemia is a common complication following thyroidectomy. The effects of hypocalcemia can range from simple numbness to life-threatening seizures. Barring stridor, haemorrhage and hypocalcemia, other complications of thyroidectomy are not seriously morbid and hence patients can be sent home. This study sought to determine whether early postoperative calcium levels can predict hypocalcemia following thyroidectomy, to help decide on early discharge.Methods: This was a prospective cohort study, conducted between July 2016 and June 2017 among 80 consecutive patients who underwent total thyroidectomy in our department. Serum calcium values were obtained pre-operatively and at 6 and 24 hours post-operatively. Serum calcium slopes were calculated and the receiver operating characteristic curve constructed to evaluate the accuracy of risk prediction.Results: The mean total calcium levels of patients with hypocalcemia were significantly lower than the levels of the normocalcemic group. The slope of change between total calcium measurements at 6 and 24 hours in patients with hypocalcemia was found to be significantly steeper than the slope in the case of normocalcemic patients.Conclusions: It is possible to predict post-thyroidectomy hypocalcemia based on the characteristics of the early post-operative serum calcium slope. On the basis of the slope’s features, all patients except those at risk can be safely discharged home early. This can cut down on the patients’ total cost of treatment as well as save unnecessary wastage of health resources.

Association of postpartum hypocalcemia with early-lactation milk yield, reproductive performance, and culling in dairy cows

Periparturient hypocalcemia is frequently observed and considered as a gateway disease that is associated with various health issues. The objective of this study was to evaluate the association of hypocalcemia with early-lactation milk yield, reproductive performance, and culling across a large number of different managerial systems. A prospective cohort study was conducted based on a convenience sample of 125 dairy herds from 8 federal states of Germany between February 2015 and August 2016. A blood sample was drawn from 1,709 animals within 48 h after parturition and analyzed for serum calcium concentration. After discarding cows (n = 283) with missing data, a total of 1,426 cows were considered for final analyses. The median time from calving to sampling was 14.0 h (interquartile range = 5.0-24.9 h). For each herd, a record of the herd management software was requested 150 d after the last cow was sampled. Serum calcium concentration of each cow was associated with early-lactation milk yield (Dairy Herd Improvement Association equivalent test 1 to 3), reproductive performance [days in milk (DIM) at first artificial insemination (AI), pregnancy at first AI, time to pregnancy within 150 DIM], and culling (until 60 DIM) data. Generalized linear mixed models were used to analyze continuous or categorical data. Shared frailty models were used for time to event data. Five different thresholds were used to define hypocalcemia. Thresholds ranged from 1.8 to 2.2 mmol/L using 0.1-mmol/L increments. Clinical hypocalcemia was defined as serum calcium concentration <2.0 mmol/L in combination with clinical signs (e.g., recumbency). The effect of hypocalcemia on milk yield was conditional on parity. In primiparous cows a serum calcium concentration <2.0 mmol/L (6.4% of cows were below this threshold) had no effect on milk production, whereas there was a tendency for multiparous cows with a serum calcium concentration <2.1 mmol/L (63.2% of cows were below this threshold) to produce 0.80 kg/d more milk compared with multiparous cows at or above the threshold. Multiparous cows suffering from clinical hypocalcemia produced 2.19 kg/d less milk compared with normocalcemic cows in early lactation. Calcium status was not associated with days to first insemination. Cows with a serum calcium concentration <1.9 mmol/L (34.6% of cows below this threshold) had decreased odds (odds ratio = 0.56) of pregnancy at first AI. A serum calcium concentration <1.8 mmol/L (24.1% of cows below this threshold) had a significant effect on time to pregnancy. Compared with animals with a serum calcium concentration ≥1.8 mmol/L, the hazard of becoming pregnant within 150 DIM was reduced when cows had a serum calcium concentration <1.8 mmol/L (hazard ratio = 0.68). Cows with a serum calcium concentration <2.0 mmol/L (44.3% of cows were below this threshold) had a 1.69 times greater hazard of being culled within the first 60 DIM compared with normocalcemic animals. The present study shows that the association of hypocalcemia with milk yield was conditional on parity and serum calcium concentration measured once within 48 h after calving. Considering reproductive performance and culling in early lactation, a negative effect of postpartum hypocalcemia was demonstrated.

P.1.e.006 - The effects of hypocalcaemia on prolactinoma cell populations

P.1.e.006 - The effects of hypocalcaemia on prolactinoma cell populations

The Hormone Exocytosis in Prolactinoma and Normal Adenohypophysis Cell Cultures by the Effects of Hypocalcaemia

The biological systems are opened, complex objects, which can regularly exchange feedbacks with their environment. The calcium ion is a universal messenger, which can regulate several cellular functions e.g. exocytosis machinery. The primary aim of this study was to investigate the response mechanisms of normal adenohypophysis and adenohypophyseal prolactinoma cell populations at different extracellular Ca2+ levels with an otherwise isoionic milieu of all other essential ions. We focused on prolactin (PRL) and adrenocorticotrophic hormone (ACTH) release. In our experimental study, female Wistar rats (n=10) were treated with estrone-acetate (150 μg/kg b.w/week) for 6 months to induce prolactinomas in the adenohypophysis. Primary, monolayer cell cultures were prepared by enzymatic and mechanical digestion. PRL and ACTH hormone presence was measured by radioimmunoassay or immuno- chemiluminescence assay. Repeated measurements of ACTH and PRL hormone release in different treatment groups on cell cultures during 80 minutes were compared using marginal models. Differences between the effects of hypocalcaemia on normal adenohypophysis cultures and prolactinoma cell populations were investigated. Significant alteration (p<0.001, n=12) in hormone exocytosis was detected in Ca2+ treated adenohypophyseal and prolactinoma cell cultures, compared to untreated groups. Diminution of Ca2+ may inhibit the SNARE mediated fusion of hormone containing vesicles to plasma membrane. In conclusion, the main finding of this study is that a strict correlation exists among certain biophysical properties, especially extracellular Ca2+ milieu and hormone vesicle exocytosis.

Hypocalcaemia and Its Role in Traumatic Brain Injury

Background: Despite an overabundance of literature the PubMed database has more than 50,000 hits for the search term “traumatic brain injury” the complex area of TBI is actually somewhat overlooked in both medical training and subsequent general medical and neuropsychiatric practice. We pretend to review the available literature on the effects of hypocalcaemia regarding prognosis in early phases after moderate- severe TBI, to identify the gaps in the literature, and to try filling these gaps by including our proposed pathophysiological schema leading to posttraumatic hypocalcaemia. Material and methods: The data from 282 patients (180 retrospective and 102 prospective) suffering moderatesevere TBI distributed in three different works was analyzed. Patients meeting the following criteria were included: Age: 16 to 87 years, Glasgow Coma Scale (GCS) from 3 to 13 points, Cranial Computed Tomography (CCT) upon admission and Calcium and/or ionized calcium measurements taken on the day of TBI, as well as on days 3 and 7. Results: The expectation that non-ionized serum calcium (serum calcium), as seen in the collective of 122 Mexican patients, would be a significant predictive factor regarding TBI was surprisingly, not the case; rather, in the retrospective and prospective German patient collectives, this factor was non-significant. Instead, a more specific calcium measure, namely ionized serum calcium, was significant as a predictor regarding mortality/morbidity in patients suffering TBI. Conclusion: Hypocalcaemia is a marker for the depth of brain damage as a result of a cascade of various pathologic mechanisms such as direct mechanical trauma, neuro-inflammation, altered vessel-autoregulation and hypoxia.

Differentially expressed serum proteins associated with calcium regulation and hypocalcemia in dairy cows.

ObjectiveHypocalcemia is an important metabolic disease of dairy cows during the transition period, although the effect of hypocalcemia on biological function in dairy cows remains unknown.MethodsIn this study, proteomic, mass spectrum, bioinformatics and western blotting were employed to identify differentially expressed proteins related to serum Ca concentration. Serum samples from dairy cows were collected at three time points: 3rd days before calving (day −3), the day of calving (day 0), and 3rd days after calving (day +3). According to the Ca concentration on day 0, a total of 27 dairy cows were assigned to one of three groups (clinical, subclinical, and healthy). Samples collected on day −3 were used for discovery of differentially expressed proteins, which were separated and identified via proteomic analysis and mass spectrometry. Bioinformatics analysis was performed to determine the function of the identified proteins (gene ontology and pathway analysis). The differentially expressed proteins were verified by western blot analysis.ResultsThere were 57 differential spots separated and eight different proteins were identified. Vitamin D-binding protein precursor (group-specific component, GC), alpha-2-macroglobulin (A2M) protein, and apolipoprotein A-IV were related to hypocalcemia by bioinformatics analysis. Due to its specific expression (up-regulated in clinical hypocalcemia and down-regulated in subclinical hypocalcemia), A2M was selected for validation. The results were consistent with those of proteomic analysis.ConclusionA2M was as an early detection index for distinguishing clinical and subclinical hypocalcemia. The possible pathogenesis of clinical hypocalcemia caused by GC and apolipoprotein A-IV was speculated. The down-regulated expression of GC was a probable cause of the decrease in calcium concentration.

Concentration‐dependent effect of hypocalcaemia on in vitro clot strength in patients at risk of bleeding: a retrospective cohort study

It is uncertain whether hypocalcaemia is associated with an increased risk of bleeding. This study assessed the dose-related relationship between ionised calcium concentrations and in vitro clot strength measured by maximum amplitude (MA) on the thromboelastograph (TEG). A total of 610 patients who were at risk of bleeding or had active bleeding between 2010 and 2014 were considered in this retrospective cohort study. A scatter plot with Pearson correlation coefficient (r) and multiple linear regression was used to assess the dose-related relationship between ionised calcium concentrations and MA on the TEG. The mean ionised calcium of the patients was 1·10 mmol L(-1) (interquartile range: 1·04-1·17) and 235 (38·5%) of them had hypocalcaemia (<1·1 mmol L(-1) ). Hypocalcaemia was more common in patients with significant coexisting coagulopathy. Ionised calcium concentrations (r = 0·285, 95% confidence interval (CI) 0·211-0·356, P = 0·001), as well as fibrinogen concentrations, platelet counts, international normalised ratio (INR) and activated Partial Thromboplastin Time (aPTT), had a significant linear correlation with the MA on the TEG. Ionised calcium concentrations and its interaction term with platelet count were both significantly associated with the MA on the TEG (slope of the regression line 1·1 per 0·1 mmol L(-1) increment, 95%CI 0·3 to 1·9, P = 0·011), after adjusting for fibrinogen concentrations, platelet counts, INR and aPTT. Ionised calcium concentrations had a concentration-dependent association with in vitro clot strength after adjusting for other coagulation abnormalities in patients with coexisting coagulopathy. Maintaining a normal ionised calcium concentration, >1 mmol L(-1) , during critical bleeding is recommended.

Влияние подкожного и внутрижелудочного введения молибдата аммония на водовыделительную и электролитовыделительную функцию почек при экспериментальном гипопаратиреозе

The aim of experiments was to study the effect of hypocalcaemia on renal function changes in&#x0D; intragastric and subcutaneous administration of ammonium molybdate. The experimental hypoparathyroidism&#x0D; was modeled by removal of parathyroid glands in narcotized and immobilized rats by electrotermocauter&#x0D; under thiopental anesthesia. 30 days after the operation calcium concentration in blood was measured&#x0D; and individuals with most severe hypocalcaemia were selected. Ammonium molybdate was introduced&#x0D; intragastrally and subcutaneously at a does of 50 mg |kg daily for 30 days. Studies showed that subcutaneous&#x0D; administration of molybdenum on the background of hypoparathyroidism was associated with more&#x0D; severе renal impairment. Spontaneous urine output increased as a result of the oppression of the relative&#x0D; tubular reabsorption of water, while the glomerular filtration rate decreased. Protein excretion was increased&#x0D; in all groups with the introduction of ammonium molybdate with respect to baseline values, but the most&#x0D; severe proteinuria was noticed in the group with subcutaneous administration of ammonium molybdate in&#x0D; the background parathyroidectomy. Excretion of all studied cations (potassium, sodium, calcium) with urine&#x0D; increased. Histology of the kidneys revealed more pronounced signs of nephropathy.

The effect of hypocalcemia in early childhood on autism-related social and communication skills in patients with 22q11 deletion syndrome.

22q11 deletion syndrome (22qDS), also known as DiGeorge syndrome, is a copy number variant disorder that has a diverse clinical presentation including hypocalcaemia, learning disabilities, and psychiatric disorders. Many patients with 22q11DS present with signs that overlap with autism spectrum disorder (ASD) yet the possible physiological mechanisms that link 22q11DS with ASD are unknown. We hypothesized that early childhood hypocalcemia influences the neurobehavioral phenotype of 22q11DS. Drawing on a longitudinal cohort of 22q11DS patients, we abstracted albumin-adjusted serum calcium levels from 151 participants ranging in age from newborn to 19.5 years (mean 2.5 years). We then examined a subset of 20 infants and toddlers from this group for the association between the lowest calcium level on record and scores on the Communication and Symbolic Behavior Scales-Developmental Profile Infant-Toddler Checklist (CSBS-DP ITC). The mean (SD) age at calcium testing was 6.2 (8.5) months, whereas the mean (SD) age at the CSBS-DP ITC assessment was 14.7 (3.8) months. Lower calcium was associated with significantly greater impairment in the CSBS-DP ITC Social (p < 0.05), Speech (p < 0.01), and Symbolic domains (p < 0.05), in regression models adjusted for sex, age at blood draw, and age at the psychological assessment. Nevertheless, these findings are limited by the small sample size of children with combined data on calcium and CSBS-DP ITC, and hence will require replication in a larger cohort with longitudinal assessments. Considering the role of calcium regulation in neurodevelopment and neuroplasticity, low calcium during early brain development could be a risk factor for adverse neurobehavioral outcomes.

Effect of serum calcium status at calving on survival, health, and performance of post-partum dairy cows and calves

Holstein dairy cows experiencing hypocalcemia at calving are more likely to experience dystocia, retain fetal membranes, and develop metritis or displaced abomasum, which affect survival, milk yield, and fertility. However, limited evidence is available in the literature about the effect of hypocalcemia (HYPO) of dams at calving on survival and health of calves. The objective was to assess the effect of clinical and subclinical HYPO (&gt;8 mg/dL) at calving on survival, health, and performance of lactating dairy cows and calves.

Microarray-based gene expression profiling of peripheral blood mononuclear cells in dairy cows with experimental hypocalcemia and milk fever

Although a molecular diagnostic assay using clinically accessible tissue, such as blood, would facilitate evaluation of disease conditions in humans and animals, little information exists on microarray-based gene expression profiling of circulating leukocytes from clinically hypocalcemic cows. Therefore, peripheral blood mononuclear cells from dairy cows with experimentally induced hypocalcemia or spontaneous milk fever were subjected to oligo-microarray analysis to identify specific biomarker genes. In experimental hypocalcemia induced by a 4-h infusion of 10% disodium EDTA (n=4), 32 genes were significantly up- or downregulated compared with control treatment (4-h infusion of 11% calcium EDTA; n=4). In cows with milk fever (n=8), 98 genes were expressed differentially (either up- or downregulated) compared with healthy parturient cows (n=5). From these data, the following 5 genes were selected as being strongly related to both experimental hypocalcemia and milk fever: protein kinase (cAMP-dependent, catalytic) inhibitor β (PKIB); DNA-damage-inducible transcript 4 (DDIT4); period homolog 1 (PER1); NUAK family, SNF1-like kinase, 1 (NUAK1); and expressed sequence tag (BI537947). Another gene (neuroendocrine secretory protein 55, NESP55) was also determined to be specific for milk fever, independently of hypocalcemia. The mRNA expression of these 6 genes in milk fever cases was verified by quantitative real-time reverse-transcription PCR and was significantly different compared with their expression in healthy parturient cows. In the present study, the selected genes appeared to be candidate biomarkers of milk fever because the continuous interactions between blood cells and the entire body suggest that subtle intracellular changes occur in association with disease. However, before any genomic biomarkers are incorporated into clinical evaluation of the disease, the effect of hypocalcemia on the mRNA expression of these genes in the tissues that regulate calcium homeostasis in dairy cows should be determined.

Regulation of PTH gene by calcium and phosphate

The mechanism of PTH gene regulation by extracellular calcium and phosphate is currently divided into two categories. One is through the transcriptional event in which negative calcium responsive element conserved in the 5'-flanking region of the PTH genes of various species and its binding protein play an crucial role. Another hypothesis is that regulation by calcium and phosphate, especially the effect of hypocalcemia and hypophosphatemia, is triggered by the post-transcriptional regulation of the PTH gene. Although both hypotheses are not mutually exclusive, in vivo effect of low calcium and low phosphate is likely to be exerted chiefly by the post-transcriptional mechanism. However, both studies have never linked their findings to the function of calcium sensing receptors. Here, I will review the current understanding of these molecular events regarding physiological regulation of the PTH gene.

Effect of Hypocalcaemia on Glucose Metabolism in Hyperketonaemic Piglets

In nine 2- to 3-month-old hyperketonaemic piglets the kinetics of glucose and D-beta-hydroxybutyrate (D-BHB) metabolism were studied during hypo- and normocalcaemia in paired experiments. Hyperketonaemia (1.3 and 2.5 mmol D-BHB (l plasma)-1) was generated by a stepwise increase of DL-BHB infusion. Hypocalcaemia spontaneously developed in five piglets due to an inherited calcitriol deficiency and was induced in four control piglets by a continuous infusion of Na2-EDTA. The method of single isotopic marker injections of glucose and D-BHB was used to calculate replacement rates, rate constants and half-lives of glucose and D-BHB in plasma. When DL-BHB was infused at the same rate into normo- and hypocalcaemic piglets, hypocalcaemia reduced the rate constant of glucose by 20-30% and the replacement rate of glucose by 34%. In the presence of hyperketonaemia, hypocalcaemia increased the rate of replacement of D-BHB by 6-40%. The replacement rate represents the sum of endogenous production and the rate of DL-BHB infusion. This observation shows that the endogenous production of D-BHB was higher during hypocalcaemia than during normocalcaemia.

Calcitonin

Calcitonin operates predominantly to regulate acute hypercalcemic states. The response to calcium challenges is lowest in elderly women; however, the contribution of calcitonin to the etiology of osteoporosis is unclear. The calcitonin receptor is a member of a supergene family consisting of G-protein-linked receptors with seven domains spanning the cellular membrane. These receptors are distributed in calcium-responsive tissues, gut, and hypothalamus and mediate calcitonin's known clinical effects of hypocalcemia, enhanced gastric motility, and analgesia. Therapeutic use of calcitonin is indicated in both perimenopausal and postmenopausal women with contraindications or intolerance to estrogen replacement therapy, Paget's disease, painful vertebral compression fractures, and steroid-induced osteopenia.