The aim of the study was to compare the efficacy of daily v. weekly oral vitamin D3 therapy in radiological healing of nutritional rickets. Children 6 months to 12 years (n 132) diagnosed with nutritional rickets were randomised into three groups (n 44): group A – 2000 IU daily vitamin D3 for 12 weeks, B – 60 000 IU weekly for 3 weeks, C – 60 000 IU weekly for 6 weeks. Serum calcium, phosphorus, 25-hydroxyvitamin D (25(OH)D), parathyroid hormone and X-ray score were estimated at baseline and 12 weeks (endline). The proportion of children who achieved complete radiological healing at endline was compared between three groups by χ2 and delta change in laboratory parameters by ANOVA (parametric data) or Kruskal Wallis test (non-parametric data), respectively. Baseline 25(OH)D ≤ 20 ng/ml was seen in 119 (90·2 %), hyperparathyroidism in 90 (68·8 %) and hypocalcaemia in 96 (72·7 %). A total of 120/132 children completed the study. Complete radiological healing seen in 30 (75 %) in group A, 23 (60·5 %) in group B and 26 (61·9 %) in group C; P = 0·15, with comparable endline X-ray scores; P = 0·31. The median (interquartile range (IQR)) delta X-ray score (baseline–endline) was 7 (4,9), 5 (2·25, 6) and 6 (4,7) in groups A, B and C, respectively; P = 0·019. Median (IQR) 25(OH)D endline levels in groups A, B and C were 50·0 (26·5, 66·5), 42·1 (28·4, 54·4) and 53·5 (33·7, 71·2) ng/ml, respectively; P = 0·045. Radiological scores were comparable at endline among daily and weekly vitamin D groups with greater change from baseline in daily supplemented group.

In comparison to monogastric animals, ruminants show some peculiarities in respect to the regulation of mineral homeostasis, which can be regarded as a concerted interplay between gastrointestinal absorption, renal excretion and bone mobilisation to maintain physiological Ca and phosphate (Pi) concentrations in serum. Intestinal absorption of Ca or Pi is mediated by two general mechanisms: paracellular, passive transport dominates when luminal Ca or Pi concentrations are high and transcellular. The contribution of active transport becomes more important when dietary Ca or Pi supply is restricted or the demand increased. Both pathways are modulated directly by dietary interventions, influenced by age and regulated by endocrine factors such as 1,25-dihydroxyvitamin D3. Similar transport processes are observed in the kidney. After filtration, Ca and Pi are resorbed along the nephron. However, as urinary Ca and Pi excretion is very low in ruminants, the regulation of these renal pathways differs from that described for monogastric species, too. Furthermore, salivary secretion, as part of endogenous Pi recycling, and bone mobilisation participate in the maintenance of Ca and Pi homeostasis in ruminants. Saliva contains large amounts of Pi for buffering rumen pH and to ensure optimal conditions for the rumen microbiome. The skeleton is a major reservoir of Ca and Pi to compensate for discrepancies between demand and uptake. But alterations of the regulation of mineral homeostasis induced by other dietary factors such as a low protein diet were observed in growing ruminants. In addition, metabolic changes, for example, at the onset of lactation have pronounced effects on gastrointestinal mineral transport processes in some ruminant species. As disturbances of mineral homeostasis do not only increase the risk of the animals to develop other diseases, but are also associated with protein and energy metabolism, further research is needed to improve our knowledge of its complex regulation.

Severe acute malnutrition (SAM) is a major cause of child mortality and morbidity. Children treated for SAM are at risk of refeeding hypophosphataemia (HP). The study was done to find out the incidence and various predictors of moderate/severe HP in SAM among North Indian children. This prospective observational study was conducted from August 2014 to July 2015 in the inpatients’ department of Department of Paediatrics at King George’s Medical University, Lucknow, Uttar Pradesh, North India, a tertiary care teaching hospital. Before inclusion, ethical approval and written informed consent was obtained. Included in the study were sixty-five children aged 6–59 months of age, who were admitted to the hospital with SAM as per the WHO guidelines. SAM was defined as a mid-upper arm circumference <115 mm and/or weight-for-height/length <–3 z-scores of the WHO growth standards and/or have bilateral oedema. Serum P levels were measured on admission and for five consecutive days after starting feed. HP was defined as mild, moderate and severe with a cut-off of 1·19–0·65, 0·65–0·32 and <0·32 mmol/l, respectively. About 60 % children had HP, with 20 % having moderate/severe HP at admission. The proportion of HP increased to 83·1 %, with 38·5 % having moderate/severe HP on day 3 after feeding. It was concluded that HP is a common biochemical abnormality in SAM. Considering its impact on the health of the child, serum P levels should be monitored in patients with SAM who are treated with enteral feeding.

Introduction: Dilated cardiomyopathy is usually idiopathic and may arise secondary to infections or metabolic or genetic causes. Another rare cause is hypocalcaemia. Owing to the fact that calcium plays an essential role in excitation and contraction of myocardial muscle, myocardial contractility may decline in patients with hypocalcaemia. Materials and Methods: Patients with symptoms of congestive heart failure and rickets-related hypocalcaemia were assessed clinically and by echocardiography in a paediatric cardiology clinic. Echocardiography was performed for all patients. Rickets was diagnosed according to the clinical, laboratory, and radiologic findings. Maternal lifestyle and living conditions were investigated, and the maternal 25-OH vitamin D3 blood level was measured. Results: We evaluated eight patients who developed heart failure as a result of severe hypocalcaemia associated with rickets between August, 1999 and June, 2012. The age distribution of the patients was 3–12 months. Laboratory results were consistent with advanced-stage rickets. Severe hypocalcaemia was detected in all patients. The maternal 25-OH vitamin D3 levels were low. Echocardiography revealed increased pre-treatment left ventricle end-systolic and end-diastolic diameters for age and reduced ejection fraction and fractional shortening. After clinical improvement, the patients were discharged. Conclusions: Severe hypocalcaemia associated with rickets must always be kept in mind among the causes of dilated cardiomyopathy and impaired cardiac function in infants. If diagnosed and treated in time, dilated cardiomyopathy and severe heart failure related to rickets respond well.

There are several studies in which a correlation between maternal vitamin D deficiency and serum mineral disorders in the mother and the newborn has been reported. The present randomised clinical trial was designed to investigate the effect of vitamin D administration on maternal and fetal Ca and vitamin D status. The trial was carried out on 160 pregnant women. Vitamin D-deficient (25-hydroxyvitamin D (25(OH)D) < 30 ng/ml) pregnant women were recruited at 26–28 weeks of pregnancy. In the control group, a multivitamin supplement containing 400 IU vitamin D3/d was given. Patients in the treatment group were treated with 50 000 IU vitamin D3 weekly for a total duration of 8 weeks. At delivery, maternal and fetal Ca and 25(OH)D levels in both groups were compared. In total, 81 % of pregnant women were vitamin D deficient. At the time of delivery, Ca and vitamin D levels were higher in the treatment group compared with the control group (92 (sd 3) v. 85 (sd 4) mg/l, respectively, P= 0·001 for serum Ca; 47·8 (sd 11·1) v. 15·9 (sd 6·6) ng/ml, respectively, P< 0·001 for vitamin D). At the time of delivery, 32·7 % of women in the control group had hypocalcaemia, while no hypocalcaemic case was detected in the vitamin D-treated group. Mean neonatal serum 25(OH)D was higher in the treatment group compared with the control group (27·7 (sd 5·2) v.10·9 (sd 4·4) ng/ml, respectively, P< 0·01). The neonatal Ca level in the treatment group was significantly higher than that of the control group (99 (sd 3) v. 91 (sd 3) mg/l, respectively, P< 0·001). The administration of vitamin D to pregnant women with vitamin D deficiency improves both maternal and neonatal Ca levels.

Nutritional rickets is still occasionally found in high-income countries, especially in populations at risk, and induced hypocalcaemia is a rare but possible cause of dilated cardiomyopathy. Although rare, physicians need to consider nutritional rickets in the differential diagnosis of hypocalcaemia cardiac failure, especially in high-risk populations such as immigrants. Despite being a reversible condition, the prognosis depends on the severity and time of diagnosis. We report two cases of exclusively breastfed infants with congestive cardiac failure due to hypokinetic dilated cardiomyopathy who had completely different outcomes. This report supports the need for prevention of this deficiency and underlies the role of vitamin D supplementation.

Periparturient hypocalcaemia (milk fever) is a disorder of Ca metabolism in dairy cattle primarily affecting multiparous cows. The major reasons for the rapid decrease of blood Ca concentration after calving are the prompt increase of Ca secretion into the colostrum and the delayed activation of Ca regulation mechanisms including calcitriol, a metabolite of vitamin D. In man, vitamin D receptor (VDR) gene polymorphisms are reported to be associated with disturbances of Ca metabolism, whereas data confirming the same in dairy cows are still missing. Moreover, polymorphisms that only affect non-coding regions are sometimes difficult to ascribe to a specific disorder as pathways and unequivocal links remain elusive. Therefore, the idea of the present study was to investigate in a small group of dairy cows with documented clinical records whether polymorphisms in the coding regions of the VDR gene existed and whether these potentially found variations were correlated with the incidence of periparturient hypocalcaemia. For this purpose, blood DNA was isolated from 26 dairy cows in their 4th to 6th lactation, out of which 17 had experienced hypocalcaemia at least once, whereas 9 cows had never undergone periparturient hypocalcaemia in their lifetime. The 10 VDR exons and small parts of adjacent introns were sequenced and compared with the Bos taurus VDR sequence published on NCBI based on the DNA of one Hereford cow. In total, 8 sequence alterations were detected in the fragments, which were primarily heterozygous. However, only 4 of them were really located on exons thereby potentially causing changes of the encoded amino acid of the VDR protein, but were not correlated with the incidence of periparturient hypocalcaemia. Certainly, this lack of statistical correlation could be due to the small number of animals included; anyhow, it was not encouraging enough to initiate a larger study with hundreds of cows and document blood Ca levels post partum for at least four lactations.

This study evaluated whether differences in milk fever incidence among Swedish dairy herds could be explained partly by differences in mineral feeding during the last weeks of gestation. A case–control study was performed on dietary risk factors for a high incidence of milk fever at the herd level using information regarding feeding and management of the dry cows collected in a written questionnaire distributed by post in spring 2008. The study was conducted from September 2004 to August 2007. Data on the diets fed to dry cows, with an emphasis on the amounts of minerals (Ca, P, Mg and K) fed 3 weeks before calving and at calving, were obtained from 30 herds belonging to the 100 Swedish herds with the highest recorded incidence of veterinary treatment for milk fever (>8.8%) and from 22 herds with no recorded milk fever treatments. Multivariable logistic regression analysis showed that a linear increase in the total amount of K and less than 26 g of Mg/day fed to dry cows 3 weeks before calving was associated with an increased risk of high milk fever incidence. A large increase in the amount of dry matter (DM) fed (>3.1 kg DM extra per day at calving compared with 3 weeks before calving) was associated with a higher incidence of milk fever, but no differences were found for Ca or P intake. Breed composition, herd average milk yield and age composition of the herd did not explain any of the observed differences between the case and the control herds. The results indicate that differences in the frequency of milk fever among herds can be associated with differences in mineral feeding of the dry cows. A high amount of K in the diet may increase the risk of milk fever linearly, whereas Mg should probably be fed at a higher level than the current Nordic recommendation to prevent milk fever.

Most dairy cows exhibit different degrees of hypocalcaemia around calving because the gestational Ca requirements shift to the disproportionately high Ca requirements of lactation. Ca homeostasis is a robust system that effectively adapts to changes in Ca demand or supply. However, these adaptations often are not rapid enough to avoid hypocalcaemia. A delay in the reconfiguration of intestinal Ca absorption and bone resorption is probably the underlying cause of this transient hypocalcaemia. Several dietary factors that affect different aspects of Ca metabolism are known to reduce the incidence of milk fever. The present review describes the interactions between nutrition and Ca homeostasis using observations from cattle and extrapolations from other species and aims to quantitatively model the effects of the nutritional approaches that are used to induce dry cows into an early adaptation of Ca metabolism. The present model suggests that reducing dietary cation–anion difference (DCAD) increases Ca clearance from the blood by dietary induction of systemic acidosis, which results in hypercalciuria due to the loss of function of the renal Ca transient receptor potential vanilloid channel TRPV5. Alternatively, reducing the gastrointestinal availability of Ca by reducing dietary Ca or its nutritional availability will also induce the activation of Ca metabolism to compensate for basal blood Ca clearance. Our model of gastrointestinal Ca availability as well as blood Ca clearance in the transition dairy cow allowed us to conclude that the most common dietary strategies for milk fever prevention may have analogous modes of action that are based on the principle of metabolic adaptation before calving.

Aims: To evaluate the risk of hypocalcaemia (transient or permanent) after total thyroidectomy for bilateral, benign, multinodular goitre, the frequency and impact of unintentional parathyroidectomy, and the value of parathyroid gland autotransplantation during thyroid surgery.

Materials and methods: This was a retrospective study of 351 surgical patients who had undergone total thyroidectomy for bilateral, benign, multinodular goitre over a seven-year period. The primary endpoint was serum calcium concentration immediately post-operatively and during follow up. Normal serum calcium concentration was defined as 2 mmol/l. Parathyroid data were collected during surgery and histological examination.

Results: In 62 per cent of cases, no hypocalcaemia had been observed after surgery. In 35 per cent of cases, transient hypocalcaemia had been observed after surgery. In 3 per cent of cases, chronic hypocalcaemia had been present six months after surgery. Permanent hypoparathyroidism had been diagnosed two years after surgery in 1.4 per cent of cases. Unintentional parathyroidectomy had been detected in 5.2 per cent of cases. Parathyroid gland autotransplantation had been performed in 7 per cent of cases during surgery.

Conclusion: Permanent hypoparathyroidism is rare, although transient hypoparathyroidism occurs relatively frequently. Unintentional parathyroidectomy and parathyroid gland autotransplantation do not affect serum calcium levels.

Acquired lengthening of the QT interval due to hypocalcaemia is a rare cause of arrhythmia in childhood. Early recognition, rapid institution of appropriate cardiac monitoring, and replacement therapy are essential. An endocrinal work-up may be necessary to exclude primary disorders of calcium metabolism. We report four cases documenting the varied clinical spectrum in which hypocalcaemic-induced prolongation of the QT interval and arrhythmia can occur in childhood.

This study was undertaken to quantify the effect of episodes of subclinical hypocalcaemia on the interval from calving to first ovulation. It incorporated three separate surveys during early lactation of 44 and 60 cows at Mutdapilly Research Station and 56 cows at Wollongbar Agricultural Institute. Twenty-five, 37 and 39% of cows respectively, experienced episodes later than 3 days after calving, of non-parturient post-partum hypocalcaemia, when plasma calcium concentration fell below 2⋅00 mmolll. Episodes of subclinical hypocalcaemia did not affect the interval to first post-partum ovulation in the two experiments conducted at Mutdapilly Research Station but ovulation was significantly delayed in cows that experienced episodes of subclinical hypocalcaemia at Wollongbar Agricultural Institute.