Modern India and Dietary Calcium Deficiency-Half a Century Nutrition Data-Retrospect-Introspect and the Road Ahead.

Calcium and vitamin D are inseparable nutrients required for bone health. In the past half a century, the dietary calcium intake of rural, tribal, and urban India has declined. Though India is the largest producer of milk and cereals, the major source of calcium in India is through non-dairy products. The highest intake of cereals and lowest intake of milk & milk products was observed in rural and tribal subjects whereas, the intake of cereals, milk & milk products were similar in both urban and metropolitan subjects. One of the reasons for lower calcium intake was the proportion of calcium derived from dairy sources. Over the past half a century, the average 30-day consumption of cereals in the rural and urban population has declined by 30%. The Per Capita Cereal Consumption (PCCC)has declined despite sustained raise in Monthly Per capita Consumption Expenditure (MPCE) in both rural and urban households. The cereal consumption was the highest in the lowest income group, despite spending smaller portion of their income, as cereals were supplied through public distribution system (PDS). About 85% of the Indian population are vitamin D deficient despite abundant sunlight. Dietary calcium deficiency can cause secondary vitamin D deficiency. Though India as a nation is the largest producer of milk, there is profound shortage of calcium intake in the diet with all negative consequences on bone health. There is a decline in dietary calcium in the background of upward revision of RDI/RDA. There is a gap in the production-consumption-supply chain with respect to dietary calcium. To achieve a strong bone health across India, it is imperative to have population based strategies addressing different segments including supplementing dietary/supplemental calcium in ICDS, mid-day-meals scheme, public distribution system, educational strategies. Other measures like mass food fortification, biofortification, bioaddition, leveraging digital technologies, investments from corporate sector are some measures which can address this problem. India is a vast country with diverse social, cultural and dietary habits. No single measure can address this problem and requires a multi-pronged strategic approach to tackle the dietary calcium deficiency to achieve strong bone health while solving the problem of nutritional deficiency.

Normocalcaemic hyperparathyroidism and primary hyperparathyroidism: least significant change for adjusted serum calcium.

INTRODUCTION: The least significant change (LSC) is a term used in individuals in order to evaluate whether one measurement has changed significantly from the previous one. It is widely used when assessing bone mineral density (BMD) scans. To the best of our knowledge, there no such estimate available in the literature for patients with disorders of calcium metabolism. Our aim was to provide an estimate of the least significant change for albumin-adjusted calcium in patients with normocalcaemic hyperparathyroidism (NPHPT) and primary hyperparathyroidism (PHPT). METHODS: We used the within-subject standard deviatio calculated in a population of NPHPT and PHPT patients and multiplied it by 2.77. RESULTS: The LSC for NPHPT and PHPT were found to be 0.25 and 0.24 mmol/L, respectively (1.00 and 0.96 mg/dL). In clinical practice, the value of 0.25 mmol/L could be used. DISCUSSION: The least significant change given, could be used in two ways in these patients. First, it gives a range to which values are expected. This can provide some reassurance for the patient and the physician in cases of intermittent hypercalcaemia. Moreover, it can be a marker of whether an individual has an actual significant change of his calcium after parathyroid surgery.

Evaluation of a New Automated Routine Measurement for Serum Adjusted Ionized Calcium (at pH 7.4) in Patients Suspected of Calcium Metabolic Disease.

BACKGROUND: Total calcium is a less accurate test in predicting ionized calcium (Ca2+) in patients suspected of calcium metabolic disease. Nevertheless, total calcium continues to be used as routine measurement instead of adjusted Ca2+ (at pH 7.4). In the current study we evaluate a new multichannel instrument, the ISE Module E1200 for adjusted Ca2+ (at pH 7.4), containing three different ion-selective electrode (ISE) units. METHODS: Serum from 1350 patients was compared to the ABL835 flex and KoneLab. Total calcium was also evaluated on the Dimension Vista 1500 system. Correlations between instruments were assessed by Deming regression and degree of agreement by Cohen's kappa (κ). RESULTS: Analytical imprecisions for the three ISE units for adjusted Ca2+ (at pH 7.4) was between 0.36% and 2.52%, and for pH between 0.32% and 3.24%. Results were comparable for each ISE unit (r = 0.797-0.917; all P < 0.0001) and in high-throughput settings (r = 0.871; P < 0.0001). The degree of agreement between instruments was moderate to good (κ = 0.52-0.77). In contrast, there was a very poor agreement (κ = -0.14) for total calcium with discrepancy in 53.4% of the samples. CONCLUSIONS: The new ISE Module E1200 is comparable with the ABL835 flex and KoneLab 30i and therefore may be used for routine analysis of serum adjusted Ca2+ (at pH 7.4). The measured adjusted Ca2+ (at pH 7.4) was less comparable with very poor agreement to total calcium measured on the Dimension Vista 1500 system.

The association between periodontal conditions, inflammation, nutritional status and calcium-phosphate metabolism disorders in hemodialysis patients.

OBJECTIVES: To analyze the association between periodontal conditions and inflammation, nutritional status and calcium-phosphate metabolism disorders in hemodialysis (HD) patients. MATERIAL AND METHODS: We analyzed 128 HD patients divided into two groups: dentate (n = 103) and edentulous (n=25). The following items were assessed: baseline characteristics, age at the start and duration of HD, biochemical data: C-reactive protein (CRP), serum albumin, calcium, phosphorus, alkaline phosphatase, parathormone. A single dentist performed a complete dental/periodontal examination, including parameters of oral hygiene and gingival bleeding. RESULTS: One person had healthy periodontium, 62.14% of the patients had gingivitis, and 36.9% had moderate or severe periodontitis. The age at HD onset had a positive impact on periodontal status and negatively correlated with the number of teeth. A positive correlation between age and CRP level and negative correlations between age and serum albumin and phosphorus were found. Pocket depth (PD) was negatively correlated with serum albumin. The number of teeth was negatively correlated with serum CRP. CONCLUSIONS: High prevalence and severity of periodontal disease are observed in hemodialysis patients. There is a high probability that periodontal disease may be present at the early stages of chronic kidney disease (CKD) before the hemodialysis onset.

The association between periodontal conditions, inflammation, nutritional status and calcium-phosphate metabolism disorders in hemodialysis patients

Abstract Objectives To analyze the association between periodontal conditions and inflammation, nutritional status and calcium-phosphate metabolism disorders in hemodialysis (HD) patients. Material and Methods We analyzed 128 HD patients divided into two groups: dentate (n = 103) and edentulous (n=25). The following items were assessed: baseline characteristics, age at the start and duration of HD, biochemical data: C-reactive protein (CRP), serum albumin, calcium, phosphorus, alkaline phosphatase, parathormone. A single dentist performed a complete dental/periodontal examination, including parameters of oral hygiene and gingival bleeding. Results One person had healthy periodontium, 62.14% of the patients had gingivitis, and 36.9% had moderate or severe periodontitis. The age at HD onset had a positive impact on periodontal status and negatively correlated with the number of teeth. A positive correlation between age and CRP level and negative correlations between age and serum albumin and phosphorus were found. Pocket depth (PD) was negatively correlated with serum albumin. The number of teeth was negatively correlated with serum CRP. Conclusions High prevalence and severity of periodontal disease are observed in hemodialysis patients. There is a high probability that periodontal disease may be present at the early stages of chronic kidney disease (CKD) before the hemodialysis onset.

Familial hypomagnesemia with hypercalciuria and nephrocalcinosis: blocking endocytosis restores surface expression of a novel Claudin-16 mutant that lacks the entire C-terminal cytosolic tail.

Mutations in the gene for Claudin-16 (CLDN16) are linked to familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), a renal Mg2+ and Ca2+ wasting disorder that leads to progressive kidney failure. More than 20 mutations have been identified in CLDN16, which, with a single exception, affect one of two extracellular loops or one of four transmembrane domains of the encoded protein. Here, we describe a novel missense mutation, Cldn16 L203X, which deletes the entire C-terminal cytosolic domain of the protein. Surface expression of Cldn16 L203X is strongly reduced and the protein is instead found in the endoplasmic reticulum (ER) and lysosomes. ER-retained Cldn16 L203X is subject to proteasomal degradation. Cldn16 L203X present in lysosomes reaches this compartment following transport to the plasma membrane and endocytosis. Blocking clathrin-mediated endocytosis increases surface expression of Cldn16 L203X. Thus, endocytosis inhibitors may provide a novel therapeutic approach for FHHNC patients carrying particular Cldn16 mutations.

Association of disorders in mineral metabolism with progression of chronic kidney disease.

Abnormalities of mineral metabolism are associated with increased mortality in patients with ESRD, but their effects in predialysis chronic kidney disease (CKD) are less well characterized. In this study, the associations between levels of serum phosphorus, calcium, and calcium-phosphorus product and progression of CKD were examined. Historical data were collected on 985 male US veterans (age 67.4 +/- 10.9; 23.9% black) with CKD stages 1 through 5. Unadjusted and multivariable-adjusted relative risks for progressive CKD (defined as the composite of ESRD or doubling of serum creatinine) were calculated for categories of serum phosphorus, calcium, and calcium-phosphorus product using Cox proportional hazards models. Higher phosphorus was associated with a higher risk for the composite end point (adjusted hazard ratio [HR] [95% confidence interval (CI)] for phosphorus levels 3.3 to 3.8, 3.81 to 4.3, and >4.3 versus <3.3 mg/dl 0.83 [0.54 to 1.27], 1.24 [0.82 to 1.88], and 1.60 [1.06 to 2.41]; P = 0.001 for trend). A 1-mg/dl higher phosphorus level was associated with an adjusted HR (95% CI) of 1.29 (1.12 to 1.48; P < 0.001). Higher calcium-phosphorus product also was associated with higher risk for progressive CKD (adjusted HR [95% CI] for calcium-phosphorus products 30 to 35, 36 to 40, and >40 versus <30 mg2/dl2 0.58 [0.36 to 0.94], 0.87 [0.57 to 1.34], and 1.37 [0.91 to 2.07]; P = 0.002 for trend). A 10-mg2/dl2 higher calcium-phosphorus product was associated with an adjusted HR (95% CI) of 1.29 (1.11 to 1.51; P = 0.001). Lower serum calcium showed a trend toward higher risk for progressive CKD but without statistical significance. Higher serum phosphorus and higher calcium-phosphorus product are associated with progression of CKD.

Hypercalciuria is a common and important finding in postmenopausal women with osteoporosis.

OBJECTIVE AND DESIGN: The prevalence and the effects of hypercalciuria on bone in patients with primary osteoporosis are poorly defined. We therefore retrospectively analyzed the data of 241 otherwise healthy women. They were 45-88 years of age and had been referred for their first visit to our Unit for Metabolic Bone Diseases over a 2-year period because of primary osteoporosis (bone density T-score < -2.5). METHODS: The main parameters of calcium and skeletal metabolism had been analyzed in all subjects. This population was then divided into two groups, according to the presence (HC+) or absence (HC-) of hypercalciuria. RESULTS: Elevated urinary calcium was present in 19% of the subjects. Due to the selection criteria, spinal and femoral bone loss was similar in the two groups. Urinary calcium, phosphate and fractional calcium excretion were higher in hypercalciuric patients. In a logistic regression model, the higher the Tm of phosphate, the lower the risk of hypercalciuria (odds ratio 0.33, confidence interval 0.18-0.62). On the contrary, hypercalciuria was the most important predictor of low bone mass in HC+ (accounting for more than 50% of the variance in spinal bone density). CONCLUSIONS: Hypercalciuria is a common feature in postmenopausal bone loss. Since increased urinary calcium excretion and low bone mass appear to be linked, hypercalciuria seems to be an important determinant of reduced bone density in this setting as well.

Reduced bone mass in children with idiopathic hypercalciuria and in their asymptomatic mothers.

BACKGROUND: Patients with nephrolithiasis and idiopathic hypercalciuria (IH) may exhibit reduced bone mineral density (BMD). Most studies measuring BMD in IH patients employing dual-energy X-ray absorptiometry (DEXA) have been performed in adults, and no study has been conducted in North-American children. Optimal bone mineral accretion during childhood and adolescence is critical to the attainment of a healthy adult skeleton. Bone mineral accretion and eventual adult peak bone mass are largely dependent on genetic factors. Hypercalciuria is also frequently linked to genetic determinants. Therefore, we carried out a cross-sectional evaluation of bone mineral metabolism in children with IH, and in their asymptomatic premenopausal mothers. METHODS: Quantitative BMD using DEXA was performed in 21 children with IH and in their asymptomatic mothers. Bone resorption was assessed by measuring the urinary concentrations of pyridinoline and deoxypiridinoline. Simultaneous calcium-modulating hormonal determinations, including serum intact immunoreactive parathyroid hormone and 1,25(OH)(2)D(3), were performed. The expression of interleukin-1alpha (IL-1alpha) by peripheral blood mononuclear cells (PBMCs) was determined by polymerase chain reaction. RESULTS: Reduced BMD values were observed in eight children (38%) and in seven mothers (33%). The children of osteopenic mothers exhibited significantly reduced BMD Z-score values of lumbar spine (P<0.05) when compared with children of mothers with normal BMD. Bone resorption markers were normal in most children with IH. Hypercalciuria was detected in five out of 20 (25%) asymptomatic mothers and it correlated (r=-0.81) to femoral BMD in mothers with osteopenia. The expression of IL-1alpha mRNA by PBMCs from IH children did not differ from controls. CONCLUSIONS: Reduced BMD was detected in a large proportion of children with IH. Hypercalciuria and reduced BMD were uncovered in a substantial number of their otherwise healthy asymptomatic mothers. The diminished BMD in adults with IH may start early in life, could be influenced by genetic factors, and may represent a risk factor for osteoporosis later in life.

Multiple electrolyte abnormalities after pamidronate administration.

Pamidronate constitutes a major advance in the treatment of tumor-associated hypercalcemia. However, transient electrolyte abnormalities have been reported after pamidronate administration. We describe here a patient with multiple myeloma and severe hypercalcemia who developed transient but significant electrolyte disturbances (mainly hypophosphatemia and hypomagnesemia) after a single dose of 90 mg of pamidronate, focusing on the underlying pathophysiological mechanisms.

Hypercalciuria and hematuria in juvenile rheumatoid arthritis.

OBJECTIVE: To investigate the frequency of hypercalciuria and the relationship between hypercalciuria and hematuria in patients with juvenile rheumatoid arthritis (JRA). METHODS: Twenty-eight children with JRA were studied, as well as 10 patients with acute arthritis unrelated to JRA and 14 healthy children as control groups. Cases with urinary calcium excretion (UCE) >4 mg/kg/day were considered hypercalciuric. Urinalysis was performed for detecting hematuria in all cases. RESULTS: UCE was 4.19 +/- 2.9 mg/kg/day in patients with JRA, 1.94 +/- 1.57 mg/kg/day in children with acute arthritis, and 2.0 +/- 1.45 mg/kg/day in healthy children. UCE was significantly higher in JRA compared with the other study groups. Of the 28 patients with JRA, 13 (46.4%) had hypercalciuria and 6 (21.4%) had hematuria. UCE was significantly higher in hematuric patients with JRA than in those with no hematuria (p<0.05). UCE in patients with JRA without hematuria was also higher than the UCE values detected in the disease and healthy control groups (p<0.05). CONCLUSION: Hypercalciuria is a frequent finding in patients with JRA [13/28 (46.4%)] and should be considered during the investigation of hematuria in patients with JRA.

[The use of xidifon for the correction of phosphorus-calcium metabolism in patients in the terminal stage of chronic kidney failure who are on programmed hemodialysis]. / Primenenie ksidifona dlia korrektsii fosforno-kal'tsievogo obmena u bol'nykh s terminal'noi stadiei khronicheskoi pochechnoi nedostatochnosti, nakhodiashchikhsia na programmnom gemodialeze.

Correction of impaired phosphoric-calcium metabolism was performed in 15 hemodialysis patients with terminal chronic renal failure (TCRF). For this purpose a synthetic analogue of pyrophosphoric acid xidiphone produced in Russia was used (2% aqueous solution 1 tablespoon 3 times a day 0.5 h before meal for 2-3 months). Prior to and in the course of xidiphone treatment all the patients received calcium gluconate (1 g x 3 daily), polyvitamins, on-demand digoxine. Measurements of serum concentrations of urea, potassium, sodium, total calcium, alkaline phosphatase activity demonstrated xidiphone-related normalization of serum total calcium, serum activity of alkaline phosphatase, a mild rise of sodium. The results say in favor of using xidiphone in the TCRF patients.

Investigation of calcium disorders.

The advent of new two-site immunometric assays for intact parathyroid hormone (PTH) measurement has enhanced the interpretation of results in many patients under investigation for hypercalcemia. The aim of this article is to give practical advice on the use of the new intact PTH methods and other tests for the investigation of the more common disorders of calcium metabolism.

Urinary citrate, bone resorption and intestinal alkali absorption in stone formers with fasting hypercalciuria.

Reduced citrate in urine and increased fasting excretion of calcium are abnormalities frequently reported in stone forming (SF) patients. Increased dietary acid (or reduced alkali) introduction or absorption may be a potential cause of both these pathological findings. To test this hypothesis, we studied 64 SF patients (32 with fasting hypercalciuria (FH) and 32 without FH (NFH)). After a basal evaluation for nephrolithiasis, while on a 500 mg calcium diet, they were evaluated for: (1) daily intestinal alkali absorption (IAA), by urinary electrolyte excretion; (2) basal concentrations of PTH, calcitonin (CT) and 1,25(OH)2-VitD; (3) oral calcium load for evaluation of changes in calcium and hydroxyproline urinary excretions; (4) intestinal calcium absorption (18 patients), with double curve analysis (stable Sr as tracer); and (5) changes in citrate excretion after an alkali load (50 mEq of a mixture of calcium gluconate, lactate and carbonate) in 10 patients. The results demonstrated: (1) FH stone formers had reduced citrate excretion and lower mean IAA levels than NFH stone formers; (2) FH stone formers also had higher bone resorption levels with lower PTH and higher CT levels; (3) IAA levels were related to both citrate excretion and bone turnover indices; and (4) the increases in citrate excretion after oral alkali load were strictly related to basal IAA values (index of alkali absorption and/or generation after oral load), demonstrating that a different absorptive capacity of alkali rather than a different dietary content may underlie these metabolic abnormalities.

[Dysregulation of plasma 1,25(OH)2D in calcium restriction in hypercalciuric children]. / Dysrégulation du 1,25(OH)2D plasmatique au cours d'une restriction calcique chez des enfants hypercalciuriques.

BACKGROUND: The effect of calcium restriction on the plasma concentration of 1,25(OH)2D in normo- and hypercalciuric children remains unknown. METHODS: We studied phosphate and calcium metabolism of 8 normocalciuric and 8 hypercalciuric children aged 4 to 16 years, under 3 conditions: on a normal dietary calcium intake after a 5-day calcium-restricted diet, and after oral calcium loading. The healthy, normocalciuric children had histories that included no renal failure of abnormalities of phosphate and calcium metabolism. Four of the 8 hypercalciuric children had urolithiasis, 1 had hematuria and the 3 others had idiopathic hypercalciuria. Blood samples were analyzed for calcium, creatinine, immunoreactive parathyroid hormone, cAMP, 25(OH)D and 1,25(OH)2D concentrations. Urine samples were analyzed for calcium, phosphorus, creatinine and cAMP. RESULTS: On the normal dietary calcium intake, the hypercalciuric children had higher urinary calcium excretion and plasma 1,25(OH)2D levels and lower TmP that did the controls. The 1,25(OH)2D levels of the normocalciuric children were significantly increased after 5 days of dietary calcium deprivation, but those of the hypercalciuric children were not. The other parameters (essentially PTH, cAMP and TmP) varied similarly in the two groups. CONCLUSION: The results suggest that: a) calcium restriction influences 1,25(OH)2D levels in normocalciuric subjects via a PTH- and phosphor-independent mechanism; b) dietary control of renal vitamin D metabolism is impaired in hypercalciuric patients.

[Vitamin A and metabolic disorders of calcium and phosphorus in patients on a long-term dialysis program]. / Vitamín A a metabolické poruchy vápnika a fosforu u chorych v dlhodobom dialyzacnom programe.

The aim of the present work was to reveal the relationship between vitamin A serum levels and some indicators of metabolic calcium and phosphorus disorders in patients in a long-term dialyzation programme. Thirty-six patients in a long-term dialyzation programme were divided into three groups. Group A comprised 11 patients who were treated for 3-9 months but without specific treatment, group B was formed by 10 patients treated for 2-5 years who were given calcium carbonate, 3 g/24 h, by the oral route for a period of six months and group C which comprised 15 patients treated for 3-10 years who were given 1 alpha, 25-dihydroxycholecalciferol (Rocaltrol), 0.25 micrograms/24 h for a period of six months. At the end of the investigation a significant rise of total calcium and serum Ca2+ occurred in all three groups of patients an a significant decrease of increased value of phosphorus, C-PTH and vitamin A in serum in groups B and C. In group A which was without treatment there was a significant increase of serum C-PTH and vitamin A after six months. The concentration of retinyl esters in serum was within the reference range of there were undetectable values throughout the investigation in all patients. A direct relationship was found between total calcium and vitamin A, alkaline phosphatase and C-PTH in serum in all 36 patients at the onset of the dialyzation programme. Moreover there was a direct relationship between C-PTH and vitamin A in groups, A, B and C at the onset of the investigation and in groups and vitamin C at the end of the investigation.(ABSTRACT TRUNCATED AT 250 WORDS)