Oral calcium supplementation reverses the biochemical pattern of parathyroid hormone resistance in underprivileged Indian toddlers

Khadilkar, Anuradha; Mughal, M Zulf; Hanumante, N. M.; Sayyad, Mehmood G; Sanwalka, Neha; Naik, Sadanand; Fraser, William D.; Joshi, Adarsh; Khadilkar, Vaman

doi:10.1136/adc.2008.149674

Cited by 16 publications

(9 citation statements)

References 27 publications

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“…In the study population, 71 % girls showed iCa concentration below the reference range, whereas high concentrations of PTH ( > 6.4 p M ) (33) were observed in 39.5 % of the girls. In the study population, 71 % girls showed iCa concentration below the reference range, whereas high concentrations of PTH ( > 6.4 p M ) (33) were observed in 39.5 % of the girls.…”

Section: Resultsmentioning

confidence: 75%

Modifiable factors associated with low bone mineral content in underprivileged premenarchal Indian girls

Kadam

Chiplonkar

Khadilkar

et al. 2011

Journal of Pediatric Endocrinology and Metabolism

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Low adolescent peak bone mass is associated with bone problems in adulthood. Our aim was to assess underprivileged premenarchal Indian girls for low bone mineral content and to study the infl uence of anthropometric, lifestyle factors on bone health. Data on anthropometry, diet, lifestyle, total body bone mineral content (TBBMC), bone area, bone mineral density, and biochemical parameters [parathyroid hormone, vitamin D (25OH-D), calcium, and zinc] were assessed in 214 premenarchal girls (8 -12 years). Compared with the Indian reference database, 15.6 % girls had TBBMC for age Z-scores below -2 and 37.5 % had Z-scores between -2 and -1. The TBBMC for total body bone area Z-scores were below -2 for one fi fth of girls, indicating undermineralized bones. Mean rate of increase in TBBMC with age and Tanner stage was lower in our study population (11.6 % and 20.7 % , respectively) than reference database (14.2 % and 33.4 % , respectively). Low weight, 25OH-D, and intake of protein, calcium, and zinc adversely affected TBBMC (p < 0.05). Many underprivileged premenarchal Indian girls are at risk of achieving low bone mass. Steps to improve underweight, 25OH-D, intakes of protein, calcium, and zinc might improve bone health.

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Section: Resultsmentioning

confidence: 75%

Modifiable factors associated with low bone mineral content in underprivileged premenarchal Indian girls

Kadam

Chiplonkar

Khadilkar

et al. 2011

Journal of Pediatric Endocrinology and Metabolism

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“…On the other hand, several cases of PHP‐Ia with documented GNAS mutations have been reported in whom PTH levels were elevated during infancy . Moreover, although the presence of GNAS mutations was not investigated, hypocalcemia owing to PTH resistance has been reported in a substantial number of infants and newborns . Hence, it has remained unclear whether the renal proximal tubular PTH resistance caused by maternal loss of Gαs manifests itself during early postnatal life.…”

Section: Introductionmentioning

confidence: 99%

Postnatal Establishment of Allelic Gαs Silencing as a Plausible Explanation for Delayed Onset of Parathyroid Hormone Resistance Owing to Heterozygous Gαs Disruption

Turan

Fernández-Rebollo

Aydın

et al. 2013

Journal of Bone and Mineral Research

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Pseudohypoparathyroidism type-Ia (PHP-Ia), characterized by renal proximal tubular resistance to parathyroid hormone (PTH), results from maternal mutations of GNAS that lead to loss of Gαs activity. Gαs expression is paternally silenced in the renal proximal tubule, and this genomic event is critical for the development of PTH-resistance, as patients display impaired hormone action only if the mutation is inherited maternally. The primary clinical finding of PHP-Ia is hypocalcemia, which can lead to various neuromuscular defects including seizures. PHP-Ia patients frequently do not present with hypocalcemia until after infancy, but it has remained uncertain whether PTH-resistance occurs in a delayed fashion. Analyzing reported cases of PHP-Ia with documented GNAS mutations and mice heterozygous for disruption of Gnas, we herein determined that the manifestation of PTH-resistance caused by the maternal loss of Gαs, i.e. hypocalcemia and elevated serum PTH, occurs after early postnatal life. To investigate whether this delay could reflect gradual development of paternal Gαs silencing, we then analyzed renal proximal tubules isolated by laser capture microdissection from mice with either maternal or paternal disruption of Gnas. Our results revealed that, whereas expression of Gαs mRNA in this tissue is predominantly from the maternal Gnas allele at weaning (three-weeks postnatal) and in adulthood, the contributions of the maternal and paternal Gnas alleles to Gαs mRNA expression are equal at postnatal day 3. In contrast, we found that paternal Gαs expression is already markedly repressed in brown adipose tissue at birth. Thus, the mechanisms silencing the paternal Gαs allele in renal proximal tubules are not operational during early postnatal development, and this finding correlates well with the latency of PTH-resistance in patients with PHP-Ia.

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“…This characteristic implies that there is resistance to the activity of PTH in the renal tubules. There is evidence to suggest that this phenotype occurs as a consequence of dietary calcium deficiency, which corrects when adequate calcium intake is supplied [37] .…”

Section: Vitamin D Deficiencymentioning

confidence: 99%

A Practical Approach to Hypocalcaemia in Children

Shaw

2015

Calcium and Bone Disorders in Children and Adolescents

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Hypocalcaemia is one of the commonest disorders of mineral metabolism seen in children and may be a consequence of several different aetiologies. These include a lack of secretion or function of parathyroid hormone, disorders of vitamin D metabolism and abnormal function of the calcium-sensing receptor. A practical approach to the investigation, diagnosis and subsequent management of hypocalcaemic disorders is presented.

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Oral calcium supplementation reverses the biochemical pattern of parathyroid hormone resistance in underprivileged Indian toddlers

Abstract: From these data the authors conclude that low dietary calcium intake is associated with resistance to PTH.

Cited by 16 publications

References 27 publications

Modifiable factors associated with low bone mineral content in underprivileged premenarchal Indian girls

Modifiable factors associated with low bone mineral content in underprivileged premenarchal Indian girls

Postnatal Establishment of Allelic Gαs Silencing as a Plausible Explanation for Delayed Onset of Parathyroid Hormone Resistance Owing to Heterozygous Gαs Disruption

A Practical Approach to Hypocalcaemia in Children

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