Search Results
Department of Nutrition, Institute of Life Sciences, Federal University of Juiz de Fora, Governador Valadares, Minas Gerais, Brazil
Department of Nutrition, Faculty of Health and Medical Sciences, University of Surrey, University of Surrey, Guildford, UK
Search for other papers by Marcela Moraes Mendes in
Google Scholar
PubMed
Search for other papers by Patricia Borges Botelho in
Google Scholar
PubMed
Search for other papers by Helena Ribeiro in
Google Scholar
PubMed
Vitamin D enhances calcium absorption and bone mineralisation, promotes maintenance of muscle function, and is crucial for musculoskeletal health. Low vitamin D status triggers secondary hyperparathyroidism, increases bone loss, and leads to muscle weakness. The primary physiologic function of vitamin D and its metabolites is maintaining calcium homeostasis for metabolic functioning, signal transduction, and neuromuscular activity. A considerable amount of human evidence supports the well-recognised contribution of adequate serum 25-hydroxyvitamin D concentrations for bone homeostasis maintenance and prevention and treatment strategies for osteoporosis when combined with adequate calcium intake. This paper aimed to review the literature published, mainly in the last 20 years, on the effect of vitamin D and its supplementation for musculoskeletal health in order to identify the aspects that remain unclear or controversial and therefore require further investigation and debate. There is a clear need for consistent data to establish realistic and meaningful recommendations of vitamin D status that consider different population groups and locations. Moreover, there is still a lack of consensus on thresholds for vitamin D deficiency and optimal status as well as toxicity, optimal intake of vitamin D, vitamin D supplement alone as a strategy to prevent fractures and falls, recommended sun exposure at different latitudes and for different skin pigmentations, and the extra skeletal effects of vitamin D.
Search for other papers by Ghazala Zaidi in
Google Scholar
PubMed
Search for other papers by Vijayalakshmi Bhatia in
Google Scholar
PubMed
Search for other papers by Saroj K Sahoo in
Google Scholar
PubMed
Search for other papers by Aditya Narayan Sarangi in
Google Scholar
PubMed
Search for other papers by Niharika Bharti in
Google Scholar
PubMed
Search for other papers by Li Zhang in
Google Scholar
PubMed
Search for other papers by Liping Yu in
Google Scholar
PubMed
Search for other papers by Daniel Eriksson in
Google Scholar
PubMed
Search for other papers by Sophie Bensing in
Google Scholar
PubMed
Science for Life Laboratory, Department of Medical Sciences, Uppsala University, Sweden
Search for other papers by Olle Kämpe in
Google Scholar
PubMed
Search for other papers by Nisha Bharani in
Google Scholar
PubMed
Search for other papers by Surendra Kumar Yachha in
Google Scholar
PubMed
Search for other papers by Anil Bhansali in
Google Scholar
PubMed
Search for other papers by Alok Sachan in
Google Scholar
PubMed
Search for other papers by Vandana Jain in
Google Scholar
PubMed
Search for other papers by Nalini Shah in
Google Scholar
PubMed
Search for other papers by Rakesh Aggarwal in
Google Scholar
PubMed
Search for other papers by Amita Aggarwal in
Google Scholar
PubMed
Search for other papers by Muthuswamy Srinivasan in
Google Scholar
PubMed
Search for other papers by Sarita Agarwal in
Google Scholar
PubMed
Search for other papers by Eesh Bhatia in
Google Scholar
PubMed
Objective
Autoimmune polyendocrine syndrome type 1 (APS1) is a rare autosomal recessive disorder characterized by progressive organ-specific autoimmunity. There is scant information on APS1 in ethnic groups other than European Caucasians. We studied clinical aspects and autoimmune regulator (AIRE) gene mutations in a cohort of Indian APS1 patients.
Design
Twenty-three patients (19 families) from six referral centres in India, diagnosed between 1996 and 2016, were followed for [median (range)] 4 (0.2–19) years.
Methods
Clinical features, mortality, organ-specific autoantibodies and AIRE gene mutations were studied.
Results
Patients varied widely in their age of presentation [3.5 (0.1–17) years] and number of clinical manifestations [5 (2–11)]. Despite genetic heterogeneity, the frequencies of the major APS1 components (mucocutaneous candidiasis: 96%; hypoparathyroidism: 91%; primary adrenal insufficiency: 55%) were similar to reports in European series. In contrast, primary hypothyroidism (23%) occurred more frequently and at an early age, while kerato-conjunctivitis, urticarial rash and autoimmune hepatitis were uncommon (9% each). Six (26%) patients died at a young age [5.8 (3–23) years] due to septicaemia, hepatic failure and adrenal/hypocalcaemic crisis from non-compliance/unexplained cause. Interferon-α and/or interleukin-22 antibodies were elevated in all 19 patients tested, including an asymptomatic infant. Eleven AIRE mutations were detected, the most common being p.C322fsX372 (haplotype frequency 37%). Four mutations were novel, while six others were previously described in European Caucasians.
Conclusions
Indian APS1 patients exhibited considerable genetic heterogeneity and had highly variable clinical features. While the frequency of major manifestations was similar to that of European Caucasians, other features showed significant differences. A high mortality at a young age was observed.
Search for other papers by E Vignali in
Google Scholar
PubMed
Search for other papers by F Cetani in
Google Scholar
PubMed
Search for other papers by S Chiavistelli in
Google Scholar
PubMed
Search for other papers by A Meola in
Google Scholar
PubMed
Search for other papers by F Saponaro in
Google Scholar
PubMed
Search for other papers by R Centoni in
Google Scholar
PubMed
Search for other papers by L Cianferotti in
Google Scholar
PubMed
Endocrine Unit 2, Department of Clinical and Experimental Medicine, Laboratory of Chemistry and Endocrinology, University Hospital of Pisa, Via Paradisa 2, 56124 Pisa, Italy
Search for other papers by C Marcocci in
Google Scholar
PubMed
We investigated the prevalence of normocalcemic primary hyperparathyroidism (NPHPT) in the adult population living in a village in Southern Italy. All residents in 2010 (n=2045) were invited by calls and 1046 individuals accepted to participate. Medical history, calcium intake, calcium, albumin, creatinine, parathyroid hormone (PTH) and 25OHD were evaluated. NPHPT was defined by normal albumin-adjusted serum calcium, elevated plasma PTH, and exclusion of common causes of secondary hyperparathyroidism (SHPT) (serum 25OHD <30 ng/ml, estimated glomerular filtration rate (eGFR) <60 ml/min per 1.73 m2 and thiazide diuretics use), overt gastrointestinal and metabolic bone diseases. Complete data were available for 685 of 1046 subjects. Twenty subjects did not meet the inclusion criteria and 341 could not be evaluated because of thawing of plasma samples. Classical PHPT was diagnosed in four women (0.58%). For diagnosing NPHPT the upper normal limit of PTH was established in the sample of the population (n=100) who had 25OHD ≥30 ng/ml and eGFR ≥60 ml/min per 1.73 m2 and was set at the mean+3s.d. Three males (0.44%) met the diagnostic criteria of NPHPT. These subjects were younger and with lower BMI than those with classical PHPT. Our data suggest, in line with previous studies, that NPHPT might be a distinct clinical entity, being either an early phenotype of asymptomatic PHPT or a distinct variant of it. However, we cannot exclude that NPHPT might also represent an early phase of non-classical SHPT, since other variables, in addition to those currently taken into account for the diagnosis of NPHPT, might cumulate in a normocalcemic subject to increase PTH secretion.
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Marie Reeberg Sass in
Google Scholar
PubMed
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark
Search for other papers by Nicolai Jacob Wewer Albrechtsen in
Google Scholar
PubMed
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Department of Endocrinology and Nephrology, Nordsjællands University Hospital, Hillerød, Denmark
Search for other papers by Jens Pedersen in
Google Scholar
PubMed
Search for other papers by Kristine Juul Hare in
Google Scholar
PubMed
Center for Neonatal Screening, Department of Congenital Disorders, Statens Serum Institute, Copenhagen, Denmark
Search for other papers by Nis Borbye-Lorenzen in
Google Scholar
PubMed
Search for other papers by Katalin Kiss in
Google Scholar
PubMed
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
Search for other papers by Tina Vilsbøll in
Google Scholar
PubMed
Steno Diabetes Center Copenhagen, Gentofte, Denmark
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
Search for other papers by Filip Krag Knop in
Google Scholar
PubMed
Search for other papers by Steen Seier Poulsen in
Google Scholar
PubMed
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Niklas Rye Jørgensen in
Google Scholar
PubMed
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Jens Juul Holst in
Google Scholar
PubMed
Search for other papers by Cathrine Ørskov in
Google Scholar
PubMed
Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Search for other papers by Bolette Hartmann in
Google Scholar
PubMed
Objective:
Parathyroid hormone (PTH) is a key hormone in regulation of calcium homeostasis and its secretion is regulated by calcium. Secretion of PTH is attenuated during intake of nutrients, but the underlying mechanism(s) are unknown. We hypothesized that insulin acts as an acute regulator of PTH secretion.
Methods:
Intact PTH was measured in plasma from patients with T1D and matched healthy individuals during 4-h oral glucose tolerance tests (OGTT) and isoglycemic i.v. glucose infusions on 2 separate days. In addition, expression of insulin receptors on surgical specimens of parathyroid glands was assessed by immunochemistry (IHC) and quantitative PCR (qPCR).
Results:
The inhibition of PTH secretion was more pronounced in healthy individuals compared to patients with T1D during an OGTT (decrementalAUC0–240min: −5256 ± 3954 min × ng/L and −2408 ± 1435 min × ng/L, P = 0.030). Insulin levels correlated significantly and inversely with PTH levels, also after adjusting for levels of several gut hormones and BMI (P = 0.002). Expression of insulin receptors in human parathyroid glands was detected by both IHC and qPCR.
Conclusion:
Our study suggests that insulin may act as an acute regulator of PTH secretion in humans.
Search for other papers by Gabriella Oliveira Lima in
Google Scholar
PubMed
Search for other papers by Alex Luiz Menezes da Silva in
Google Scholar
PubMed
Search for other papers by Julianne Elba Cunha Azevedo in
Google Scholar
PubMed
Search for other papers by Chirlene Pinheiro Nascimento in
Google Scholar
PubMed
Search for other papers by Luana Rodrigues Vieira in
Google Scholar
PubMed
Search for other papers by Akira Otake Hamoy in
Google Scholar
PubMed
Search for other papers by Luan Oliveira Ferreira in
Google Scholar
PubMed
Search for other papers by Verônica Regina Lobato Oliveira Bahia in
Google Scholar
PubMed
Search for other papers by Nilton Akio Muto in
Google Scholar
PubMed
Search for other papers by Dielly Catrina Favacho Lopes in
Google Scholar
PubMed
Search for other papers by Moisés Hamoy in
Google Scholar
PubMed
Low plasma levels of vitamin D causes bone mineral change that can precipitate osteopenia and osteoporosis and could aggravate autoimmune diseases, hypertension and diabetes. The demand for vitamin D supplementation becomes necessary; however, the consumption of vitamin D is not without risks, which its toxicity could have potentially serious consequences related to hypervitaminosis D, such as hypercalcemia and cerebral alterations. Thus, the present study describes the electroencephalographic changes caused by supraphysiological doses of vitamin D in the brain electrical dynamics and the electrocardiographic changes. After 4 days of treatment with vitamin D at a dose of 25,000 IU/kg, the serum calcium levels found were increased in comparison with the control group. The electrocorticogram analysis found a reduction in wave activity in the delta, theta, alpha and beta frequency bands. For ECG was observed changes with shortened QT follow-up, which could be related to serum calcium concentration. This study presented important evidence about the cerebral and cardiac alterations caused by high doses of vitamin D, indicating valuable parameters in the screening and decision-making process for diagnosing patients with symptoms suggestive of intoxication.
Search for other papers by Glenville Jones in
Google Scholar
PubMed
Vitamin D has many physiological functions including upregulation of intestinal calcium and phosphate absorption, mobilization of bone resorption, renal reabsorption of calcium as well as actions on a variety of pleiotropic functions. It is believed that many of the hormonal effects of vitamin D involve a 1,25-dihydroxyvitamin D3-vitamin D receptor-mediated transcriptional mechanism involving binding to the cellular chromatin and regulating hundreds of genes in many tissues. This comprehensive historical review provides a unique perspective of the many steps of the discovery of vitamin D and its deficiency disease, rickets, stretching from 1650 until the present. The overview is divided into four distinct historical phases which cover the major developments in the field and in the process highlighting the: (a) first recognition of rickets or vitamin D deficiency; (b) discovery of the nutritional factor, vitamin D and its chemical structure; (c) elucidation of vitamin D metabolites including the hormonal form, 1,25-dihydroxyvitamin D3; (d) delineation of the vitamin D cellular machinery, functions and vitamin D-related diseases which focused on understanding the mechanism of action of vitamin D in its many target cells.
Search for other papers by E M Winter in
Google Scholar
PubMed
Search for other papers by A Ireland in
Google Scholar
PubMed
Search for other papers by N C Butterfield in
Google Scholar
PubMed
Search for other papers by M Haffner-Luntzer in
Google Scholar
PubMed
Search for other papers by M-N Horcajada in
Google Scholar
PubMed
Jan van Goyen Medical Center, Department of Internal Medicine, Amsterdam, the Netherlands
Search for other papers by A G Veldhuis-Vlug in
Google Scholar
PubMed
Department of Epidemiology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands
Search for other papers by L Oei in
Google Scholar
PubMed
Search for other papers by G Colaianni in
Google Scholar
PubMed
Search for other papers by N Bonnet in
Google Scholar
PubMed
In this review we discuss skeletal adaptations to the demanding situation of pregnancy and lactation. Calcium demands are increased during pregnancy and lactation, and this is effectuated by a complex series of hormonal changes. The changes in bone structure at the tissue and whole bone level observed during pregnancy and lactation appear to largely recover over time. The magnitude of the changes observed during lactation may relate to the volume and duration of breastfeeding and return to regular menses. Studies examining long-term consequences of pregnancy and lactation suggest that there are small, site-specific benefits to bone density and that bone geometry may also be affected. Pregnancy- and lactation-induced osteoporosis (PLO) is a rare disease for which the pathophysiological mechanism is as yet incompletely known; here, we discuss and speculate on the possible roles of genetics, oxytocin, sympathetic tone and bone marrow fat. Finally, we discuss fracture healing during pregnancy and lactation and the effects of estrogen on this process.
Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada
Search for other papers by Huma Qamar in
Google Scholar
PubMed
Department of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada
Search for other papers by Nandita Perumal in
Google Scholar
PubMed
Search for other papers by Eszter Papp in
Google Scholar
PubMed
Search for other papers by Alison D Gernand in
Google Scholar
PubMed
Search for other papers by Abdullah Al Mahmud in
Google Scholar
PubMed
Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada
Department of Paediatrics, Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada
Search for other papers by Daniel E Roth in
Google Scholar
PubMed
Intrauterine growth restriction (IUGR) reflects inadequate growth in-utero and is prevalent in low resource settings. This study aimed to assess the association of maternal delivery parathyroid hormone (PTH) – a regulator of bone turnover and calcium homeostasis – with newborn anthropometry, to identify regulators of PTH, and to delineate pathways by which maternal PTH regulates birth size using path analysis. This was a cross-sectional analysis of data from participants (n = 537) enrolled in the Maternal Vitamin D for Infant Growth trial in Dhaka, Bangladesh. Primary exposures were maternal delivery intact PTH (iPTH) or whole PTH (wPTH) and outcomes were gestational age- and sex-standardized z-scores for birth length (LAZ), weight (WAZ), and head circumference (HCAZ). Hypothesized regulators of PTH included calcium and protein intake, vitamin D, magnesium, fibroblast-like growth factor-23 (FGF23), and C-reactive protein. Maternal iPTH was not associated with birth size in linear regression analyses; however, in path analysis models, every SD increase in log(iPTH) was associated with 0.08SD (95% CI: 0.002, 0.162) higher LAZ. In linear regression and path analysis models, wPTH was positively associated with WAZ. Vitamin D suppressed PTH, while FGF23 was positively associated with PTH. In path analysis models, higher magnesium was negatively associated with LAZ; FGF23 was positively associated and protein intake was negatively associated with LAZ, WAZ, and HCAZ. Higher maternal PTH in late pregnancy is unlikely to contribute to IUGR. Future studies should investigate maternal FGF23, magnesium and protein intake as regulators of fetal growth, particularly in settings where food insecurity and IUGR are public health problems.
Search for other papers by Laura J Reid in
Google Scholar
PubMed
Search for other papers by Bala Muthukrishnan in
Google Scholar
PubMed
Search for other papers by Dilip Patel in
Google Scholar
PubMed
Search for other papers by Mike S Crane in
Google Scholar
PubMed
Search for other papers by Murat Akyol in
Google Scholar
PubMed
Search for other papers by Andrew Thomson in
Google Scholar
PubMed
Centre for Cardiovascular Science, Queen’s Medical Research Unit, University of Edinburgh, Edinburgh, UK
Search for other papers by Jonathan R Seckl in
Google Scholar
PubMed
Search for other papers by Fraser W Gibb in
Google Scholar
PubMed
Objective
Primary hyperparathyroidism (PHPT) is a common reason for referral to endocrinology but the evidence base guiding assessment is limited. We evaluated the clinical presentation, assessment and subsequent management in PHPT.
Design
Retrospective cohort study.
Patients
PHPT assessed between 2006 and 2014 (n = 611) in a university hospital.
Measurements
Symptoms, clinical features, biochemistry, neck radiology and surgical outcomes.
Results
Fatigue (23.8%), polyuria (15.6%) and polydipsia (14.9%) were associated with PHPT biochemistry. Bone fracture was present in 16.4% but was not associated with biochemistry. A history of nephrolithiasis (10.0%) was associated only with younger age (P = 0.006) and male gender (P = 0.037). Thiazide diuretic discontinuation was not associated with any subsequent change in calcium (P = 0.514). Urine calcium creatinine clearance ratio (CCCR) was <0.01 in 18.2% of patients with confirmed PHPT. Older age (P < 0.001) and lower PTH (P = 0.043) were associated with failure to locate an adenoma on ultrasound (44.0% of scans). When an adenoma was identified on ultrasound the lateralisation was correct in 94.5%. Non-curative surgery occurred in 8.2% and was greater in those requiring more than one neck imaging modality (OR 2.42, P = 0.035).
Conclusions
Clinical features associated with PHPT are not strongly related to biochemistry. Thiazide cessation does not appear to attenuate hypercalcaemia. PHPT remains the likeliest diagnosis in the presence of low CCCR. Ultrasound is highly discriminant when an adenoma is identified but surgical failure is more likely when more than one imaging modality is required.
Search for other papers by Stan Ursem in
Google Scholar
PubMed
Search for other papers by Vito Francic in
Google Scholar
PubMed
Search for other papers by Martin Keppel in
Google Scholar
PubMed
Search for other papers by Verena Schwetz in
Google Scholar
PubMed
Search for other papers by Christian Trummer in
Google Scholar
PubMed
Search for other papers by Marlene Pandis in
Google Scholar
PubMed
Search for other papers by Felix Aberer in
Google Scholar
PubMed
Search for other papers by Martin R Grübler in
Google Scholar
PubMed
Search for other papers by Nicolas D Verheyen in
Google Scholar
PubMed
Search for other papers by Winfried März in
Google Scholar
PubMed
Search for other papers by Andreas Tomaschitz in
Google Scholar
PubMed
Search for other papers by Stefan Pilz in
Google Scholar
PubMed
Search for other papers by Barbara Obermayer-Pietsch in
Google Scholar
PubMed
Department of Clinical Chemistry, Amsterdam Gastroenterology & Metabolism, Amsterdam UMC, University of Amsterdam, Endocrine Laboratory, Amsterdam, Netherlands
Search for other papers by Annemieke C Heijboer in
Google Scholar
PubMed
Objective
PTH can be oxidised in vivo, rendering it biologically inactive. Non-oxidised PTH (n-oxPTH) may therefore give a better image of the hormonal status of the patient. While vitamin D supplementation decreases total PTH (tPTH) concentration, the effect on n-oxPTH concentration is unexplored. We investigated the effect of vitamin D on n-oxPTH concentration in comparison to tPTH and compared the correlations between parameters of calcium, bone and lipid metabolism with n-oxPTH and tPTH.
Methods
N-oxPTH was measured in 108 vitamin D-insufficient (25(OH)D <75 nmol/L) hypertensive patients, treated with vitamin D (2800 IE daily) or placebo for 8 weeks in the Styrian Vitamin D Hypertension Trial (NCT02136771). We calculated the treatment effect and performed correlation analyses of n-oxPTH and tPTH with parameters of calcium, bone and lipid metabolism and oxidative stress.
Results
After treatment, compared to placebo, 25(OH)D concentrations increased, tPTH decreased by 9% (P < 0.001), n-oxPTH by 7% (P = 0.025) and the ratio of n-oxPTH/tPTH increased (P = 0.027). Changes in phosphate and HDL concentration correlated with changes in n-oxPTH, but not tPTH.
Conclusions
tPTH and n-oxPTH decrease upon vitamin D supplementation. Our study suggests that vitamin D supplementation reduces the oxidation of PTH, as we observed a small but significant increase in the non-oxidised proportion of PTH upon treatment. In addition, we found that changes in phosphate and HDL concentration showed a relationship with changes in n-oxPTH, but not tPTH. This may be explained by the biological activity of n-oxPTH. Further research should be carried out to establish the clinical relevance of n-oxPTH.