Effect of vitamin D replacement on maternal and neonatal outcomes: a randomised controlled trial in pregnant women with hypovitaminosis D. A protocol

Introduction: The vitamin D recommended doses during pregnancy differ between societies. The WHO guidelines do not recommend routine prenatal supplementation, but they underscore the fact that women with the lowest levels may benefit most. The effects of routine supplementation during pregnancy on maternal and neonatal clinical outcomes have not been investigated in the Middle East, where hypovitaminosis D is prevalent. Our hypothesis is that in Middle Eastern pregnant women, a vitamin D dose of 3000?IU/day is required to reach a desirable maternal 25-hydroxyvitamin D [25(OH)D] level, and to positively impact infant bone mineral content (BMC).Methods and analysis: This is a multicentre blinded randomised controlled trial. Pregnant women presenting to the Obstetrics and Gynaecology clinics will be approached. Eligible women will be randomised to daily equivalent doses of cholecalciferol, 600?IU or 3000?IU, from 15 to 18?weeks gestation until delivery. Maternal 25(OH)D and chemistries will be assessed at study entry, during the third trimester and at delivery. Neonatal anthropometric variables and 25(OH)D level will be measured at birth, and bone and fat mass assessment by dual-energy X-ray absorptiometry scan at 1?month. A sample size of 280 pregnant women is needed to demonstrate a statistically significant difference in the proportion of women reaching a 25(OH)D level ?50?nmol/L at delivery, and a difference in infant BMC of 6 (10)g, for a 90% power and a 2.5% level of significance. The proportions of women achieving a target 25(OH)D level will be compared between the two arms, using ?2. An independent t test will be used to compare mean infant BMC between the two arms. The primary analysis is an intention-to-treat analysis of unadjusted results.Ethics and dissemination: The protocol has been approved by the Institutional Review Board at the American University of Beirut-Lebanon (IM.GEHF.22). The trial results will be published in peer-reviewed medical journals and presented at scientific conferences.Trial registration number: NCT02434380.<br/

Ethnic differences in calcium, phosphate and bone metabolism

The prevalence of osteoporosis and the incidence of age-related fragility fracture vary by ethnicity. There is greater than 10-fold variation in fracture probabilities between countries across the world. Mineral and bone metabolism are intimately interlinked, and both are known to exhibit patterns of daily variation, known as the diurnal rhythm (DR). Ethnic differences are described for Ca and P metabolism. The importance of these differences is described in detail between select ethnic groups, within the USA between African-Americans and White-Americans, between the Gambia and the UK and between China and the UK. Dietary Ca intake is higher in White-Americans compared with African-Americans, and is higher in White-British compared with Gambian and Chinese adults. Differences are observed also for plasma 25-hydroxy vitamin D, related to lifestyle differences, skin pigmentation and skin exposure to UVB-containing sunshine. Higher plasma 1,25-dihydroxy vitamin D and parathyroid hormone are observed in African-American compared with White-American adults. Plasma parathyroid hormone is also higher in Gambian adults and, in winter, in Chinese compared with White-British adults. There may be ethnic differences in the bone resorptive effects of parathyroid hormone, with a relative skeletal resistance to parathyroid hormone observed in some, but not all ethnic groups. Renal mineral excretion is also influenced by ethnicity; urinary Ca (uCa) and urinary P (uP) excretions are lower in African-Americans compared with White-Americans, and in Gambians compared with their White-British counterparts. Little is known about ethnic differences in the DR of Ca and P metabolism, but differences may be expected due to known differences in lifestyle factors, such as dietary intake and sleep/wake pattern. The ethnic-specific DR of Ca and P metabolism may influence the net balance of Ca and P conservation and bone remodelling. These ethnic differences in Ca, P and the bone metabolism may be important factors in the variation in skeletal health

Classical and nonclassical manifestations of primary hyperparathyroidism

This narrative review summarizes data on classical and nonclassical manifestations of primary hyperparathyroidism (PHPT). It is based on a rigorous literature search, inclusive of a Medline search for systematic reviews from 1940 to December 2020, coupled with a targeted search for original publications, covering four databases, from January 2013-December 2020, and relevant articles from authors' libraries. We present the most recent information, identify knowledge gaps, and suggest a research agenda. The shift in the presentation of PHPT from a predominantly symptomatic to an asymptomatic disease, with its varied manifestations, has presented several challenges. Subclinical nephrolithiasis and vertebral fractures are common in patients with asymptomatic disease. The natural history of asymptomatic PHPT with no end organ damage at diagnosis is unclear. Some observational and cross-sectional studies continue to show associations between PHPT and cardiovascular and neuropsychological abnormalities, among the different disease phenotypes. Their causal relationship is uncertain. Limited new data are available on the natural history of skeletal, renal, cardiovascular, neuropsychological, and neuromuscular manifestations and quality of life. Normocalcemic PHPT (NPHPT) is often diagnosed without the fulfillment of rigorous criteria. Randomized clinical trials have not demonstrated a consistent long-term benefit of parathyroidectomy (PTX) versus observation on nonclassical manifestations. We propose further refining the definition of asymptomatic disease, into two phenotypes: one without and one with evidence of target organ involvement, upon the standard evaluation detailed in our recommendations. Each of these phenotypes can present with or without non-classical manifestations. We propose multiple albumin-adjusted serum calcium determinations (albumin-adjusted and ionized) and exclusion of all secondary causes of high parathyroid hormone (PTH) when establishing the diagnosis of NPHPT. Refining the definition of asymptomatic disease into the phenotypes proposed will afford insights into their natural history and response to interventions. This would also pave the way for the development of evidence-based guidance and recommendations. (c) 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

Regional variation and determinants of vitamin D status in sunshine-abundant Thailand

<p>Abstract</p> <p>Background</p> <p>Vitamin D insufficiency is highly prevalent. Most of the studies concerning vitamin D status were generated from countries situated at temperate latitudes. It is less clear what the extent of vitamin D insufficiency is in countries situated in the tropics and how geographical regions within country would affect vitamin D status. In the present study, we investigated vitamin D status in Thais according to geographical regions and other risk factors.</p> <p>Methods</p> <p>Subjects consisted of 2,641 adults, aged 15 - 98 years, randomly selected from the Thai 4th National Health Examination Survey (2008-9) cohort. Serum 25 hydroxyvitamin D were measured by liquid chromatography/tandem mass spectrometry. Data were expressed as mean ± SE.</p> <p>Results</p> <p>Subjects residing in Bangkok, the capital city of Thailand, had lower 25(OH)D levels than other parts of the country (Bangkok, central, northern, northeastern and southern regions: 64.8 ± 0.7, 79.5 ± 1.1, 81.7 ± 1.2, 82.2 ± 0.8 and 78.3 ± 1.3 nmol/L, respectively; <it>p </it>< 0.001). Within each region, except for the northeastern part of the country, subjects living inside municipal areas had lower circulating 25(OH)D (central, 77.0 ± 20.9 nmol/L vs 85.0 ± 22.1 nmol/L, <it>p </it>< 0.001; north 79.3 ± 22.1 nmol/L vs 86.8 ± 21.8 nmol/L, <it>p </it>< 0.001; northeast 84.1 ± 23.3 nmol/L vs 87.3 ± 20.9 nmol/L, <it>p </it>= 0.001; south, 76.6 ± 20.5 nmol/L vs 85.2 ± 24.7 nmol/L, <it>p </it>< 0.001). Overall, the prevalence of vitamin D insufficiency was 64.6%, 46.7%, and 33.5% in Bangkok, municipal areas except Bangkok, and outside municipal area in other parts of the country, respectively. In addition, the prevalence of vitamin D insufficiency according to geographical regions was 43.1%, 39.1%, 34.2% and 43.8% in the central, north, northeast and south, respectively. After controlling for covariates in multiple linear regression analysis, the results showed that low serum 25(OH)D levels were associated with being female, younger age, living in urban and Bangkok.</p> <p>Conclusions</p> <p>Vitamin D insufficiency is common and varies across geographical regions in Thailand.</p

Prediction of winter vitamin D status and requirements in the UK population based on 25(OH) vitamin D half-life and dietary intake data

On a population basis, there is a gradual decline in vitamin D status (plasma 25(OH)D) throughout winter. We developed a mathematical model to predict the population winter plasma 25(OH)D concentration longitudinally, using age-specific values for 25(OH)D expenditure (25(OH)D3t1/2), cross-sectional plasma 25(OH)D concentration and vitamin D intake (VDI) data from older (70+ years; n=492) and younger adults (18-69 years; n=448) participating in the UK National Diet and Nutrition Survey. From this model, the population VDI required to maintain the mean plasma 25(OH)D at a set concentration can be derived. As expected, both predicted and measured population 25(OH)D (mean (95%CI)) progressively declined from September to March (from 51 (40-61) to 38 (36-41)nmol/L (predicted) vs 38 (27-48)nmol/L (measured) in older people and from 59 (54-65) to 34 (31-37)nmol/L (predicted) vs 37 (31-44)nmol/L (measured) in younger people). The predicted and measured mean values closely matched. The predicted VDIs required to maintain mean winter plasma 25(OH)D at 50nmol/L at the population level were 10 (0-20) to 11 (9-14) and 11 (6-16) to 13(11-16)μg/d for older and younger adults, respectively dependent on the month. In conclusion, a prediction model accounting for 25(OH)D3t1/2, VDI and scaling factor for the 25(OH)D response to VDI, closely predicts measured population winter values. Refinements of this model may include specific scaling factors accounting for the 25(OH)D response at different VDIs and as influenced by body composition and specific values for 25(OH)D3 t1/2 dependent on host factors such as kidney function. This model may help to reduce the need for longitudinal measurements

Cancer-associated bone disease

Bone is commonly affected in cancer. Cancer-induced bone disease results from the primary disease, or from therapies against the primary condition, causing bone fragility. Bone-modifying agents, such as bisphosphonates and denosumab, are efficacious in preventing and delaying cancer-related bone disease. With evidence-based care pathways, guidelines assist physicians in clinical decision-making. Of the 57 million deaths in 2008 worldwide, almost two thirds were due to non-communicable diseases, led by cardiovascular diseases and cancers. Bone is a commonly affected organ in cancer, and although the incidence of metastatic bone disease is not well defined, it is estimated that around half of patients who die from cancer in the USA each year have bone involvement. Furthermore, cancer-induced bone disease can result from the primary disease itself, either due to circulating bone resorbing substances or metastatic bone disease, such as commonly occurs with breast, lung and prostate cancer, or from therapies administered to treat the primary condition thus causing bone loss and fractures. Treatment-induced osteoporosis may occur in the setting of glucocorticoid therapy or oestrogen deprivation therapy, chemotherapy-induced ovarian failure and androgen deprivation therapy. Tumour skeletal-related events include pathologic fractures, spinal cord compression, surgery and radiotherapy to bone and may or may not include hypercalcaemia of malignancy while skeletal complication refers to pain and other symptoms. Some evidence demonstrates the efficacy of various interventions including bone-modifying agents, such as bisphosphonates and denosumab, in preventing or delaying cancer-related bone disease. The latter includes treatment of patients with metastatic skeletal lesions in general, adjuvant treatment of breast and prostate cancer in particular, and the prevention of cancer-associated bone disease. This has led to the development of guidelines by several societies and working groups to assist physicians in clinical decision making, providing them with evidence-based care pathways to prevent skeletal-related events and bone loss. The goal of this paper is to put forth an IOF position paper addressing bone diseases and cancer and summarizing the position papers of other organization

Diurnal rhythms of bone turnover markers in three ethnic groups

Context: Ethnic groups differ in fragility fracture risk and bone metabolism. Differences in diurnal rhythms (DRs) of bone turnover and PTH may play a role.  Objective: We investigated the DRs of plasma bone turnover markers (BTMs), PTH, and 1,25(OH)2D in three groups with pronounced differences in bone metabolism and plasma PTH.  Participants: Healthy Gambian, Chinese, and white British adults (ages 60–75 years; 30 per country).  Interventions: Observational study with sample collection every 4 hours for 24 hours.  Main Outcomes: Levels of plasma C-terminal telopeptide of type I collagen, procollagen type-1 N-propeptide, N-mid osteocalcin, bone alkaline phosphatase, PTH, and 1,25-dihydroxyvitamin D were measured. DRs were analyzed with random-effects Fourier regression and cross-correlation and regression analyses to assess associations between DRs and fasting and 24-hour means of BTMs and PTH.  Results: Concentrations of BTMs, PTH, and 1,25-dihydroxyvitamin D were higher in Gambians compared to other groups (P < .05). The DRs were significant for all variables and groups (P < .03) and were unimodal, with a nocturnal peak and a daytime nadir for BTMs, whereas PTH had two peaks. The DRs of BTMs and PTH were significantly cross-correlated for all groups (P < .05). There was a significant positive association between C-terminal telopeptide of type I collagen and PTH in the British and Gambian groups (P = .03), but not the Chinese group.  Conclusions: Despite ethnic differences in plasma BTMs and PTH, DRs were similar. This indicates that alteration of rhythmicity and loss of coupling of bone resorption and formation associated with an elevated PTH in other studies may not uniformly occur across different populations and needs to be considered in the interpretation of PTH as a risk factor of increased bone loss

IOF position statement: vitamin D recommendations for older adults

This position paper of the International Osteoporosis Foundation makes recommendations for vitamin D nutrition in elderly men and women from an evidence-based perspective. © 2010 International Osteoporosis Foundation and National Osteoporosis Foundation

High prevalence of vitamin D insufficiency and its association with BMI-for-age among primary school children in Kuala Lumpur, Malaysia

<p>Abstract</p> <p>Background</p> <p>Deficiencies of micronutrients can affect the growth and development of children. There is increasing evidence of vitamin D deficiency world-wide resulting in nutritional rickets in children and osteoporosis in adulthood. Data on the micronutrient status of children in Malaysia is limited. The aim of this study was to determine the anthropometric and micronutrient status of primary school children in the capital city of Kuala Lumpur.</p> <p>Methods</p> <p>A cross sectional study of primary aged school children was undertaken in 2008. A total of 402 boys and girls aged 7-12 years, attending primary schools in Kuala Lumpur participated in the study. Fasting blood samples were taken to assess vitamin D [as 25(OH)D], vitamin B₁₂, folate, zinc, iron, and ferritin and haemoglobin concentrations. Height-for-age and body mass index for age (BMI-for-age) of the children were computed.</p> <p>Results</p> <p>Most of the children had normal height-for-age (96.5%) while slightly over half (58.0%) had normal BMI-for-age. A total of 17.9% were overweight and 16.4% obese. Prevalence of obesity was significantly higher among the boys (25%) than in the girls (9.5%) (χ²= 22.949; <it>P </it>< .001). Most children had adequate concentrations of haemoglobin, serum ferritin, zinc, folate and vitamin B₁₂. In contrast, 35.3% of the children had serum 25(OH)D concentrations indicative of vitamin D deficiency(≤37.5 nmol/L) and a further 37.1% had insufficiency concentrations (> 37.5-≤50 nmol/L). Among the boys, a significant inverse association was found between serum vitamin D status and BMI-for-age (χ²= 5.958; <it>P </it>= .016).</p> <p>Conclusions</p> <p>This study highlights the presence of a high prevalence of sub-optimal vitamin D status among urban primary school children in a tropical country. In light of the growing problem of obesity in Malaysian children, these findings emphasize the important need for appropriate interventions to address both problems of obesity and poor vitamin D status in children.</p