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Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
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Background
Nutritional rickets is a growing global public health concern despite existing prevention programmes and health policies. We aimed to compare infant and childhood vitamin D supplementation policies, implementation strategies and practices across Europe and explore factors influencing adherence.
Methods
European Society for Paediatric Endocrinology Bone and Growth Plate Working Group members and other specialists completed a questionnaire on country-specific vitamin D supplementation policy and child health care programmes, socioeconomic factors, policy implementation strategies and adherence. Factors influencing adherence were assessed using Kendall’s tau-b correlation coefficient.
Results
Responses were received from 29 of 30 European countries (97%). Ninety-six per cent had national policies for infant vitamin D supplementation. Supplements are commenced on day 1–5 in 48% (14/29) of countries, day 6–21 in 48% (14/29); only the UK (1/29) starts supplements at 6 months. Duration of supplementation varied widely (6 months to lifelong in at-risk populations). Good (≥80% of infants), moderate (50–79%) and low adherence (<50%) to supplements was reported by 59% (17/29), 31% (9/29) and 10% (3/29) of countries, respectively. UK reported lowest adherence (5–20%). Factors significantly associated with good adherence were universal supplementation independent of feeding mode (P = 0.007), providing information at neonatal unit (NNU) discharge (P = 0.02), financial family support (P = 0.005); monitoring adherence at surveillance visits (P = 0.001) and the total number of factors adopted (P < 0.001).
Conclusions
Good adherence to supplementation is a multi-task operation that works best when parents are informed at birth, all babies are supplemented, and adherence monitoring is incorporated into child health surveillance visits. Implementation strategies matter for delivering efficient prevention policies.
Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
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Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
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Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
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Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
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Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
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Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
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Beijing Key Laboratory of Diabetes Research and Care, Beijing, China
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Osteoporosis (OP) is a systemic bone disease in which bone density and quality decrease and bone fragility increases due to a variety of causes, making it prone to fractures. The development of OP is closely related to oxidative stress. Uric acid (UA) is the end product of purine metabolism in the human body. Extracellular UA has antioxidant properties and is thought to have a protective effect on bone metabolism. However, the process of UA degradation can lead to intracellular oxidative stress, which together with UA-induced inflammatory factors, leads to increased bone destruction. In addition, UA can inhibit vitamin D production, resulting in secondary hyperparathyroidism and further exacerbating UA-associated bone loss. This review summarizes the relationship between serum UA levels and bone mineral density, bone turnover markers, and so on, in the hope of providing new insights into the pathogenesis and treatment of OP.
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X-linked hypophosphataemia (XLH) is caused by a pathogenic variant in the PHEX gene, which leads to elevated circulating FGF23. High FGF23 causes hypophosphataemia, reduced active vitamin D concentration and clinically manifests as rickets in children and osteomalacia in children and adults. Conventional therapy for XLH includes oral phosphate and active vitamin D analogues but does not specifically treat the underlying pathophysiology of elevated FGF23-induced hypophosphataemia. In addition, adherence to conventional therapy is limited by frequent daily dosing and side effects such as gastrointestinal symptoms, secondary hyperparathyroidism and nephrocalcinosis. Burosumab, a recombinant human IgG1 MAB that binds to and inhibits the activity of FGF23, is administered subcutaneously every 2 weeks. In clinical trials (phase 2 and 3) burosumab was shown to improve phosphate homeostasis that consequently resolves the skeletal/non-skeletal manifestations of XLH. Burosumab was licensed in Europe (February 2018) with the National Institute for Health and Care Excellence, UK approving use within its marketing authorisation in October 2018. In this publication, the British Paediatric and Adolescent Bone Group (BPABG) reviewed current evidence and provide expert recommendations for care pathway and management of XLH with burosumab.
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Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
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Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
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Objective
Low serum 25(OH)D levels are associated with cardiovascular disease (CVD) and some of its risk factors. However, in interventional studies, the effects of vitamin D supplementation have been uncertain, possibly due to inclusion of vitamin D-sufficient subjects. Our aim was therefore to examine effects of vitamin D supplementation on CVD risk factors in vitamin D-insufficient subjects.
Design
Double-blinded randomized controlled trial.
Methods
A 4-month interventional study with high-dose vitamin D (100,000 IU loading dose, followed by 20,000 IU/week) or placebo with measurements of blood pressure, lipids (total-, LDL- and HDL-cholesterol, triglycerides, apolipoproteins A1 and B), and glucose metabolism parameters (blood glucose, HbA1c, serum human receptors for advanced glycation end products (sRAGE), insulin, C-peptide and HOMA-IR).
Results
A total of 422 subjects with mean serum 25(OH)D level 34 nmol/L were included, with 411 subjects completing the study. Serum 25(OH)D levels increased with 56 nmol/L and decreased with 4 nmol/L in the vitamin D and placebo group, respectively. We found no statistically significant differences between the two groups in any of the measured CVD risk factors, except for a minor increase in sRAGE in the vitamin D group. Stratified analyses of subjects with low baseline serum 25(OH)D levels alone, or combined with blood pressure, lipid and HOMA-IR values above the median for the cohort, did not skew the results in favour of vitamin D supplementation.
Conclusion
Supplementation with vitamin D in subjects with baseline vitamin D insufficiency does not improve CVD risk factor profile.
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Department of Endocrinology, Diabetes and Metabolic diseases, Elias Hospital, Bucharest, Romania
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Department of Gastroenterology, Fundeni Clinical Institute, Bucharest, Romania
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Department of Gastroenterology, Colentina Hospital, Bucharest, Romania
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Department of Gastroenterology, Elias Hospital, Bucharest, Romania
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Department of Endocrinology, Diabetes and Metabolic diseases, Elias Hospital, Bucharest, Romania
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Department of Endocrinology, Diabetes and Metabolic diseases, Elias Hospital, Bucharest, Romania
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Department of Gastroenterology, Elias Hospital, Bucharest, Romania
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Department of Endocrinology, Diabetes and Metabolic diseases, Elias Hospital, Bucharest, Romania
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Background and aim
Low bone mineral density (BMD) is a common complication in patients with inflammatory bowel disease (IBD). However, debates are ongoing with regard to the other involved factors, especially in younger patients. This study aimed to evaluate the parameters that contribute to decreased BMD, focusing on premenopausal women and men aged <50 years.
Methods
This study included 81 patients with IBD and 81 age-, sex- and BMI-matched controls. Blood tests were conducted on IBD patients, and a dual-energy X-ray absorptiometry (DXA) scan was performed on both groups.
Results
Low BMD and fragility fracture were found to be more prevalent in IBD patients than in healthy subjects (49.3% vs 23.4%, P = 0.001 and 9.8% vs 1.2%, P = 0.01, respectively). Patients with low BMD were older, with a longer disease duration, higher faecal calprotectin (FC) levels and lower magnesium and lean mass (appreciated as appendicular skeletal muscle index (ASMI)). Multiple regression analysis revealed that ASMI, age and use of glucocorticoids were the independent parameters for decreased BMD. Although 91.3% of the patients had a 25-hydroxy vitamin D level of <30 ng/mL, it was not a statistically significant factor for decreased BMD.
Conclusion
In our study, the levels of vitamin D did not seem to have an important impact on BMD. Conversely, FC, magnesium and lean mass are important factors, suggesting that good control of disease, adequate magnesium intake and increased lean mass can have a good impact on bone metabolism in patients with IBD.
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In post-menopausal women, aged individuals, and patients with diabetes mellitus or chronic renal disease, bone mineral density (BMD) decreases while the vasculature accumulates arterial calcifications (ACs). AC can be found in the tunica intima and/or in the tunica media. Prospective studies have shown that patients with initially low BMD and/or the presence of fragility fractures have at follow-up a significantly increased risk for coronary and cerebrovascular events and for overall cardiovascular mortality. Similarly, patients presenting with abdominal aorta calcifications (an easily quantifiable marker of vascular pathology) show a significant decrease in the BMD (and an increase in the fragility) of bones irrigated by branches of the abdominal aorta, such as the hip and lumbar spine. AC induction is an ectopic tissue biomineralization process promoted by osteogenic transdifferentiation of vascular smooth muscle cells as well as by local and systemic secreted factors. In many cases, the same regulatory molecules modulate bone metabolism but in reverse. Investigation of animal and in vitro models has identified several potential mechanisms for this reciprocal bone–vascular regulation, such as vitamin K and D sufficiency, advanced glycation end-products–RAGE interaction, osteoprotegerin/RANKL/RANK, Fetuin A, oestrogen deficiency and phytooestrogen supplementation, microbiota and its relation to diet, among others. Complete elucidation of these potential mechanisms, as well as their clinical validation via controlled studies, will provide a basis for pharmacological intervention that could simultaneously promote bone and vascular health.
Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
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Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
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Objective
In addition to its skeletal effects, vitamin D may also be important for health in general. It is uncertain what level of serum 25-hydroxyvitamin D (25(OH)D), marker of vitamin D status, is sufficient for these effects. With decreasing serum 25(OH)D levels there is an increase in serum PTH. The point at which this occurs has been considered as a threshold for vitamin D sufficiency. The thresholds found have varied widely and have mainly been based on observational studies. However, to truly establish a threshold for vitamin D effects, this has to be based on randomized controlled trials (RCTs).
Methods
The study included 2803 subjects from a general health survey, the Tromsø study, and pooled individual person data from five vitamin D intervention studies (n = 1544). Serum parathyroid hormone (PTH) and change in PTH after vitamin D supplementation were related to serum 25(OH)D levels in steps of 25 nmol/L (<24, 25–49, 50–74, 75–99, and >99 nmol/L).
Results
In the Tromsø study, in the females there was a gradual decrease in serum PTH with increasing serum 25(OH)D with no apparent plateau, whereas in the males the decrease in PTH in subjects with serum 25(OH)D >74 nmol/l was marginal. In pooled RCTs, there was a significant reduction in serum PTH by vitamin D supplementation regardless of baseline serum 25(OH)D level.
Conclusions
The use of the serum PTH–25(OH)D relation from observational studies to determine a threshold for vitamin D sufficiency is highly questionable.
Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
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Department of General Surgery, St. Elisabeth’s Hospital, Graz, Austria
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The prevalence of vitamin D deficiency in intensive care units ranges typically between 40 and 70%. There are many reasons for being or becoming deficient in the ICU. Hepatic, parathyroid and renal dysfunction additionally increases the risk for developing vitamin D deficiency. Moreover, therapeutic interventions like fluid resuscitation, dialysis, surgery, extracorporeal membrane oxygenation, cardiopulmonary bypass and plasma exchange may significantly reduce vitamin D levels. Many observational studies have consistently shown an association between low vitamin D levels and poor clinical outcomes in critically ill adults and children, including excess mortality and morbidity such as acute kidney injury, acute respiratory failure, duration of mechanical ventilation and sepsis. It is biologically plausible that vitamin D deficiency is an important and modifiable contributor to poor prognosis during and after critical illness. Although vitamin D supplementation is inexpensive, simple and has an excellent safety profile, testing for and treating vitamin D deficiency is currently not routinely performed. Overall, less than 800 patients have been included in RCTs worldwide, but the available data suggest that high-dose vitamin D supplementation could be beneficial. Two large RCTs in Europe and the United States, together aiming to recruit >5000 patients, have started in 2017, and will greatly improve our knowledge in this field. This review aims to summarize current knowledge in this interdisciplinary topic and give an outlook on its highly dynamic future.
Birmingham Women’s Foundation Hospital, Edgbaston, Birmingham, UK
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
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Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
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Birmingham Women’s Foundation Hospital, Edgbaston, Birmingham, UK
Centre for Endocrinology, Diabetes and Metabolism, Birmingham Health Partners, Birmingham, UK
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Vitamin D deficiency is common in pregnant women and may contribute to adverse events in pregnancy such as preeclampsia (PET). To date, studies of vitamin D and PET have focused primarily on serum concentrations vitamin D, 25-hydroxyvitamin D3 (25(OH)D3) later in pregnancy. The aim here was to determine whether a more comprehensive analysis of vitamin D metabolites earlier in pregnancy could provide predictors of PET. Using samples from the SCOPE pregnancy cohort, multiple vitamin D metabolites were quantified by liquid chromatography–tandem mass spectrometry in paired serum and urine prior to the onset of PET symptoms. Samples from 50 women at pregnancy week 15 were analysed, with 25 (50%) developing PET by the end of the pregnancy and 25 continuing with uncomplicated pregnancy. Paired serum and urine from non-pregnant women (n = 9) of reproductive age were also used as a control. Serum concentrations of 25(OH)D3, 25(OH)D2, 1,25(OH)2D3, 24,25(OH)2D3 and 3-epi-25(OH)D3 were measured and showed no significant difference between women with uncomplicated pregnancies and those developing PET. As previously reported, serum 1,25(OH)2D3 was higher in all pregnant women (in the second trimester), but serum 25(OH)D2 was also higher compared to non-pregnant women. In urine, 25(OH)D3 and 24,25(OH)2D3 were quantifiable, with both metabolites demonstrating significantly lower (P < 0.05) concentrations of both of these metabolites in those destined to develop PET. These data indicate that analysis of urinary metabolites provides an additional insight into vitamin D and the kidney, with lower urinary 25(OH)D3 and 24,25(OH)2D3 excretion being an early indicator of a predisposition towards developing PET.
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Objectives
It has not been established whether vitamin D deficiency is associated with anthropometric state; therefore, this systematic review examined the relationship between serum vitamin D levels with anthropometrics and adiposity across different ages.
Methods
Studies that examined vitamin D deficiency with adiposity measures in different age groups were searched in the PubMed, Scopus, Embase, and Google Scholar databases until November 2023. Two investigators independently reviewed titles and abstracts, examined full-text articles, extracted data, and rated the quality in accordance with the Newcastle–Ottawa criteria.
Results
Seventy-two studies, with a total of 59,430 subjects, were included. Of these studies, 27 cross-sectional studies and one longitudinal study (with 25,615 participants) evaluated the possible link between 25(OH)D serum concentrations and anthropometric/adiposity indices in the pediatric population. Forty-two cross-sectional studies and two cohort investigations (with 33,815 participants) investigated the relationship between serum 25(OH)D levels and adiposity measures in adults and/or the elderly population. There is evidence supporting links between vitamin D deficiency and obesity, and revealed an inverse association between vitamin D and adiposity indicators, specifically in female subjects. However, the effects of several confounding factors should also be considered.
Conclusion
Most published studies, most of which were cross-sectional, reported a negative association between vitamin D and female adiposity indicators. Therefore, serum vitamin D levels should be monitored in overweight/obese individuals.