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S Westra Department of Internal Medicine, Medical Centre Alkmaar, Alkmaar, the Netherlands

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Y H M Krul-Poel Department of Internal Medicine, Medical Centre Alkmaar, Alkmaar, the Netherlands

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H J van Wijland Department of General Practice, DIAZON, Alkmaar, the Netherlands

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M M ter Wee Department of Epidemiology and Biostatistics, VU Medical Centre, Amsterdam, the Netherlands

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F Stam Department of Internal Medicine, Medical Centre Alkmaar, Alkmaar, the Netherlands

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P Lips Department of Internal Medicine, Endocrine Section, VU Medical Centre, Amsterdam, the Netherlands

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F Pouwer Department of Medical and Clinical Psychology, Tilburg University, Tilburg, the Netherlands

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S Simsek Department of Internal Medicine, Medical Centre Alkmaar, Alkmaar, the Netherlands

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Objective

Increased levels of depressive symptoms, fatigue or pain (all dimensions of reduced health-related quality of life (HRQOL)) are common in people with type 2 diabetes mellitus (DM). Earlier studies have reported associations between low vitamin D status and fatigue and depressive symptoms. The aim of the present study was to examine the effects of vitamin D supplementation on dimensions of HRQOL in people with type 2 DM.

Design

Randomised, double-blind, placebo-controlled trial.

Methods

The effect of monthly cholecalciferol 50,000 IU vs placebo on HRQOL was assessed in 275 adults with type 2 DM derived from general practices. HRQOL at baseline and after six months using the Short Form 36 Health Survey (SF-36) was collected. Linear regression analyses were used to compare the change in HRQOL over time between the vitamin D and placebo group.

Results

187/275 (68%) completed baseline and follow-up SF-36 and were included in the analysis. Median serum 25-hydroxyvitamin D almost doubled in the intervention group compared to that in the placebo group (58.5–106.0 nmol/L vs 60.0–61.5 nmol/L, respectively). A small significant difference (adjusted B: −8.90; 95% CI: −17.16 to −0.65) between both groups was seen concerning the SF-36 domain role limitations due to physical problems in disadvantage of the vitamin D group.

Conclusions

Six months of vitamin D supplementation did not improve HRQOL in non-vitamin D-deficient people with type 2 DM managed on oral antidiabetic therapy.

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A Gizard Department of Pediatric Orthopedic Surgery, Besançon University Hospital, Paris, France

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A Rothenbuhler APHP, Department of Pediatric Endocrinology, Bicêtre Paris Sud, Le Kremlin Bicêtre, France
Reference Center for Rare Disorders of Calcium and Phosphate Metabolism, Le Kremlin Bicêtre, France
Plateforme d’Expertise Paris Sud Maladies Rares and Filière OSCAR, Bicêtre Paris Sud, Le Kremlin Bicêtre, France

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Z Pejin APHP, Department of Pediatric Orthopedic Surgery, Necker Hospital, Paris, France

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G Finidori APHP, Department of Pediatric Orthopedic Surgery, Necker Hospital, Paris, France

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C Glorion APHP, Department of Pediatric Orthopedic Surgery, Necker Hospital, Paris, France

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B de Billy Department of Pediatric Orthopedic Surgery, Besançon University Hospital, Paris, France

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A Linglart APHP, Department of Pediatric Endocrinology, Bicêtre Paris Sud, Le Kremlin Bicêtre, France
Reference Center for Rare Disorders of Calcium and Phosphate Metabolism, Le Kremlin Bicêtre, France
Plateforme d’Expertise Paris Sud Maladies Rares and Filière OSCAR, Bicêtre Paris Sud, Le Kremlin Bicêtre, France
INSERM U1169, Hôpital Bicêtre, Le Kremlin Bicêtre, et Université Paris-Saclay, Le Kremlin Bicêtre, France

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P Wicart Reference Center for Rare Disorders of Calcium and Phosphate Metabolism, Le Kremlin Bicêtre, France
APHP, Department of Pediatric Orthopedic Surgery, Necker Hospital, Paris, France

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Background

X-linked hypophosphatemic rickets (XLHR) is due to mutations in PHEX leading to unregulated production of FGF23 and hypophosphatemia. XLHR is characterized by leg bowing of variable severity. Phosphate supplements and oral vitamin analogs, partially or, in some cases, fully restore the limb straightness. Surgery is the alternative for severe or residual limb deformities.

Objective

To retrospectively assess the results of surgical limb correction in XLHR (osteotomies and bone alignment except for 3 transient hemiepiphysiodesis).

Methods

We analyzed the incidence of recurrence and post-surgical complications in 49 XLHR patients (29F, 20M) (mean age at diagnosis 6.0 years (± 7.1)).

Results

At first surgery, the mean age was 13.4 years (± 5.0). Recurrence was observed in 14/49 (29%) patients. The number of additional operations significantly decreased with age (2.0 (± 0.9), 1.7 (± 1.0) and 1.2 (± 0.4) in children <11 years, between 11 and 15, and >15 years; P < 0.001). Incidence of recurrence seemed to be lower in patients with good metabolic control of the rickets (25% vs 33%). Complications were observed in 57% of patients.

Conclusion

We report a large series of surgical procedures in XLHR. Our results confirm that phosphate supplements and vitamin D analog therapy is the first line of treatment to correct leg bowing. Surgery before puberty is associated with a high risk of recurrence of the limb deformity. Such procedures should only be recommended, following multidisciplinary discussions, in patients with severe distortion leading to mechanical joint and ligament complications, or for residual deformities once growth plates have fused.

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Göran Oleröd Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Lillemor Mattsson Hultén Department of Clinical Chemistry, Sahlgrenska University Hospital, Gothenburg, Sweden

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Ola Hammarsten Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Eva Klingberg Department of Rheumatology and Inflammation Research, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden

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Purpose

Serum 25-hydroxy vitamin D [25(OH)D] varies greatly with season at northern latitudes. The purpose of this study was to determine if the seasonal variations in serum total 25(OH)D are followed by a concomitant variation in free 25(OH)D or if the variation is damped by alterations in the binding capacity of DBP.

Methods

Serum was collected from 540 healthy blood donors (60% men; mean age 41 ± 13 years) during 12 months and analyzed for total 25(OH)D, directly measured free 25(OH)D, vitamin D-binding protein (DBP) and albumin. Calculated free 25(OH)D was estimated.

Results

The UV-B radiation during the sampling month was positively correlated with the serum levels of total 25(OH)D (r = 0.355, P < 0.001), directly measured free (r = 0.336, P < 0.001) and calculated free 25(OH)D (r = 0.275, P < 0.001), but not with DBP and albumin. The percentage of free 25(OH)D was higher during the winter months than that during the summer months (0.020 ± 0.005% vs 0.019 ± 0.004%; P = 0.007) and higher in participants with a serum 25(OH)D below 25 nmol/L than that in participants with a serum 25(OH)D above 75 nmol/L (0.031 ± 0.007% vs 0.017 ± 0.003%; P < 0.001). iPTH was correlated with directly measured free 25(OH)D (r = −0.226; P < 0.001), but only weakly with calculated free 25(OH)D (r = −0.095; P = 0.027).

Conclusions

Directly measured free serum 25(OH)D was highly correlated with total serum 25(OH)D and followed the same seasonal variation, whereas the serum concentrations of DBP and albumin were stable. The fluctuation in free 25(OH)D was only marginally damped with an increase in the percentage of free 25(OH)D during the winter months and in participants with vitamin D deficiency.

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Giuseppe Grande Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy

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Andrea Graziani Department of Medicine, University of Padova, Padova, Italy

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Antonella Di Mambro Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy

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Riccardo Selice Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy

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Alberto Ferlin Unit of Andrology and Reproductive Medicine, University Hospital of Padova, Padova, Italy
Department of Medicine, University of Padova, Padova, Italy

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Low bone mass is common in men with Klinefelter syndrome (KS), with a prevalence of 6–15% of osteoporosis and of 25–48% of osteopenia. Reduced bone mass has been described since adolescence and it might be related to both reduced bone formation and higher bone resorption. Although reduced testosterone levels are clearly involved in the pathogenesis, this relation is not always evident. Importantly, fracture risk is increased independently from bone mineral density (BMD) and testosterone levels. Here we discuss the pathogenesis of osteoporosis in patients with KS, with a particular focus on the role of testosterone and testis function. In fact, other hormonal mechanisms, such as global Leydig cell dysfunction, causing reduced insulin-like factor 3 and 25-OH vitamin D levels, and high follicle-stimulating hormone and estradiol levels, might be involved. Furthermore, genetic aspects related to the supernumerary X chromosome might be involved, as well as androgen receptor expression and function. Notably, body composition, skeletal mass and strength, and age at diagnosis are other important aspects. Although dual-energy x-ray absorptiometry is recommended in the clinical workflow for patients with KS to measure BMD, recent evidence suggests that alterations in the microarchitecture of the bones and vertebral fractures might be present even in subjects with normal BMD. Therefore, analysis of trabecular bone score, high-resolution peripheral quantitative computed tomography and vertebral morphometry seem promising tools to better estimate the fracture risk of patients with KS. This review also summarizes the evidence on the best available treatments for osteoporosis in men with KS, with or without hypogonadism.

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Magdalena Zgliczyńska Department of Obstetrics, Perinatology and Neonatology, Centre of Postgraduate Medical Education, Cegłowska, Warsaw, Poland

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Magdalena Ostrowska Department of Endocrinology, Centre of Postgraduate Medical Education, Cegłowska, Warsaw, Poland

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Kinga Żebrowska Department of Obstetrics, Perinatology and Neonatology, Centre of Postgraduate Medical Education, Cegłowska, Warsaw, Poland

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Iwona Szymusik Department of Obstetrics, Perinatology and Neonatology, Centre of Postgraduate Medical Education, Cegłowska, Warsaw, Poland

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Konrad Kowalski Masdiag Sp. z o.o., Stefana Żeromskiego, Warsaw, Poland

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Dorota Leszczyńska Department of Endocrinology, Centre of Postgraduate Medical Education, Cegłowska, Warsaw, Poland

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Katarzyna Kosińska-Kaczyńska Department of Obstetrics, Perinatology and Neonatology, Centre of Postgraduate Medical Education, Cegłowska, Warsaw, Poland

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Objective

Vitamin D plays an important role during pregnancy. The aim was to compare vitamin D status in a group of singleton (SP) and twin pregnancies (TP) using two diagnostic methods: chemiluminescence immunoassay (CLIA) and liquid chromatography with tandem mass spectrometry (LC-MS/MS).

Design

This is a cross-sectional study.

Methods

The study was conducted in the population of SP and TP at the gestational age above 20 + 0 at the Bielanski Hospital in Warsaw, Poland, between October 2020 and January 2023. All patients had their venous blood samples collected and were given an original survey containing questions on demography and vitamin D supplementation.

Results

The study group included 53 Caucasian women with SP and 78 with TP aged from 21 to 47. Considering LC-MS/MS, patients with TP had lower concentrations of 25-hydroxyvitamin D (25(OH)D) than patients with SP. However, no significant difference was observed in the frequency of the occurrence of vitamin D deficiency (25(OH)D < 30 ng/mL). In both groups, the levels obtained with CLIA were significantly lower than in case of LC-MS/MS, however, strongly correlated. The intermethod agreement accounted for 52.4% and the Cohen’s kappa coefficient was 0.142.

Conclusions

The concentration of 25(OH)D in pregnant women depends on the type of gestation (SP/TP) and on the diagnostic methods used (CLIA/LC-MS/MS). Based on LC-MS/MS, the incidence of vitamin D deficiency was low in our group and no differences occurred in its frequency between SP and TP. The intermethod agreement between CLIA and LC-MS/MS on the detection of vitamin D deficiency was low.

Significance statement

This is the first study to compare the concentration of 25(OH)D levels between SP and TP using two methods: CLIA and the gold standard – LC-MS/MS. Based on LC-MS/MS, a low incidence of vitamin D deficiency was observed in our group, in which the vast majority of patients took cholecalciferol supplements. Moreover, there were no differences in its frequency between SP and TP. However, the 25(OH)D level was significantly lower in TP. The intermethod agreement between CLIA and LC-MS/MS on the detection of vitamin D deficiency was low, which is associated with substantial clinical implications.

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Bingbing Wang Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA

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Mayra Cruz Ithier Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA

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Nataliya Parobchak Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA

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Stacy M Yadava Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA

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Jay Schulkin Department of Obstetrics, Gynecology, University of Washington, Seattle, Washington, USA

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Todd Rosen Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA

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Maternal vitamin D deficiency is linked to adverse pregnancy outcomes including spontaneous preterm birth (SPB). Placental corticotropin-releasing hormone (CRH) has been proposed to be part of a clock that governs the length of gestation in humans, with elevated maternal serum levels predicting early delivery. In this study, we test the hypothesis that vitamin D could contribute to the prevention of preterm labor by inhibiting CRH and other pro-labor mediators. The biological activity of vitamin D occurs via two pathways: non-genomic and genomic responses, both of which involve binding of 1,25-dihydroxyvitamin D (1,25(OH)2D), the active metabolite of vitamin D binding to the vitamin D receptor (VDR). By using chromatin immunoprecipitation followed by sequencing (ChIP-seq), we found that 1,25(OH)2D stimulates association of VDR with a number of miRNA genes including MIR181B2 and MIR26B, and their mature products miR-181b-5p and miR-26b-5p are predicted to target CRH and cyclooxygenase-2 (COX-2) mRNA at 3′-untranslated region (UTR), respectively. We performed RT-qPCR analysis to validate that expression of mature miR-181b-5p and miR-26b-5p in term human syncytiotrophoblast increased in response to treatment with 1,25(OH)2D. miR-181b-5p- or miR-26b-5p-mediated inhibition of CRH or COX-2 was further assessed by the use of miRNA mimics/inhibitors and a luciferase reporter assay. Taken together, this study has identified novel mechanisms by which vitamin D downregulates pro-labor genes and could lower the risk of preterm delivery.

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Gunjan Garg Departments of Endocrinology, Obstetrics and Gynecology, Biostatics

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Garima Kachhawa Departments of Endocrinology, Obstetrics and Gynecology, Biostatics

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Rekha Ramot Departments of Endocrinology, Obstetrics and Gynecology, Biostatics

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Rajesh Khadgawat Departments of Endocrinology, Obstetrics and Gynecology, Biostatics

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Nikhil Tandon Departments of Endocrinology, Obstetrics and Gynecology, Biostatics

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V Sreenivas Departments of Endocrinology, Obstetrics and Gynecology, Biostatics

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Alka Kriplani Departments of Endocrinology, Obstetrics and Gynecology, Biostatics

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N Gupta Departments of Endocrinology, Obstetrics and Gynecology, Biostatics

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To assess the effect of vitamin D supplementation on parameters of insulin sensitivity/resistance (IS/IR) and insulin secretion in subjects with polycystic ovarian syndrome (PCOS). A prospective double-blind randomized control trial was conducted to assess the effect of vitamin D on insulin kinetics in women with PCOS. The trial was conducted in a tertiary care research hospital. A total of 36 subjects with PCOS, aged 18–35 years, were included in this study. Vitamin D3 4000 IU/day versus placebo was given once a month for 6 months and both groups received metformin. IS (by whole-body IS index or Matsuda index), IR (by homeostasis model assessment IR (HOMA-IR)), and insulin secretion (by insulinogenic index; II30) were the main outcome measures. Secondary outcome included blood pressure (BP), lipid profile, disposition index (DI), and vascular stiffness. Out of 36 subjects who consented, 32 completed the study. Subjects were randomized into two groups: group A (n=15; metformin and vitamin D 4000 IU/day) or group B (n=17; metformin and placebo). Oral glucose tolerance tests with 75 g glucose were carried out at baseline and 6 months after supplementation. Hypovitaminosis D was observed in 93.8% of all subjects with mean serum 25 hydroxy vitamin D level of 7.30±4.45 ng/ml. After 6 months of vitamin D supplementation, there was no significant difference in any of the parameters of IS/IR (area under curve (AUC)–glucose, AUC–insulin, insulin:glucose ratio, HOMA-IR, Matsuda index, insulinogenic index, and DI), II30, and cardiovascular risk factors between the two groups. Supplementation of vitamin D, at a dose of 4000 IU/day for 6 months, did not have any significant effect on parameters of IS/IR and insulin secretion in subjects with PCOS.

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Ann R Webb Department of Earth and Environmental Sciences, University of Manchester, Manchester, UK

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Rehab Alghamdi Department of Earth and Environmental Sciences, University of Manchester, Manchester, UK
Department of Clinical Nutrition, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia

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Richard Kift Department of Earth and Environmental Sciences, University of Manchester, Manchester, UK

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Lesley E Rhodes Centre for Dermatology Research, School of Biological Sciences, The University of Manchester and Salford Royal NHS Foundation Trust, Manchester, UK

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A systematic review of publications addressing change in vitamin D status (25-hydroxyvitamin D (25OHD)) after exposure to UV radiation identified 2001 independent peer-reviewed publications. Of these, 21 used artificial sources of UV radiation, met all inclusion criteria and were quality assured; 13 publications used solar radiation and met sufficient inclusion criteria to be retained as supporting evidence; 1 further included publication used both solar and artificial sources. The review consistently identified that low dose, sub-erythemal doses are more effective for vitamin D synthesis than doses close to a minimum erythema dose; increasing skin area exposed increases the amount of vitamin D synthesised although not necessarily in a linear manner; constant dosing leads to a dose-dependent plateau in 25OHD, and dose–response is greatest at the start of a dosing regime; there is a large interpersonal variation in response to UV exposure. Fourteen of the studies using artificial sources of radiation were used to determine a dose–response relationship for change in 25OHD on whole-body exposure to repeated sub-erythemal doses of UV radiation, taking the form Δ25OHD (nmol/L) = A ln(standard vitamin D dose) + B. This helps quantify our understanding of UV as a source of vitamin D and enables exposure regimes for safe synthesis of vitamin D to be assessed. Specific studies of people with pigmented skin (Fitzpatrick skin types 5 and 6) were rare, and this dose–response relationship is only applicable to white-skinned individuals as skin type is a determinant of response to UV radiation. Findings provide information for vitamin D guidance updates.

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Karolien Van De Maele Division of Pediatric Endocrinology, KidZ Health Castle, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium

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Jean De Schepper Division of Pediatric Endocrinology, KidZ Health Castle, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium

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Jesse Vanbesien Division of Pediatric Endocrinology, KidZ Health Castle, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium

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Monique Van Helvoirt Zeepreventorium, De Haan, Belgium

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Ann De Guchtenaere Zeepreventorium, De Haan, Belgium

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Inge Gies Division of Pediatric Endocrinology, KidZ Health Castle, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium

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Background

Vitamin D deficiency is common in obese adolescents and a risk factor for insulin resistance. We investigated if prevailing serum 25-OH vitamin D might predict the body fat loss in a group of obese adolescents undergoing a residential weight loss program.

Methods

In 92 (35 male) obese adolescents (aged 10.6–19 years) undergoing a residential weight loss program in Belgium, fasting serum 25-OH vitamin D (25-OH-D), insulin, glucose and lipid levels were measured and body composition was assessed by dual-energy X-ray absorptiometry (DXA).

Results

Baseline median (range) serum 25-OH-D level was 17.7 µg/L (3.8–41.8). In total, 55 adolescents had a serum 25-OH-D below 20 µg/L. In 31 adolescents with a low baseline 25-OH-D level, median increase in serum 25-OH-D was 2.4 µg/L (−4.2 to 7.2) after 10 months. This resulted in normal 25-OH-D levels in seven adolescents, whereas median BMI decreased with 1.0 SDS and body fat percentage diminished with 9.9%. Obese adolescents with or without a 25-OH-D level below or above 20 µg/L at baseline had similar changes in body weight, BMI SDS, body fat percentage and body fat mass at the end of the program. The change in serum 25-OH-D did not correlate with change in serum insulin, BMI SDS or body fat percentage and body fat mass.

Conclusion

Vitamin D deficiency was present in 55 out of 92 obese adolescents at the start of the summer. Serum 25-OH-D concentration did not predict changes in body fat loss after a residential weight loss program.

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Maxime Duval Department of Medicine, Clinique Jules Verne, Nantes, France

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Kalyane Bach-Ngohou Department of Biology, Laboratory of Clinical Biochemistry, CHU Nantes, Nantes, France

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Damien Masson Department of Biology, Laboratory of Clinical Biochemistry, CHU Nantes, Nantes, France

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Camille Guimard Department of Emergency Medicine, CHU Nantes, Nantes, France

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Philippe Le Conte Department of Emergency Medicine, CHU Nantes, Nantes, France

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David Trewick Department of Medicine, Clinique Jules Verne, Nantes, France
Department of Emergency Medicine, CHU Nantes, Nantes, France

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Objective

Severe hypocalcemia (Ca <1.9 mmol/L) is often considered an emergency because of a potential risk of cardiac arrest or seizures. However, there is little evidence to support this. The aim of our study was to assess whether severe hypocalcemia was associated with immediately life-threatening cardiac arrhythmias or neurological complications.

Methods

A retrospective observational study was carried out over a 2-year period in the Adult Emergency Department (ED) of Nantes University Hospital. All patients who had a protein-corrected calcium concentration measure were eligible for inclusion. Patients with multiple myeloma were excluded. The primary outcome was the number of life-threatening cardiac arrhythmias and/or neurological complications during the stay in the ED.

Results

A total of 41,823 patients had protein-corrected calcium (pcCa) concentrations measured, 155 had severe hypocalcemia, 22 were excluded because of myeloma leaving 133 for analysis. Median pcCa concentration was 1.73 mmol/L (1.57–1.84). Seventeen (12.8%) patients presented a life-threatening condition, 14 (10.5%) neurological and 3 (2.2%) cardiac during ED stay. However, these complications could be explained by the presence of underlying co-morbidities and or electrolyte disturbances other than hypocalcemia. Overall, 24 (18%) patients died in hospital. Vitamin D deficiency, chronic kidney disease and hypoparathyroidism were the most frequently found causes of hypocalcemia.

Conclusion

Thirteen percent of patients with severe hypocalcemia presented a life-threatening cardiac or neurological complication on the ED. However, a perfectly valid alternative cause could account for these complications. Further research is warranted to define the precise role of hypocalcemia.

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