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Vito Francic Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

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Martin Keppel Department of Laboratory Medicine, Paracelsus Medical University, Salzburg, Austria

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Verena Schwetz Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

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Christian Trummer Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

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Marlene Pandis Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

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Valentin Borzan Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

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Martin R Grübler Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

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Nicolas D Verheyen Division of Cardiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

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Marcus E Kleber Vth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

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Graciela Delgado Vth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

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Angela P Moissl Vth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany

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Benjamin Dieplinger Department of Laboratory Medicine, Konventhospital Barmherzige Brueder Linz, Linz, Austria

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Winfried März Vth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany
Synlab Academy, Synlab Holding Germany GmbH, Heidelberg, Germany

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Andreas Tomaschitz Specialist Clinic of Rehabilitation Bad Gleichenberg, Bad Gleichenberg, Austria

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Stefan Pilz Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

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Barbara Obermayer-Pietsch Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria

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Objective

Cardiovascular disease manifestation and several associated surrogate markers, such as vitamin D, have shown substantial seasonal variation. A promising cardiovascular biomarker, soluble ST2 (sST2), has not been investigated in this regard – we therefore determined if systemic levels of sST2 are affected by seasonality and/or vitamin D in order to investigate their clinical interrelation and usability.

Design

sST2 levels were measured in two cohorts involving hypertensive patients at cardiovascular risk, the Styrian Vitamin D Hypertension Trial (study A; RCT design, 8 weeks 2800 IU cholecalciferol daily) and the Ludwigshafen Risk and Cardiovascular Health Study (LURIC; study B; cross-sectional design).

Methods

The effects of a vitamin D intervention on sST2 levels were determined in study A using ANCOVA, while seasonality of sST2 levels was determined in study B using ANOVA.

Results

The concentrations of sST2 remained unchanged by a vitamin D intervention in study A, with a mean treatment effect (95% confidence interval) of 0.1 (−0.6 to 0.8) ng/mL; P = 0.761), despite a rise in 25(OH)D (11.3 (9.2–13.5) ng/mL; P < 0.001) compared to placebo. In study B, seasonal variations were present in 25(OH)D levels in men and women with or without heart failure (P < 0.001 for all subgroups), while sST2 levels remained unaffected by the seasons in all subgroups.

Conclusions

Our study provides the first evidence that systemic sST2 levels are not interrelated with vitamin D levels or influenced by the seasons in subjects at cardiovascular risk.

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Ying-Lien Cheng Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

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Ting-I Lee Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

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Yu-Mei Chien Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

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Ting-Wei Lee Division of Endocrinology and Metabolism, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

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Yi-Jen Chen Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
Cardiovascular Research Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan
Taipei Heart Institute, Taipei Medical University, Taipei, Taiwan

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Vitamin D deficiency is associated with hyperlipidemia, but it remains unclear whether vitamin D supplementation reduces serum lipid levels. The aims of this study were to investigate the associations between increased serum 25-hydroxyvitamin D (25(OH)D) concentrations and lipid levels and identify the characteristics of people with or without lipid reduction associated with increased 25(OH)D levels. The medical records of 118 individuals (53 men; mean age, 54.4 ± 10.6 years) whose serum 25(OH)D levels increased between 2 consecutive measurements were retrospectively reviewed. People with increased 25(OH)D levels (from 22.7 (17.6–29.2) to 32.1 (25.6–36.8) mg/dL; P < 0.01) had a significant reduction in serum levels of triglycerides (TGs) (from 111.0 (80–164) to 104.5 (73–142) mg/dL; P < 0.01) and total cholesterol (TC) (from 187.5 (155–213) to 181.0 (150–210) mg/dL; P < 0.05). The individuals who responded to vitamin D (≥10% reduction in TG or TC levels) exhibited significantly higher baseline TG and TC levels than those who did not. Only patients with hyperlipidemia (not those without hyperlipidemia) at baseline exhibited significantly reduced TG and TC levels at follow-up. However, increasing serum 25(OH)D concentrations were significantly correlated with decreasing lipid levels in individuals with baseline 25(OH)D levels less than 30 ng/mL and in individuals aged 50–65 years (not in patients younger than 50 years or older than 65 years). In conclusion, increasing serum 25(OH)D concentrations may be potentially helpful for the treatment of hyperlipidemia in people with vitamin D deficiency.

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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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Melissa Braga Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA

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Zena Simmons Department of Health & Life Sciences, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA

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Keith C Norris Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA

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Monica G Ferrini Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA
Department of Health & Life Sciences, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA
Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA

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Jorge N Artaza Department of Internal Medicine, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA
Department of Health & Life Sciences, Charles R. Drew University of Medicine and Science, Los Angeles, California, USA
Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, California, USA

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Skeletal muscle wasting is a serious disorder associated with health conditions such as aging, chronic kidney disease and AIDS. Vitamin D is most widely recognized for its regulation of calcium and phosphate homeostasis in relation to bone development and maintenance. Recently, vitamin D supplementation has been shown to improve muscle performance and reduce the risk of falls in vitamin D deficient older adults. However, little is known of the underlying molecular mechanism(s) or the role it plays in myogenic differentiation. We examined the effect of 1,25-D3 on myogenic cell differentiation in skeletal muscle derived stem cells. Primary cultures of skeletal muscle satellite cells were isolated from the tibialis anterior, soleus and gastrocnemius muscles of 8-week-old C57/BL6 male mice and then treated with 1,25-D3. The efficiency of satellite cells isolation determined by PAX7+ cells was 81%, and they expressed VDR. Incubation of satellite cells with 1,25-D3 induces increased expression of: (i) MYOD, (ii) MYOG, (iii) MYC2, (iv) skeletal muscle fast troponin I and T, (v) MYH1, (vi) IGF1 and 2, (vii) FGF1 and 2, (viii) BMP4, (ix) MMP9 and (x) FST. It also promotes myotube formation and decreases the expression of MSTN. In conclusion, 1,25-D3 promoted a robust myogenic effect on satellite cells responsible for the regeneration of muscle after injury or muscle waste. This study provides a mechanistic justification for vitamin D supplementation in conditions characterized by loss of muscle mass and also in vitamin D deficient older adults with reduced muscle mass and strength, and increased risk of falls.

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Zhen-yu Song Department of Urology, Jinshan Hospital of Fudan University, Shanghai, China

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Qiuming Yao Department of Endocrinology, Jinshan Hospital of Fudan University, Shanghai, China

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Zhiyuan Zhuo Department of Urology, Jinshan Hospital of Fudan University, Shanghai, China

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Zhe Ma Department of Urology, Jinshan Hospital of Fudan University, Shanghai, China

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Gang Chen Department of Urology, Jinshan Hospital of Fudan University, Shanghai, China

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Previous studies investigating the association of circulating 25-hydroxyvitamin D level with prognosis of prostate cancer yielded controversial results. We conducted a dose–response meta-analysis to elucidate the relationship. PubMed and EMBASE were searched for eligible studies up to July 15, 2018. We performed a dose–response meta-analysis using random-effect model to calculate the summary hazard ratio (HR) and 95% CI of mortality in patients with prostate cancer. Seven eligible cohort studies with 7808 participants were included. The results indicated that higher vitamin D level could reduce the risk of death among prostate cancer patients. The summary HR of prostate cancer-specific mortality correlated with an increment of every 20 nmol/L in circulating vitamin D level was 0.91, with 95% CI 0.87–0.97, P = 0.002. The HR for all-cause mortality with the increase of 20 nmol/L vitamin D was 0.91 (95% CI: 0.84–0.98, P = 0.01). Sensitivity analysis suggested the pooled HRs were stable and not obviously changed by any single study. No evidence of publications bias was observed. This meta-analysis suggested that higher 25-hydroxyvitamin D level was associated with a reduction of mortality in prostate cancer patients and vitamin D is an important protective factor in the progression and prognosis of prostate cancer.

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Malachi J McKenna Metabolism Laboratory, Department of Endocrinology, School of Medicine and Medical Sciences, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland
Metabolism Laboratory, Department of Endocrinology, School of Medicine and Medical Sciences, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland
Metabolism Laboratory, Department of Endocrinology, School of Medicine and Medical Sciences, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland

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Barbara F Murray Metabolism Laboratory, Department of Endocrinology, School of Medicine and Medical Sciences, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland

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Myra O'Keane Metabolism Laboratory, Department of Endocrinology, School of Medicine and Medical Sciences, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland

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Mark T Kilbane Metabolism Laboratory, Department of Endocrinology, School of Medicine and Medical Sciences, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland

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Background

The Institute of Medicine 2011 Report on Dietary Reference Intakes for Calcium and Vitamin D specified higher intakes for all age groups compared to the 1997 report, but also cautioned against spurious claims about an epidemic of vitamin D deficiency and against advocates of higher intake requirements. Over 40 years, we have noted marked improvement in vitamin D status but we are concerned about hypervitaminosis D.

Objective

We sought to evaluate the 25-hydroxyvitamin D (25OHD) trend over 20 years.

Design

We retrieved all results of serum 25OHD from 1993 to 2013 (n=69 012) that was trimmed to one sample per person (n=43 782). We conducted a time series analysis of the monthly averages for 25OHD using a simple sequence chart and a running median smoothing function. We modelled the data using univariate auto-regressive integrated moving average (ARIMA) and forecast 25OHD levels up to 2016.

Results

The time series sequence chart and smoother function demonstrated a steady upward trend with seasonality. The yearly average 25OHD increased from 36.1 nmol/l in 1993 to 57.3 nmol/l in 2013. The ARIMA model was a good fit for the 25OHD time series; it forecasted monthly average 25OHD up to the end of 2016 with a positive stationary R 2 of 0.377.

Conclusions

Vitamin D status improved over the past 40 years, but there remains a dual problem: there are groups at risk of vitamin D deficiency who need public health preventative measures; on the other hand, random members of the population are taking unnecessarily high vitamin D intakes for unsubstantiated claims.

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Maria Luisa Brandi Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy
Fondazione Italiana Ricerca sulle Malattie dell’Osso (FIRMO Onlus), Florence, Italy

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Stefania Bandinelli Geriatric Unit, Azienda Sanitaria Toscana Centro, Florence, Italy

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Teresa Iantomasi Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy

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Francesca Giusti Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy

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Eleonora Talluri Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy

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Giovanna Sini Department of Experimental and Clinical Biomedical Sciences, University of Florence, Florence, Italy

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Fabrizio Nannipieri Clinical Research, Abiogen Pharma, Pisa, Italy

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Santina Battaglia Clinical Research, Abiogen Pharma, Pisa, Italy

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Riccardo Giusti Clinical Research, Abiogen Pharma, Pisa, Italy

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Colin Gerard Egan CE Medical Writing SRLS, Pisa, Italy

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Luigi Ferrucci Longitudinal Study Section, Translation Gerontology Branch, National Institute on Aging, Baltimore, Maryland, USA

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Objective

This study aimed to evaluate the association between the endocrine-disrupting chemical, bisphenol A (BPA) on circulating levels of 25-hydroxy vitamin D (25(OD)D) and other vitamin D metabolites in an elderly population in Italy.

Methods

This was a retrospective analysis of the InCHIANTI Biobank in Italy. The association between vitamin D metabolites namely 1,25(OH)D, 25(OH)D, parathyroid hormone (PTH) and BPA levels were evaluated. Multiple regression models were used to examine the association between predictor variables with 1,25(OH)D or 25(OH)D levels.

Results

Samples from 299 individuals aged 72.8 ± 15.7 years were examined. Mean levels of BPA, 1,25(OH)D and 25(OH)D were 351.2 ± 511.6 ng/dL, 43.7 ± 16.9 pg/mL and 20.2 ± 12.1 ng/mL, respectively. One hundred eighty individuals (60.2%) were deficient (<20 ng/mL) in 25(OH)D and this population also presented higher BPA levels (527.9 ± 1289.5 ng/dL vs 86.9 ± 116.8 ng/dL, P  < 0.0001). Univariate analysis revealed that BPA levels were negatively correlated with both 1,25(OH)D (r= −0.67, P  < 0.0001) and 25(OH)D (r= −0.69, P  < 0.0001). Multivariate regression revealed that PTH (β: −0.23, 95% CI: −0.34, −0.13, P  < 0.0001) and BPA (β: −0.25, 95% CI: −0.3, −0.19, P  < 0.0001) remained significantly associated with 25(OH)D levels while BPA was also associated with 1,25(OH)D levels (β: −0.19, 95% CI: −0.22, −0.15, P  < 0.0001). Receiver operating characteristic curve analysis showed that a BPA concentration of >113 ng/dL was the best cut-off to predict individuals deficient in 25(OH)D (area under the curve: 0.87, 95% CI: 0.82–0.90, P  < 0.0001).

Conclusion

The strong negative association between BPA and vitamin D in this elderly population warrants further investigation, particularly since this population is already at greatest risk of hypovitaminosis and fracture.

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Eliana Piantanida Department of Medicine and Surgery, University of Insubria, Varese, Italy

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Daniela Gallo Department of Medicine and Surgery, University of Insubria, Varese, Italy

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Giovanni Veronesi Department of Medicine and Surgery, University of Insubria, Varese, Italy
Research Center in Epidemiology and Preventive Medicine (EPIMED), University of Insubria, Varese, Italy

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Eugenia Dozio Department of Medicine and Surgery, University of Insubria, Varese, Italy

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Eugenia Trotti Department of Medicine and Surgery, University of Insubria, Varese, Italy

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Adriana Lai Department of Medicine and Surgery, University of Insubria, Varese, Italy

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Silvia Ippolito Department of Medicine and Surgery, University of Insubria, Varese, Italy

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Jessica Sabatino Department of Medicine and Surgery, University of Insubria, Varese, Italy

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Maria Laura Tanda Department of Medicine and Surgery, University of Insubria, Varese, Italy

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Antonio Toniolo Department of Biotechnology and Life Science, University of Insubria, Varese, Italy

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Marco Ferrario Department of Medicine and Surgery, University of Insubria, Varese, Italy
Research Center in Epidemiology and Preventive Medicine (EPIMED), University of Insubria, Varese, Italy

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Luigi Bartalena Department of Medicine and Surgery, University of Insubria, Varese, Italy

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Objective

The aim of this observational study was to clarify the link between vitamin D status and metabolic syndrome (MetS) in people with visceral obesity.

Design and methods

One hundred ninety-six consecutive patients (152 women; mean age 51 ± 13 years) with visceral obesity (mean body weight 103 ± 20 kg, mean waist circumference (WC) 119 ± 13 cm) were enrolled at the Obesity Outpatient Clinic of the University of Insubria in Varese. Anthropometric measurements were recorded. Laboratory tests, including vitamin D (25(OH)D)), fasting blood glucose (FBG), lipid profile, liver and kidney function tests were assessed. Vitamin D status was defined according to the European Society of Endocrinology guidelines, MetS to the 2009 harmonized definition.

Results

An inverse association emerged among 25(OH)D, body mass index (BMI) (P = 0.001) and WC (all P = 0.003). Serum 25(OH)D levels were inversely related to FBG and systolic blood pressure (SBP) (respectively, P = 0.01 and 0.02). Median serum 25(OH)D levels were 13.3 ng/mL (CI 95% 12; 15) in MetS and 16 ng/mL (CI 95% 14; 18) (P = 0.01) in non-MetS patients. Among patients with MetS, lower 25(OH)D concentrations were related to higher risk of hypertension (HT) (odds ratio (OR) 1.7, CI 95%, 0.7;4) and hyperglycemia (IFG)/type 2 diabetes (OR 5.5, CI 95% 2; 14).

Conclusion

Vitamin D status and MetS are inversely correlated in visceral obesity, particularly with regard to glucose homeostasis and BP. More extensive studies are required to investigate the potential for causality.

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Silvia Ciancia Department of Internal Medicine and Pediatrics, Ghent University, Ghent, Belgium

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Vanessa Dubois Basic and Translational Endocrinology (BaTE), Department of Basic and Applied Medical Sciences, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium

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Martine Cools Department of Internal Medicine and Pediatrics, Ghent University, Pediatric Endocrinology Service, Ghent University Hospital, Ghent, Belgium

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Both in the United States and Europe, the number of minors who present at transgender healthcare services before the onset of puberty is rapidly expanding. Many of those who will have persistent gender dysphoria at the onset of puberty will pursue long-term puberty suppression before reaching the appropriate age to start using gender-affirming hormones. Exposure to pubertal sex steroids is thus significantly deferred in these individuals. Puberty is a critical period for bone development: increasing concentrations of estrogens and androgens (directly or after aromatization to estrogens) promote progressive bone growth and mineralization and induce sexually dimorphic skeletal changes. As a consequence, safety concerns regarding bone development and increased future fracture risk in transgender youth have been raised. We here review published data on bone development in transgender adolescents, focusing in particular on differences in age and pubertal stage at the start of puberty suppression, chosen strategy to block puberty progression, duration of puberty suppression, and the timing of re-evaluation after estradiol or testosterone administration. Results consistently indicate a negative impact of long-term puberty suppression on bone mineral density, especially at the lumbar spine, which is only partially restored after sex steroid administration. Trans girls are more vulnerable than trans boys for compromised bone health. Behavioral health measures that can promote bone mineralization, such as weight-bearing exercise and calcium and vitamin D supplementation, are strongly recommended in transgender youth, during the phase of puberty suppression and thereafter.

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Marc Blondon Division of Angiology and Hemostasis, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland

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Emmanuel Biver Division of Bone Diseases, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland

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Olivia Braillard Division of Primary Care Medicine, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland

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Marc Righini Division of Angiology and Hemostasis, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland

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Pierre Fontana Division of Angiology and Hemostasis, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland

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Alessandro Casini Division of Angiology and Hemostasis, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland

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Objective

Vitamin D deficiency is associated with increased risks of arterial and venous cardiovascular events. Hypothetically, supplementation with vitamin D may lead to a less prothrombotic phenotype, as measured by global coagulation assays and fibrin clot structure.

Methods

In this prospective cohort study, we enrolled adult outpatients attending the Primary Care Division of the Geneva University Hospitals with a severe vitamin D deficiency (25-hydroxyvitamin-D3 (25-OHD) <25 nmol/L), excluding obese patients or with a recent acute medical event. We evaluated changes in coagulation times, thrombin generation assay, clot formation and clot lysis time, 25-OHD and parathormone before and 1–3 months after cholecalciferol oral supplementation with one-time 300,000 IU then 800 IU daily. Paired t-tests with a two-sided alpha of 0.05 compared absolute mean differences.

Results

The 48 participants had a mean age of 43.8 ± 13.8 years. After supplementation, 25-OHD levels increased from 17.9 ± 4.6 nmol/L to 62.5 ± 20.7 nmol/L 6.4 ± 3.0 weeks after inclusion. Endogenous thrombin potential and thrombin generation peak values both decreased significantly (−95.4 nM × min (95%CI −127.9 to −62.8), P < 0.001; −15.1 nM (−23.3 to −6.8), P < 0.001). The maximum absorbance by turbidimetry decreased significantly (P = 0.001) after supplementation. There was no change in clot lysis time, coagulation times or plasminogen activator inhibitor-1 and homocysteine levels.

Conclusions

In severe vitamin D deficiency, a high-dose cholecalciferol supplementation was associated with a reduction in thrombin generation and an average decreased number of fibrin protofibrils per fibers and fibrin fiber size measured by turbidimetry. This suggests that severe vitamin D deficiency may be associated with a potentially reversible prothrombotic profile.

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