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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.
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Fundación Santa Fe de Bogotá, Section of Endocrinology, Bogotá, Colombia
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Data on dietary calcium and vitamin D intake from Latin America are scarce. We explored the main correlates and dietary sources of calcium and vitamin D in a probabilistic, population-based sample from Colombia. We studied 1554 participants aged 18–75 from five different geographical regions. Dietary intake was assessed by employing a 157-item semi-quantitative food frequency questionnaire and national and international food composition tables. Daily vitamin D intake decreased with increasing age, from 230 IU/day in the 18–39 age group to 184 IU/day in the 60–75 age group (P -trend < 0.001). Vitamin D intake was positively associated with socioeconomic status (SES) (196 IU/day in lowest vs 234 in highest SES, P-trend < 0.001), and with educational level (176 IU/day in lowest vs 226 in highest education level, P-trend < 0.001). Daily calcium intake also decreased with age, from 1376 mg/day in the 18–39 age group to 1120 mg/day in the 60–75 age group (P -trend < 0.001). Calcium intake was lowest among participants with only elementary education, but the absolute difference in calcium intake between extreme education categories was smaller than for vitamin D (1107 vs 1274 mg/day, P-trend = 0.023). Daily calcium intake did not correlate with SES (P -trend = 0.74). Eggs were the main source of overall vitamin D, albeit their contribution decreased with increasing age. Dairy products contributed at least 48% of dietary calcium in all subgroups, mostly from cheese-containing traditional foods. SES and education were the key correlates of vitamin D and calcium intake. These findings may contribute to shape public health interventions in Latin American countries.
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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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Background
Bone is thought to be the reservoir of the human lead burden, and vitamin D is associated with bone turnover. We aimed to explore whether exposure to lower 25-hydroxy vitamin D (25(OH)D) levels was associated with higher blood lead levels (BLLs) by increasing the bone turnover rate in individuals with type 2 diabetes.
Methods
A total of 4103 type 2 diabetic men and postmenopausal women in Shanghai, China, were enrolled in 2018. Their 25(OH)D, β-C-terminal telopeptide (β-CTX), N-MID osteocalcin and procollagen type 1 N-peptide (P1NP) levels were detected. Their BLLs were determined by atomic absorption spectrometry. Mediation analyses were performed to identify the possible role that bone turnover played in the underlying mechanisms.
Results
In both the men and postmenopausal women, all three bone turnover markers were inversely associated with 25(OH)D and positively associated with the BLL (all P < 0.01) after adjusting for age, current smoking habits, metabolic parameters, duration of diabetes, vitamin D intake, and use of anti-osteoporosis medication. In the mediation analyses, none of the direct associations between 25(OH)D and BLL was significant for the three bone turnover markers, but all three bone turnover markers were found to be significant mediators of the indirect associations between 25(OH)D and BLL.
Conclusion
The association between vitamin D and BLL was fully mediated by bone turnover markers in type 2 diabetic patients (mediation effect). This finding suggested that vitamin D may protect against blood lead exposure from the bone reservoir by decreasing bone turnover in individuals with type 2 diabetes.
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Synlab Academy, Synlab Holding Germany GmbH, Heidelberg, Germany
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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.
Search for other papers by Ying-Lien Cheng in
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Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
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Division of Endocrinology and Metabolism, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
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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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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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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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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.
Centre de Référence des Maladies Rares du Calcium et du Phosphore Filière de Santé Maladies Rares OSCAR, Paris, France
Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, INSERM, UMRS1138, Paris, France
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Université Paris-Saclay, Inserm U1185, Physiologie et Physiopathologie Endocriniennes, Assistance Publique-Hôpitaux de Paris, Service d’Endocrinologie et Diabète de l’Enfant, Centre de Référence des Maladies Rares du Calcium et du Phosphore et Filière de Santé Maladies Rares OSCAR, Hôpital Bicêtre Paris Saclay, Le Kremlin-Bicêtre, France
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Centre de Référence des Maladies Rares du Calcium et du Phosphore Filière de Santé Maladies Rares OSCAR, Paris, France
Assistance Publique-Hôpitaux de Paris, Institut Necker-Enfants Malades, INSERM U1151 – CNRS UMR 8253, Paris, France
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Association Francophone de Chirurgie Endocrinienne (AFCE), France
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Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, Biochimie et Génétique Moléculaires, Paris, France
INSERM, U1169, Université Paris Sud, Hôpital Bicêtre, Le Kremlin Bicêtre, France
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INSERM, U1418, CIC-EC, Hôpital Européen Georges Pompidou, Paris, France
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Centre de Référence des Maladies Rares du Calcium et du Phosphore Filière de Santé Maladies Rares OSCAR, Paris, France
Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, INSERM, UMRS1138, Paris, France
CNRS, ERL8228, Paris, France
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Context
Recent guidelines have provided recommendations for the care of patients with chronic hypoparathyroidism. Very little is known about actual physicians’ practices or their adherence to such guidelines.
Objective
To describe the physicians’ practice patterns and their compliance with international guidelines.
Design
The cohort studies included were Épi-Hypo (118 physicians and 107 patients, from September 2016 to December 2019) and ePatients (110 patients, November 2019).
Methods
Internet-based cohorts involving all settings at a nationwide level (France). Participants were (i) physicians treating patients with chronic hypoparathyroidism and patients with chronic hypoparathyroidism either participating in the (ii) Épi-Hypo study (Épi-Hypo 2019 patients), or (iii) Hypoparathyroidism France, the national representative association (ePatients).
Results
The physicians’ specialties were mainly endocrinology (61%), nephrology (28%), family medicine (2.5%), pediatrics (2.5%), rheumatology (2%), or miscellaneous (4%) and 45% were practicing in public universities. The median number of pharmaceutical drug classes prescribed was three per patient. The combination of active vitamin D and calcium salt was given to 59 and 58% of ePatients and Épi-Hypo 2019 patients, respectively. Eighty-five percent of ePatients and 87% of physicians reported monitoring plasma calcium concentrations at a steady state at least twice a year. In 32 and 26% of cases, respectively, ePatients and physicians reported being fully in accordance with international guidelines that recommend targeting symptoms, plasma calcium and phosphate values, and urine calcium excretion.
Conclusions
The care of patients with chronic hypoparathyroidism involves physicians with very different practices, so guidelines should include and target other specialists as well as endocrinologists. Full adherence to the guidelines is low in France.
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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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.
