Recommended vitamin D levels in the general population | Endocrinología, Diabetes y Nutrición (English ed.)

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Spain" "etiqueta" => "i" "identificador" => "aff0045" ] 9 => array:3 [ "entidad" => "Unidad de Endocrinología y Nutrición, Complejo Hospitalario Torrecárdenas; Servicio de Endocrinología, Clínica San Pedro, Almería, Spain" "etiqueta" => "j" "identificador" => "aff0050" ] 10 => array:3 [ "entidad" => "Departamento de Endocrinología y Nutrición, Hospitales Universitarios Quirón Salud Madrid; Facultad de Ciencias de la Salud, Universidad Europea de Madrid, Madrid, Spain" "etiqueta" => "k" "identificador" => "aff0055" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Recomendaciones de vitamina D para la población general" ] ] "textoCompleto" => "IntroductionIn recent years there has been a growing interest in vitamin D, not only because of its role in mineral and bone metabolism, but also because of its extraskeletal effects and the high prevalence of hypovitaminosis D. The main biochemical forms are vitamin D3 (cholecalciferol) and vitamin D2 (ergocalciferol). The main source of the vitamin in humans is synthesis in the skin, followed by food1. Vitamin D3 or D2 is first hydroxylated at position 25 of the molecule by hepatic 25-hydroxylase to hydroxycholecalciferol (25OHD), also called calcifediol or calcidiol. Additional hydroxylation by 1α-hydroxylase at renal tubular cells leads to 1,25 dihydroxyvitamin D (1,25OH2D), the most hormonally active metabolite of this endocrine system.<a class="elsevierStyleCrossRef" href="#bib0295">1</a> Its main role is maintenance of phosphorus and calcium metabolism through its actions at renal and intestinal level1. It also has other autocrine and paracrine functions throughout the body.<a class="elsevierStyleCrossRef" href="#bib0300">2</a>Development of evidence-based recommendationsRecommendations were made based on the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system to establish the strength of recommendations and the level of evidence.<a class="elsevierStyleCrossRef" href="#bib0305">3</a> A distinction is made between strong recommendations, expressed as “We recommend” and number 1, and weak recommendations, expressed as “We suggest” and number 2. The quality of evidence is expressed using symbols as follows: ⊕, very low evidence; ⊕⊕, low evidence; ⊕⊕⊕, moderate evidence; and ⊕⊕⊕, high evidence.<a class="elsevierStyleCrossRef" href="#bib0305">3</a>Prevalence of vitamin D insufficiency/deficiency in SpainVitamin D insufficiency/deficiency represents an apparent worldwide epidemic. Thus, it has been reported that 88% of the population has plasma levels of 25OHD less than 30ng/mL, 37% levels less than 20ng/mL, and up to 7% mean levels under 10ng/mL.<a class="elsevierStyleCrossRef" href="#bib0310">4</a>The situation in Spain is very similar. In subjects over 65 years of age, 25OHD levels less than 20ng/mL have been reported in 80%–100% of cases, and 40% of those under 65 years have deficient values.<a class="elsevierStyleCrossRefs" href="#bib0315">5–10</a> This apparent paradox of low vitamin D levels in Spain has been explained by low dietary provision, protection from sun exposure in the summer months, and by the fact that the greatest part of Spain is above the 35°N parallel, where the possibility of synthesizing vitamin D is low in winter and spring.Definition of optimum vitamin D levelsRecommendation<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">-We suggest that serum 25OHD levels ranging from 30 and 50ng/mL (75–125nmol/L) are maintained to achieve the health benefits provided by vitamin D (2⊕○○).</li></ul>EvidenceThe definition of adequate 25OHD levels continues to be controversial. Thus, the values proposed by the Institute of Medicine (IOM) of the United States<a class="elsevierStyleCrossRef" href="#bib0345">11</a> for the healthy general population are over 20ng/mL, while the International Osteoporosis Federation (IOF) suggests levels higher than 30ng/mL for patients.<a class="elsevierStyleCrossRef" href="#bib0350">12</a> This recommendation is supported by the US Endocrine Society<a class="elsevierStyleCrossRef" href="#bib0355">13</a> and by other scientific associations from many countries, including Spain.<a class="elsevierStyleCrossRef" href="#bib0360">14</a> Serum 25OHD levels higher than 30ng/mL will ensure adequate bone health, but higher levels may possibly be required to achieve favorable outcomes in other health objectives.<a class="elsevierStyleCrossRefs" href="#bib0365">15–17</a> On the other hand, the maximum recommended serum 25OHD value is also controversial. There are data suggesting that levels less than 100ng/mL are not associated to toxic effects,<a class="elsevierStyleCrossRef" href="#bib0380">18</a> and some authors have therefore proposed levels of 60–70ng/mL as recommended cut-off point.<a class="elsevierStyleCrossRef" href="#bib0355">13</a> However, there is a current debate as to whether high 25OHD levels (>50–60ng/mL) could be associated to risk of death from cardiovascular or any other causes.<a class="elsevierStyleCrossRef" href="#bib0385">19</a>In our view, until more solid evidence is available of the extraosseous benefits of higher vitamin D levels, serum 25OHD levels ranging from 30 and 50ng/mL (75–125nmol/L) ensure benefits for bone while maintaining an adequate safety profile and minimizing the inaccuracy seen with the different commercial tests.Causes of vitamin D deficiency/insufficiencyVitamin D deficiency may be of an extrinsic or intrinsic origin.<a class="elsevierStyleCrossRefs" href="#bib0355">13,20</a> Its main causes are described in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>Screening for vitamin D deficiencyRecommendation<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0010">-Screening for vitamin D deficiency is recommended in subjects with risk factors (1⊕⊕○○).</li><li class="elsevierStyleListItem" id="lsti0015">-Screening is not recommended in people with no risk factors (1⊕⊕○○).</li></ul>EvidenceUniversal screening for vitamin D deficiency is not recommended13 and should only be done in risk subjects or groups (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>Recommended vitamin D intakeRecommendation<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0020">-We suggest a daily intake of 600 international units (IU) of vitamin D in people aged less than 70 years old, and 800IU in those over 70 years of age (2⊕⊕○○).</li></ul>EvidenceDaily provision of vitamin D is currently controversial. The IOM, endocrinological societies, and the US Task Force do not agree on the daily amount required.<a class="elsevierStyleCrossRefs" href="#bib0345">11,13</a> The reason for this is that the recommendations of the IOM and US Task Force would be for the general healthy population, and those of medical societies for patients.<a class="elsevierStyleCrossRefs" href="#bib0345">11,13,21</a> The IOM committee recommends a daily amount of 600IU of vitamin D to meet the requirements of almost all the general population in the United States and Canada. The amount for people older than 70 years would be 800IU (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).<a class="elsevierStyleCrossRef" href="#bib0345">11</a><elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Treatment with vitamin D supplementsRecommendation<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0025">-We recommend use of vitamin D3 (cholecalciferol) or 25OHD (calcifediol) to treat vitamin D deficiency (1⊕⊕⊕○).</li><li class="elsevierStyleListItem" id="lsti0030">-We suggest that the required dose of vitamin D is calculated depending on etiology and severity of the deficiency, and on the type of vitamin D that will be used for treatment (2⊕⊕○○).</li><li class="elsevierStyleListItem" id="lsti0035">-We suggest monitoring of serum 25OHD levels to assess response to treatment at 3–4 month intervals until the adequate 25OHD are reached, and every 6 months thereafter (2⊕⊕○○).</li></ul>EvidenceIn Spain, vitamin D deficiency may be treated with preparations of vitamin D (cholecalciferol), 25OHD3 (calcifediol), 1,25OH2D3 (calcitriol), and 1αOHD3 (alfacalcidiol) (<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>). 1,25OH2D3 and 1αOHD3 have a short half-life and greater risk of hypercalcemia, and are therefore not recommended for standard treatment of vitamin D deficiency. It should be reminded that vitamin D and 25OHD are not equipotent. 25OHD is more hydrophilic, has a shorter half-life and a faster start of action, and is 3–6 times more potent to increase serum 25OHD3 levels.<a class="elsevierStyleCrossRefs" href="#bib0400">22,23</a> The dose to be used will depend on the cause and severity of deficiency, and also on the vitamin D formulation used.<elsevierMultimedia ident="tbl0020"></elsevierMultimedia>In patients with normal absorption capacity, it has been seen that each 100IU of vitamin D increase serum 25OHD levels by 0.7–1ng/mL. The biological potency of vitamin D is established so that 40IU are equivalent to 1μg of colecalciferol.<a class="elsevierStyleCrossRef" href="#bib0410">24</a> Multiple dosage schemes have been tested, and similar results have been reported with daily, weekly, monthly, bimonthly, and even quarterly schemes.<a class="elsevierStyleCrossRef" href="#bib0415">25</a> However, annual administration of high doses (300,000IU) should be avoided because of the increased risk of fall and fracture reported.<a class="elsevierStyleCrossRefs" href="#bib0420">26,27</a>Treatment should be monitored at 3–4 month intervals, and once the desired serum 25OHD levels are reached, maintenance doses should be given to prevent a new decrease in 25OHD levels.<a class="elsevierStyleCrossRef" href="#bib0355">13</a>Bone effects of vitamin D supplementation in the general populationRecommendation<ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0040">-We recommend that people over 65 years of age and institutionalized are given 800–1000IU/day of vitamin D to improve bone health and decrease the risk of non-vertebral fracture (1⊕⊕⊕⊕).</li><li class="elsevierStyleListItem" id="lsti0045">-We suggest that adults over 50 years of age are given at least 800IU/day of vitamin D in addition to an adequate calcium (1000–1200mg/day) to improve bone health and decrease risk of fracture (2⊕⊕⊕⊕).</li><li class="elsevierStyleListItem" id="lsti0050">-There is no evidence to recommend routine supplementation in all adults under 50 years of age to improve bone health (2⊕⊕⊕○).</li></ul>EvidenceIn adults under 50 years of age, no adequate evidence is available showing the benefit of vitamin D supplementation on risk of fracture.Studies analyzing the relationship between vitamin D supplementation and bone mineral density (BMD) in people over 50 years of age were relatively small, used doses ≤400IU/day, and did not find a significant effect, but showed a preventive effect on the spine and hip when calcium was coadministered.<a class="elsevierStyleCrossRef" href="#bib0430">28</a> A recent meta-analysis of randomized clinical trials with vitamin D supplementation in non-osteoporotic populations showed no changes of BMD in any tested site, except for a minimum increase in the femoral neck, which was considered by the authors an incidental finding.<a class="elsevierStyleCrossRef" href="#bib0435">29</a>As regards fractures, meta-analyses of controlled trials published in the past 10 years showed that use of vitamin D alone, as compared to placebo, did not decrease the risk of fracture,<a class="elsevierStyleCrossRefs" href="#bib0440">30–32</a> except for the Bischoff-Ferrari meta-analysis, where a subgroup analysis showed that high vitamin D doses (>800IU) achieved prevention of non-vertebral fractures irrespective of calcium supplementation especially in elderly subjects, and particularly in those institutionalized.<a class="elsevierStyleCrossRefs" href="#bib0455">33,34</a> Variable results have been reported for the combination of calcium and vitamin D, but there was a trend to a significant decrease in hip, non-vertebral, and all fractures with doses higher than 400IU of vitamin D daily and 500–1200mg of calcium.<a class="elsevierStyleCrossRef" href="#bib0465">35</a>Effects of treatment with vitamin D supplements on incidence of fallsRecommendation<ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0055">-We recommend measurement of serum 25OHD levels in subjects with muscle weakness and falls (1⊕⊕○○).</li><li class="elsevierStyleListItem" id="lsti0060">-We recommend that patients with vitamin D deficiency and high risk of fall are treated with supplements (1⊕⊕○○).</li></ul>EvidenceVitamin D has different effects on muscle. 1,25OH2D, by binding to the vitamin D receptor (VDR), regulates gene transcription and promotes de novo synthesis of proteins involved in calcium and phosphorus transport and in muscle fiber proliferation and differentiation.<a class="elsevierStyleCrossRefs" href="#bib0295">1,2</a> In addition, it also appears to have non-genomic effects through a receptor different from vitamin D located at the cell membrane which would promote the active calcium transport into the sarcoplasmic reticulum required for adequate muscle contraction.<a class="elsevierStyleCrossRefs" href="#bib0295">1,2,36</a>Vitamin D deficiency is associated to muscle weakness (particularly proximal). In patients with this deficiency, muscle biopsy shows selective loss and atrophy of type II muscle fibers, the main ones involved in fall prevention.<a class="elsevierStyleCrossRef" href="#bib0470">36</a> This observation may explain the increased risk of falls in people with vitamin D deficiency.<a class="elsevierStyleCrossRef" href="#bib0470">36</a> Data from observational studies suggest that 25OHD levels less than 20ng/mL are related to poorer lower limb muscle function in elderly patients.<a class="elsevierStyleCrossRef" href="#bib0300">2</a> Different clinical trials have found that supplementation with vitamin D in elderly patients improves strength, muscle function, and balance.<a class="elsevierStyleCrossRef" href="#bib0475">37</a>As regards the protective effect of vitamin D supplementation on fall rate, results appear to depend on prior serum levels, subject age, and their living environment. In a review of 25 RCTs published in 2011, supplementation with vitamin D with or without calcium decreased 14% the overall risk of fall and up to 47% in patients with prior deficiency.<a class="elsevierStyleCrossRef" href="#bib0480">38</a> In turn, the US Task Force recently concluded that vitamin D supplementation decreased the risk of fall by 11%.<a class="elsevierStyleCrossRef" href="#bib0485">39</a> Serum 25OHD levels higher than 24ng/mL appear to have greater protective effect.<a class="elsevierStyleCrossRef" href="#bib0490">40</a> On the other hand, the last Cochrane review and a sequential meta-analysis of clinical trials showed no benefit of vitamin D supplementation on risk of fall in the general population.<a class="elsevierStyleCrossRefs" href="#bib0495">41,42</a> However, there is a benefit in elderly subjects with high risk of falls, such as those who are institutionalized and those living in the community and have lower vitamin D levels before treatment.<a class="elsevierStyleCrossRefs" href="#bib0495">41–46</a>Extraosseous benefits of treatment with vitamin D supplementsRecommendation<ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0065">-There is no adequate evidence to support use of vitamin D supplements to obtain extraosseous benefits (2⊕⊕○○).</li><li class="elsevierStyleListItem" id="lsti0070">-We do not recommend supplementation with vitamin D to decrease the incidence of cancer in the general population (1⊕⊕⊕○).</li></ul>EvidenceVitamin D supplements have not shown benefits on cardiovascular morbidity and mortality.<a class="elsevierStyleCrossRefs" href="#bib0525">47–51</a>In pregnant women, supplements non-significantly decrease the risk of preeclampsia (relative risk [RR] 0.52; 95% confidence interval [CI]: 0.25–1.05), with no effect on risk of gestational diabetes. In studies with small patient samples, supplements have been related to a lower risk of preterm delivery (RR 0.36; 95% CI: 0.14–0.93) and low birthweight (RR 0.40; 95% CI: 0.24–0.67).<a class="elsevierStyleCrossRef" href="#bib0550">52</a>A great controversy exists on the effect of vitamin D supplementation and incidence of cancer. In a randomized study, Lappe et al.<a class="elsevierStyleCrossRef" href="#bib0555">53</a> showed a reduced incidence of cancer (RR 0.402; 95% CI: 0.20–0.82; p=0.01) in women over 55 years of age who received daily supplements of calcium and vitamin D3. Treatment with calcitriol or alfacalcidiol for three years after kidney transplant was associated to a lower risk of tumors (HR 0.25; 95% CI: 0.07–0.82).<a class="elsevierStyleCrossRef" href="#bib0560">54</a> In the study Women's Health Initiative, however, daily treatment with 1g of calcium and 400IU of D3 for 7 years had no influence on incidence of colorectal cancer and invasive breast cancer.<a class="elsevierStyleCrossRef" href="#bib0565">55</a> In addition, a systematic review of 18 randomized studies found no association between vitamin D supplementation for up to 7 years and incidence of cancer.<a class="elsevierStyleCrossRef" href="#bib0570">56</a>A meta-analysis of 56 randomized studies showed a slight reduction in total mortality (RR 0.94; 95% CI: 0.91–0.98) and cancer mortality (RR 0.88; 95% CI: 0.78–0.98) in patients treated with vitamin D3 after 4.4 years of follow-up; the effect was only seen when the vitamin was administered daily associated to calcium at doses >800IU/day, and in patients with vitamin D insufficiency.<a class="elsevierStyleCrossRef" href="#bib0575">57</a>Note of authorsThis article is the executive summary of the complete document, which may be consulted at the web site of the Spanish Society of Endocrinology and Nutrition.<a class="elsevierStyleCrossRef" href="#bib0580">58</a>FundingNo funding was received to conduct this study.Conflicts of interestThe authors state that they have no conflicts of interest in relation to preparation of this article." "textoCompletoSecciones" => array:1 [ "secciones" => array:19 [ 0 => array:3 [ "identificador" => "xres834798" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Participants" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec830714" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres834799" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Participantes" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec830713" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Development of evidence-based recommendations" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Prevalence of vitamin D insufficiency/deficiency in Spain" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Definition of optimum vitamin D levels" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Recommendation" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Evidence" ] ] ] 8 => array:2 [ "identificador" => "sec0035" "titulo" => "Causes of vitamin D deficiency/insufficiency" ] 9 => array:3 [ "identificador" => "sec0040" "titulo" => "Screening for vitamin D deficiency" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Recommendation" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Evidence" ] ] ] 10 => array:3 [ "identificador" => "sec0055" "titulo" => "Recommended vitamin D intake" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0060" "titulo" => "Recommendation" ] 1 => array:2 [ "identificador" => "sec0065" "titulo" => "Evidence" ] ] ] 11 => array:3 [ "identificador" => "sec0070" "titulo" => "Treatment with vitamin D supplements" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0075" "titulo" => "Recommendation" ] 1 => array:2 [ "identificador" => "sec0080" "titulo" => "Evidence" ] ] ] 12 => array:3 [ "identificador" => "sec0085" "titulo" => "Bone effects of vitamin D supplementation in the general population" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0090" "titulo" => "Recommendation" ] 1 => array:2 [ "identificador" => "sec0095" "titulo" => "Evidence" ] ] ] 13 => array:3 [ "identificador" => "sec0100" "titulo" => "Effects of treatment with vitamin D supplements on incidence of falls" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0105" "titulo" => "Recommendation" ] 1 => array:2 [ "identificador" => "sec0110" "titulo" => "Evidence" ] ] ] 14 => array:3 [ "identificador" => "sec0115" "titulo" => "Extraosseous benefits of treatment with vitamin D supplements" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0120" "titulo" => "Recommendation" ] 1 => array:2 [ "identificador" => "sec0125" "titulo" => "Evidence" ] ] ] 15 => array:2 [ "identificador" => "sec0130" "titulo" => "Note of authors" ] 16 => array:2 [ "identificador" => "sec0135" "titulo" => "Funding" ] 17 => array:2 [ "identificador" => "sec0140" "titulo" => "Conflicts of interest" ] 18 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec830714" "palabras" => array:14 [ 0 => "Vitamin D" 1 => "25-Hydroxyvitamin D" 2 => "Cholecalciferol" 3 => "Ergocalciferol" 4 => "Calcitriol" 5 => "Calcidiol" 6 => "Osteoporosis" 7 => "Fractures" 8 => "Muscle strength" 9 => "Falls" 10 => "Cancer" 11 => "Cardiovascular diseases" 12 => "Mortality" 13 => "Pregnancy" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec830713" "palabras" => array:14 [ 0 => "Vitamina D" 1 => "25-Hidroxivitamina D" 2 => "Colecalciferol" 3 => "Ergocalciferol" 4 => "Calcitriol" 5 => "Calcidiol" 6 => "Osteoporosis" 7 => "Fracturas" 8 => "Fuerza muscular" 9 => "Caídas" 10 => "Cáncer" 11 => "Enfermedad cardiovascular" 12 => "Mortalidad" 13 => "Embarazo" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveTo provide recommendations based on evidence on the management of vitamin D deficiency in the general population. ParticipantsMembers of the Bone Metabolism Working Group of the Spanish Society of Endocrinology. MethodsRecommendations were formulated using the GRADE system (Grading of Recommendations, Assessment, Development, and Evaluation) to describe both the strength of recommendations and the quality of evidence. A systematic search was made in MEDLINE (Pubmed) using the term Vitamin D and the name of each issue. Papers in English and Spanish with publication date before 17 March 2016 were included. Recommendations were jointly discussed by the Working Group. ConclusionsThis document summarizes the data about vitamin D deficiency in terms of prevalence, etiology, screening indications, adequate levels and effects of supplementation on bone and non-skeletal health outcomes." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Participants" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivoProporcionar recomendaciones basadas en la evidencia sobre el manejo del déficit de vitamina D en población general. ParticipantesMiembros del Grupo de Trabajo de Osteoporosis y Metabolismo Mineral de la SEEN. MétodosSe empleó el sistema Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) para establecer tanto la fuerza de las recomendaciones como el grado de evidencia. Se realizo¿ una bu¿squeda sistemática en Medline de la evidencia disponible para vitaminaD y el título de cada capítulo. Se revisaron arti¿culos escritos en inglés con fecha de inclusio¿n hasta 17 de marzo del 2016. Tras la formulacio¿n de las recomendaciones, estas se discutieron de manera conjunta en el grupo de trabajo. ConclusionesEste documento resume los datos acerca del déficit de vitamina D en lo que respecta a su prevalencia, etiología, indicaciones de cribado, niveles adecuados y efectos de la suplementación a nivel óseo y extraóseo." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Participantes" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Métodos" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Varsavsky M, Rozas Moreno P, Becerra Fernández A, Luque Fernández I, Quesada Gómez JM, Ávila Rubio V, et al. Recomendaciones de vitamina D para la población general. Endocrinol Diabetes Nutr. 2017;64:7–14." ] ] "multimedia" => array:4 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Adapted from Varsavsky et al.<a class="elsevierStyleCrossRef" href="#bib0390">20</a>." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Extrinsic \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Inadequate intake \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Low sunlight exposure \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Use of creams with ultraviolet radiation filter (protection factor > 8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Skin hyperpigmentation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Intrinsic \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Advanced age (decreased skin synthesis of vitamin D) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Malabsorption: \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gastrectomy (total, partial, gastric bypass) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Intestinal diseases (e.g. celiac disease, Crohn disease) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Primary biliary cirrhosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pancreatic insufficiency (e.g. cystic fibrosis) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Treatment with cholestyramine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chronic colostasis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Increased vitamin D catabolism: \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Anticonvulsants \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antiretrovirals for HIV \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tuberculostatics \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hyperparathyroidism \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Paget's disease of bone \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chronic granulomatous disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Some lymphomas \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Obesity (decreased vitamin D bioavailability) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Deficient 25-hydroxylation in the liver \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Severe chronic liver disease/hepatic cirrhosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Deficient 1α-hydroxylation in the kidney \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chronic kidney failure \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Vitamin D-dependent rickets type I \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hypoparathyroidism \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pseudohypoparathyroidism \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Renal loss of 25-hydroxyvitamin D \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nephrotic syndrome \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Abnormalities in 1,25-OH-vitamin D receptor \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Vitamin D-dependent rickets type II \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1407704.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Pathogenic mechanism and causes of vitamin D deficiency." ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "HIV: human immunodeficiency virus.Adapted from Holick et al.<a class="elsevierStyleCrossRef" href="#bib0355">13</a>." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Rickets \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Osteomalacia \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Osteoporosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chronic kidney disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Liver disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Malabsorption syndromes: \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cystic fibrosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Inflammatory bowel disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Crohn disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bariatric surgery \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Post-radiation enteritis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hyperparathyroidism \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Drugs: \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Anticonvulsants \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Glucocorticoids \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antiretrovirals for HIV \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Antifungals \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Cholestyramine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pregnancy and lactation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Institutionalized elderly subjects with history of falls or non-traumatic fractures \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Obesity \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Inadequate sun exposure \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Granulomatous diseases \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sarcoidosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Tuberculosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Histoplasmosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Coccidiomyicosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Berylliosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Some lymphomas \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1407705.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Indications of screening for vitamin D deficiency." ] ] 2 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "Adapted from the US Institute of Medicine.<a class="elsevierStyleCrossRef" href="#bib0345">11</a>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age group \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Estimated mean requirements (IU/day) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Recommended dietary provision (IU/day) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Tolerable upper intake level (IU/day) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">0–6 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">400 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">400 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.000 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">6–12 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">400 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">400 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.500 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1–3 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">400 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">600 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.500 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">4–8 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">400 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">600 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.000 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">9–70 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">400 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">600 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.000 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">>70 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">400 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">800 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.000 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1407706.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Recommended dietary intake of vitamin D." ] ] 3 => array:8 [ "identificador" => "tbl0020" "etiqueta" => "Table 4" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at4" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Drug \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Name \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Dose \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">How supplied \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="middle">Cholecalciferol (vitamin D3)</td><td class="td" title="table-entry " align="left" valign="top">Deltius \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25,000IU/mL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Single dose vials \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Vitamin D3 Kern Pharma \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20,000IU/10mL (1 drop=66IU) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Bottle containing 10 or 30mL \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="middle">Calcifediol (25OH vitamin D)</td><td class="td" title="table-entry " align="left" valign="top">Hidroferol \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16,000IU \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Single dose vials or soft capsules \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hidroferol drops \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.1mg/mL (1 drop=240IU) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Bottle containing 10 or 20mL \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1407707.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Commercial vitamin D preparations." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:58 [ 0 => array:3 [ "identificador" => "bib0295" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Papel del calcio y la vitamina D en la salud ósea" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. 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Recommended vitamin D levels in the general population

Recomendaciones de vitamina D para la población general

Mariela Varsavskya, Pedro Rozas Morenob,

Corresponding author

pedrorozasm@yahoo.es

Corresponding author.

, Antonio Becerra Fernándezc, Inés Luque Fernándezd, José Manuel Quesada Gómeze, Verónica Ávila Rubiof, Antonia García Martínf, María Cortés Berdoncesg, Silvia Naf Cortésh, Manuel Romero Muñozi, Rebeca Reyes Garcíaj, Esteban Jódar Gimenok, Manuel Muñoz Torresf, on behalf of the Bone Metabolism Working Group of the Spanish Society of Endocrinology

a Servicio de Endocrinología, Hospital Italiano de Buenos Aires, Buenos Aires, Argentina

b Servicio de Endocrinología, Hospital General Universitario de Ciudad Real, Ciudad Real, Spain

c Unidad de Identidad de Género, Hospital Universitario Ramón y Cajal; Facultad de Medicina, Universidad de Alcalá, Madrid, Spain

d Servicio de Endocrinología y Nutrición, Hospital Virgen de la Salud, Toledo, Spain

e Unidad de Metabolismo Mineral, UGC Endocrinología y Nutrición; Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Hospital Universitario Reina Sofía; RETICEF, Córdoba, Spain

f Unidad de Metabolismo Óseo, UGC Endocrinología y Nutrición, Complejo Hospitalario Universitario de Granada; RETICEF, Granada, Spain

g Servicio de Endocrinología y Nutrición, Hospital Ruber Juan Bravo, Madrid, Spain

h Hospital Universitari Joan XXIII, IISPV, Universitat Rovira i Virgili; CIBERDEM, Tarragona, Spain

i Unidad de Endocrinología y Nutrición, HGU Rafael Méndez, Lorca, Murcia, Spain

j Unidad de Endocrinología y Nutrición, Complejo Hospitalario Torrecárdenas; Servicio de Endocrinología, Clínica San Pedro, Almería, Spain

k Departamento de Endocrinología y Nutrición, Hospitales Universitarios Quirón Salud Madrid; Facultad de Ciencias de la Salud, Universidad Europea de Madrid, Madrid, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">In recent years there has been a growing interest in vitamin D&#44; not only because of its role in mineral and bone metabolism&#44; but also because of its extraskeletal effects and the high prevalence of hypovitaminosis D&#46; The main biochemical forms are vitamin D<span class="elsevierStyleInf">3</span> &#40;cholecalciferol&#41; and vitamin D<span class="elsevierStyleInf">2</span> &#40;ergocalciferol&#41;&#46; The main source of the vitamin in humans is synthesis in the skin&#44; followed by food1&#46; Vitamin D<span class="elsevierStyleInf">3</span> or D<span class="elsevierStyleInf">2</span> is first hydroxylated at position 25 of the molecule by hepatic 25-hydroxylase to hydroxycholecalciferol &#40;25OHD&#41;&#44; also called calcifediol or calcidiol&#46; Additional hydroxylation by 1&#945;-hydroxylase at renal tubular cells leads to 1&#44;25 dihydroxyvitamin D &#40;1&#44;25OH<span class="elsevierStyleInf">2</span>D&#41;&#44; the most hormonally active metabolite of this endocrine system&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">1</span></a> Its main role is maintenance of phosphorus and calcium metabolism through its actions at renal and intestinal level1&#46; It also has other autocrine and paracrine functions throughout the body&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">2</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Development of evidence-based recommendations</span><p id="par0010" class="elsevierStylePara elsevierViewall">Recommendations were made based on the Grading of Recommendations&#44; Assessment&#44; Development&#44; and Evaluation &#40;GRADE&#41; system to establish the strength of recommendations and the level of evidence&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">3</span></a> A distinction is made between strong recommendations&#44; expressed as &#8220;We recommend&#8221; and number 1&#44; and weak recommendations&#44; expressed as &#8220;We suggest&#8221; and number 2&#46; The quality of evidence is expressed using symbols as follows&#58; &#8853;&#44; very low evidence&#59; &#8853;&#8853;&#44; low evidence&#59; &#8853;&#8853;&#8853;&#44; moderate evidence&#59; and &#8853;&#8853;&#8853;&#44; high evidence&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">3</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Prevalence of vitamin D insufficiency&#47;deficiency in Spain</span><p id="par0015" class="elsevierStylePara elsevierViewall">Vitamin D insufficiency&#47;deficiency represents an apparent worldwide epidemic&#46; Thus&#44; it has been reported that 88&#37; of the population has plasma levels of 25OHD less than 30<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#44; 37&#37; levels less than 20<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#44; and up to 7&#37; mean levels under 10<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The situation in Spain is very similar&#46; In subjects over 65 years of age&#44; 25OHD levels less than 20<span class="elsevierStyleHsp" style=""></span>ng&#47;mL have been reported in 80&#37;&#8211;100&#37; of cases&#44; and 40&#37; of those under 65 years have deficient values&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">5&#8211;10</span></a> This apparent paradox of low vitamin D levels in Spain has been explained by low dietary provision&#44; protection from sun exposure in the summer months&#44; and by the fact that the greatest part of Spain is above the 35&#176;N parallel&#44; where the possibility of synthesizing vitamin D is low in winter and spring&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Definition of optimum vitamin D levels</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Recommendation</span><p id="par0025" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0030" class="elsevierStylePara elsevierViewall">We suggest that serum 25OHD levels ranging from 30 and 50<span class="elsevierStyleHsp" style=""></span>ng&#47;mL &#40;75&#8211;125<span class="elsevierStyleHsp" style=""></span>nmol&#47;L&#41; are maintained to achieve the health benefits provided by vitamin D &#40;2&#8853;&#9675;&#9675;&#41;&#46;</p></li></ul></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Evidence</span><p id="par0035" class="elsevierStylePara elsevierViewall">The definition of adequate 25OHD levels continues to be controversial&#46; Thus&#44; the values proposed by the Institute of Medicine &#40;IOM&#41; of the United States<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">11</span></a> for the healthy general population are over 20<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#44; while the International Osteoporosis Federation &#40;IOF&#41; suggests levels higher than 30<span class="elsevierStyleHsp" style=""></span>ng&#47;mL for patients&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">12</span></a> This recommendation is supported by the US Endocrine Society<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">13</span></a> and by other scientific associations from many countries&#44; including Spain&#46;<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">14</span></a> Serum 25OHD levels higher than 30<span class="elsevierStyleHsp" style=""></span>ng&#47;mL will ensure adequate bone health&#44; but higher levels may possibly be required to achieve favorable outcomes in other health objectives&#46;<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">15&#8211;17</span></a> On the other hand&#44; the maximum recommended serum 25OHD value is also controversial&#46; There are data suggesting that levels less than 100<span class="elsevierStyleHsp" style=""></span>ng&#47;mL are not associated to toxic effects&#44;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">18</span></a> and some authors have therefore proposed levels of 60&#8211;70<span class="elsevierStyleHsp" style=""></span>ng&#47;mL as recommended cut-off point&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">13</span></a> However&#44; there is a current debate as to whether high 25OHD levels &#40;&#62;50&#8211;60<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#41; could be associated to risk of death from cardiovascular or any other causes&#46;<a class="elsevierStyleCrossRef" href="#bib0385"><span class="elsevierStyleSup">19</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">In our view&#44; until more solid evidence is available of the extraosseous benefits of higher vitamin D levels&#44; serum 25OHD levels ranging from 30 and 50<span class="elsevierStyleHsp" style=""></span>ng&#47;mL &#40;75&#8211;125<span class="elsevierStyleHsp" style=""></span>nmol&#47;L&#41; ensure benefits for bone while maintaining an adequate safety profile and minimizing the inaccuracy seen with the different commercial tests&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Causes of vitamin D deficiency&#47;insufficiency</span><p id="par0045" class="elsevierStylePara elsevierViewall">Vitamin D deficiency may be of an extrinsic or intrinsic origin&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">13&#44;20</span></a> Its main causes are described in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Screening for vitamin D deficiency</span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Recommendation</span><p id="par0050" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0055" class="elsevierStylePara elsevierViewall">Screening for vitamin D deficiency is recommended in subjects with risk factors &#40;1&#8853;&#8853;&#9675;&#9675;&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0060" class="elsevierStylePara elsevierViewall">Screening is not recommended in people with no risk factors &#40;1&#8853;&#8853;&#9675;&#9675;&#41;&#46;</p></li></ul></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Evidence</span><p id="par0065" class="elsevierStylePara elsevierViewall">Universal screening for vitamin D deficiency is not recommended13 and should only be done in risk subjects or groups &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Recommended vitamin D intake</span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Recommendation</span><p id="par0070" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0075" class="elsevierStylePara elsevierViewall">We suggest a daily intake of 600 international units &#40;IU&#41; of vitamin D in people aged less than 70 years old&#44; and 800<span class="elsevierStyleHsp" style=""></span>IU in those over 70 years of age &#40;2&#8853;&#8853;&#9675;&#9675;&#41;&#46;</p></li></ul></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Evidence</span><p id="par0080" class="elsevierStylePara elsevierViewall">Daily provision of vitamin D is currently controversial&#46; The IOM&#44; endocrinological societies&#44; and the US Task Force do not agree on the daily amount required&#46;<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">11&#44;13</span></a> The reason for this is that the recommendations of the IOM and US Task Force would be for the general healthy population&#44; and those of medical societies for patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">11&#44;13&#44;21</span></a> The IOM committee recommends a daily amount of 600<span class="elsevierStyleHsp" style=""></span>IU of vitamin D to meet the requirements of almost all the general population in the United States and Canada&#46; The amount for people older than 70 years would be 800<span class="elsevierStyleHsp" style=""></span>IU &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">11</span></a></p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Treatment with vitamin D supplements</span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Recommendation</span><p id="par0085" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0090" class="elsevierStylePara elsevierViewall">We recommend use of vitamin D<span class="elsevierStyleInf">3</span> &#40;cholecalciferol&#41; or 25OHD &#40;calcifediol&#41; to treat vitamin D deficiency &#40;1&#8853;&#8853;&#8853;&#9675;&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0095" class="elsevierStylePara elsevierViewall">We suggest that the required dose of vitamin D is calculated depending on etiology and severity of the deficiency&#44; and on the type of vitamin D that will be used for treatment &#40;2&#8853;&#8853;&#9675;&#9675;&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0100" class="elsevierStylePara elsevierViewall">We suggest monitoring of serum 25OHD levels to assess response to treatment at 3&#8211;4 month intervals until the adequate 25OHD are reached&#44; and every 6 months thereafter &#40;2&#8853;&#8853;&#9675;&#9675;&#41;&#46;</p></li></ul></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Evidence</span><p id="par0105" class="elsevierStylePara elsevierViewall">In Spain&#44; vitamin D deficiency may be treated with preparations of vitamin D &#40;cholecalciferol&#41;&#44; 25OHD<span class="elsevierStyleInf">3</span> &#40;calcifediol&#41;&#44; 1&#44;25OH<span class="elsevierStyleInf">2</span>D<span class="elsevierStyleInf">3</span> &#40;calcitriol&#41;&#44; and 1&#945;OHD<span class="elsevierStyleInf">3</span> &#40;alfacalcidiol&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0020">Table 4</a>&#41;&#46; 1&#44;25OH<span class="elsevierStyleInf">2</span>D<span class="elsevierStyleInf">3</span> and 1&#945;OHD<span class="elsevierStyleInf">3</span> have a short half-life and greater risk of hypercalcemia&#44; and are therefore not recommended for standard treatment of vitamin D deficiency&#46; It should be reminded that vitamin D and 25OHD are not equipotent&#46; 25OHD is more hydrophilic&#44; has a shorter half-life and a faster start of action&#44; and is 3&#8211;6 times more potent to increase serum 25OHD<span class="elsevierStyleInf">3</span> levels&#46;<a class="elsevierStyleCrossRefs" href="#bib0400"><span class="elsevierStyleSup">22&#44;23</span></a> The dose to be used will depend on the cause and severity of deficiency&#44; and also on the vitamin D formulation used&#46;</p><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">In patients with normal absorption capacity&#44; it has been seen that each 100<span class="elsevierStyleHsp" style=""></span>IU of vitamin D increase serum 25OHD levels by 0&#46;7&#8211;1<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#46; The biological potency of vitamin D is established so that 40<span class="elsevierStyleHsp" style=""></span>IU are equivalent to 1<span class="elsevierStyleHsp" style=""></span>&#956;g of colecalciferol&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">24</span></a> Multiple dosage schemes have been tested&#44; and similar results have been reported with daily&#44; weekly&#44; monthly&#44; bimonthly&#44; and even quarterly schemes&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">25</span></a> However&#44; annual administration of high doses &#40;300&#44;000<span class="elsevierStyleHsp" style=""></span>IU&#41; should be avoided because of the increased risk of fall and fracture reported&#46;<a class="elsevierStyleCrossRefs" href="#bib0420"><span class="elsevierStyleSup">26&#44;27</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Treatment should be monitored at 3&#8211;4 month intervals&#44; and once the desired serum 25OHD levels are reached&#44; maintenance doses should be given to prevent a new decrease in 25OHD levels&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">13</span></a></p></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Bone effects of vitamin D supplementation in the general population</span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Recommendation</span><p id="par0120" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0025"><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">-</span><p id="par0125" class="elsevierStylePara elsevierViewall">We recommend that people over 65 years of age and institutionalized are given 800&#8211;1000<span class="elsevierStyleHsp" style=""></span>IU&#47;day of vitamin D to improve bone health and decrease the risk of non-vertebral fracture &#40;1&#8853;&#8853;&#8853;&#8853;&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">-</span><p id="par0130" class="elsevierStylePara elsevierViewall">We suggest that adults over 50 years of age are given at least 800<span class="elsevierStyleHsp" style=""></span>IU&#47;day of vitamin D in addition to an adequate calcium &#40;1000&#8211;1200<span class="elsevierStyleHsp" style=""></span>mg&#47;day&#41; to improve bone health and decrease risk of fracture &#40;2&#8853;&#8853;&#8853;&#8853;&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">-</span><p id="par0135" class="elsevierStylePara elsevierViewall">There is no evidence to recommend routine supplementation in all adults under 50 years of age to improve bone health &#40;2&#8853;&#8853;&#8853;&#9675;&#41;&#46;</p></li></ul></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Evidence</span><p id="par0140" class="elsevierStylePara elsevierViewall">In adults under 50 years of age&#44; no adequate evidence is available showing the benefit of vitamin D supplementation on risk of fracture&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Studies analyzing the relationship between vitamin D supplementation and bone mineral density &#40;BMD&#41; in people over 50 years of age were relatively small&#44; used doses &#8804;400<span class="elsevierStyleHsp" style=""></span>IU&#47;day&#44; and did not find a significant effect&#44; but showed a preventive effect on the spine and hip when calcium was coadministered&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">28</span></a> A recent meta-analysis of randomized clinical trials with vitamin D supplementation in non-osteoporotic populations showed no changes of BMD in any tested site&#44; except for a minimum increase in the femoral neck&#44; which was considered by the authors an incidental finding&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">29</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">As regards fractures&#44; meta-analyses of controlled trials published in the past 10 years showed that use of vitamin D alone&#44; as compared to placebo&#44; did not decrease the risk of fracture&#44;<a class="elsevierStyleCrossRefs" href="#bib0440"><span class="elsevierStyleSup">30&#8211;32</span></a> except for the Bischoff-Ferrari meta-analysis&#44; where a subgroup analysis showed that high vitamin D doses &#40;&#62;800<span class="elsevierStyleHsp" style=""></span>IU&#41; achieved prevention of non-vertebral fractures irrespective of calcium supplementation especially in elderly subjects&#44; and particularly in those institutionalized&#46;<a class="elsevierStyleCrossRefs" href="#bib0455"><span class="elsevierStyleSup">33&#44;34</span></a> Variable results have been reported for the combination of calcium and vitamin D&#44; but there was a trend to a significant decrease in hip&#44; non-vertebral&#44; and all fractures with doses higher than 400<span class="elsevierStyleHsp" style=""></span>IU of vitamin D daily and 500&#8211;1200<span class="elsevierStyleHsp" style=""></span>mg of calcium&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">35</span></a></p></span></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Effects of treatment with vitamin D supplements on incidence of falls</span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Recommendation</span><p id="par0155" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0030"><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">-</span><p id="par0160" class="elsevierStylePara elsevierViewall">We recommend measurement of serum 25OHD levels in subjects with muscle weakness and falls &#40;1&#8853;&#8853;&#9675;&#9675;&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">-</span><p id="par0165" class="elsevierStylePara elsevierViewall">We recommend that patients with vitamin D deficiency and high risk of fall are treated with supplements &#40;1&#8853;&#8853;&#9675;&#9675;&#41;&#46;</p></li></ul></p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Evidence</span><p id="par0170" class="elsevierStylePara elsevierViewall">Vitamin D has different effects on muscle&#46; 1&#44;25OH<span class="elsevierStyleInf">2</span>D&#44; by binding to the vitamin D receptor &#40;VDR&#41;&#44; regulates gene transcription and promotes de novo synthesis of proteins involved in calcium and phosphorus transport and in muscle fiber proliferation and differentiation&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">1&#44;2</span></a> In addition&#44; it also appears to have non-genomic effects through a receptor different from vitamin D located at the cell membrane which would promote the active calcium transport into the sarcoplasmic reticulum required for adequate muscle contraction&#46;<a class="elsevierStyleCrossRefs" href="#bib0295"><span class="elsevierStyleSup">1&#44;2&#44;36</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Vitamin D deficiency is associated to muscle weakness &#40;particularly proximal&#41;&#46; In patients with this deficiency&#44; muscle biopsy shows selective loss and atrophy of type II muscle fibers&#44; the main ones involved in fall prevention&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">36</span></a> This observation may explain the increased risk of falls in people with vitamin D deficiency&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">36</span></a> Data from observational studies suggest that 25OHD levels less than 20<span class="elsevierStyleHsp" style=""></span>ng&#47;mL are related to poorer lower limb muscle function in elderly patients&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">2</span></a> Different clinical trials have found that supplementation with vitamin D in elderly patients improves strength&#44; muscle function&#44; and balance&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">37</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">As regards the protective effect of vitamin D supplementation on fall rate&#44; results appear to depend on prior serum levels&#44; subject age&#44; and their living environment&#46; In a review of 25 RCTs published in 2011&#44; supplementation with vitamin D with or without calcium decreased 14&#37; the overall risk of fall and up to 47&#37; in patients with prior deficiency&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">38</span></a> In turn&#44; the US Task Force recently concluded that vitamin D supplementation decreased the risk of fall by 11&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">39</span></a> Serum 25OHD levels higher than 24<span class="elsevierStyleHsp" style=""></span>ng&#47;mL appear to have greater protective effect&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">40</span></a> On the other hand&#44; the last Cochrane review and a sequential meta-analysis of clinical trials showed no benefit of vitamin D supplementation on risk of fall in the general population&#46;<a class="elsevierStyleCrossRefs" href="#bib0495"><span class="elsevierStyleSup">41&#44;42</span></a> However&#44; there is a benefit in elderly subjects with high risk of falls&#44; such as those who are institutionalized and those living in the community and have lower vitamin D levels before treatment&#46;<a class="elsevierStyleCrossRefs" href="#bib0495"><span class="elsevierStyleSup">41&#8211;46</span></a></p></span></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Extraosseous benefits of treatment with vitamin D supplements</span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0180">Recommendation</span><p id="par0185" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0035"><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">-</span><p id="par0190" class="elsevierStylePara elsevierViewall">There is no adequate evidence to support use of vitamin D supplements to obtain extraosseous benefits &#40;2&#8853;&#8853;&#9675;&#9675;&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">-</span><p id="par0195" class="elsevierStylePara elsevierViewall">We do not recommend supplementation with vitamin D to decrease the incidence of cancer in the general population &#40;1&#8853;&#8853;&#8853;&#9675;&#41;&#46;</p></li></ul></p></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0185">Evidence</span><p id="par0200" class="elsevierStylePara elsevierViewall">Vitamin D supplements have not shown benefits on cardiovascular morbidity and mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0525"><span class="elsevierStyleSup">47&#8211;51</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">In pregnant women&#44; supplements non-significantly decrease the risk of preeclampsia &#40;relative risk &#91;RR&#93; 0&#46;52&#59; 95&#37; confidence interval &#91;CI&#93;&#58; 0&#46;25&#8211;1&#46;05&#41;&#44; with no effect on risk of gestational diabetes&#46; In studies with small patient samples&#44; supplements have been related to a lower risk of preterm delivery &#40;RR 0&#46;36&#59; 95&#37; CI&#58; 0&#46;14&#8211;0&#46;93&#41; and low birthweight &#40;RR 0&#46;40&#59; 95&#37; CI&#58; 0&#46;24&#8211;0&#46;67&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0550"><span class="elsevierStyleSup">52</span></a></p><p id="par0210" class="elsevierStylePara elsevierViewall">A great controversy exists on the effect of vitamin D supplementation and incidence of cancer&#46; In a randomized study&#44; Lappe et al&#46;<a class="elsevierStyleCrossRef" href="#bib0555"><span class="elsevierStyleSup">53</span></a> showed a reduced incidence of cancer &#40;RR 0&#46;402&#59; 95&#37; CI&#58; 0&#46;20&#8211;0&#46;82&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41; in women over 55 years of age who received daily supplements of calcium and vitamin D<span class="elsevierStyleInf">3</span>&#46; Treatment with calcitriol or alfacalcidiol for three years after kidney transplant was associated to a lower risk of tumors &#40;HR 0&#46;25&#59; 95&#37; CI&#58; 0&#46;07&#8211;0&#46;82&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0560"><span class="elsevierStyleSup">54</span></a> In the study Women&#39;s Health Initiative&#44; however&#44; daily treatment with 1<span class="elsevierStyleHsp" style=""></span>g of calcium and 400<span class="elsevierStyleHsp" style=""></span>IU of D<span class="elsevierStyleInf">3</span> for 7 years had no influence on incidence of colorectal cancer and invasive breast cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0565"><span class="elsevierStyleSup">55</span></a> In addition&#44; a systematic review of 18 randomized studies found no association between vitamin D supplementation for up to 7 years and incidence of cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0570"><span class="elsevierStyleSup">56</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">A meta-analysis of 56 randomized studies showed a slight reduction in total mortality &#40;RR 0&#46;94&#59; 95&#37; CI&#58; 0&#46;91&#8211;0&#46;98&#41; and cancer mortality &#40;RR 0&#46;88&#59; 95&#37; CI&#58; 0&#46;78&#8211;0&#46;98&#41; in patients treated with vitamin D<span class="elsevierStyleInf">3</span> after 4&#46;4 years of follow-up&#59; the effect was only seen when the vitamin was administered daily associated to calcium at doses &#62;800<span class="elsevierStyleHsp" style=""></span>IU&#47;day&#44; and in patients with vitamin D insufficiency&#46;<a class="elsevierStyleCrossRef" href="#bib0575"><span class="elsevierStyleSup">57</span></a></p></span></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0190">Note of authors</span><p id="par0220" class="elsevierStylePara elsevierViewall">This article is the executive summary of the complete document&#44; which may be consulted at the web site of the Spanish Society of Endocrinology and Nutrition&#46;<a class="elsevierStyleCrossRef" href="#bib0580"><span class="elsevierStyleSup">58</span></a></p></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0195">Funding</span><p id="par0225" class="elsevierStylePara elsevierViewall">No funding was received to conduct this study&#46;</p></span><span id="sec0140" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0200">Conflicts of interest</span><p id="par0230" class="elsevierStylePara elsevierViewall">The authors state that they have no conflicts of interest in relation to preparation of this article&#46;</p></span></span>"
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            1 => "25-Hydroxyvitamin D"
            2 => "Cholecalciferol"
            3 => "Ergocalciferol"
            4 => "Calcitriol"
            5 => "Calcidiol"
            6 => "Osteoporosis"
            7 => "Fractures"
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            3 => "Ergocalciferol"
            4 => "Calcitriol"
            5 => "Calcidiol"
            6 => "Osteoporosis"
            7 => "Fracturas"
            8 => "Fuerza muscular"
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            10 => "C&#225;ncer"
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To provide recommendations based on evidence on the management of vitamin D deficiency in the general population&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Participants</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Members of the Bone Metabolism Working Group of the Spanish Society of Endocrinology&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Recommendations were formulated using the GRADE system &#40;Grading of Recommendations&#44; Assessment&#44; Development&#44; and Evaluation&#41; to describe both the strength of recommendations and the quality of evidence&#46; A systematic search was made in MEDLINE &#40;Pubmed&#41; using the term Vitamin D and the name of each issue&#46; Papers in English and Spanish with publication date before 17 March 2016 were included&#46; Recommendations were jointly discussed by the Working Group&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">This document summarizes the data about vitamin D deficiency in terms of prevalence&#44; etiology&#44; screening indications&#44; adequate levels and effects of supplementation on bone and non-skeletal health outcomes&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Objective"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Participants"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Methods"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusions"
          ]
        ]
      ]
      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Proporcionar recomendaciones basadas en la evidencia sobre el manejo del d&#233;ficit de vitamina D en poblaci&#243;n general&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Participantes</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Miembros del Grupo de Trabajo de Osteoporosis y Metabolismo Mineral de la SEEN&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">M&#233;todos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se emple&#243; el sistema <span class="elsevierStyleItalic">Grading of Recommendations&#44; Assessment&#44; Development&#44; and Evaluation</span> &#40;GRADE&#41; para establecer tanto la fuerza de las recomendaciones como el grado de evidencia&#46; Se realizo¿ una bu¿squeda sistem&#225;tica en Medline de la evidencia disponible para vitamina<span class="elsevierStyleHsp" style=""></span>D y el t&#237;tulo de cada cap&#237;tulo&#46; Se revisaron arti¿culos escritos en ingl&#233;s con fecha de inclusio¿n hasta 17 de marzo del 2016&#46; Tras la formulacio¿n de las recomendaciones&#44; estas se discutieron de manera conjunta en el grupo de trabajo&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Este documento resume los datos acerca del d&#233;ficit de vitamina D en lo que respecta a su prevalencia&#44; etiolog&#237;a&#44; indicaciones de cribado&#44; niveles adecuados y efectos de la suplementaci&#243;n a nivel &#243;seo y extra&#243;seo&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Objetivo"
          ]
          1 => array:2 [
            "identificador" => "abst0030"
            "titulo" => "Participantes"
          ]
          2 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "M&#233;todos"
          ]
          3 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "Conclusiones"
          ]
        ]
      ]
    ]
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Varsavsky M&#44; Rozas Moreno P&#44; Becerra Fern&#225;ndez A&#44; Luque Fern&#225;ndez I&#44; Quesada G&#243;mez JM&#44; &#193;vila Rubio V&#44; et al&#46; Recomendaciones de vitamina D para la poblaci&#243;n general&#46; Endocrinol Diabetes Nutr&#46; 2017&#59;64&#58;7&#8211;14&#46;</p>"
      ]
    ]
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        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "detalles" => array:1 [
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            "identificador" => "at1"
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            "rol" => "short"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Adapted from Varsavsky et al&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">20</span></a>&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">Extrinsic</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Inadequate intake</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Low sunlight exposure</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Use of creams with ultraviolet radiation filter &#40;protection factor &#62; 8&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Skin hyperpigmentation</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleBold">Intrinsic</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Advanced age &#40;decreased skin synthesis of vitamin D&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Malabsorption&#58;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Gastrectomy &#40;total&#44; partial&#44; gastric bypass&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Intestinal diseases &#40;e&#46;g&#46; celiac disease&#44; Crohn disease&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Primary biliary cirrhosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Pancreatic insufficiency &#40;e&#46;g&#46; cystic fibrosis&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Treatment with cholestyramine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Chronic colostasis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Increased vitamin D catabolism&#58;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Anticonvulsants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Antiretrovirals for HIV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Tuberculostatics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Hyperparathyroidism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Paget&#39;s disease of bone</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Chronic granulomatous disease</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Some lymphomas</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Obesity &#40;decreased vitamin D bioavailability&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Deficient 25-hydroxylation in the liver</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Severe chronic liver disease&#47;hepatic cirrhosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Deficient 1&#945;-hydroxylation in the kidney</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Chronic kidney failure&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Vitamin D-dependent rickets type I&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Hypoparathyroidism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Pseudohypoparathyroidism&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Renal loss of 25-hydroxyvitamin D</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Nephrotic syndrome</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Abnormalities in 1&#44;25-OH-vitamin D receptor</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Vitamin D-dependent rickets type II</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Pathogenic mechanism and causes of vitamin D deficiency&#46;</p>"
        ]
      ]
      1 => array:8 [
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        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
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            "identificador" => "at2"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">HIV&#58; human immunodeficiency virus&#46;</p><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Adapted from Holick et al&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">13</span></a>&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Rickets</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Osteomalacia</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Osteoporosis</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Chronic kidney disease</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Liver disease</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Malabsorption syndromes&#58;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Cystic fibrosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Inflammatory bowel disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Crohn disease&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Bariatric surgery&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Post-radiation enteritis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Hyperparathyroidism</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Drugs&#58;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Anticonvulsants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Glucocorticoids&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Antiretrovirals for HIV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Antifungals&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Cholestyramine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Pregnancy and lactation</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Institutionalized elderly subjects with history of falls or non-traumatic fractures</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Obesity</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Inadequate sun exposure</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Granulomatous diseases</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Sarcoidosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Tuberculosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Histoplasmosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Coccidiomyicosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Berylliosis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Some lymphomas</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Indications of screening for vitamin D deficiency&#46;</p>"
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          "leyenda" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Adapted from the US Institute of Medicine&#46;<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">11</span></a></p>"
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                  <table border="0" frame="\n
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                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Estimated mean requirements &#40;IU&#47;day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Recommended dietary provision &#40;IU&#47;day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Tolerable upper intake level &#40;IU&#47;day&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">0&#8211;6 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">400&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">400&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">6&#8211;12 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">400&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">400&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;500&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">1&#8211;3 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">400&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">600&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;500&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">4&#8211;8 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">400&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">600&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">9&#8211;70 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">400&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">600&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;000&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">&#62;70 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">400&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">800&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;000&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Name&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="middle">Cholecalciferol &#40;vitamin D<span class="elsevierStyleInf">3</span>&#41;</td><td class="td" title="table-entry  " align="left" valign="top">Deltius&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Single dose vials&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Bottle containing 10 or 30<span class="elsevierStyleHsp" style=""></span>mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " rowspan="2" align="left" valign="middle">Calcifediol &#40;25OH vitamin D&#41;</td><td class="td" title="table-entry  " align="left" valign="top">Hidroferol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16&#44;000<span class="elsevierStyleHsp" style=""></span>IU&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Single dose vials or soft capsules&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Hidroferol drops&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Bottle containing 10 or 20<span class="elsevierStyleHsp" style=""></span>mL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
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            2 => array:3 [
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            3 => array:3 [
              "identificador" => "bib0310"
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              "referencia" => array:1 [
                0 => array:2 [
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            4 => array:3 [
              "identificador" => "bib0315"
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
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                            1 => "A&#46; Ferrer"
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            5 => array:3 [
              "identificador" => "bib0320"
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              "referencia" => array:1 [
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                  "contribucion" => array:1 [
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            7 => array:3 [
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              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
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                      "titulo" => "Vitamin D in pregnancy and attention deficit hyperactivity disorder-like symptoms in childhood"
                      "autores" => array:1 [
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                          "etal" => true
                          "autores" => array:6 [
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Article information

ISSN: 25300180
Original language: English

DOI:10.1016/j.endien.2016.11.003

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Year/Month	Html	Pdf	Total

2024 November	13	1	14
2024 October	188	6	194
2024 September	204	27	231
2024 August	129	25	154
2024 July	150	13	163
2024 June	150	17	167
2024 May	168	10	178
2024 April	175	12	187
2024 March	253	15	268
2024 February	236	11	247
2024 January	264	24	288
2023 December	172	20	192
2023 November	231	17	248
2023 October	213	13	226
2023 September	254	20	274
2023 August	134	24	158
2023 July	129	16	145
2023 June	195	29	224
2023 May	205	21	226
2023 April	161	19	180
2023 March	192	36	228
2023 February	109	18	127
2023 January	145	23	168
2022 December	143	22	165
2022 November	142	36	178
2022 October	171	36	207
2022 September	129	38	167
2022 August	141	19	160
2022 July	136	25	161
2022 June	190	26	216
2022 May	116	18	134
2022 April	130	22	152
2022 March	158	41	199
2022 February	126	32	158
2022 January	191	44	235
2021 December	124	98	222
2021 November	99	31	130
2021 October	143	44	187
2021 September	131	26	157
2021 August	130	10	140
2021 July	186	34	220
2021 June	116	30	146
2021 May	163	31	194
2021 April	467	58	525
2021 March	305	70	375
2021 February	344	40	384
2021 January	354	43	397
2020 December	357	39	396
2020 November	353	36	389
2020 October	167	29	196
2020 September	250	24	274
2020 August	138	17	155
2020 July	106	11	117
2020 June	111	15	126
2020 May	153	15	168
2020 April	108	20	128
2020 March	66	4	70
2020 February	53	6	59
2020 January	58	15	73
2019 December	41	12	53
2019 November	30	16	46
2019 October	50	6	56
2019 September	46	13	59
2019 August	38	5	43
2019 July	40	11	51
2019 June	53	18	71
2019 May	84	20	104
2019 April	77	20	97
2019 March	20	4	24
2019 February	22	3	25
2019 January	23	7	30
2018 December	18	7	25
2018 November	18	4	22
2018 October	7	5	12
2018 September	24	6	30
2018 August	15	3	18
2018 July	24	13	37
2018 June	25	3	28
2018 May	13	5	18
2018 April	17	0	17
2018 March	25	1	26
2018 February	22	0	22
2018 January	28	0	28
2017 December	18	2	20
2017 November	14	1	15
2017 October	10	1	11
2017 September	6	0	6
2017 August	1	0	1
2017 July	0	1	1

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