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Varsavsky, G. Alonso, A. García-Martín" "autores" => array:3 [ 0 => array:3 [ "nombre" => "M." "apellidos" => "Varsavsky" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:4 [ "nombre" => "G." "apellidos" => "Alonso" "email" => array:1 [ 0 => "galonso.humane@gmail.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 2 => array:3 [ "nombre" => "A." "apellidos" => "García-Martín" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] ] "afiliaciones" => array:3 [ 0 => array:3 [ "entidad" => "Unidad de Endocrinología, Hospital Sant Pau i Santa Tecla, Tarragona, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Departamento de Endocrinología. Humane Especialidades Médicas, Río Cuarto, Argentina" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Servicio de Endocrinología y Nutrición, Hospital Universitario San Cecilio, Granada, Spain" "etiqueta" => "c" "identificador" => "aff0015" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Vitamina D: presente y futuro" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Clinical case</span><p id="par0005" class="elsevierStylePara elsevierViewall">This case concerns a 78-year-old woman with a history of type 2 diabetes mellitus, arterial hypertension, dyslipidemia and osteoporosis who was on treatment with alendronate (70<span class="elsevierStyleHsp" style=""></span>mg/week), metformin (1700<span class="elsevierStyleHsp" style=""></span>mg/day) and enalapril (20<span class="elsevierStyleHsp" style=""></span>mg/day). The patient presented the following serum concentrations: parathyroid hormone (PTH), 130<span class="elsevierStyleHsp" style=""></span>pg/mL (normal values [NV], 14–72); calcemia, 9<span class="elsevierStyleHsp" style=""></span>mg/dL (NV, 8.5–10.5); phosphatemia, 3.4<span class="elsevierStyleHsp" style=""></span>mg/dL (NV, 2.4–4.1); 25-hydroxy vitamin D, 9<span class="elsevierStyleHsp" style=""></span>ng/mL (NV, >30); and creatinine, 0.9<span class="elsevierStyleHsp" style=""></span>mg/dL (NV, 0.60–1.2). After analyzing the laboratory results, we arrived at the first diagnostic option that our patient presented hyperparathyroidism secondary to vitamin D deficiency. We then considered the following questions:<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">–</span><p id="par0010" class="elsevierStylePara elsevierViewall">What are the possible causes of the patient's vitamin D deficiency?</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">–</span><p id="par0015" class="elsevierStylePara elsevierViewall">Is there an indication for treatment with vitamin D supplements?</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">–</span><p id="par0020" class="elsevierStylePara elsevierViewall">What vitamin D levels should we establish as an objective for this patient?</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">–</span><p id="par0025" class="elsevierStylePara elsevierViewall">What benefits would our patient receive by normalizing her vitamin D levels?</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">–</span><p id="par0030" class="elsevierStylePara elsevierViewall">Which vitamin D supplements should we use?</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">–</span><p id="par0035" class="elsevierStylePara elsevierViewall">What dosage should we use to normalize her levels?</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">–</span><p id="par0040" class="elsevierStylePara elsevierViewall">What adverse effects could the patient experience from vitamin D supplements?</p></li></ul></p><p id="par0045" class="elsevierStylePara elsevierViewall">Vitamins are essential substances that the body cannot synthesize in sufficient concentrations and that therefore must be obtained through dietary intake. In this regard, vitamin D would be better defined as a prohormone, given that it is mostly produced in the epidermis after exposure to sunlight. Subsequently, successive processes of hydroxylation generate vitamin D's active metabolite. To maintain appropriate vitamin D levels, a healthy individual with sufficient sun exposure does not need to eat food with vitamin D. The most important and studied action of vitamin D is related to bone mineral metabolism. Sustained vitamin D deficiency causes rickets in children and osteomalacia in adults.<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> There has been a growing interest in vitamin D in recent years, not only because of its significant role in bone mineral metabolism, but also because of its increasingly known extraskeletal effects. Various diseases such as cancer, multiple sclerosis, type 2 diabetes mellitus, inflammatory bowel disease, other autoimmune diseases, arterial hypertension and various cardiovascular diseases could be related to low serum vitamin D concentrations.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> A high prevalence of vitamin D deficiency or insufficiency has been observed in various populations, both healthy and sick. Vitamin D deficiency can have an extrinsic (lack of solar exposure or supply) or intrinsic (absorption or metabolism disorders) origin (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Assessment of vitamin D levels in the body</span><p id="par0050" class="elsevierStylePara elsevierViewall">The best method for determining the body state of vitamin D deposits consists of measuring the serum concentration of 25-hydroxy-vitamin D. The hepatic production of 25-hydroxy-vitamin D is substrate-dependent, is not hormonally regulated and has a long half-life (2–3 weeks).</p><p id="par0055" class="elsevierStylePara elsevierViewall">A fundamental problem in determining 25-hydroxy-vitamin D levels lies in the precision and reproducibility of available biochemical methods. Until fairly recently, the measurement of 25-hydroxy-vitamin D was restricted to research institutions, which employed methods based on protein competition or high-performance liquid chromatography (HPLC). Other methods were later validated for healthcare use, such as radioimmunoassay, immunoenzyme methods and chemiluminescence. The dissemination of HPLC technology in tandem with mass spectrometry (LC–MS/MS) has improved the performance of 25-hydroxy-vitamin D measurements and is enabling the standardization of results with conventional techniques. However, the coefficients of variation among the various laboratories that use HPLC and mass spectrometry are still high (20%), due to the lack of standardized procedures for the analysis of vitamin D. Given the variety of applied methods, a number of authors suggest conducting a follow-up of every individual patient using the same methodology for all cases.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Adequate vitamin D levels</span><p id="par0060" class="elsevierStylePara elsevierViewall">The reading of 25-hydroxy-vitamin D serum concentrations enables the classification of the state of vitamin D body deposits into “normal” (concentrations of 30–75<span class="elsevierStyleHsp" style=""></span>ng/mL), “insufficient” (20–30<span class="elsevierStyleHsp" style=""></span>ng/mL) or “deficient” (<20<span class="elsevierStyleHsp" style=""></span>ng/mL). The cutoff points can vary, however, depending on the criterion used by the various scientific societies. From a physiological perspective, appropriate serum concentrations of 25-hydroxy-vitamin D are those that are able to maintain normal concentrations of PTH and maximum intestinal calcium absorption. The relationship between PTH and 25-hydroxy-vitamin D concentrations is not linear and has considerable variability when the 25-hydroxy-vitamin D levels are between 20 and 30<span class="elsevierStyleHsp" style=""></span>ng/mL. When 25-hydroxy-vitamin D concentrations of 20<span class="elsevierStyleHsp" style=""></span>ng/mL are achieved, the plateau or maximum suppression of PTH is reached.<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5–8</span></a> At present, most scientific societies suggest that deposits are sufficient if their plasma concentration is above 30<span class="elsevierStyleHsp" style=""></span>ng/mL<a class="elsevierStyleCrossRefs" href="#bib0045"><span class="elsevierStyleSup">9–16</span></a> and deficient if they are below 20<span class="elsevierStyleHsp" style=""></span>ng/mL. However, the Institute of Medicine (IOM) suggests that concentrations of 20<span class="elsevierStyleHsp" style=""></span>ng/mL are sufficient to protect 97.5% of the population from the deleterious effects of vitamin D insufficiency.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Vitamin D and the risk of fractures</span><p id="par0065" class="elsevierStylePara elsevierViewall">It is generally accepted that the isolated administration of vitamin D supplements does not help prevent osteoporotic fractures. However, the combined administration of calcium and vitamin D supplements reduces the incidence of osteoporotic fractures by approximately 20%.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> Bischoff-Ferrari et al.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> published a meta-analysis that analyzed the effect of the administration of calcium and vitamin D supplements in preventing hip and nonvertebral fractures. The authors concluded that a dosage of 700–800<span class="elsevierStyleHsp" style=""></span>IU/day of vitamin D reduced the risk of hip fractures by 26% (relative risk [RR]: 0.74; 95% confidence interval (95% CI): 0.61–0.88) and the risk of nonvertebral fractures by 23% (RR: 0.77; 95% CI: 0.68–0.87), while lower dosages (less than 400<span class="elsevierStyleHsp" style=""></span>IU/day) did not reduce the risk of fractures. Boonen et al.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> conducted an in-depth analysis of the data from the previous meta-analysis and assessed the 6 clinical trials that jointly administered calcium and vitamin D, with a total of 45,509 patients. The authors found that the risk of hip fractures was reduced by 18% (RR: 0.82; 95% CI: 0.71–0.94). An adjusted indirect comparison of the collection of relative risks of both meta-analyses determined a 25% reduction in the risk of hip fractures in the patients who had been treated with calcium and vitamin D compared with those patients who had only been treated with vitamin D (RR: 0.75; 95% CI: 0.58–0.96).<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">In a recent meta-analysis, Reid et al.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> examined the bone mineral density of 4082 patients treated exclusively with vitamin D at dosages lower than 800<span class="elsevierStyleHsp" style=""></span>IU/day. The authors observed only small increases in bone mineral density in the femoral neck. Tang et al.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> assessed 17 studies (with a total of 52,625 patients) whose main objective was the reduction of fracture risk. The authors observed a 12% reduction (RR: 0.88; 95% CI: 0.83–0.95; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.0004). The efficacy of the isolated administration of calcium supplements was marginal compared with the efficacy achieved by the combined administration of calcium and vitamin D. The authors concluded that, for the prevention of osteoporosis in individuals older than 50 years, it is advisable to administer calcium and vitamin D supplements and that the necessary dosage to achieve a maximum effect was 1200<span class="elsevierStyleHsp" style=""></span>mg/day of calcium and 800<span class="elsevierStyleHsp" style=""></span>IU/day of vitamin D.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Most guidelines indicate that to effectively prevent the risk of osteoporotic fractures, a daily dose of 1000–1200<span class="elsevierStyleHsp" style=""></span>mg of calcium and 800<span class="elsevierStyleHsp" style=""></span>IU of vitamin D3 should be administered.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10–13,15,16</span></a> However, a recent document by the U.S. Preventive Services Task Force<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> referencing calcium and vitamin D supplementation in noninstitutionalized adults (men and premenopausal women with no history of osteoporosis or fractures) concluded that current evidence is insufficient to evaluate its effectiveness in this population.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Approximately 75% of the fractures occur in individuals over 65 years of age. It is estimated that by 2050 the worldwide incidence of hip fractures will increase by 240% in women and 310% in men. A potential strategy for preventing fractures in this population could be universal vitamin D supplementation. However, the results of available studies have been inconsistent. These conflicting results could be explained, at least in part, by variations in designs, participant inclusion criteria, vitamin D formulations administered and compliance to the intervention.</p><p id="par0085" class="elsevierStylePara elsevierViewall">Bischoff-Ferrari et al.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a> conducted a systematic analysis of the available studies assessing the effect of the actual quantities of vitamin D taken by participants compared with the amount estimated for the assigned dosage. The authors concluded that there is only a reduction in the risk of osteoporotic fractures in the quartile of highest doses (mean 800<span class="elsevierStyleHsp" style=""></span>IU, range 792–2000<span class="elsevierStyleHsp" style=""></span>IU) and that this reduction was 30% for hip fractures (hazard ratio [HR] 0.70; 95% CI, 0.58–0.86) and 14% for nonvertebral fractures (HR, 0.86; 95% CI, 0.76–0.96). The authors suggested that that the analyses conducted with the intention-to-treat methodology could have underestimated the benefits of vitamin D supplementation and that dosages of at least 800<span class="elsevierStyleHsp" style=""></span>IU/day would be necessary to achieve a reduction in the incidence of fractures in individuals older than 65 years, attempting to maintain serum levels of 25-hydroxy-vitamin D greater than 24<span class="elsevierStyleHsp" style=""></span>mg/mL. Although previous studies had suggested that the reduction in the risk of osteoporotic fractures was limited to institutional patients, this study observed a reduction in the general noninstitutionalized population. It has also been reported that patients with vitamin D deficiency respond to a lesser degree to the administration of bisphosphonates.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Effects of vitamin D on muscle strength, equilibrium and the incidence of falls</span><p id="par0090" class="elsevierStylePara elsevierViewall">Vitamin D deficiency is also associated with the presence of muscle weakness, predominantly in proximal muscles. A number of studies have demonstrated that vitamin D metabolites influence muscle maturation and functioning.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> Muscle weakness can affect functional capacity and mobility and can lead to an increased risk of falls and fractures. Other studies have indicated that the administration of vitamin D supplements reduces the risk of falls in the elderly. However, to be effective, the vitamin D dosage should be at least 700–1000<span class="elsevierStyleHsp" style=""></span>IU/day, given that lower dosages or serum concentrations <24<span class="elsevierStyleHsp" style=""></span>ng/mL show no beneficial effect.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26,27</span></a> This observation is consistent with the review by Cochrane of Gillespie et al.,<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> which concluded that vitamin D supplements do not reduce the risk of falls (RR 0.96; 95% CI: 0.92–1.01), although the supplements could reduce the risk for individuals with low vitamin D levels (RR 0.57, 95% CI: 0.37–0.89). These disagreements explain the lack of uniform recommendations in the various available guidelines. Thus, while a number of societies<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> support vitamin D supplementation with the objective of preventing falls, other societies find the available evidence to be insufficient to make recommendations.<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12,16</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Other extraskeletal effects of vitamin D</span><p id="par0095" class="elsevierStylePara elsevierViewall">Vitamin D deficiency has been related to increases in the incidence of various neoplasms, cardiovascular diseases, type 2 diabetes mellitus, neuropsychological disorders, pre-eclampsia, autoimmune diseases, immune response disorders, etc.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> It is not clear, however, whether the administration of vitamin D supplements is accompanied by a reduction in the incidence of these diseases. The Women's Health Initiative study,<a class="elsevierStyleCrossRefs" href="#bib0150"><span class="elsevierStyleSup">30,31</span></a> which administered low dosages of vitamin D (400<span class="elsevierStyleHsp" style=""></span>IU/day) to more than 36,000 postmenopausal women, found no significant difference after a 7-year follow-up in the incidence of type 2 diabetes mellitus and colorectal carcinoma. However, another study that administered calcium and high doses of vitamin D (1100<span class="elsevierStyleHsp" style=""></span>IU/day) to 1179 postmenopausal women found a 60% reduction in the incidence of breast carcinoma after a 4-year follow-up.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> There appears to be a clear relationship between vitamin D deficiency and the risk of cardiovascular events. However, there are few studies designed to assess the effect of vitamin D supplementation on cardiovascular disease, and these studies have generally failed to demonstrate a reduction in the number of cardiovascular events.<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">33–35</span></a> A meta-analyses performed by the Cochrane reported that vitamin D supplementation was associated with a slight but significant reduction in overall mortality (RR 0.94, 95% CI 0.91–0.98) compared with placebo.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> There are several studies currently underway attempting to assess the effect of high doses of vitamin D on the prevention of various diseases, especially cardiovascular diseases and neoplasms.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Treatment of vitamin D deficiency</span><p id="par0100" class="elsevierStylePara elsevierViewall">The main guidelines recommend that a daily dosage of 600<span class="elsevierStyleHsp" style=""></span>IU of vitamin D should be taken to maintain adequate levels of vitamin D in young and healthy populations. The recommended dosage for individuals older than 65 years and for patients with osteoporosis would be 800–1000<span class="elsevierStyleHsp" style=""></span>IU/day; for patients at risk for vitamin D deficiency, the dosage would be 1500–2000<span class="elsevierStyleHsp" style=""></span>IU/day.<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10–16</span></a> Oral vitamin D supplements can be administered daily, weekly, monthly or quarterly. Single annual doses are not recommended given that the annual administration of vitamin D2 (3,000,000<span class="elsevierStyleHsp" style=""></span>IU/year, intramuscularly) or vitamin D3 (500,000<span class="elsevierStyleHsp" style=""></span>IU/year, orally) is accompanied by increases in the incidence of falls and osteoporotic fractures.<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">37,38</span></a> The treatment of vitamin D deficiency can be performed with vitamin D2, vitamin D3 or any of its active metabolites, such as calcidiol and calcitriol. The most frequently used supplements in clinical trials are vitamin D2 and D3. A recently published meta-analysis showed that in terms of increasing plasma levels of 25-hydroxy-vitamin D, vitamin D3 is more powerful than vitamin D2, increasing the levels by 0.78<span class="elsevierStyleHsp" style=""></span>ng/mL for each 40<span class="elsevierStyleHsp" style=""></span>UI of vitamin D3 administered orally.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">39</span></a> The consumption of calcium-rich food is preferable to the administration of calcium supplements, given that the supplements cause constipation and abdominal distension and are therefore not well tolerated. Additionally, recent studies have raised concern about the potential increased cardiovascular risk caused by the use of calcium supplements.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">40</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">There are multiple schedules for the treatment of vitamin D deficiency. A number of scientific societies, such as the International Osteoporosis Foundation (IOF) and the Spanish Society for Research on Bone and Mineral Metabolism (SEIOMM), have proposed performing a calculation regarding the desired objective for vitamin D levels, taking into account that 100<span class="elsevierStyleHsp" style=""></span>IU/day of vitamin D increases the levels of 25-hydroxy-vitamin D by 1<span class="elsevierStyleHsp" style=""></span>ng/mL.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">14,16</span></a> The Endocrine Society recommends treatment with 50,000<span class="elsevierStyleHsp" style=""></span>IU of vitamin D2 or D3 once a week for 8 weeks or 6000<span class="elsevierStyleHsp" style=""></span>IU/day and reassessment at 3 months. Once the desired vitamin D levels have been achieved, the society recommends continuing with 1500–2000<span class="elsevierStyleHsp" style=""></span>IU/day.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> An alternative regimen consists of the administration of 200,000–600,000<span class="elsevierStyleHsp" style=""></span>IU in a single dose. Oral treatment with calcidiol is performed at dosages of 250<span class="elsevierStyleHsp" style=""></span>μg (10,000<span class="elsevierStyleHsp" style=""></span>IU/day) until vitamin D levels have been normalized, continuing with 10–30<span class="elsevierStyleHsp" style=""></span>μg/day (400–1200<span class="elsevierStyleHsp" style=""></span>IU/day) or 0.5–1<span class="elsevierStyleHsp" style=""></span>μg/day (20–40<span class="elsevierStyleHsp" style=""></span>IU/day) of calcitriol orally as maintenance.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> The administration of these vitamin D metabolites is especially indicated when there is an intestinal absorption or vitamin D metabolism disorder. Higher dosages might be required when treating this disorder and/or when administering parenterally. When higher doses are used, it is advisable to conduct phosphocalcic metabolism checkups, especially at the start of treatment, to avoid overdosing. It is also advisable to maintain 25-0H-vitamin D concentrations between 30 and 50<span class="elsevierStyleHsp" style=""></span>ng/mL and avoid hypercalciuria.</p><p id="par0110" class="elsevierStylePara elsevierViewall">In the treatment of osteomalacia, the improvement or disappearance of clinical, radiological and biochemical disorders is usually observed during the first 6 months of treatment, although more time might be required for PTH and alkaline phosphatase levels to normalize.</p><p id="par0115" class="elsevierStylePara elsevierViewall">Obese patients might require larger quantities of vitamin D supplements to reach optimal vitamin D levels.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> It has been calculated that obese patients need 2 to 3 times larger vitamin D dosages (6000–10,000<span class="elsevierStyleHsp" style=""></span>IU/day) to correct their vitamin D deficiency and maintain appropriate levels (2000<span class="elsevierStyleHsp" style=""></span>IU/day of vitamin D) than patients of normal weight.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Concentrations of 1,25-OH-vitamin D are reduced in patients with chronic renal failure. It is believed that this condition is due to the loss of renal mass, with less availability of the 1-α hydroxylase enzyme activator, a reduced glomerular filtration rate that results in reduced tubular 25-hydroxy-vitamin D levels and to phosphate retention, which decreases the renal synthesis of calcitriol, directly or indirectly, through the increase of FGF-23. For patients with chronic renal failure, it is recommended that 25-hydroxy-vitamin D concentrations be measured every 6 months. The treatment for the deficiency will vary depending on the degree of renal failure. In stages I-II, however, the same recommendations as for the general population should be followed. For stages III-IV, the use of active vitamin D metabolites (calcitriol or alfacalcidol) or selective vitamin D receptor activators (paricalcitol) is recommended.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">Vitamin D toxicity is uncommon and consists mainly of acute hypercalcemia, which typically occurs when the dosage exceeds 10,000<span class="elsevierStyleHsp" style=""></span>IU/day, with 25-OH vitamin D levels greater than 150<span class="elsevierStyleHsp" style=""></span>ng/mL. There is, however, individual idiosyncrasy and toxicity can occur at lower levels. The incidence of toxicity is greatly increased when treatment is performed with active metabolites.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a> The IOM established 4000<span class="elsevierStyleHsp" style=""></span>IU/day as the maximum tolerated dosage in healthy individuals and 10,000<span class="elsevierStyleHsp" style=""></span>IU/day in individuals with a risk of vitamin D deficiency.<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> The recommendations of the Endocrine Society and SEIOMM are summarized in <a class="elsevierStyleCrossRefs" href="#tbl0010">Tables 2 and 3</a>.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0130" class="elsevierStylePara elsevierViewall">In terms of the hypothetical benefits of vitamin D supplement administration on various extraskeletal conditions (cardiovascular events, neoplasms, autoimmune diseases, diabetes mellitus, effects on gestation, etc.) and despite the fact that the US Task Force has suggested that vitamin D supplements greater than 1000<span class="elsevierStyleHsp" style=""></span>IU/day could decrease the incidence of colorectal carcinoma, most guidelines have concluded that they cannot currently recommend their use, either in the treatment or the prevention of these types of diseases.<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">44,45</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">Based on all of the above and the questions proposed by the clinical case, which is the subject of this manuscript, we can conclude the following:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">–</span><p id="par0140" class="elsevierStylePara elsevierViewall">The causes that could explain the vitamin D deficiency in our patient are deficient sun exposure and age-related reduced cutaneous synthesis of vitamin D.</p></li><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">–</span><p id="par0145" class="elsevierStylePara elsevierViewall">There is an indication for treatment with vitamin D supplements because the patient's plasma levels of 25-OH vitamin D (9<span class="elsevierStyleHsp" style=""></span>ng/mL) are within the range of deficiency (<20<span class="elsevierStyleHsp" style=""></span>ng/mL).</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">–</span><p id="par0150" class="elsevierStylePara elsevierViewall">As a treatment objective, we should attempt to reach serum 25-OH-vitamin D concentrations >30<span class="elsevierStyleHsp" style=""></span>ng/dL.</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">–</span><p id="par0155" class="elsevierStylePara elsevierViewall">The expected clinical benefits in our patients lie in the prevention of fractures due to frailty, improvements in muscle function and equilibrium, a reduced risk of falls and the addition of extraskeletal benefits (cardiovascular, metabolic, immunologic, etc.).</p></li><li class="elsevierStyleListItem" id="lsti0060"><span class="elsevierStyleLabel">–</span><p id="par0160" class="elsevierStylePara elsevierViewall">We should preferentially administer vitamin D3 supplements orally or, as an alternative, vitamin D2 supplements, calcidiol or calcitriol.</p></li><li class="elsevierStyleListItem" id="lsti0065"><span class="elsevierStyleLabel">–</span><p id="par0165" class="elsevierStylePara elsevierViewall">The dosage to administer should be 50,000<span class="elsevierStyleHsp" style=""></span>IU of vitamin D3 once a week for 8 weeks or 6000<span class="elsevierStyleHsp" style=""></span>IU/day and reassess in 3 months. Subsequently and once the desired 2-OH-vitamin D levels have been achieved, we should continue with 1500–2000<span class="elsevierStyleHsp" style=""></span>IU/day. An alternative regimen consists of the administration of 200,000–600,000<span class="elsevierStyleHsp" style=""></span>IU in a single dose.</p></li><li class="elsevierStyleListItem" id="lsti0070"><span class="elsevierStyleLabel">–</span><p id="par0170" class="elsevierStylePara elsevierViewall">The expected adverse effects are few, given that vitamin D toxicity is uncommon and consists mainly of acute hypercalcemia, which typically occurs when the dosage exceeds 10,000<span class="elsevierStyleHsp" style=""></span>IU/day, with 2-OH-vitamin D levels >150<span class="elsevierStyleHsp" style=""></span>ng/mL. There is, however, individual idiosyncrasy and this toxicity can occur at lower levels.</p></li></ul></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conflicts of interest</span><p id="par0175" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:2 [ "identificador" => "xres373105" "titulo" => "Abstract" ] 1 => array:2 [ "identificador" => "xpalclavsec352186" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "xres373106" "titulo" => "Resumen" ] 3 => array:2 [ "identificador" => "xpalclavsec352185" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Clinical case" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Assessment of vitamin D levels in the body" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Adequate vitamin D levels" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Vitamin D and the risk of fractures" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Effects of vitamin D on muscle strength, equilibrium and the incidence of falls" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Other extraskeletal effects of vitamin D" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Treatment of vitamin D deficiency" ] 11 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflicts of interest" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-02-17" "fechaAceptado" => "2014-04-14" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec352186" "palabras" => array:5 [ 0 => "Vitamin D" 1 => "Vitamin D deficiency" 2 => "Fractures, Stress" 3 => "Osteoporotic fractures" 4 => "Osteoporosis" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec352185" "palabras" => array:5 [ 0 => "Vitamina D" 1 => "Deficiencia de vitamina D" 2 => "Fracturas de estrés" 3 => "Fracturas osteoporóticas" 4 => "Osteoporosis" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">In recent years there has been a growing interest in vitamin D, not only for its important role in the bone mineral metabolism, but also for the extra-osseous effects. Most of the scientific societies consider that deposits are sufficient if the serum concentration of 25-OH vitamin D is above 30<span class="elsevierStyleHsp" style=""></span>ng/ml and are considered deficient if levels are below 20<span class="elsevierStyleHsp" style=""></span>ng/ml. The majority of studies found that supplements of calcium plus vitamin D have a positive effect in reducing the risk of fracture and the risk of falls in the elderly, although several specifies that doses should be 700–1000<span class="elsevierStyleHsp" style=""></span>IU daily. The treatment of the deficit can be performed with vitamin D2, D3 as well as calcidiol or the active metabolite calcitriol. In certain pathologies also selective vitamin D receptor activators can be used.</p>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">En los últimos años se ha producido un creciente interés por la vitamina D, no solo por su importante papel en el metabolismo mineral óseo, sino también por sus efectos extraóseos. La mayoría de las sociedades científicas consideran que los depósitos son suficientes si la concentración plasmática de 25-OH vitamina D está por encima de 30<span class="elsevierStyleHsp" style=""></span>ng/ml y deficientes si están por debajo de 20<span class="elsevierStyleHsp" style=""></span>ng/ml. La mayoría de los estudios encuentran que los suplementos de calcio más vitamina D tienen un efecto positivo en la reducción del riesgo de fractura en un 20% aproximadamente y del riesgo de caída en los ancianos, y las dosis deberían ser de 700–1.000 UI diarias. El tratamiento del déficit se puede realizar con vitamina D2, D3 o sus metabolitos activos como el calcidiol o el calcitriol. En ciertas patologías también puede utilizarse los activadores selectivos del receptor de la vitamina D.</p>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Varsavsky M, Alonso G, García-Martín A. Vitamina D: presente y futuro. Rev Clin Esp. 2014;214:396–402.</p>" ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "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=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Extrinsic</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>• Inadequate dietary intake \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>• Little exposure to the sun \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>• Use of creams with ultraviolet radiation filters (sun protection factor >8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>• Skin hyperpigmentation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Intrinsic</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>• Advanced age (reduced cutaneous vitamin D synthesis) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>• Malabsorption \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>– 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" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>– Celiac disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>– Primary biliary cirrhosis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>– Crohn's disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>– 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" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>– Treatment with cholestyramine \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>– Chronic cholestasis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>• Increased vitamin D catabolism \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>– Anticonvulsants \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>– HIV antiretroviral agents \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>– Tuberculostatics agents \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>– Hyperparathyroidism \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>– 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" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>• 25-hydroxy hepatic deficiency \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>– Severe chronic liver disease \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>• Renal 1α-hydroxylation deficiency \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>– Chronic renal failure \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>– 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" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>• Renal loss of 25-hydroxy vitamin D \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>– Nephrotic syndrome \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>• 1.25-OH-vitamin D receptor abnormalities \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>– 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 => "xTab564175.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Pathogenic mechanisms involved and causes of vitamin D deficiency.</p>" ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "<span class="elsevierStyleItalic">Source</span>: Holick et al.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a>." "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=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Diagnostic procedure</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Determine serum 25(OH)D with a reliable method<span class="elsevierStyleHsp" style=""></span>Deficiency: <20<span class="elsevierStyleHsp" style=""></span>ng/ml<span class="elsevierStyleHsp" style=""></span>No population screening, only individuals at risk \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Objective</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Serum 25(OH)D >30<span class="elsevierStyleHsp" style=""></span>ng/ml \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Recommended dietary intake in groups at risk</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>0–1 year: 400<span class="elsevierStyleHsp" style=""></span>IU/day<span class="elsevierStyleHsp" style=""></span>1–18 years: 600<span class="elsevierStyleHsp" style=""></span>IU/day<span class="elsevierStyleHsp" style=""></span>19–50 years: 600<span class="elsevierStyleHsp" style=""></span>IU/day<span class="elsevierStyleHsp" style=""></span>50–70 years: 600<span class="elsevierStyleHsp" style=""></span>IU/day<span class="elsevierStyleHsp" style=""></span>>70 years: 800<span class="elsevierStyleHsp" style=""></span>IU/day<span class="elsevierStyleHsp" style=""></span>Pregnancy-breastfeeding: 600<span class="elsevierStyleHsp" style=""></span>IU/day<span class="elsevierStyleHsp" style=""></span>Obesity, anticonvulsant therapy, corticosteroids, ketoconazole, antiretroviral therapy: 2–3 times dosage by age<span class="elsevierStyleHsp" style=""></span>Occasionally, 1500–2000<span class="elsevierStyleHsp" style=""></span>IU doses might be required to achieve the objective \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Maximum tolerated dosages</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>0–6 months: 1000<span class="elsevierStyleHsp" style=""></span>IU/day<span class="elsevierStyleHsp" style=""></span>6–12 months: 1500<span class="elsevierStyleHsp" style=""></span>IU/day<span class="elsevierStyleHsp" style=""></span>1–3 years: 2500<span class="elsevierStyleHsp" style=""></span>IU/day<span class="elsevierStyleHsp" style=""></span>4–8 years: 3000<span class="elsevierStyleHsp" style=""></span>IU/day<span class="elsevierStyleHsp" style=""></span>>8 years: 4000<span class="elsevierStyleHsp" style=""></span>IU/day \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Treatment of deficiency</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Oral vitamin D2 or D3, interchangeably<span class="elsevierStyleHsp" style=""></span>0–18 years: 2000<span class="elsevierStyleHsp" style=""></span>IU/day or 50,000<span class="elsevierStyleHsp" style=""></span>IU/week, 6 weeks(maintenance 600–1000<span class="elsevierStyleHsp" style=""></span>IU/day)<span class="elsevierStyleHsp" style=""></span>>19 years: 6000<span class="elsevierStyleHsp" style=""></span>IU/day or 50,000<span class="elsevierStyleHsp" style=""></span>IU/week, 8 weeks(maintenance 1500–2000<span class="elsevierStyleHsp" style=""></span>IU/day)<span class="elsevierStyleHsp" style=""></span>Obesity, anticonvulsant therapy, corticosteroids, ketoconazole, antiretroviral therapy: 2–3 times dosage by age \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Extraskeletal benefits</span> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Prevention of falls: recommend vitamin D supplementation<span class="elsevierStyleHsp" style=""></span>Cardiovascular risk prevention, death, quality of life: supplementation is not recommended for these objectives \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab564176.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Main recommendations for the evaluation, prevention and treatment of vitamin D deficiency from the clinical practice guidelines of the endocrine society.</p>" ] ] 2 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "fuente" => "<span class="elsevierStyleItalic">Source</span>: Gómez de Tejada Romero et al.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a>." "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=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">* Optimal levels of vitamin D are considered to be between 30 and 75<span class="elsevierStyleHsp" style=""></span>ng/mL; levels below 20<span class="elsevierStyleHsp" style=""></span>ng/mL are clearly pathological levels. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">* The prevalence of vitamin D deficiency in Spanish populations (< 20<span class="elsevierStyleHsp" style=""></span>ng/mL) varies between 30% in the young and 87% in elderly institutionalized patients; the intermediate age groups (adult, postmenopausal) and noninstitutionalized elderly have a prevalence of 50% to 70%. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">* Vitamin D requirements: \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>• Children, adolescents: 400–600<span class="elsevierStyleHsp" style=""></span>IU/day. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>• Postmenopausal: 600–800<span class="elsevierStyleHsp" style=""></span>IU/day. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>• Elderly: 800–1000<span class="elsevierStyleHsp" style=""></span>IU/day. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>• Patients with osteoporosis: 800–1000<span class="elsevierStyleHsp" style=""></span>IU/day. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>• Patients with osteoporosis: 800–1000<span class="elsevierStyleHsp" style=""></span>IU/day. It is recommended that25(OH)D levels be measured; when this is not possible, the use of larger dosages is recommended. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>• Patients who are taking corticosteroids: 800–1000<span class="elsevierStyleHsp" style=""></span>IU/day. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">* It has been established that higher dosages are needed to achieve optimal levels when there is vitamin D deficiency. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">* In the special case of elderly institutionalized patients (due to the considerable difficulty in reaching the necessary levels of vitamin D through dietary and general health measures), the requirements should be satisfied using vitamin D supplements. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">* There are insufficient data to conclude that the provision of vitamin D improves muscle strength. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">* The prevention of osteoporosis should be performed with good hygienic-dietary habits (appropriate sun exposure, calcium-rich foods). The use of supplements is justified for situations in which achieving optimal levels is difficult. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">* There is no evidence that exclusive treatment with calcium and vitamin D has antifractural efficacy, except in specific populations, such as elderly institutionalized patients. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">* Anytime an antiosteoporotic drug is employed, vitamin D supplements should be added. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab564174.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Main recommendations of the position paper on the needs and optimal vitamin D levels from the Spanish society for research on bone and mineral metabolism and related societies.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:45 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Breve visión histórica de la vitamina D" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "J.M. 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