Vitamin D supplementation and musculoskeletal health. A controversial necessity

Quesada Gómez, José Manuel; Nogues, Xavier; Sosa Henríquez, Manuel; Bouillon, Roger
doi:10.1016/j.medcle.2019.05.007
 array:24 [
  "pii" => "S2387020619304966"
  "issn" => "23870206"
  "doi" => "10.1016/j.medcle.2019.05.007"
  "estado" => "S300"
  "fechaPublicacion" => "2019-12-13"
  "aid" => "4901"
  "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46;. All rights reserved"
  "copyrightAnyo" => "2019"
  "documento" => "article"
  "crossmark" => 1
  "subdocumento" => "sco"
  "cita" => "Med Clin. 2019;153:432-6"
  "abierto" => array:3 [
    "ES" => false
    "ES2" => false
    "LATM" => false
  ]
  "gratuito" => false
  "lecturas" => array:1 [
    "total" => 0
  ]
  "Traduccion" => array:1 [
    "es" => array:19 [
      "pii" => "S0025775319304191"
      "issn" => "00257753"
      "doi" => "10.1016/j.medcli.2019.05.010"
      "estado" => "S300"
      "fechaPublicacion" => "2019-12-13"
      "aid" => "4901"
      "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46;"
      "documento" => "article"
      "crossmark" => 1
      "subdocumento" => "sco"
      "cita" => "Med Clin. 2019;153:432-6"
      "abierto" => array:3 [
        "ES" => false
        "ES2" => false
        "LATM" => false
      ]
      "gratuito" => false
      "lecturas" => array:2 [
        "total" => 76
        "formatos" => array:2 [
          "HTML" => 66
          "PDF" => 10
        ]
      ]
      "es" => array:11 [
        "idiomaDefecto" => true
        "cabecera" => "<span class="elsevierStyleTextfn">Art&#237;culo especial</span>"
        "titulo" => "Suplementaci&#243;n con vitamina D y salud musculoesquel&#233;tica&#46; Una necesidad discutida"
        "tienePdf" => "es"
        "tieneTextoCompleto" => "es"
        "paginas" => array:1 [
          0 => array:2 [
            "paginaInicial" => "432"
            "paginaFinal" => "436"
          ]
        ]
        "titulosAlternativos" => array:1 [
          "en" => array:1 [
            "titulo" => "Vitamin D supplementation and musculoskeletal health&#46; A controversial necessity"
          ]
        ]
        "contieneTextoCompleto" => array:1 [
          "es" => true
        ]
        "contienePdf" => array:1 [
          "es" => true
        ]
        "resumenGrafico" => array:2 [
          "original" => 0
          "multimedia" => array:7 [
            "identificador" => "fig0005"
            "etiqueta" => "Figura 1"
            "tipo" => "MULTIMEDIAFIGURA"
            "mostrarFloat" => true
            "mostrarDisplay" => false
            "figura" => array:1 [
              0 => array:4 [
                "imagen" => "gr1.jpeg"
                "Alto" => 1498
                "Ancho" => 2500
                "Tamanyo" => 181253
              ]
            ]
            "descripcion" => array:1 [
              "es" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Contribuci&#243;n del sistema endocrino de la vitamina D al balance homeost&#225;tico de calcio en situaciones de A&#41; balance positivo de calcio y B&#41; balance negativo de calcio y su repercusi&#243;n fisiopatol&#243;gica en hueso&#46; Ca<span class="elsevierStyleSup">&#43;&#43;</span>&#58; calcio en sangre&#59; PPi&#58; pirofosfato&#59; PTH&#58; parathormona&#59; RANK&#58; <span class="elsevierStyleItalic">receptor activator of nuclear factor &#954; B</span> &#40;&#171;receptor activador para el factor nuclear &#954; B&#187;&#41;&#59; RANKL&#58; <span class="elsevierStyleItalic">receptor activator for nuclear factor &#954; B ligand</span> &#40;&#171;ligando del receptor activador para el factor nuclear &#954; B&#187;&#41;&#59; 1&#44;25&#40;OH&#41;<span class="elsevierStyleInf">2</span>D<span class="elsevierStyleInf">3</span>&#58; 1&#44;25 dihidroxivitamina D<span class="elsevierStyleInf">3</span> o calcitriol&#59; 25OHD<span class="elsevierStyleBold"><span class="elsevierStyleInf">3</span></span>&#58; 25 dihidroxivitamina D<span class="elsevierStyleInf">3</span> o calcifediol&#46;</p>"
            ]
          ]
        ]
        "autores" => array:1 [
          0 => array:2 [
            "autoresLista" => "Jos&#233; Manuel Quesada G&#243;mez, Xavier Nogues, Manuel Sosa Henr&#237;quez, Roger Bouillon"
            "autores" => array:4 [
              0 => array:2 [
                "nombre" => "Jos&#233; Manuel"
                "apellidos" => "Quesada G&#243;mez"
              ]
              1 => array:2 [
                "nombre" => "Xavier"
                "apellidos" => "Nogues"
              ]
              2 => array:2 [
                "nombre" => "Manuel"
                "apellidos" => "Sosa Henr&#237;quez"
              ]
              3 => array:2 [
                "nombre" => "Roger"
                "apellidos" => "Bouillon"
              ]
            ]
          ]
        ]
      ]
      "idiomaDefecto" => "es"
      "Traduccion" => array:1 [
        "en" => array:9 [
          "pii" => "S2387020619304966"
          "doi" => "10.1016/j.medcle.2019.05.007"
          "estado" => "S300"
          "subdocumento" => ""
          "abierto" => array:3 [
            "ES" => false
            "ES2" => false
            "LATM" => false
          ]
          "gratuito" => false
          "lecturas" => array:1 [
            "total" => 0
          ]
          "idiomaDefecto" => "en"
          "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020619304966?idApp=UINPBA00004N"
        ]
      ]
      "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775319304191?idApp=UINPBA00004N"
      "url" => "/00257753/0000015300000011/v1_201911280926/S0025775319304191/v1_201911280926/es/main.assets"
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S2387020619305054"
    "issn" => "23870206"
    "doi" => "10.1016/j.medcle.2019.04.027"
    "estado" => "S300"
    "fechaPublicacion" => "2019-12-13"
    "aid" => "4876"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46;"
    "documento" => "simple-article"
    "crossmark" => 1
    "subdocumento" => "crp"
    "cita" => "Med Clin. 2019;153:437-40"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:13 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Clinical report</span>"
      "titulo" => "Sporadic inclusion body myositis&#58; Diagnostic value of p62 immunostaining"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => array:2 [
        0 => "en"
        1 => "es"
      ]
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "437"
          "paginaFinal" => "440"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Miositis con cuerpos de inclusi&#243;n&#58; valor de la inmunohistoqu&#237;mica para p62 en su diagn&#243;stico"
        ]
      ]
      "contieneResumen" => array:2 [
        "en" => true
        "es" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Fig&#46; 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 588
              "Ancho" => 1305
              "Tamanyo" => 97370
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">&#40;A&#44; B&#41; The typical clinical picture of sIBM&#46; Quadriceps muscle and finger flexor atrophy &#40;arrows&#41;&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Jos&#233; C&#46; Milisenda, Ana Matas Garc&#237;a, Cristina Jou, Iago Pinal-Fernandez, Albert Selva O&#8217;Callaghan, Josep Mar&#237;a Grau"
          "autores" => array:6 [
            0 => array:2 [
              "nombre" => "Jos&#233; C&#46;"
              "apellidos" => "Milisenda"
            ]
            1 => array:2 [
              "nombre" => "Ana Matas"
              "apellidos" => "Garc&#237;a"
            ]
            2 => array:2 [
              "nombre" => "Cristina"
              "apellidos" => "Jou"
            ]
            3 => array:2 [
              "nombre" => "Iago"
              "apellidos" => "Pinal-Fernandez"
            ]
            4 => array:2 [
              "nombre" => "Albert Selva"
              "apellidos" => "O&#8217;Callaghan"
            ]
            5 => array:2 [
              "nombre" => "Josep Mar&#237;a"
              "apellidos" => "Grau"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "en" => array:9 [
        "pii" => "S0025775319303501"
        "doi" => "10.1016/j.medcli.2019.04.022"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "en"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775319303501?idApp=UINPBA00004N"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020619305054?idApp=UINPBA00004N"
    "url" => "/23870206/0000015300000011/v1_201911300659/S2387020619305054/v1_201911300659/en/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S2387020619304954"
    "issn" => "23870206"
    "doi" => "10.1016/j.medcle.2019.04.026"
    "estado" => "S300"
    "fechaPublicacion" => "2019-12-13"
    "aid" => "4882"
    "copyright" => "Elsevier Espa&#241;a&#44; S&#46;L&#46;U&#46;"
    "documento" => "article"
    "crossmark" => 1
    "subdocumento" => "sco"
    "cita" => "Med Clin. 2019;153:430-1"
    "abierto" => array:3 [
      "ES" => false
      "ES2" => false
      "LATM" => false
    ]
    "gratuito" => false
    "lecturas" => array:1 [
      "total" => 0
    ]
    "en" => array:10 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Editorial</span>"
      "titulo" => "Predictive scores of mortality in patients with influenza&#58; lessons learned and way to go"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "430"
          "paginaFinal" => "431"
        ]
      ]
      "titulosAlternativos" => array:1 [
        "es" => array:1 [
          "titulo" => "Escalas predictoras de mortalidad en pacientes con gripe&#58; lecciones aprendidas y camino por recorrer"
        ]
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Felipe P&#233;rez-Garc&#237;a"
          "autores" => array:1 [
            0 => array:2 [
              "nombre" => "Felipe"
              "apellidos" => "P&#233;rez-Garc&#237;a"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "Traduccion" => array:1 [
      "es" => array:9 [
        "pii" => "S0025775319304002"
        "doi" => "10.1016/j.medcli.2019.04.024"
        "estado" => "S300"
        "subdocumento" => ""
        "abierto" => array:3 [
          "ES" => false
          "ES2" => false
          "LATM" => false
        ]
        "gratuito" => false
        "lecturas" => array:1 [
          "total" => 0
        ]
        "idiomaDefecto" => "es"
        "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775319304002?idApp=UINPBA00004N"
      ]
    ]
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020619304954?idApp=UINPBA00004N"
    "url" => "/23870206/0000015300000011/v1_201911300659/S2387020619304954/v1_201911300659/en/main.assets"
  ]
  "en" => array:17 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Special article</span>"
    "titulo" => "Vitamin D supplementation and musculoskeletal health&#46; A controversial necessity"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "432"
        "paginaFinal" => "436"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Jos&#233; Manuel Quesada G&#243;mez, Xavier Nogues, Manuel Sosa Henr&#237;quez, Roger Bouillon"
        "autores" => array:4 [
          0 => array:3 [
            "nombre" => "Jos&#233; Manuel"
            "apellidos" => "Quesada G&#243;mez"
            "referencia" => array:2 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          1 => array:4 [
            "nombre" => "Xavier"
            "apellidos" => "Nogues"
            "email" => array:1 [
              0 => "xnogues@hospitaldelmar.cat"
            ]
            "referencia" => array:3 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
              2 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Manuel"
            "apellidos" => "Sosa Henr&#237;quez"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Roger"
            "apellidos" => "Bouillon"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">e</span>"
                "identificador" => "aff0025"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:5 [
          0 => array:3 [
            "entidad" => "Unidad de Gesti&#243;n Cl&#237;nica de Endocrinolog&#237;a y Nutrici&#243;n&#44; Instituto Maim&#243;nides de Investigaci&#243;n Biom&#233;dica de C&#243;rdoba &#40;IMIBIC&#41;&#44; Hospital Universitario Reina Sof&#237;a&#44; C&#243;rdoba&#44; Spain"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "CIBER de Fragilidad y Envejecimiento Saludable &#40;CIBERFES&#41;&#44; Instituto de Salud Carlos III&#44; Madrid&#44; Spain"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "Servicio de Medicina Interna&#44; Hospital del Mar&#44; Grupo de Investigaci&#243;n Musculo-Esquel&#233;tica &#40;GIME&#41;&#44; Instituto Hospital del Mar de Investigaciones M&#233;dicas&#44; Universitat Aut&#243;noma de Barcelona&#44; Barcelona&#44; Spain"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
          3 => array:3 [
            "entidad" => "Unidad Metab&#243;lica &#211;sea&#44; Instituto Universitario de Investigaciones Biom&#233;dicas y Sanitarias&#44; Hospital Universitario Insular&#44; Grupo de investigaci&#243;n en osteoporosis y metabolismo mineral&#44; Universidad de Las Palmas de Gran Canaria&#44; Las Palmas de Gran Canaria&#44; Spain"
            "etiqueta" => "d"
            "identificador" => "aff0020"
          ]
          4 => array:3 [
            "entidad" => "Clinical and Experimental Endocrinology&#44; Department of Chronic Diseases&#44; Metabolism and Ageing&#44; KU Leuven&#44; Leuven&#44; Belgium"
            "etiqueta" => "e"
            "identificador" => "aff0025"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author&#46;"
          ]
        ]
      ]
    ]
    "titulosAlternativos" => array:1 [
      "es" => array:1 [
        "titulo" => "Suplementaci&#243;n con vitamina D y salud musculoesquel&#233;tica&#46; Una necesidad discutida"
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1498
            "Ancho" => 2501
            "Tamanyo" => 206659
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0010"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Contribution of the vitamin D endocrine system to the homeostatic calcium balance in situations of A&#41; positive calcium balance and B&#41; negative calcium balance and its pathophysiological impact on bone&#46; Ca<span class="elsevierStyleSup">&#43;&#43;</span>&#58; calcium in blood&#59; PPi&#58; inorganic pyrophosphate&#59; PTH&#58; parathyroid hormone&#59; RANK&#58; <span class="elsevierStyleItalic">receptor activator of nuclear factor &#954; B</span>&#59; RANKL&#58; <span class="elsevierStyleItalic">receptor activator for nuclear factor &#954; B ligand</span>&#59; 1&#46;25 &#40;OH&#41;<span class="elsevierStyleInf">2</span>D<span class="elsevierStyleInf">3</span>&#58; 1&#46;25 dihydroxyvitamin D<span class="elsevierStyleInf">3</span> or calcitriol&#59; 25OHD<span class="elsevierStyleBold"><span class="elsevierStyleInf">3</span></span>&#58; 25 dihydroxyvitamin D<span class="elsevierStyleInf">3</span> or calcifediol&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Physiological effects of vitamin D</span><p id="par0005" class="elsevierStylePara elsevierViewall">Since the discovery in 1922 of vitamin D &#40;Vit D&#41; by Professor McCollum&#44; evidence has been accumulating regarding the key role of &#34;vitamin&#34; D&#44; or better still&#44; of the Vit D endocrine system &#40;VDES&#41; in calcium homeostasis and in maintaining skeletal integrity&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The pathophysiological mechanisms by which Vit D deficiency impairs bone health are complex&#46; Most of the available evidence focuses on the intestine as the main vehicle for the effects of VDES on bone&#46; The interaction of 125 dihydroxyvitamin D<span class="elsevierStyleInf">3</span> &#40;1&#46;25 &#40;OH&#41;<span class="elsevierStyleInf">2</span>D<span class="elsevierStyleInf">3</span>&#41; or calcitriol on <span class="elsevierStyleItalic">vitamin D receptor</span> &#40;VDR&#44; &#34;Vit D receptor&#34;&#41; improves intestinal calcium absorption by regulating calcium transport proteins &#40;TRPV6&#44; TRPV5&#44; calbindins and calcium-ATPases&#41;&#44; therefore&#44; it promotes transcellular calcium transport&#59; it also enhances passive intercellular transport&#44; mediated by its action on several claudins&#44; cadherin-17 &#40;a cell adhesion protein&#41; and aquaporin&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> Regarding the direct effects on the skeleton&#44; VDES clearly regulates the expression of genes related to numerous bone cell properties&#44; such as the compromise of stem cell lineage&#44; cell proliferation and differentiation&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">In normal or positive calcium balance conditions and adequate levels of calcifediol &#40;25OHD<span class="elsevierStyleInf">3</span>&#41; to synthesize 1&#46;25 &#40;OH&#41;<span class="elsevierStyleInf">2</span>D<span class="elsevierStyleInf">3</span>&#44; it promotes intestinal calcium and phosphate absorption and an adequate renal management&#44; maintaining serum levels that facilitate bone matrix mineralization &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; At the same time&#44; 1&#46;25 &#40;OH&#41;<span class="elsevierStyleInf">2</span>D<span class="elsevierStyleInf">3</span>&#44; acting on mature osteoblasts&#44; modifies the expression of <span class="elsevierStyleItalic">receptor activator for nuclear factor &#954; B ligand</span> &#40;RANKL&#41; and the osteoprotegerin&#47;RANKL ratio stimulates plasma lipoprotein 5 receptor signalling&#44; Wnt pathway co-receptor&#44; which mediates anabolic effects in osteoblasts and&#44; therefore&#44; has predominantly anabolic actions&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a></p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">When the dietary calcium intake is insufficient&#44; a negative calcium balance is produced&#46; Serum calcium levels remain normal by an increase in parathyroid hormone that hyperstimulates the synthesis of 1&#46;25 &#40;OH&#41;<span class="elsevierStyleInf">2</span>D<span class="elsevierStyleInf">3</span>&#44; both acting &#34;ex aequo&#34; in the osteoblast&#46; RANKL expression is induced in its membrane&#44; binding to its <span class="elsevierStyleItalic">receptor activator for nuclear factor &#954; B</span> &#40;RANK&#41;&#44; in the mature monocyte membrane&#44; promoting their transformation into osteoclasts&#44; which resorb bone and release calcium and phosphorus into the circulation&#46; This action can be blocked by osteoprotegerin&#44; soluble receptor and natural decoy for RANKL&#46; In addition to stimulating bone resorption&#44; 1&#46;25 &#40;OH&#41;<span class="elsevierStyleInf">2</span>D<span class="elsevierStyleInf">3</span> can also inhibit bone matrix mineralization by increasing pyrophosphate levels and osteopontin expression&#44; potent mineralization inhibitors &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The main function of VDES is to preserve normal serum calcium homeostasis&#44; even at the expense of bone&#44; if necessary&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;3</span></a> Therefore&#44; Vit D deficiency causes secondary hyperparathyroidism that allows the body to normalize serum calcium by increasing 1&#46;25 &#40;OH&#41;<span class="elsevierStyleInf">2</span>D<span class="elsevierStyleInf">3</span> renal production from a minimum amount of 25OHD<span class="elsevierStyleInf">3</span>&#44; substrate for its formation&#44; increasing bone resorption&#46; This compensatory mechanism results in an increase in bone turnover and loss of bone mass &#40;initially mainly trabecular bone&#41;&#46; Therefore&#44; it is not surprising that even a moderate Vit D deficiency can accelerate age-related bone loss&#44; advance the process of osteoporosis and increase the risk of fragility fractures&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Observational data in humans associate Vit D deficiency&#44; especially when serum 25-hydroxyvitamin D falls below 10&#8722;12<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#44; with the risk of lower bone mineral density &#40;BMD&#41; values&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">On the other hand&#44; the mechanisms of action of Vit D in muscular biology and the impact of its deficiency show that a link between muscle and Vit D is plausible&#44;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a> with increased risk of falls in patients with low levels&#44;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> also increasing the risk of fragility fractures&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">These pathophysiological data support the importance of maintaining adequate serum levels of 25OHD<span class="elsevierStyleInf">3</span>&#44; involving enough substrate for the synthesis of calcitriol&#46; Thus&#44; the body&#39;s musculoskeletal health and calcium-phosphorus homeostasis needs can be adequately covered throughout life&#44; as the main guidelines recommend&#44; making Vit D supplementation a common practice in most Western countries&#44; especially for new-borns&#44; children and the elderly&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> However&#44; there is a great diversity of opinions about adequate serum 25OHD<span class="elsevierStyleInf">3</span> levels&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> The most recommended values of 25OHD<span class="elsevierStyleInf">3</span> stand above 20<span class="elsevierStyleHsp" style=""></span>ng&#47;ml or 30<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#44; although some authors recommend values of 50<span class="elsevierStyleHsp" style=""></span>ng&#47;ml &#40;equivalent to serum concentrations of 25OHD<span class="elsevierStyleInf">3</span> found in native African tribes with a sun exposure lifestyle that might resemble that of primitive humans&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Controversies in vitamin D supplementation</span><p id="par0040" class="elsevierStylePara elsevierViewall">Recently&#44; Bolland et al&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> have published an extensive meta-analysis that reviews 81 randomized controlled trials &#40;RCTs&#41;&#44; published until the end of February 2018&#44; and that include a total of 53&#44;537 patients&#46; They studied the effect of vitamin D supplementation on fractures and falls as primary endpoint and BMD as secondary endpoint&#44; measured in lumbar spine&#44; total hip&#44; femoral neck&#44; total body and forearm&#46; Based on all the combined data&#44; the authors concluded that Vit D supplementation has no effect on fractures as a whole &#40;36 trials&#59; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>44&#44;790&#59; relative risk &#91;RR&#93;&#58; 1&#59; confidence interval &#91;95 &#37; CI&#93;&#58; 0&#46;93&#8211;1&#46;07&#41;&#59; in hip fracture &#40;20 trials&#59; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>65&#44;536&#59; RR&#58; 1&#46;11&#59; 95 &#37; CI&#58; 0&#46;97&#8211;1&#46;26&#41; and also in falls &#40;37 trials&#59; n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>34&#44;144&#59; RR&#58; 0&#46;97&#59; 95 &#37; CI&#58; 0&#46;93&#8211;1&#46;02&#41;&#46; Vitamin D supplementation did not generate a clinically relevant difference in BMD at any anatomical site studied&#46; The differences between the groups were 0&#46;25&#44; 0&#46;76 and 0&#46;13 &#37; &#40;95 &#37; CI&#58; 0-0&#46;49&#59; 0&#46;42&#8211;1&#46;09 and 0&#46;16-0&#46;42&#41; for the lumbar spine&#44; femoral neck and whole body&#44; respectively&#46; The results were similar for randomized controlled trials that used high in Vit D doses compared to low doses and in RCTs of subgroups with doses above 800<span class="elsevierStyleHsp" style=""></span>IU&#47;day&#46; The authors concluded that &#8220;Vitamin D supplementation has no significant effects on fractures&#44; falls or BMD&#44; and future trials are unlikely to alter these conclusions&#46; Therefore&#44; there is little justification for the use of Vit D supplements to maintain or improve musculoskeletal health&#44; and clinical guidelines should reflect these findings&#8221;&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Based on that meta-analysis&#44; many doctors and patients could mistakenly conclude that they can stop prescribing or taking Vit D supplements&#44; which is a potentially dangerous message given the high prevalence of Vit D deficiency worldwide<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> and also in Spain&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a> Although clinical guidelines do not agree on the necessary serum 25OHD<span class="elsevierStyleInf">3</span> concentrations&#44; the American Institute of Medicine recommends levels<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>ng&#47;ml to ensure a suitable 25OHD<span class="elsevierStyleInf">3</span> for 97&#46;5 &#37; of the population&#44; with an average target value of 16<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> The <span class="elsevierStyleItalic">International Osteoporosis Foundation</span> &#40;IOF&#41;&#44; the <span class="elsevierStyleItalic">Endocrine Society</span> and other authors recommend levels<span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a> However&#44; despite this disagreement&#44; there is a consensus that 25OHD<span class="elsevierStyleInf">3</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>ng&#47;ml represents a very serious deficiency&#44; and recent UK guidelines on vitamin D supplementation suggests maintaining serum 25OHD<span class="elsevierStyleInf">3</span> levels above this value&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> Based on these cut-off points&#44; approximately 7 &#37; of the world&#39;s population suffers from very serious Vit D deficiency &#40;25OHD<span class="elsevierStyleInf">3</span> serum<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>10&#8722;12<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41;&#44; 37 &#37;<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>ng&#47;ml and therefore suffers from Vit D deficiency&#44; and more than 80 &#37; have serum 25OHD<span class="elsevierStyleInf">3</span> levels considered as insufficient&#44; that is<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>30<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41;&#44; with similar levels in Spain&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;11</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">Therefore&#44; the conclusions of the Bolland et al&#46; meta-analysis<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> must be interpreted with caution&#44; because they have intrinsic limitations or even errors as reflected in several letters published in the <span class="elsevierStyleItalic">Lancet Diabetes Endocrinology itself</span><a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;16</span></a> in response to the authors&#46; Potential errors have been suggested in the selection of the primary data entered in the meta-analysis&#44; regarding which&#44; &#34;paradoxically&#34;&#44; the same authors had commented beforehand&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">Most patients in the RCTs included in the meta-analysis<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> were individuals who lived in the community &#40;85 &#37;&#41; and were not selected based on their baseline Vit D status&#44; in addition&#44; most studies did not provide data on possible underlying diseases&#44; or their fall and fracture risks&#44; thus jeopardising the power of most studies to generate relevant data&#46; In addition&#44; many studies lasted less than a year and&#44; therefore&#44; should be excluded from a meta-analysis of fracture outcomes&#44; since all experts know that&#44; even most osteoporosis drugs must be administered for several years to be able to show a clear reduction in fractures&#46; There was also much variability on how falls were evaluated &#40;telephone interviews&#44; questionnaires&#44; etc&#46;&#41;&#46; In addition&#44; although the authors included 81 studies in their meta-analysis&#44; 79 &#37; of the total experimental power was supported by only 7 of them as described in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;<a class="elsevierStyleCrossRefs" href="#bib0085"><span class="elsevierStyleSup">17&#8211;23</span></a> In addition&#44; most of the studies in it are heterogeneous in relation to the Vit D used&#44; the dose&#44; the route of administration and the frequency of intake&#59; including treatments with ergocalciferol &#40;vitamin D<span class="elsevierStyleBold"><span class="elsevierStyleInf">2</span></span>&#41; for which there is extensive information about the fact of being less effective than cholecalciferol &#40;vitamin D<span class="elsevierStyleInf">3</span>&#41;&#44; especially when administered intermittently&#46;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Another important error is that the authors included studies that used intermittent supplementation regimens&#44; with megadoses of oral cholecalciferol <span class="elsevierStyleHsp" style=""></span>&#8805;<span class="elsevierStyleHsp" style=""></span>100&#44;000<span class="elsevierStyleHsp" style=""></span>IU&#41; at variable intervals&#44; monthly or every 4 months&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> They also included studies that used 300&#44;000 <span class="elsevierStyleHsp" style=""></span>IU<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a> or 500&#44;000<span class="elsevierStyleHsp" style=""></span>IU<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a> intramuscular administration annually&#46; We now know that these megadoses administered in pulses are not only not beneficial&#44; but even increase the risk of falls and fractures temporarily&#46; Therefore&#44; these regimens are not recommended in guidelines&#44; nor in normal practice&#44; because they are associated with changes in serum 25OHD<span class="elsevierStyleInf">3</span> concentrations &#40;which means that serum concentrations are not maintained above the normal threshold during the entire treatment period&#41;&#44; and have become obsolete&#44; ineffective or harmful treatments&#46; Therefore&#44; these types of studies should not have been included in the meta-analysis<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;16</span></a> and yet they represent 50 &#37; of its power&#46; At the opposite end&#44; as Bolland himself had paradoxically pointed out&#44; small short-term studies must always be interpreted with caution&#59; in this meta-analysis<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> 52 &#37; of the RCTs selected included less than 200 patients and 68 &#37; had a total duration of less than one year&#46; Therefore&#44; most of the RCTs included did not have enough power to answer questions about fracture prevention as the primary endpoint&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Another very important limitation is that most of the studies included in its meta-analysis were conducted with participants with a good Vit D status at the start of the study&#58; 43 &#37; of the studies reported initial average concentrations of 25OHD<span class="elsevierStyleInf">3</span> above 20<span class="elsevierStyleHsp" style=""></span>ng&#47;ml and only 4 &#40;6 &#37;&#41; were carried out in populations with reference levels below 10<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#46; This consideration makes any clear conclusion about the effect of Vit D supplements on the risk of fracture manifestly questionable&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Vit D is a threshold nutritional factor as is iodide for thyroid hormones and other vitamins for other health effects&#46; As pointed by Robert Heaney&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> enough contribution is needed to allow its transformation into active substance &#40;prehormone or hormone&#41;&#44; and once a certain threshold is exceeded&#44; plus contribution&#44; it is no longer better than that obtained with the minimum requirements&#46; For VDES&#44; cholecalciferol or Vit D<span class="elsevierStyleInf">3</span>in itself is the nutritional factor&#44; inactive precursor substrate&#44; for the formation of calcifediol or 25OHD<span class="elsevierStyleInf">3</span> &#40;prehormone D&#41; which&#44; in itself&#44; is a deficient VDR agonist and needs a second hydroxylation to form calcitriol or 1&#46;25 &#40;OH&#41;<span class="elsevierStyleInf">2</span>D<span class="elsevierStyleInf">3</span>&#44; hormonally active system metabolite&#46; This conversion is strongly regulated by parathyroid hormone and fibroblast growth factor23 and some other factors&#59; calcitriol behaves like other steroid hormones acting on its nuclear receptors &#40;VDR&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">The fact that Vit D can be obtained in the skin by endogenous biosynthesis during exposure to solar ultraviolet light for the most part&#44; or to a lesser extent by the intake of foods rich in Vit D does not imply that it is not a threshold nutritional factor&#44;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24&#44;25</span></a> which implies that there will be a nutritional deficiency below a given threshold&#44; but no beneficial effect will be obtained above it&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">This has clear implications when designing clinical intervention studies for said nutrient&#44;<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">24</span></a> since the beneficial effects of Vit D could be hidden if a high percentage of participants in the RCT had enough levels of 25OHD<span class="elsevierStyleInf">3</span> at the beginning of the study&#46; In fact&#44; such trials could be considered a waste of research resources&#44; and even mislead as &#34;interfering background noise&#34;&#44; when the results were analysed and conclusions were obtained&#44; as seems to be the case with the meta-analysis of Bolland et al&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Unfortunately&#44; most studies included in the meta-analysis do not provide information on the time at which they were performed&#46; The impact of the circannual variation on serum 25OHD<span class="elsevierStyleInf">3</span> levels will occur in treated and untreated patients&#44; so the possibility that the seasonal changes on 25OHD<span class="elsevierStyleInf">3</span> could favour the untreated group could be another important confounding factor in the results of the included trials&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Therefore&#44; another important problem is that most of the studies included were conducted in participants with enough Vit D&#46; A careful review of the meta-analysis data indicates that serum Vit D levels measured as 25OHD<span class="elsevierStyleInf">3</span> at the beginning of the study were not considered as exclusion or inclusion criteria in most studies&#46; Thus&#44; 43 &#37; of the studies considered in the meta-analysis had average baseline levels of 25OHD<span class="elsevierStyleInf">3</span> above 20<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#44; and only 4 &#40;6 &#37;&#41; were performed in populations with baseline 25OHD<span class="elsevierStyleInf">3</span> levels below 10<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">The Bolland et al&#46; meta-analysis<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> only included 25 &#37; of trials that combined Vit D and calcium and compared with placebo&#44; excluding high quality trials&#46; Bolland et al&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> conclude that their own meta-analysis does not go against the beneficial effects of the treatment combining calcium and Vit D&#44; which in elderly people can reduce the risk of non-vertebral or hip fractures up to 30 &#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> As a whole&#44; it is an example of how the biased selection of published data and the exclusion of specific studies can generate misleading general conclusions that can add to the confusion that already exists between doctors and patients about the use of Vit D&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Adequate values of vitamin D and clinical application of vitamin D recommendations</span><p id="par0100" class="elsevierStylePara elsevierViewall">The thresholds of adequate Vit D status reported to date are variable&#44; depending on the health objective evaluated&#44; from 10<span class="elsevierStyleHsp" style=""></span>ng&#47;ml for bone disease up to 40<span class="elsevierStyleHsp" style=""></span>ng&#47;ml for cancer&#46;<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">26</span></a> For example&#44; a Cochrane meta-analysis<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> reported that vitamin D supplementation&#44; compared to placebo&#44; reduced the risk of falls in the 4 studies that selected people with lower levels of Vit D&#46; The cut-off points of the 4 studies were&#58; &#60;<span class="elsevierStyleHsp" style=""></span>12<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#44; &#60;<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#44; &#60;<span class="elsevierStyleHsp" style=""></span>24<span class="elsevierStyleHsp" style=""></span>ng&#47;ml and &#60;<span class="elsevierStyleHsp" style=""></span>31<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#41;&#46; The 30 &#37; reduction in the risk of falls in these studies &#40;risk index<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;70&#59; 95 &#37; CI&#58; 0&#46;56-0&#46;87&#41; was significantly lower than in the other 9 studies that did not select participants according to Vit D status &#40;risk index<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>1&#59; 95 &#37; CI&#58; 0&#46;93&#8211;1&#46;07&#59; interaction p<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;01&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Therefore&#44; in our usual practice we must be clear that the available evidence consistently indicates that Vit D has important physiological&#44; skeletal &#40;administered with adequate calcium supplementation&#41; and extra-skeletal effects&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">In short&#44; the conclusions of the meta-analysis<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> should not modify the routine practice of Vit D and calcium combined supplementation in patients who show a deficiency in these nutrients&#44; an action for which there is sufficient evidence of moderate&#44; but important enough&#44; antifracture efficacy that justifies its use and indication in the guidelines&#44; so maintaining adequate levels of 25OHD<span class="elsevierStyleInf">3</span> must be an essential population health goal&#46; We must&#44; of course&#44; avoid supplementation with megadoses administered at intervals&#44; already obsolete because they are ineffective or harmful&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">Nor do they affect the use recommendations in patients receiving medical treatment for osteoporosis&#44; where supplementation is required to comply with the licensing stipulations derived from regulatory trials of antiosteoporosis treatments&#44; which ensure the replacement of calcium and Vit D&#44; at the same time as the anti-resorptives or bone formers evaluated&#46; On the other hand&#44; observational studies indicate that an adequate status of serum 25OHD<span class="elsevierStyleInf">3</span> levels&#44; above 20<span class="elsevierStyleHsp" style=""></span>ng&#47;ml or 30<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#44; are critical for the optimal efficacy of antiresorptive treatments&#46;<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Vitamin D supplementation</span><p id="par0120" class="elsevierStylePara elsevierViewall">Taking into account the difficulty of obtaining&#44; in normal life conditions&#44; the necessary serum levels of 25OHD<span class="elsevierStyleInf">3</span> from the diet or the sun&#44; the difficulty to take it in an appropriate way or the risk of cancer and skin aging&#44; the use of Vitamin D supplements should be the strategy used to improve its status&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Vit D<span class="elsevierStyleInf">3</span> and Vit D<span class="elsevierStyleInf">2</span> are the most used compounds&#59; the relative use of both products depends on historical or practical reasons &#40;in Spain&#44; we do not have vitamin D<span class="elsevierStyleInf">2</span>&#44; but we do have cholecalciferol &#40;vitamin D<span class="elsevierStyleInf">3</span>&#41; and hydroxyvitamin D<span class="elsevierStyleInf">3</span> &#40;calcifediol&#59; 25OHD<span class="elsevierStyleBold"><span class="elsevierStyleInf">3</span></span>&#41;&#46; For years both have been used as if the 2 metabolites were equipotent&#59; but it&#39;s not like that&#44; 25OHD<span class="elsevierStyleInf">3</span> is more hydrophilic&#44; has a shorter half-life&#44; its action onset is faster and 3&#8211;6 times more potent to raise the available serum concentrations of 25OHD<span class="elsevierStyleInf">3</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Under usual conditions&#44; if the levels of 25OHD<span class="elsevierStyleInf">3</span> need to be above 20<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#44; the average requirements in the elderly are at least 600 to 800-1&#44;000<span class="elsevierStyleHsp" style=""></span>IU of Vit D<span class="elsevierStyleInf">3</span> daily&#44; and if the levels need to be above 30<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#44; 1&#44;800-4&#44;000<span class="elsevierStyleHsp" style=""></span>IU of Vit D<span class="elsevierStyleInf">3</span> may be required daily&#44; administered once a day&#44; once a week or once a month&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">29</span></a> Therefore&#44; the recommended dosage for Vit D<span class="elsevierStyleInf">3</span> should be 800<span class="elsevierStyleHsp" style=""></span>IU&#47;day or its monthly equivalent &#40;25&#44;000<span class="elsevierStyleHsp" style=""></span>IU&#41; and 0&#46;266<span class="elsevierStyleHsp" style=""></span>&#956;g for calcifediol every 15&#8211;30 days&#44; adding calcium if dietary intake is insufficient&#46; It is recommended to increase doses up to 50<span class="elsevierStyleHsp" style=""></span>&#956;g&#47;day &#40;2000<span class="elsevierStyleHsp" style=""></span>IU&#47;day&#41; in patients with some types of secondary osteoporosis&#44; malabsorption&#44; anticonvulsant treatment&#44; etc&#46; limited sun exposure &#40;institutionalized or home-bound&#41; and obesity&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a> The recommendations of current scientific societies and&#47;or clinical guidelines consistently support those recommendations&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a></p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conflict of interests</span><p id="par0135" class="elsevierStylePara elsevierViewall">The authors declare that they have no conflicts of interest&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:6 [
        0 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Physiological effects of vitamin D"
        ]
        1 => array:2 [
          "identificador" => "sec0010"
          "titulo" => "Controversies in vitamin D supplementation"
        ]
        2 => array:2 [
          "identificador" => "sec0015"
          "titulo" => "Adequate values of vitamin D and clinical application of vitamin D recommendations"
        ]
        3 => array:2 [
          "identificador" => "sec0020"
          "titulo" => "Vitamin D supplementation"
        ]
        4 => array:2 [
          "identificador" => "sec0025"
          "titulo" => "Conflict of interests"
        ]
        5 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2019-03-28"
    "fechaAceptado" => "2019-05-07"
    "NotaPie" => array:1 [
      0 => array:2 [
        "etiqueta" => "&#9734;"
        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Quesada G&#243;mez JM&#44; Nogues X&#44; Sosa Henr&#237;quez M&#44; Bouillon R&#46; Suplementaci&#243;n con vitamina D y salud musculoesquel&#233;tica&#46; Una necesidad discutida&#46; Med Clin &#40;Barc&#41;&#46; 153&#59;2019&#58;432&#8211;436&#46;</p>"
      ]
    ]
    "multimedia" => array:2 [
      0 => array:8 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1498
            "Ancho" => 2501
            "Tamanyo" => 206659
          ]
        ]
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0010"
            "detalle" => "Fig&#46; "
            "rol" => "short"
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Contribution of the vitamin D endocrine system to the homeostatic calcium balance in situations of A&#41; positive calcium balance and B&#41; negative calcium balance and its pathophysiological impact on bone&#46; Ca<span class="elsevierStyleSup">&#43;&#43;</span>&#58; calcium in blood&#59; PPi&#58; inorganic pyrophosphate&#59; PTH&#58; parathyroid hormone&#59; RANK&#58; <span class="elsevierStyleItalic">receptor activator of nuclear factor &#954; B</span>&#59; RANKL&#58; <span class="elsevierStyleItalic">receptor activator for nuclear factor &#954; B ligand</span>&#59; 1&#46;25 &#40;OH&#41;<span class="elsevierStyleInf">2</span>D<span class="elsevierStyleInf">3</span>&#58; 1&#46;25 dihydroxyvitamin D<span class="elsevierStyleInf">3</span> or calcitriol&#59; 25OHD<span class="elsevierStyleBold"><span class="elsevierStyleInf">3</span></span>&#58; 25 dihydroxyvitamin D<span class="elsevierStyleInf">3</span> or calcifediol&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at0015"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">IU&#58; international units&#59; Vit D&#58; vitamin D&#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=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Vit D type&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Dose&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Duration&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">N&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Power over meta-analysis &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Baseline Vit D levels&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lyons et al&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">D<span class="elsevierStyleInf">2</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">100&#44;000<span class="elsevierStyleHsp" style=""></span>uI&#47;4 months&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">3 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">3&#46;440&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">Controls had 21&#46;6<span class="elsevierStyleHsp" style=""></span>ng&#47;ml at the end of the study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Meyer et al&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">D<span class="elsevierStyleInf">3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">400<span class="elsevierStyleHsp" style=""></span>IU&#47;day&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">2 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">1&#46;144&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">18&#46;8<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Grant et al&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">D<span class="elsevierStyleInf">3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">800<span class="elsevierStyleHsp" style=""></span>IU&#47;day&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">2-5 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">5&#46;292&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">&#47;&#47;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lips et al&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">D<span class="elsevierStyleInf">3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">400<span class="elsevierStyleHsp" style=""></span>IU&#47;day&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">Maximum 3&#46;5 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">2&#46;578&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">&#47;&#47;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Smith et al&#46;<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">21</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">D<span class="elsevierStyleInf">3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">300&#44;000<span class="elsevierStyleHsp" style=""></span>IU&#47;year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">3 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">9&#46;440&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">&#47;&#47;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sanders et al&#46;<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">22</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">D<span class="elsevierStyleInf">3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">500&#44;000<span class="elsevierStyleHsp" style=""></span>IU&#47;year&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">3-5 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">2&#46;256&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">19&#46;6<span class="elsevierStyleHsp" style=""></span>ng&#47;ml &#40;Only 3&#37;<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>10<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Khaw et al&#46;<span class="elsevierStyleSup">2&#46; 3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">D<span class="elsevierStyleInf">3</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">100&#44;000<span class="elsevierStyleHsp" style=""></span>IU&#47;month&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">2&#46;5-4&#46;2 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">5&#46;110&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">25&#46;2<span class="elsevierStyleHsp" style=""></span>ng&#47;ml &#40;Only 30&#37;<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>20<span class="elsevierStyleHsp" style=""></span>ng&#47;ml&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">Total&#58; 79&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><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">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2172964.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Description of the studies with greater statistical power included in the Bolland et al&#46; meta-analysis&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a></p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:30 [
            0 => array:3 [
              "identificador" => "bib0005"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "How much vitamin D is needed for healthy bones&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "R&#46; Bouillon"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/joim.12677"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Intern Med&#46;"
                        "fecha" => "2017"
                        "volumen" => "282"
                        "paginaInicial" => "461"
                        "paginaFinal" => "464"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28901035"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0010"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Normocalcemia is maintained in mice under conditions of calcium malabsorption by vitamin D-induced inhibition of bone mineralization"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46; Lieben"
                            1 => "R&#46; Masuyama"
                            2 => "S&#46; Torrekens"
                            3 => "R&#46; Van Looveren"
                            4 => "J&#46; Schrooten"
                            5 => "P&#46; Baatsen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1172/JCI45890"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Invest"
                        "fecha" => "2012"
                        "volumen" => "122"
                        "paginaInicial" => "1803"
                        "paginaFinal" => "1815"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22523068"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0015"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Carmeliet G&#46; Vitamin D&#58; Metabolism&#44; Molecular Mechanism of Action&#44; and Pleiotropic Effects"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "S&#46; Christakos"
                            1 => "P&#46; Dhawan"
                            2 => "A&#46; Verstuyf"
                            3 => "L&#46; Verlinden"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1152/physrev.00014.2015"
                      "Revista" => array:6 [
                        "tituloSerie" => "Physiol Rev&#46;"
                        "fecha" => "2016"
                        "volumen" => "96"
                        "paginaInicial" => "365"
                        "paginaFinal" => "408"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/26681795"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0020"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The unitary model for estrogen deficiency and the pathogenesis of osteoporosis&#58; is a revision needed&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "S&#46; Khosla"
                            1 => "L&#46;J&#46; Melton 3rd"
                            2 => "B&#46;L&#46; Riggs"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/jbmr.262"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Bone Miner Res&#46;"
                        "fecha" => "2011"
                        "volumen" => "26"
                        "paginaInicial" => "441"
                        "paginaFinal" => "451"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20928874"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0025"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vitamin D status&#44; parathyroid function&#44; bone turnover&#44; and BMD in postmenopausal women with osteoporosis&#58; global perspective"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "N&#46;O&#46; Kuchuk"
                            1 => "N&#46;M&#46; van Schoor"
                            2 => "S&#46;M&#46; Pluijm"
                            3 => "A&#46; Chines"
                            4 => "P&#46; Lips"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1359/jbmr.081209"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Bone Miner Res&#46;"
                        "fecha" => "2009"
                        "volumen" => "24"
                        "paginaInicial" => "693"
                        "paginaFinal" => "701"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19049341"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0030"
              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The roles of vitamin D in skeletal muscle&#58; form&#44; function&#44; and metabolism"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "C&#46;M&#46; Girgis"
                            1 => "R&#46;J&#46; Clifton-Bligh"
                            2 => "M&#46;W&#46; Hamrick"
                            3 => "M&#46;F&#46; Holick"
                            4 => "J&#46;E&#46; Gunton"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/er.2012-1012"
                      "Revista" => array:6 [
                        "tituloSerie" => "Endocr Rev&#46;"
                        "fecha" => "2013"
                        "volumen" => "34"
                        "paginaInicial" => "33"
                        "paginaFinal" => "83"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23169676"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0035"
              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Interventions for preventing falls in older people living in the community"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "L&#46;D&#46; Gillespie"
                            1 => "M&#46;C&#46; Robertson"
                            2 => "W&#46;J&#46; Gillespie"
                            3 => "C&#46; Sherrington"
                            4 => "S&#46; Gates"
                            5 => "L&#46;M&#46; Clemson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:3 [
                        "tituloSerie" => "Cochrane Database Syst&#46; Rev&#46;"
                        "fecha" => "2012"
                        "volumen" => "9"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0040"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comparative analysis of nutritional guidelines for vitamin D"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "R&#46; Bouillon"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1038/nrendo.2017.31"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nat Rev Endocrinol&#46;"
                        "fecha" => "2017"
                        "volumen" => "13"
                        "paginaInicial" => "466"
                        "paginaFinal" => "479"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28387318"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0045"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effects of vitamin D supplementation on musculoskeletal health&#58; a systematic review&#44; meta-analysis&#44; and trial sequential analysis"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "M&#46;J&#46; Bolland"
                            1 => "A&#46; Grey"
                            2 => "A&#46; Avenell"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S2213-8587(18)30265-1"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Diabetes Endocrinol&#46;"
                        "fecha" => "2018"
                        "volumen" => "6"
                        "paginaInicial" => "847"
                        "paginaFinal" => "858"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30293909"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0050"
              "etiqueta" => "10"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A systematicreview of vitamin D status in populations worldwide"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46; Hilger"
                            1 => "A&#46; Friedel"
                            2 => "R&#46; Herr"
                            3 => "T&#46; Rausch"
                            4 => "F&#46; Roos"
                            5 => "D&#46;A&#46; Wahl"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1017/S0007114513001840"
                      "Revista" => array:6 [
                        "tituloSerie" => "Br J Nutr"
                        "fecha" => "2014"
                        "volumen" => "111"
                        "paginaInicial" => "23"
                        "paginaFinal" => "45"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23930771"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0055"
              "etiqueta" => "11"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Low calcium intake and inadequate vitamin D status in postmenopausal osteoporotic women"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;M&#46; Quesada-G&#243;mez"
                            1 => "M&#46; Diaz-Curiel"
                            2 => "M&#46; Sosa-Henriquez"
                            3 => "J&#46; Malouf-Sierra"
                            4 => "X&#46; Nogues-Solan"
                            5 => "C&#46; Gomez-Alonso"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.jsbmb.2012.10.013"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Steroid Biochem Mol Biol&#46;"
                        "fecha" => "2013"
                        "volumen" => "136"
                        "paginaInicial" => "175"
                        "paginaFinal" => "177"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23142144"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0060"
              "etiqueta" => "12"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Dietary reference intakes for calcium and vitamin D"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "IOM &#40;Institute of Medicine&#41;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:3 [
                        "fecha" => "2011"
                        "editorial" => "The National Academies Press"
                        "editorialLocalizacion" => "Washington&#44; DC"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0065"
              "etiqueta" => "13"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Evaluation&#44; treatment&#44; and prevention of vitamin D deficiency&#58; an Endocrine Society clinical practice guideline"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "M&#46;F&#46; Holick"
                            1 => "N&#46;C&#46; Binkley"
                            2 => "H&#46;A&#46; Bischoff-Ferrari"
                            3 => "C&#46;M&#46; Gordon"
                            4 => "D&#46;A&#46; Hanley"
                            5 => "R&#46;P&#46; Heaney"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/jc.2011-0385"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Endocrinol Metab&#46;"
                        "fecha" => "2011"
                        "volumen" => "96"
                        "paginaInicial" => "1911"
                        "paginaFinal" => "1930"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21646368"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0070"
              "etiqueta" => "14"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vitamin D and Health"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "Scientific Advisory Committee on Nutrition&#40;SACN&#41;"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2016"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0075"
              "etiqueta" => "15"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vitamin D supplementation and musculoskeletal health"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "R&#46; Bouillon"
                            1 => "P&#46; Lips"
                            2 => "J&#46;P&#46; Bilezikian"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S2213-8587(18)30347-4"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Diabetes Endocrinol"
                        "fecha" => "2019"
                        "volumen" => "7"
                        "paginaInicial" => "85"
                        "paginaFinal" => "86"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30683217"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0080"
              "etiqueta" => "16"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vitamin D supplementation and musculoskeletal health"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "H&#46;A&#46; Bischoff-Ferrari"
                            1 => "E&#46;J&#46; Orav"
                            2 => "L&#46; Abderhalden"
                            3 => "B&#46; Dawson-Hughes"
                            4 => "W&#46;C&#46; Willett"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Lancet Diabetes Endocrinol&#46;"
                        "fecha" => "2019"
                        "volumen" => "7"
                        "paginaInicial" => "85"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0085"
              "etiqueta" => "17"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Preventing fractures amongolderpeople living in institutionalcare&#58; a pragmatic randomised double blind placebo controlled trial of vitamin D supplementation"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46;A&#46; Lyons"
                            1 => "A&#46; Johansen"
                            2 => "S&#46; Brophy"
                            3 => "R&#46;G&#46; Newcombe"
                            4 => "C&#46;J&#46; Phillips"
                            5 => "B&#46; Lervy"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00198-006-0309-5"
                      "Revista" => array:6 [
                        "tituloSerie" => "Osteoporos Int&#46;"
                        "fecha" => "2007"
                        "volumen" => "18"
                        "paginaInicial" => "811"
                        "paginaFinal" => "818"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17473911"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0090"
              "etiqueta" => "18"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Can vitamin D supplementation reduce therisk of fracture in theelderly&#63; A randomized controlled trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "H&#46;E&#46; Meyer"
                            1 => "G&#46;B&#46; Smedshaug"
                            2 => "E&#46; Kvaavik"
                            3 => "J&#46;A&#46; Falch"
                            4 => "A&#46; Tverdal"
                            5 => "J&#46;I&#46; Pedersen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1359/jbmr.2002.17.4.709"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Bone Miner Res&#46;"
                        "fecha" => "2002"
                        "volumen" => "17"
                        "paginaInicial" => "709"
                        "paginaFinal" => "715"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11918228"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0095"
              "etiqueta" => "19"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "RECORD Trial Group&#46; Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people &#40;Randomised Evaluation of Calcium Orvitamin D&#44; RECORD&#41;&#58; a randomised placebo-controlled trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46;M&#46; Grant"
                            1 => "A&#46; Avenell"
                            2 => "M&#46;K&#46; Campbell"
                            3 => "A&#46;M&#46; McDonald"
                            4 => "G&#46;S&#46; MacLennan"
                            5 => "G&#46;C&#46; McPherson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S0140-6736(05)63013-9"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet&#46;"
                        "fecha" => "2005"
                        "volumen" => "365"
                        "paginaInicial" => "1621"
                        "paginaFinal" => "1628"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15885294"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0100"
              "etiqueta" => "20"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Vitamin D supplementation and fracture incidence in elderlypersons&#46; A randomized&#44; placebo-controlled clinical trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "P&#46; Lips"
                            1 => "W&#46;C&#46; Graafmans"
                            2 => "M&#46;E&#46; Ooms"
                            3 => "P&#46;D&#46; Bezemer"
                            4 => "L&#46;M&#46; Bouter"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.7326/0003-4819-124-4-199602150-00003"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Intern Med&#46;"
                        "fecha" => "1996"
                        "volumen" => "124"
                        "paginaInicial" => "400"
                        "paginaFinal" => "406"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8554248"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0105"
              "etiqueta" => "21"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of annual intramuscular vitamin D on fracture risk in elderlymen and women--a population-based&#44; randomized&#44; double-blind&#44; placebo-controlled trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "H&#46; Smith"
                            1 => "F&#46; Anderson"
                            2 => "H&#46; Raphael"
                            3 => "P&#46; Maslin"
                            4 => "S&#46; Crozier"
                            5 => "C&#46; Cooper"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1093/rheumatology/kem240"
                      "Revista" => array:6 [
                        "tituloSerie" => "Rheumatology &#40;Oxford&#41;&#46;"
                        "fecha" => "2007"
                        "volumen" => "46"
                        "paginaInicial" => "1852"
                        "paginaFinal" => "1857"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17998225"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            21 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "22"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Annualhigh-dose oral vitamin D and falls and fractures in olderwomen&#58; a randomizedcontrolled trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46;M&#46; Sanders"
                            1 => "A&#46;L&#46; Stuart"
                            2 => "E&#46;J&#46; Williamson"
                            3 => "J&#46;A&#46; Simpson"
                            4 => "M&#46;A&#46; Kotowicz"
                            5 => "D&#46; Young"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1001/jama.303.24.2544"
                      "Revista" => array:5 [
                        "tituloSerie" => "JAMA&#46;"
                        "fecha" => "2010"
                        "volumen" => "303"
                        "numero" => "1815"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20571023"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            22 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "23"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Effect of monthly high-dose vitamin D supplementation on falls and non-vertebral fractures&#58; secondary and post-hoc outcomesfromtherandomised&#44; double-blind&#44; placebo-controlledViDA trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "K&#46;T&#46; Khaw"
                            1 => "A&#46;W&#46; Stewart"
                            2 => "D&#46; Waayer"
                            3 => "C&#46;M&#46;M&#46; Lawes"
                            4 => "L&#46; Toop"
                            5 => "C&#46;A&#46; Camargo Jr"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S2213-8587(17)30103-1"
                      "Revista" => array:6 [
                        "tituloSerie" => "Lancet Diabetes Endocrinol&#46;"
                        "fecha" => "2017"
                        "volumen" => "5"
                        "paginaInicial" => "438"
                        "paginaFinal" => "447"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/28461159"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            23 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "24"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Guidelines for optimizing design and analysis of clinical studies of nutrient effects"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "R&#46;P&#46; Heaney"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1111/nure.12148"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nutr Rev&#46;"
                        "fecha" => "2014"
                        "volumen" => "72"
                        "paginaInicial" => "48"
                        "paginaFinal" => "54"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25293543"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            24 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "25"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Skeletal and extra-skeletalactions of vitamin D&#58; Current evidence and outstanding questions"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "R&#46; Bouillon"
                            1 => "C&#46; Marcocci"
                            2 => "G&#46; Carmeliet"
                            3 => "D&#46; Bikle"
                            4 => "J&#46;H&#46; White"
                            5 => "B&#46; Dawson-Hughes"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/er.2018-00126"
                      "Revista" => array:2 [
                        "tituloSerie" => "Endocr Rev&#46;"
                        "fecha" => "2018"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            25 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "26"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Does vitamin D sufficiency equate to a single serum 25-hydroxy vitamin D level or are different levels required for non-skeletal diseases&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "S&#46; Spedding"
                            1 => "S&#46; Vanlint"
                            2 => "H&#46; Morris"
                            3 => "R&#46; Scragg"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.3390/nu5125127"
                      "Revista" => array:6 [
                        "tituloSerie" => "Nutrients&#46;"
                        "fecha" => "2013"
                        "volumen" => "5"
                        "paginaInicial" => "5127"
                        "paginaFinal" => "5139"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24352091"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            26 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "27"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Risk factors for prediction of inadequate response to antiresorptives"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "A&#46; D&#237;ez-P&#233;rez"
                            1 => "J&#46;M&#46; Olmos"
                            2 => "X&#46; Nogu&#233;s"
                            3 => "M&#46; Sosa"
                            4 => "M&#46; D&#237;az-Curiel"
                            5 => "J&#46;L&#46; P&#233;rez-Castrill&#243;n"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1002/jbmr.1496"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Bone Miner Res"
                        "fecha" => "2012"
                        "volumen" => "27"
                        "paginaInicial" => "817"
                        "paginaFinal" => "824"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22161773"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            27 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "28"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Is calcifediol better than cholecalciferol for vitamin D supplementation&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "J&#46;M&#46; Quesada-Gomez"
                            1 => "R&#46; Bouillon"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00198-018-4520-y"
                      "Revista" => array:6 [
                        "tituloSerie" => "Osteoporos Int&#46;"
                        "fecha" => "2018"
                        "volumen" => "29"
                        "paginaInicial" => "1697"
                        "paginaFinal" => "1711"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29713796"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            28 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "29"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Comparison of daily&#44; weekly&#44; and monthly vitamin D3 in ethanol dosing protocols for two months in elderly hip fracture patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "S&#46; Ish-Shalom"
                            1 => "E&#46; Segal"
                            2 => "T&#46; Salganik"
                            3 => "B&#46; Raz"
                            4 => "I&#46;L&#46; Bromberg"
                            5 => "R&#46; Vieth"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1210/jc.2008-0241"
                      "Revista" => array:6 [
                        "tituloSerie" => "J Clin Endocrinol Metab&#46;"
                        "fecha" => "2008"
                        "volumen" => "93"
                        "paginaInicial" => "3430"
                        "paginaFinal" => "3435"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18544622"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            29 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "30"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Scientific Advisory Board of the European Society for Clinical and Economic Aspects of Osteoporosis &#40;ESCEO&#41; and the Committees of Scientific Advisors and National Societies of the International Osteoporosis Foundation &#40;IOF&#41;&#46; European guidance for the diagnosis and management of osteoporosis in postmenopausal women"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "J&#46;A&#46; Kanis"
                            1 => "C&#46; Cooper"
                            2 => "R&#46; Rizzoli"
                            3 => "J&#46;Y&#46; Reginster"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s00198-018-4704-5"
                      "Revista" => array:6 [
                        "tituloSerie" => "Osteoporos Int"
                        "fecha" => "2019"
                        "volumen" => "30"
                        "paginaInicial" => "3"
                        "paginaFinal" => "44"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/30324412"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
          ]
        ]
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/23870206/0000015300000011/v1_201911300659/S2387020619304966/v1_201911300659/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "44145"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Special article"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/23870206/0000015300000011/v1_201911300659/S2387020619304966/v1_201911300659/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020619304966?idApp=UINPBA00004N"
]
Indexed in:

Follow us:

Subscribe:

Article

Indexed in:

Follow us:

Subscribe:

Article

Subscribe to our newsletter
