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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Since the middle of the last decade&#44; there is consensus that in the adult population&#44; vitamin D deficiency can be defined as levels of calcifediol &#40;25&#40;OH&#41;D&#41; of less than 50 nmol&#47;L &#40;20&#8239;ng&#47;mL&#41; and vitamin D insufficiency as levels between 50 and 80&#8239;nmol&#47;L &#40;20&#8211;32&#8239;ng&#47;mL&#41;&#44; while values greater than 80&#8239;nmol&#47;L are considered sufficient&#46; These thresholds are also taken as valid in everyday paediatric clinical practice&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The consequence of these definitions is that levels of calcifediol of less than 32&#8239;ng&#47;mL may be considered pathological and consequently an indication for replacement therapy&#44; with the drawback that healthy children are considered to be in the stage preceding disease&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">In 2017&#44; we gathered the calcifediol measurements recorded in our hospital over a period of 18 months &#40;<span class="elsevierStyleItalic">n</span>&#8239;&#61;&#8239;161&#41;&#46; We found that 41 patients &#40;25&#46;5&#37;&#41; had normal levels&#44; 85 &#40;52&#46;8&#37;&#41; insufficient levels and 35 &#40;21&#46;7&#37;&#41; deficient levels&#46; The levels of intact parathyroid hormone &#40;iPTH&#41; were low &#40;&#60;10&#8239;pg&#47;mL&#41; in 12 patients &#40;7&#46;5&#37;&#41; and normal &#40;10&#8211;65&#8239;pg&#47;mL&#41; in the rest&#46; We did not find statistically significant differences in the levels of iPTH in relation to the 3 groups of calcifediol levels &#40;ANOVA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Recently&#44; we measured calcifediol levels in 42 obese children&#46; We compared the results with those of a group of 76 healthy children in the same geographical area&#46; The levels of calcifediol in the obese group were lower compared to the other group &#40;24&#46;7&#8239;&#177;&#8239;7&#46;9 vs 28&#46;9&#8239;&#177;&#8239;7&#46;7 ng&#47;mL&#44; <span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;006&#41;&#46; In the obese group&#44; 24&#46;4&#37; of children had sufficient levels&#44; 42&#46;9&#37; insufficiency and 35&#46;7&#37; deficiency&#46; In the healthy group&#44; 35&#46;5&#37; had sufficient levels&#44; 55&#46;3&#37; insufficiency and 9&#46;2&#37; deficiency&#46; The differences in the proportion of children corresponding to each range of calcifediol levels were statistically significant &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;002&#41;&#46; None of the children had manifestations compatible with rickets &#40;subclinical vitamin D deficiency&#41; or elevated levels of iPTH&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">How can it be that in 3 different samples of children residing in the island of Tenerife&#44; which receives more than 3000&#8239;h a year of sunshine&#44; this many have vitamin D deficiency or insufficiency&#63;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Leaving aside that calcifediol levels do not always accurately reflect the levels of calcitriol&#44; which is the active form of vitamin D&#44; the assessment of vitamin D metabolism should take into account other basic and influential aspects&#44; such as the levels of vitamin D binding protein &#40;DBP&#41;&#44; the existence of variants of this transport protein with different affinities for vitamin D metabolites&#44; and the variability in the functionality&#44; density and number of nuclear vitamin D receptors &#40;VDRs&#41;&#46; In regard to the latter&#44; a study conducted in 1993 demonstrated that rats with spontaneous hypercalciuria &#40;genetic hypercalciuric stone-forming rats&#41; exhibited increased VDR gene expression in intestinal cells&#46; Yao et al&#46; demonstrated that these animals had hyperresponsiveness of VDR gene expression even at low levels of calcitriol&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Thus&#44; a child or adult with levels of vitamin D considered insufficient or lower that happens to carry a genetic variant promoting the function of DBP or VDR and&#47;or with an adequate density of VDRs is likely to exhibit adequate intestinal absorption of calcium&#46; While all of these factors cannot be assessed in everyday clinical practice&#44; clinicians should be cautious in prescribing vitamin D replacement based solely on calcifediol levels and consider other clinical or biochemical parameters&#46; We also believe that while awaiting further data&#44; it would be advisable that the &#8220;insufficiency&#8221; term that often accompanies values in the normal range in laboratory reports no longer be used&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">In our region&#44; vitamin D supplementation is frequently used in children and adults with insufficient levels of calcifediol&#44; and we assume that this practice is also widespread in all of Spain&#46; In this regard&#44; the Agencia Espa&#241;ola de Medicamentos y Productos Sanitarios &#40;Spanish Agency of Medicines and Medical Devices&#41; recently published an <span class="elsevierStyleItalic">informational note</span> citing cases of hypercalcaemia in children receiving &#8220;daily doses much higher than recommended for prevention of vitamin D deficiency&#46;&#8221; It is important to consider that this note does not differentiate between overdosing and toxic doses&#46; We must not forget the cases of so-called &#8220;idiopathic hypercalcaemia&#8221; that emerged in the United Kingdom in the 1950s as a result of vitamin D fortification of foods consumed by children&#44; which gave rise to the novel concept of vitamin D hypersensitivity&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Let us hope that in upcoming years we will not be reminded of the historic quote that &#8220;those who cannot remember the past are condemned to repeat it&#46;&#8221;</p></span>"
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Scientific letter
Vitamin D and its receptor: Reflections on the unusual tendency to create supposed diseases
La vitamina D y su receptor. Reflexiones sobre la inusitada tendencia a crear supuestas enfermedades
Víctor García-Nieto
Corresponding author
, M. Cristina Ontoria Betancort, Pedro Carballo Martin, Mónica Ruiz Pons
Departamento de Pediatría, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Tenerife, Spain
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    "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Since the middle of the last decade&#44; there is consensus that in the adult population&#44; vitamin D deficiency can be defined as levels of calcifediol &#40;25&#40;OH&#41;D&#41; of less than 50 nmol&#47;L &#40;20&#8239;ng&#47;mL&#41; and vitamin D insufficiency as levels between 50 and 80&#8239;nmol&#47;L &#40;20&#8211;32&#8239;ng&#47;mL&#41;&#44; while values greater than 80&#8239;nmol&#47;L are considered sufficient&#46; These thresholds are also taken as valid in everyday paediatric clinical practice&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The consequence of these definitions is that levels of calcifediol of less than 32&#8239;ng&#47;mL may be considered pathological and consequently an indication for replacement therapy&#44; with the drawback that healthy children are considered to be in the stage preceding disease&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">In 2017&#44; we gathered the calcifediol measurements recorded in our hospital over a period of 18 months &#40;<span class="elsevierStyleItalic">n</span>&#8239;&#61;&#8239;161&#41;&#46; We found that 41 patients &#40;25&#46;5&#37;&#41; had normal levels&#44; 85 &#40;52&#46;8&#37;&#41; insufficient levels and 35 &#40;21&#46;7&#37;&#41; deficient levels&#46; The levels of intact parathyroid hormone &#40;iPTH&#41; were low &#40;&#60;10&#8239;pg&#47;mL&#41; in 12 patients &#40;7&#46;5&#37;&#41; and normal &#40;10&#8211;65&#8239;pg&#47;mL&#41; in the rest&#46; We did not find statistically significant differences in the levels of iPTH in relation to the 3 groups of calcifediol levels &#40;ANOVA&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Recently&#44; we measured calcifediol levels in 42 obese children&#46; We compared the results with those of a group of 76 healthy children in the same geographical area&#46; The levels of calcifediol in the obese group were lower compared to the other group &#40;24&#46;7&#8239;&#177;&#8239;7&#46;9 vs 28&#46;9&#8239;&#177;&#8239;7&#46;7 ng&#47;mL&#44; <span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;006&#41;&#46; In the obese group&#44; 24&#46;4&#37; of children had sufficient levels&#44; 42&#46;9&#37; insufficiency and 35&#46;7&#37; deficiency&#46; In the healthy group&#44; 35&#46;5&#37; had sufficient levels&#44; 55&#46;3&#37; insufficiency and 9&#46;2&#37; deficiency&#46; The differences in the proportion of children corresponding to each range of calcifediol levels were statistically significant &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#61;&#8239;&#46;002&#41;&#46; None of the children had manifestations compatible with rickets &#40;subclinical vitamin D deficiency&#41; or elevated levels of iPTH&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">How can it be that in 3 different samples of children residing in the island of Tenerife&#44; which receives more than 3000&#8239;h a year of sunshine&#44; this many have vitamin D deficiency or insufficiency&#63;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Leaving aside that calcifediol levels do not always accurately reflect the levels of calcitriol&#44; which is the active form of vitamin D&#44; the assessment of vitamin D metabolism should take into account other basic and influential aspects&#44; such as the levels of vitamin D binding protein &#40;DBP&#41;&#44; the existence of variants of this transport protein with different affinities for vitamin D metabolites&#44; and the variability in the functionality&#44; density and number of nuclear vitamin D receptors &#40;VDRs&#41;&#46; In regard to the latter&#44; a study conducted in 1993 demonstrated that rats with spontaneous hypercalciuria &#40;genetic hypercalciuric stone-forming rats&#41; exhibited increased VDR gene expression in intestinal cells&#46; Yao et al&#46; demonstrated that these animals had hyperresponsiveness of VDR gene expression even at low levels of calcitriol&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Thus&#44; a child or adult with levels of vitamin D considered insufficient or lower that happens to carry a genetic variant promoting the function of DBP or VDR and&#47;or with an adequate density of VDRs is likely to exhibit adequate intestinal absorption of calcium&#46; While all of these factors cannot be assessed in everyday clinical practice&#44; clinicians should be cautious in prescribing vitamin D replacement based solely on calcifediol levels and consider other clinical or biochemical parameters&#46; We also believe that while awaiting further data&#44; it would be advisable that the &#8220;insufficiency&#8221; term that often accompanies values in the normal range in laboratory reports no longer be used&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">In our region&#44; vitamin D supplementation is frequently used in children and adults with insufficient levels of calcifediol&#44; and we assume that this practice is also widespread in all of Spain&#46; In this regard&#44; the Agencia Espa&#241;ola de Medicamentos y Productos Sanitarios &#40;Spanish Agency of Medicines and Medical Devices&#41; recently published an <span class="elsevierStyleItalic">informational note</span> citing cases of hypercalcaemia in children receiving &#8220;daily doses much higher than recommended for prevention of vitamin D deficiency&#46;&#8221; It is important to consider that this note does not differentiate between overdosing and toxic doses&#46; We must not forget the cases of so-called &#8220;idiopathic hypercalcaemia&#8221; that emerged in the United Kingdom in the 1950s as a result of vitamin D fortification of foods consumed by children&#44; which gave rise to the novel concept of vitamin D hypersensitivity&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> Let us hope that in upcoming years we will not be reminded of the historic quote that &#8220;those who cannot remember the past are condemned to repeat it&#46;&#8221;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Garc&#237;a-Nieto V&#44; Cristina Ontoria Betancort M&#44; Martin PC&#44; Pons MR&#46; La vitamina D y su receptor&#46; Reflexiones sobre la inusitada tendencia a crear supuestas enfermedades&#46; An Pediatr &#40;Barc&#41;&#46; 2020&#59;92&#58;167&#8211;168&#46;</p>"
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Article information
ISSN: 23412879
Original language: English
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