Evaluation of bone mineral density in children with sickle cell disease

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Garrido Colino, C. Beléndez Bieler, M. Pérez Díaz, E. Cela de Julián" "autores" => array:4 [ 0 => array:4 [ "nombre" => "C." "apellidos" => "Garrido Colino" "email" => array:1 [ 0 => "cgarridoc.@salud.madrid.org" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "C." "apellidos" => "Beléndez Bieler" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "M." "apellidos" => "Pérez Díaz" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 3 => array:3 [ "nombre" => "E." "apellidos" => "Cela de Julián" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Sección Oncología-Hematología Pediátrica, Hospital General Universitario Gregorio Marañón, Madrid, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Radiología, Hospital General Universitario Gregorio Marañón, Madrid, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Evaluación de la densidad mineral ósea en pacientes con enfermedad de células falciformes" ] ] "textoCompleto" => "IntroductionIn recent years, bone mass alterations or low bone mineral density has been the subject of ongoing attention. The peak bone mass acquired by the end of maturation is a good predictor for the risk of future fractures. Clinicians are generally familiar with the terms “osteopaenia” (decrease in bone mass) and “osteoporosis” (a more severe loss of bone mass associated with a greater risk of fracture).<a class="elsevierStyleCrossRefs" href="#bib0205">1–3</a> The diagnosis of osteoporosis in children is defined as low bone mineral density (BMD) and a fracture history with long bone fracture of the lower extremities, vertebral compression fracture, or two or more long bone fractures of the upper extremities.<a class="elsevierStyleCrossRef" href="#bib0205">1</a>The earliest studies that analysed the role of bone health in fractures in the paediatric age group were conducted in New Zealand.<a class="elsevierStyleCrossRefs" href="#bib0220">4,5</a>A prospective study in healthy African children 5–9 years of age that analysed the relationship between vitamin D and fractures concluded that a significant number of children with fractures also have low vitamin D levels (59%).<a class="elsevierStyleCrossRef" href="#bib0230">6</a> Vitamin D deficiency seems to play a previously unknown role in fractures in the paediatric age group.Furthermore, there is evidence that vitamin D supplementation in healthy children and adults with deficiency leads to a significant increase in BMD, decreasing the risk of fractures.<a class="elsevierStyleCrossRefs" href="#bib0235">7,8</a>Children with sickle cell disease (SCD) often develop bone complications manifested as vaso-occlusive bone pain crises, dactylitis, osteomyelitis, avascular necrosis or vertebral deformity. In this population, the literature describes a decrease in BMD secondary to chronic anaemia and bone marrow hyperplasia and associated with a higher risk of osteopaenia and osteoporosis.<a class="elsevierStyleCrossRefs" href="#bib0245">9,10</a>Recent studies show that children with SCD frequently have severe vitamin D deficiency. For instance, a cross-sectional study of 78 children with SCD performed in our hospital found that only 20.5% had 25-hydroxyvitamin D (25(OH)D) levels above 30ng/mL, the threshold considered optimal for bone health.<a class="elsevierStyleCrossRef" href="#bib0255">11</a>Despite the higher risk of bone disease in this population, there is little information on BMD in children with SCD and its association with 25(OH)D levels and the risk of fractures. Our study assessed the prevalence of BMD abnormalities in children with SCD from the autonomous community of Madrid using densitometry (dual-energy X-ray absorptiometry [DXA])<a class="elsevierStyleCrossRefs" href="#bib0260">12,13</a> and analysed potential risk factors associated with low BMD.Materials and methodsWe conducted a cross-sectional study between October 2009 and February 2011 in a cohort of 120 children with SCD residing in the autonomous community of Madrid and who were being followed up at the paediatric haematology department of the Hospital Gregorio Marañón (HGUGM) to evaluate BMD in this population by means of DXA.We included a total of 40 patients, starting at age 3–4 years to avoid the need for sedation during DXA. We included all possible patients who made at least one visit to the hospital during the study period. We excluded children known to have conditions affecting growth or nutritional status, with chronic liver or kidney function abnormalities, undergoing treatment with drugs that affect the skeleton, or who had had SCD complications the previous month (vaso-occlusive crisis, fever, acute chest syndrome).The study was approved by the board of ethics of our hospital, and we obtained the signed informed consent from all participants.We collected the demographic and anthropometric data in the course of routine follow-up visits to a physician in the team.Bone mineral density was assessed by means of DXA. We measured BMD at the posterior–anterior spine, and not at the hip and proximal femur due to the great variability of the latter areas during growth, adhering to the International Society for Clinical Densitometry (ISCD) recommendations for children. The instrument used for this study was a LUNAR DPX-IQ 5539 machine that met the requirements for research in paediatrics. The results were interpreted by an experienced DXA radiologist and expressed as Z-scores, that is, the number of standard deviations (SDs) from the mean BMD of a child compared to other children of the same age, sex and ethnicity. Z-scores below −2 SD were considered abnormal. Low BMD or osteopaenia was defined as a Z-score between −1 and −2 SDs, and a normal BMD as a Z-score above −1 SD. Osteoporosis was not defined on the sole basis of an abnormal Z-score in any instances. Children were only diagnosed with osteoporosis if the following two conditions were met: low BMC and a fracture history with long bone fracture of the lower extremities, vertebral compression fracture, or two or more long bone fractures of the upper extremities.<a class="elsevierStyleCrossRef" href="#bib0205">1</a>Other laboratory tests were performed on the same day as the DXA scan. Haemoglobin, reticulocytes and calcium and phosphorus levels were measured with standard laboratory techniques. Vitamin D levels were assessed by quantitative determination of 25(OH)D using the LIASON 25 OH Vitamin D TOTAL Assay (310600). Vitamin D deficiency was defined as a 25(OH)D level below 20ng/mL (50nmol/L). Vitamin D insufficiency was defined as a 25(OH)D level between 21 and 29ng/mL (52.5–72.5nmol/L) and a normal vitamin D level as a 25(OH)D level equal or above 30ng/mL (75nmol/L). We also defined hyperparathyroidism as a serum parathyroid hormone (PTH) concentration above 50ng/L. We measured osteocalcin by immunoradiometric assay (IRMA) and bone alkaline phosphatase (BAP) by the Access Ostase immunoenzymatic assay.Statistical analysisAll the data were entered in an SPSS statistics 18 database and analysed using the same application. Descriptive statistics were used to summarise population data, and measures of central tendency to describe quantitative variables. We used Student's t-test and ANOVA to compare parametric distributions and the Mann–Whitney U-test and the Kruskall–Wallis test for nonparametric distributions. We expressed qualitative variables as frequencies and percentages, and compared them by means of the chi square test, Fisher's exact test or McNemar's test depending on the samples. We analysed correlation by means of Pearson's and Spearman's correlation coefficients. We also performed simple and multiple regression analysis.Results<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarises the descriptive statistics results for patients who underwent DXA for bone mass assessment.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>We analysed data for a sample of 40 children that underwent DXA between October 2009 and September 2011.<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> presents the main data pertaining to the children with abnormal DXA results.<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>The analysis of the association between age at the time of the DXA scan and Z-score values showed that the median age was below 7 and a half years in children with a normal or low BMD (n=33), while the median age of children with an abnormal BMD was higher, 12 and a half years (n=7).The correlation analyses for the association between the Z-score and other quantitative variables only found a statistically significant linear Pearson correlation between Z-score values and Hb levels (r=0.368; P=.019), that is, children with higher Hb levels had higher Z-scores.We found no correlation with the remaining quantitative variables we analysed: total calcium, ionised calcium, magnesium, phosphorus, alkaline phosphatase, BAP, PTH, osteocalcin, 25(OH)D, iron and ferritin levels, age at the time of the DXA scan, duration of breastfeeding in months, duration of vitamin D prophylaxis in months, and number of hospitalisation days per year.The simple and multiple regression analyses that we performed did not find a linear association or an explanatory model (cause-effect) between the various quantitative variables and the Z-score values.The Mann–Whitney's U nonparametric test did not find significant differences in the comparison of the DXA results expressed as Z-scores between different groups of children classified by sex (P=.21). The same test also found no differences in the Z-scores of the group that received prophylaxis in the first year of life compared to the group that did not (P=.65), nor in the group that received hydroxyurea versus the group that did not (P=.467). The nonparametric Kruskal–Wallis test also showed no significant differences (P=.45) between different ethnic groups or between patients with different types of SCD (P=.28).The analysis of the categorical variables by means of the chi square test or Fisher's exact test did not find significant results in the comparison of abnormal Z-scores with 25(OH)D levels below 20 and 30ng/L, respectively.The chi square test for the comparison of the Z-scores of patients who were treated with hydroxyurea and of patients who were not showed that 36% of the latter had abnormal Z-scores. This percentage reached 53.3% in the group treated with hydroxyurea, but the difference was not statistically significant (P=.336). There were also no statistically significant differences (P=.531) between children with and without hyperparathyroidism (39.1% vs 50%), or between sexes (28.6% in girls vs 50% in boys; P=.191). Eighty percent of the children treated with a transfusion regimen had normal DXA results, and 20% had abnormal results (P=.373).DiscussionWe conducted a cross-sectional observational study to assess bone health by means of DXA in children 3–16 years of age (n=40). Z-scores were abnormal in some patients younger than 5 years, so we could not clearly define the cut-off age at which DXA results start to be significantly abnormal, although most patients in the abnormal Z-score group (Z<−2), which amounted to 17.5% of the sample, were older than 10 years. This finding is consistent with the ISDC recommendation of starting to take DXA measurements at 10 years of age, as proposed for other haemoglobinopathies like thalassaemia major.<a class="elsevierStyleCrossRef" href="#bib0270">14</a>The studies conducted in children with SCD to assess bone mass by means of DXA have had a cross-sectional design, small samples, and insufficient data to evaluate the technique in this population and in individuals 9 years of age and older in general.<a class="elsevierStyleCrossRefs" href="#bib0275">15,16</a> They concluded that poor bone mineralisation probably starts at earlier ages, and that further research should be devoted to the impact of correcting insufficient or deficient levels of calcium and vitamin D.The most interesting study is the one conducted by Buison et al.<a class="elsevierStyleCrossRef" href="#bib0285">17</a> It was a case–control study of 90 children with SCD (HbSS phenotype) 4–19 years of age that were compared to 198 healthy children of similar characteristics. They found a significantly lower BMD, assessed by DXA, in children with SCD (P<.0001).Among all the analysed variables, our study only found a linear correlation between the Z-scores and haemoglobin levels. This may be explained by a decrease in erythropoiesis in children that have higher haemoglobin levels and lesser degrees of haemolysis, which prevents bone marrow hyperplasia and the subsequent cortical thinning. This finding is consistent with the work of Buison et al.<a class="elsevierStyleCrossRef" href="#bib0285">17</a> and has also been described in Brazilian adults with SCD.<a class="elsevierStyleCrossRef" href="#bib0290">18</a>Similarly, a retrospective study of 103 adults with SCD by Sarrai et al.<a class="elsevierStyleCrossRef" href="#bib0295">19</a> found a high prevalence of altered bone density (79.6%) assessed by means of DXA. The study did not find an association with age, but found an association with haemoglobin levels, as low Hb was a predictor for abnormal bone density.Some authors have also proposed that the level of 25(OH)D is a factor that influences BMD in patients with SCD. In this regard, a study conducted in adults in Saudi Arabia that compared SCD patients with a healthy population of similar characteristics described a significantly lower BMD in the group of affected patients compared to the control group (P<.001 for measurements at both the spine and the femur). The prevalence of osteoporosis in patients with SCD and vitamin D deficiency is 73.8% (45/61) in male patients and 92.4% (85/92) in female patients, while in the control group the prevalence of osteoporosis was 30% in men and 63.6% in women. This study did not analyse other causes of low BMD, such as hypogonadism, altered sex hormones or iron overload.<a class="elsevierStyleCrossRef" href="#bib0300">20</a>Our study did not find a correlation between 25(OH)D levels and BMC measured as a Z-score, a finding that is consistent with studies conducted in children with SCD.<a class="elsevierStyleCrossRef" href="#bib0305">21</a> Understanding this fact would require prospective studies with repeated measurement of 25(OH)D levels.The risk of osteoporosis and osteopaenia in paediatric patients with SCD has not been properly established yet either, and at present we do not know the threshold for abnormal DXA values. There are studies in adults that demonstrate that adults with SCD are at increased risk of osteopaenia and osteoporosis. A study of 36 adults conducted in Saudi Arabia found that 82% of the men and 76% of the women had osteoporosis or osteopaenia.<a class="elsevierStyleCrossRef" href="#bib0310">22</a> This study was later expanded to 87 patients, showing a prevalence of osteopaenia and/or osteoporosis in 65% of male patients and 65.2% of female patients.<a class="elsevierStyleCrossRef" href="#bib0315">23</a>A few studies of healthy adults have analysed the association between 25(OH)D levels and bone health and obtained disparate results.<a class="elsevierStyleCrossRefs" href="#bib0320">24,25</a> Many observational studies in adults have sought to determine the threshold level of 25(OH)D beyond which there is increased risk of fracture. Some studies proposed levels below 16ng/mL, while others placed the threshold at 20ng/mL.<a class="elsevierStyleCrossRefs" href="#bib0330">26–30</a>There are very few published studies on the subject of fractures in SCD patients. Most of them are isolated case reports, and one is a study of a cohort of children with osteomyelitis and SCD.<a class="elsevierStyleCrossRefs" href="#bib0355">31–33</a>Paradoxically, individuals of African descent without SCD, despite having a higher 25(OH)D deficit than Caucasian individuals of similar characteristics, have a lower risk of bone fracture due to a greater bone mass (10–15% greater than other ethnic groups).<a class="elsevierStyleCrossRef" href="#bib0370">34</a> We do not know whether this advantage is maintained in the SCD population.Although many questions have yet to be resolved and the current literature has not established a threshold for abnormal DXA results in children, studies in adults and children published in 2011 and 2012 have described an association between vitamin D deficiency and a greater risk of fractures, low BMD and chronic musculoskeletal pain.<a class="elsevierStyleCrossRefs" href="#bib0375">35–40</a>The results of our study are limited by the sample size, it being a single-centre study, and the lack of a control group.ConclusionsWhile our study did not determine the age from which alterations in BMC develop in children with SCD, it suggested the presence of a low BMD from 10 years of age, with abnormal DXA results starting at age 12 years. At present, there are no evidence-based recommendations on when to assess BMD and 25(OH)D levels in this population. Still, the development of a strategy to improve peak bone mass and prevent fractures and osteoporosis would probably be beneficial. It is essential that we intervene during childhood, and in this sense it would be worth considering the serial measurement of vitamin D levels and their subsequent correction.Conflicts of interestThe authors have no conflicts of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres502755" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Materials and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec523913" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres502756" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec523914" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:1 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Statistical analysis" ] ] ] 6 => array:2 [ "identificador" => "sec0020" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0025" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0030" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0035" "titulo" => "Conflicts of interest" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2013-11-17" "fechaAceptado" => "2014-04-03" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec523913" "palabras" => array:5 [ 0 => "Bone mineral density" 1 => "Densitometry" 2 => "Sickle cell disease" 3 => "Low bone mineral density" 4 => "Osteoporosis" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec523914" "palabras" => array:5 [ 0 => "Densidad mineral ósea" 1 => "Densitometría" 2 => "Enfermedad de células falciformes" 3 => "Osteopenia" 4 => "Osteoporosis" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveTo evaluate bone mineral density (BMD) in children with sickle cell disease (SCD) in the Community of Madrid. Materials and methodsThe BMD was estimated in 40 children with SCD, and with an age range between 3 and 16 years, using densitometry (DXA), as recommended by the International Society for Clinical Densitometry (ISCD). ResultsThe mean age at the time of the study was 7.97±3.95 years, the mean value of the DXA expressed in Z-score was −0.91±1.46 with a range of minimum values −5.30 and 2.30 maximum. More than half (57.5%) of all the children had normal BMD (Z>−1), 25% had low BMD (Z between −1 and −2), and 17.5% showed abnormal Z-score values of osteoporosis (Z-score<−2). The Pearson linear correlation was statistically significant between Z-score value and the haemoglobin level (r=0.368, p=.019), finding no correlation with the levels of 25 (OH) vitamin D. ConclusionProspective studies are needed with a larger number of patients to understand the future implications of bone densitometry changes and associated risk factors." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Materials and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivoEvaluar la densidad mineral ósea (DMO) en niños con enfermedad de células falciformes (ECF) de la Comunidad de Madrid. Material y métodosSe valora la DMO en un total de 40 niños con ECF y rango de edad entre 3-16 años, mediante densitometría (DEXA) siguiendo las recomendaciones de la Sociedad Internacional de Densitometría Clínica (ISCD). ResultadosLa edad media en el momento del estudio fue de 7,97±3,95 años; el valor medio de la DEXA expresado en Z-score es de -0,91±1,46 con un rango de valores mínimo de -5,30 y máximo de 2,30. Un 57,5% de los niños tiene DMO normal (Z>-1), un 25% tienen DMO baja (Z entre -1 y -2) y un 17,5% presentan Z-score patológico con valores de osteoporosis (Z-score<-2). Los estudios de correlación solo encuentran una correlación lineal de Pearson significativa estadísticamente entre valor de Z-score y valor de Hb (r=0,368, p=0,019), no encontrando correlación con los niveles de 25 (OH) D. ConclusiónSe necesitan estudios prospectivos, con mayor número de enfermos para conocer las implicaciones futuras de la densitometría alterada y los factores de riesgo asociados." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusión" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: Garrido Colino C, Beléndez Bieler C, Pérez Díaz M, Cela de Julián E. Evaluación de la densidad mineral ósea en pacientes con enfermedad de células falciformes. An Pediatr (Barc). 2015;82:216–221." ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "AP: alkaline phosphatase; BAP: bone alkaline phosphatase; CRR: C reactive protein; Hb: haemoglobin; Mg: magnesium; P: phosphorus; PTH: parathyroid hormone; SD: standard deviation." "tablatextoimagen" => array:2 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">n (%) \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Female sex \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14 (35) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26 (65) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">African ethnicity \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">25 (62.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">African American \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 (30) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Type of haemoglobinopathy</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">HbSS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">34 (85) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Tanner stage</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Preadolescent \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31 (77.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Adolescent \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9 (29.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Transfusion regimen \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5 (12.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Treatment with hydroxyurea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">15 (37.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab802076.png" ] ] 1 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">N \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Range \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Mean±DS \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Variance \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Breastfeeding (months) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0–9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.50±3.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9.02 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Vitamin D prophylaxis (months) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2–24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.54±6.24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">38.93 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hospitalisation (days/year) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0–2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.24±0.64 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.41 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4–16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.97±3.95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15.66 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top">DXA results</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Z-score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−5.30–2.30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.91±1.46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.15 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="5" align="left" valign="top">Laboratory tests</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hb g/dL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5–11.30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.74±1.36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.87 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Reticulocytes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">75–355.600 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">119,470±101,919.34 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10,387,553,157.52 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Total calcium mg/dL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">38 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.40–10.30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.39±0.52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.27 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Ionised calcium mmol/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.64–1.30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.07±0.12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.016 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Mg mg/dL \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.70–3.00 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.18±0.26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.068 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">P mg/dl \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4–6.50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.36±0.57 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.326 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">PTH ng/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6–185 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">65.33±47.61 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2267.22 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Total AP U/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">64–461 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">199.75±79.40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6305.45 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">BAP μg/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19–115 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">57.93±26.63 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">712.06 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Osteocalcin μg/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1–10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.74±2.76 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.64 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">25(OH)D ng/ml \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4–44.50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16.89±8.28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">68.58 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">CRP mg/L \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.10–2.60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.44±16.89 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.29 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab802075.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Summary of epidemiological and laboratory data and Z-scores for the group of children with sickle cell disease (n=40) whose bone mineral density was assessed by densitometry (DXA)." ] ] 1 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "Hb: haemoglobin; PTH: parathyroid hormone." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Cases \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">1 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">2 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">3 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">4 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">5 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">6 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">7 \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Sex \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Female \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Female \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hb type \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Sβ0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">SS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Ethnic group \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">African \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">African \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">African \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">African \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">African \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">African \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">African American \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Tanner \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hb (g/dL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.40 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">PTH (ng/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">65 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">151 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">25(OH)D (ng/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10.40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13.80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10.20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.40 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Z-score \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−2.70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−3.50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−2.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−3.10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−5.30 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Fractures \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Hydroxyurea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Transfusion regimen \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Yes \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="left" valign="top">Vitamin D prophylaxis \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab802077.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Data of the children with a pathological densitometry result." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:40 [ 0 => array:3 [ "identificador" => "bib0205" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Osteoporosis in children and adolescents" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "M.L. Bianchi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.bone.2007.07.008" "Revista" => array:6 [ "tituloSerie" => "Bone" "fecha" => "2007" "volumen" => "41" "paginaInicial" => "486" "paginaFinal" => "495" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17706477" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0210" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Official Positions of the International Society for Clinical Densitometry and executive summary of the 2007 ISCD Position Development Conference" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Baim" 1 => "N. Binkley" 2 => "J.P. Bilezikian" 3 => "D.L. Kendler" 4 => "D.B. Hans" 5 => "E.M. 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Evaluation of bone mineral density in children with sickle cell disease

Evaluación de la densidad mineral ósea en pacientes con enfermedad de células falciformes

C. Garrido Colinoa,

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cgarridoc.@salud.madrid.org

Corresponding author.

, C. Beléndez Bielera, M. Pérez Díazb, E. Cela de Juliána

a Sección Oncología-Hematología Pediátrica, Hospital General Universitario Gregorio Marañón, Madrid, Spain

b Servicio de Radiología, Hospital General Universitario Gregorio Marañón, Madrid, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">In recent years&#44; bone mass alterations or low bone mineral density has been the subject of ongoing attention&#46; The peak bone mass acquired by the end of maturation is a good predictor for the risk of future fractures&#46; Clinicians are generally familiar with the terms &#8220;osteopaenia&#8221; &#40;decrease in bone mass&#41; and &#8220;osteoporosis&#8221; &#40;a more severe loss of bone mass associated with a greater risk of fracture&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">1&#8211;3</span></a> The diagnosis of osteoporosis in children is defined as low bone mineral density &#40;BMD&#41; and a fracture history with long bone fracture of the lower extremities&#44; vertebral compression fracture&#44; or two or more long bone fractures of the upper extremities&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The earliest studies that analysed the role of bone health in fractures in the paediatric age group were conducted in New Zealand&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">4&#44;5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">A prospective study in healthy African children 5&#8211;9 years of age that analysed the relationship between vitamin D and fractures concluded that a significant number of children with fractures also have low vitamin D levels &#40;59&#37;&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">6</span></a> Vitamin D deficiency seems to play a previously unknown role in fractures in the paediatric age group&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Furthermore&#44; there is evidence that vitamin D supplementation in healthy children and adults with deficiency leads to a significant increase in BMD&#44; decreasing the risk of fractures&#46;<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">7&#44;8</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Children with sickle cell disease &#40;SCD&#41; often develop bone complications manifested as vaso-occlusive bone pain crises&#44; dactylitis&#44; osteomyelitis&#44; avascular necrosis or vertebral deformity&#46; In this population&#44; the literature describes a decrease in BMD secondary to chronic anaemia and bone marrow hyperplasia and associated with a higher risk of osteopaenia and osteoporosis&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">9&#44;10</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Recent studies show that children with SCD frequently have severe vitamin D deficiency&#46; For instance&#44; a cross-sectional study of 78 children with SCD performed in our hospital found that only 20&#46;5&#37; had 25-hydroxyvitamin D &#40;25&#40;OH&#41;D&#41; levels above 30<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#44; the threshold considered optimal for bone health&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">11</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Despite the higher risk of bone disease in this population&#44; there is little information on BMD in children with SCD and its association with 25&#40;OH&#41;D levels and the risk of fractures&#46; Our study assessed the prevalence of BMD abnormalities in children with SCD from the autonomous community of Madrid using densitometry &#40;dual-energy X-ray absorptiometry &#91;DXA&#93;&#41;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">12&#44;13</span></a> and analysed potential risk factors associated with low BMD&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><p id="par0040" class="elsevierStylePara elsevierViewall">We conducted a cross-sectional study between October 2009 and February 2011 in a cohort of 120 children with SCD residing in the autonomous community of Madrid and who were being followed up at the paediatric haematology department of the Hospital Gregorio Mara&#241;&#243;n &#40;HGUGM&#41; to evaluate BMD in this population by means of DXA&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">We included a total of 40 patients&#44; starting at age 3&#8211;4 years to avoid the need for sedation during DXA&#46; We included all possible patients who made at least one visit to the hospital during the study period&#46; We excluded children known to have conditions affecting growth or nutritional status&#44; with chronic liver or kidney function abnormalities&#44; undergoing treatment with drugs that affect the skeleton&#44; or who had had SCD complications the previous month &#40;vaso-occlusive crisis&#44; fever&#44; acute chest syndrome&#41;&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">The study was approved by the board of ethics of our hospital&#44; and we obtained the signed informed consent from all participants&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">We collected the demographic and anthropometric data in the course of routine follow-up visits to a physician in the team&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Bone mineral density was assessed by means of DXA&#46; We measured BMD at the posterior&#8211;anterior spine&#44; and not at the hip and proximal femur due to the great variability of the latter areas during growth&#44; adhering to the International Society for Clinical Densitometry &#40;ISCD&#41; recommendations for children&#46; The instrument used for this study was a LUNAR DPX-IQ 5539 machine that met the requirements for research in paediatrics&#46; The results were interpreted by an experienced DXA radiologist and expressed as <span class="elsevierStyleItalic">Z</span>-scores&#44; that is&#44; the number of standard deviations &#40;SDs&#41; from the mean BMD of a child compared to other children of the same age&#44; sex and ethnicity&#46; <span class="elsevierStyleItalic">Z</span>-scores below &#8722;2 SD were considered abnormal&#46; Low BMD or osteopaenia was defined as a <span class="elsevierStyleItalic">Z</span>-score between &#8722;1 and &#8722;2 SDs&#44; and a normal BMD as a <span class="elsevierStyleItalic">Z</span>-score above &#8722;1 SD&#46; Osteoporosis was not defined on the sole basis of an abnormal <span class="elsevierStyleItalic">Z</span>-score in any instances&#46; Children were only diagnosed with osteoporosis if the following two conditions were met&#58; low BMC and a fracture history with long bone fracture of the lower extremities&#44; vertebral compression fracture&#44; or two or more long bone fractures of the upper extremities&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">1</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">Other laboratory tests were performed on the same day as the DXA scan&#46; Haemoglobin&#44; reticulocytes and calcium and phosphorus levels were measured with standard laboratory techniques&#46; Vitamin D levels were assessed by quantitative determination of 25&#40;OH&#41;D using the LIASON 25 OH Vitamin D TOTAL Assay &#40;310600&#41;&#46; Vitamin D deficiency was defined as a 25&#40;OH&#41;D level below 20<span class="elsevierStyleHsp" style=""></span>ng&#47;mL &#40;50<span class="elsevierStyleHsp" style=""></span>nmol&#47;L&#41;&#46; Vitamin D insufficiency was defined as a 25&#40;OH&#41;D level between 21 and 29<span class="elsevierStyleHsp" style=""></span>ng&#47;mL &#40;52&#46;5&#8211;72&#46;5<span class="elsevierStyleHsp" style=""></span>nmol&#47;L&#41; and a normal vitamin D level as a 25&#40;OH&#41;D level equal or above 30<span class="elsevierStyleHsp" style=""></span>ng&#47;mL &#40;75<span class="elsevierStyleHsp" style=""></span>nmol&#47;L&#41;&#46; We also defined hyperparathyroidism as a serum parathyroid hormone &#40;PTH&#41; concentration above 50<span class="elsevierStyleHsp" style=""></span>ng&#47;L&#46; We measured osteocalcin by immunoradiometric assay &#40;IRMA&#41; and bone alkaline phosphatase &#40;BAP&#41; by the Access Ostase immunoenzymatic assay&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Statistical analysis</span><p id="par0070" class="elsevierStylePara elsevierViewall">All the data were entered in an SPSS statistics 18 database and analysed using the same application&#46; Descriptive statistics were used to summarise population data&#44; and measures of central tendency to describe quantitative variables&#46; We used Student&#39;s <span class="elsevierStyleItalic">t</span>-test and ANOVA to compare parametric distributions and the Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span>-test and the Kruskall&#8211;Wallis test for nonparametric distributions&#46; We expressed qualitative variables as frequencies and percentages&#44; and compared them by means of the chi square test&#44; Fisher&#39;s exact test or McNemar&#39;s test depending on the samples&#46; We analysed correlation by means of Pearson&#39;s and Spearman&#39;s correlation coefficients&#46; We also performed simple and multiple regression analysis&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><p id="par0075" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarises the descriptive statistics results for patients who underwent DXA for bone mass assessment&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">We analysed data for a sample of 40 children that underwent DXA between October 2009 and September 2011&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> presents the main data pertaining to the children with abnormal DXA results&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">The analysis of the association between age at the time of the DXA scan and <span class="elsevierStyleItalic">Z</span>-score values showed that the median age was below 7 and a half years in children with a normal or low BMD &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>33&#41;&#44; while the median age of children with an abnormal BMD was higher&#44; 12 and a half years &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>7&#41;&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">The correlation analyses for the association between the <span class="elsevierStyleItalic">Z</span>-score and other quantitative variables only found a statistically significant linear Pearson correlation between <span class="elsevierStyleItalic">Z</span>-score values and Hb levels &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;368&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;019&#41;&#44; that is&#44; children with higher Hb levels had higher <span class="elsevierStyleItalic">Z</span>-scores&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">We found no correlation with the remaining quantitative variables we analysed&#58; total calcium&#44; ionised calcium&#44; magnesium&#44; phosphorus&#44; alkaline phosphatase&#44; BAP&#44; PTH&#44; osteocalcin&#44; 25&#40;OH&#41;D&#44; iron and ferritin levels&#44; age at the time of the DXA scan&#44; duration of breastfeeding in months&#44; duration of vitamin D prophylaxis in months&#44; and number of hospitalisation days per year&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">The simple and multiple regression analyses that we performed did not find a linear association or an explanatory model &#40;cause-effect&#41; between the various quantitative variables and the <span class="elsevierStyleItalic">Z</span>-score values&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The Mann&#8211;Whitney&#39;s <span class="elsevierStyleItalic">U</span> nonparametric test did not find significant differences in the comparison of the DXA results expressed as <span class="elsevierStyleItalic">Z</span>-scores between different groups of children classified by sex &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;21&#41;&#46; The same test also found no differences in the <span class="elsevierStyleItalic">Z</span>-scores of the group that received prophylaxis in the first year of life compared to the group that did not &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;65&#41;&#44; nor in the group that received hydroxyurea versus the group that did not &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;467&#41;&#46; The nonparametric Kruskal&#8211;Wallis test also showed no significant differences &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;45&#41; between different ethnic groups or between patients with different types of SCD &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;28&#41;&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">The analysis of the categorical variables by means of the chi square test or Fisher&#39;s exact test did not find significant results in the comparison of abnormal <span class="elsevierStyleItalic">Z</span>-scores with 25&#40;OH&#41;D levels below 20 and 30<span class="elsevierStyleHsp" style=""></span>ng&#47;L&#44; respectively&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">The chi square test for the comparison of the <span class="elsevierStyleItalic">Z</span>-scores of patients who were treated with hydroxyurea and of patients who were not showed that 36&#37; of the latter had abnormal <span class="elsevierStyleItalic">Z</span>-scores&#46; This percentage reached 53&#46;3&#37; in the group treated with hydroxyurea&#44; but the difference was not statistically significant &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;336&#41;&#46; There were also no statistically significant differences &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;531&#41; between children with and without hyperparathyroidism &#40;39&#46;1&#37; vs 50&#37;&#41;&#44; or between sexes &#40;28&#46;6&#37; in girls vs 50&#37; in boys&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#46;</span>191&#41;&#46; Eighty percent of the children treated with a transfusion regimen had normal DXA results&#44; and 20&#37; had abnormal results &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">&#46;</span>373&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Discussion</span><p id="par0125" class="elsevierStylePara elsevierViewall">We conducted a cross-sectional observational study to assess bone health by means of DXA in children 3&#8211;16 years of age &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>40&#41;&#46; <span class="elsevierStyleItalic">Z</span>-scores were abnormal in some patients younger than 5 years&#44; so we could not clearly define the cut-off age at which DXA results start to be significantly abnormal&#44; although most patients in the abnormal <span class="elsevierStyleItalic">Z</span>-score group &#40;<span class="elsevierStyleItalic">Z</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#8722;2&#41;&#44; which amounted to 17&#46;5&#37; of the sample&#44; were older than 10 years&#46; This finding is consistent with the ISDC recommendation of starting to take DXA measurements at 10 years of age&#44; as proposed for other haemoglobinopathies like thalassaemia major&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">14</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">The studies conducted in children with SCD to assess bone mass by means of DXA have had a cross-sectional design&#44; small samples&#44; and insufficient data to evaluate the technique in this population and in individuals 9 years of age and older in general&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">15&#44;16</span></a> They concluded that poor bone mineralisation probably starts at earlier ages&#44; and that further research should be devoted to the impact of correcting insufficient or deficient levels of calcium and vitamin D&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">The most interesting study is the one conducted by Buison et al&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">17</span></a> It was a case&#8211;control study of 90 children with SCD &#40;HbSS phenotype&#41; 4&#8211;19 years of age that were compared to 198 healthy children of similar characteristics&#46; They found a significantly lower BMD&#44; assessed by DXA&#44; in children with SCD &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;0001&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Among all the analysed variables&#44; our study only found a linear correlation between the <span class="elsevierStyleItalic">Z</span>-scores and haemoglobin levels&#46; This may be explained by a decrease in erythropoiesis in children that have higher haemoglobin levels and lesser degrees of haemolysis&#44; which prevents bone marrow hyperplasia and the subsequent cortical thinning&#46; This finding is consistent with the work of Buison et al&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">17</span></a> and has also been described in Brazilian adults with SCD&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">18</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">Similarly&#44; a retrospective study of 103 adults with SCD by Sarrai et al&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">19</span></a> found a high prevalence of altered bone density &#40;79&#46;6&#37;&#41; assessed by means of DXA&#46; The study did not find an association with age&#44; but found an association with haemoglobin levels&#44; as low Hb was a predictor for abnormal bone density&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Some authors have also proposed that the level of 25&#40;OH&#41;D is a factor that influences BMD in patients with SCD&#46; In this regard&#44; a study conducted in adults in Saudi Arabia that compared SCD patients with a healthy population of similar characteristics described a significantly lower BMD in the group of affected patients compared to the control group &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;001 for measurements at both the spine and the femur&#41;&#46; The prevalence of osteoporosis in patients with SCD and vitamin D deficiency is 73&#46;8&#37; &#40;45&#47;61&#41; in male patients and 92&#46;4&#37; &#40;85&#47;92&#41; in female patients&#44; while in the control group the prevalence of osteoporosis was 30&#37; in men and 63&#46;6&#37; in women&#46; This study did not analyse other causes of low BMD&#44; such as hypogonadism&#44; altered sex hormones or iron overload&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">20</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">Our study did not find a correlation between 25&#40;OH&#41;D levels and BMC measured as a <span class="elsevierStyleItalic">Z</span>-score&#44; a finding that is consistent with studies conducted in children with SCD&#46;<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">21</span></a> Understanding this fact would require prospective studies with repeated measurement of 25&#40;OH&#41;D levels&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">The risk of osteoporosis and osteopaenia in paediatric patients with SCD has not been properly established yet either&#44; and at present we do not know the threshold for abnormal DXA values&#46; There are studies in adults that demonstrate that adults with SCD are at increased risk of osteopaenia and osteoporosis&#46; A study of 36 adults conducted in Saudi Arabia found that 82&#37; of the men and 76&#37; of the women had osteoporosis or osteopaenia&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">22</span></a> This study was later expanded to 87 patients&#44; showing a prevalence of osteopaenia and&#47;or osteoporosis in 65&#37; of male patients and 65&#46;2&#37; of female patients&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">23</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">A few studies of healthy adults have analysed the association between 25&#40;OH&#41;D levels and bone health and obtained disparate results&#46;<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">24&#44;25</span></a> Many observational studies in adults have sought to determine the threshold level of 25&#40;OH&#41;D beyond which there is increased risk of fracture&#46; Some studies proposed levels below 16<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#44; while others placed the threshold at 20<span class="elsevierStyleHsp" style=""></span>ng&#47;mL&#46;<a class="elsevierStyleCrossRefs" href="#bib0330"><span class="elsevierStyleSup">26&#8211;30</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">There are very few published studies on the subject of fractures in SCD patients&#46; Most of them are isolated case reports&#44; and one is a study of a cohort of children with osteomyelitis and SCD&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">31&#8211;33</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Paradoxically&#44; individuals of African descent without SCD&#44; despite having a higher 25&#40;OH&#41;D deficit than Caucasian individuals of similar characteristics&#44; have a lower risk of bone fracture due to a greater bone mass &#40;10&#8211;15&#37; greater than other ethnic groups&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">34</span></a> We do not know whether this advantage is maintained in the SCD population&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">Although many questions have yet to be resolved and the current literature has not established a threshold for abnormal DXA results in children&#44; studies in adults and children published in 2011 and 2012 have described an association between vitamin D deficiency and a greater risk of fractures&#44; low BMD and chronic musculoskeletal pain&#46;<a class="elsevierStyleCrossRefs" href="#bib0375"><span class="elsevierStyleSup">35&#8211;40</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">The results of our study are limited by the sample size&#44; it being a single-centre study&#44; and the lack of a control group&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Conclusions</span><p id="par0190" class="elsevierStylePara elsevierViewall">While our study did not determine the age from which alterations in BMC develop in children with SCD&#44; it suggested the presence of a low BMD from 10 years of age&#44; with abnormal DXA results starting at age 12 years&#46; At present&#44; there are no evidence-based recommendations on when to assess BMD and 25&#40;OH&#41;D levels in this population&#46; Still&#44; the development of a strategy to improve peak bone mass and prevent fractures and osteoporosis would probably be beneficial&#46; It is essential that we intervene during childhood&#44; and in this sense it would be worth considering the serial measurement of vitamin D levels and their subsequent correction&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conflicts of interest</span><p id="par0195" class="elsevierStylePara elsevierViewall">The authors have no conflicts of interest to declare&#46;</p></span></span>"
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    "fechaRecibido" => "2013-11-17"
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            0 => "Bone mineral density"
            1 => "Densitometry"
            2 => "Sickle cell disease"
            3 => "Low bone mineral density"
            4 => "Osteoporosis"
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            0 => "Densidad mineral &#243;sea"
            1 => "Densitometr&#237;a"
            2 => "Enfermedad de c&#233;lulas falciformes"
            3 => "Osteopenia"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To evaluate bone mineral density &#40;BMD&#41; in children with sickle cell disease &#40;SCD&#41; in the Community of Madrid&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Materials and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The BMD was estimated in 40 children with SCD&#44; and with an age range between 3 and 16 years&#44; using densitometry &#40;DXA&#41;&#44; as recommended by the International Society for Clinical Densitometry &#40;ISCD&#41;&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The mean age at the time of the study was 7&#46;97<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;95 years&#44; the mean value of the DXA expressed in <span class="elsevierStyleItalic">Z</span>-score was &#8722;0&#46;91<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;46 with a range of minimum values &#8722;5&#46;30 and 2&#46;30 maximum&#46; More than half &#40;57&#46;5&#37;&#41; of all the children had normal BMD &#40;<span class="elsevierStyleItalic">Z</span><span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>&#8722;1&#41;&#44; 25&#37; had low BMD &#40;<span class="elsevierStyleItalic">Z</span> between &#8722;1 and &#8722;2&#41;&#44; and 17&#46;5&#37; showed abnormal <span class="elsevierStyleItalic">Z</span>-score values of osteoporosis &#40;<span class="elsevierStyleItalic">Z</span>-score<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#8722;2&#41;&#46; The Pearson linear correlation was statistically significant between <span class="elsevierStyleItalic">Z</span>-score value and the haemoglobin level &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;368&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;019&#41;&#44; finding no correlation with the levels of 25 &#40;OH&#41; vitamin D&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Prospective studies are needed with a larger number of patients to understand the future implications of bone densitometry changes and associated risk factors&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Evaluar la densidad mineral &#243;sea &#40;DMO&#41; en ni&#241;os con enfermedad de c&#233;lulas falciformes &#40;ECF&#41; de la Comunidad de Madrid&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se valora la DMO en un total de 40 ni&#241;os con ECF y rango de edad entre 3-16 a&#241;os&#44; mediante densitometr&#237;a &#40;DEXA&#41; siguiendo las recomendaciones de la Sociedad Internacional de Densitometr&#237;a Cl&#237;nica &#40;ISCD&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La edad media en el momento del estudio fue de 7&#44;97<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#44;95 a&#241;os&#59; el valor medio de la DEXA expresado en Z-score es de -0&#44;91<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;46 con un rango de valores m&#237;nimo de -5&#44;30 y m&#225;ximo de 2&#44;30&#46; Un 57&#44;5&#37; de los ni&#241;os tiene DMO normal &#40;Z<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>-1&#41;&#44; un 25&#37; tienen DMO baja &#40;Z entre -1 y -2&#41; y un 17&#44;5&#37; presentan Z-score patol&#243;gico con valores de osteoporosis &#40;Z-score<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>-2&#41;&#46; Los estudios de correlaci&#243;n solo encuentran una correlaci&#243;n lineal de Pearson significativa estad&#237;sticamente entre valor de Z-score y valor de Hb &#40;r<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;368&#44; p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;019&#41;&#44; no encontrando correlaci&#243;n con los niveles de 25 &#40;OH&#41; D&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusi&#243;n</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se necesitan estudios prospectivos&#44; con mayor n&#250;mero de enfermos para conocer las implicaciones futuras de la densitometr&#237;a alterada y los factores de riesgo asociados&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Garrido Colino C&#44; Bel&#233;ndez Bieler C&#44; P&#233;rez D&#237;az M&#44; Cela de Juli&#225;n E&#46; Evaluaci&#243;n de la densidad mineral &#243;sea en pacientes con enfermedad de c&#233;lulas falciformes&#46; An Pediatr &#40;Barc&#41;&#46; 2015&#59;82&#58;216&#8211;221&#46;</p>"
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          "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">AP&#58; alkaline phosphatase&#59; BAP&#58; bone alkaline phosphatase&#59; CRR&#58; C reactive protein&#59; Hb&#58; haemoglobin&#59; Mg&#58; magnesium&#59; P&#58; phosphorus&#59; PTH&#58; parathyroid hormone&#59; SD&#58; standard deviation&#46;</p>"
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#46;50<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Vitamin D prophylaxis &#40;months&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#8211;24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&#46;54<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">38&#46;93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Hospitalisation &#40;days&#47;year&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#8211;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;24<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Age &#40;years&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#8211;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;97<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;95&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15&#46;66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">DXA results</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Z</span>-score&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;5&#46;30&#8211;2&#46;30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;91<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;46&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="5" align="left" valign="top"><span class="elsevierStyleItalic">Laboratory tests</span></td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hb g&#47;dL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#8211;11&#46;30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&#46;74<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Reticulocytes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">75&#8211;355&#46;600&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">119&#44;470<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>101&#44;919&#46;34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#44;387&#44;553&#44;157&#46;52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Total calcium mg&#47;dL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">38&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">7&#46;40&#8211;10&#46;30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&#46;39<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;52&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Ionised calcium mmol&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;64&#8211;1&#46;30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;07<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;016&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Mg mg&#47;dL&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;70&#8211;3&#46;00&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&#46;18<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;068&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>P mg&#47;dl&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#8211;6&#46;50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;36<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;57&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;326&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>PTH ng&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&#8211;185&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">65&#46;33<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>47&#46;61&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2267&#46;22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Total AP U&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">64&#8211;461&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">199&#46;75<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>79&#46;40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6305&#46;45&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>BAP &#956;g&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19&#8211;115&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">57&#46;93<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>26&#46;63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">712&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Osteocalcin &#956;g&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">27&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#8211;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;74<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;76&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;64&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>25&#40;OH&#41;D ng&#47;ml&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&#8211;44&#46;50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&#46;89<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">68&#46;58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>CRP mg&#47;L&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;10&#8211;2&#46;60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;44<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>16&#46;89&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Summary of epidemiological and laboratory data and <span class="elsevierStyleItalic">Z</span>-scores for the group of children with sickle cell disease &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>40&#41; whose bone mineral density was assessed by densitometry &#40;DXA&#41;&#46;</p>"
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          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Hb&#58; haemoglobin&#59; PTH&#58; parathyroid hormone&#46;</p>"
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Cases&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Sex&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Hb type&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">SS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">SS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">SS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">SS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">S&#946;<span class="elsevierStyleSup">0</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">SS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">SS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Ethnic group&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">African&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">African&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">African&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">African&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">African&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">African&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">African American&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Tanner&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Hb &#40;g&#47;dL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#46;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#46;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">PTH &#40;ng&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">65&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">151&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">25&#40;OH&#41;D &#40;ng&#47;mL&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#46;40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13&#46;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10&#46;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#46;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">Z</span>-score&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;2&#46;70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;3&#46;50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;2&#46;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;3&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;5&#46;30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Fractures&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Hydroxyurea&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Transfusion regimen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Yes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " align="left" valign="top">Vitamin D prophylaxis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">No&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Data of the children with a pathological densitometry result&#46;</p>"
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    ]
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      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
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                  "host" => array:1 [
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                            0 => "L&#46;M&#46; Ryan"
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Article information

ISSN: 23412879
Original language: English

DOI:10.1016/j.anpede.2015.03.006

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Year/Month	Html	Pdf	Total

2024 November	12	7	19
2024 October	87	43	130
2024 September	65	40	105
2024 August	85	72	157
2024 July	48	32	80
2024 June	62	34	96
2024 May	78	35	113
2024 April	68	58	126
2024 March	46	29	75
2024 February	46	29	75
2024 January	45	19	64
2023 December	85	26	111
2023 November	29	25	54
2023 October	61	28	89
2023 September	27	20	47
2023 August	35	19	54
2023 July	33	18	51
2023 June	39	28	67
2023 May	34	19	53
2023 April	31	18	49
2023 March	64	21	85
2023 February	48	12	60
2023 January	33	21	54
2022 December	67	19	86
2022 November	65	36	101
2022 October	53	52	105
2022 September	41	27	68
2022 August	38	49	87
2022 July	34	33	67
2022 June	34	25	59
2022 May	52	35	87
2022 April	45	38	83
2022 March	66	38	104
2022 February	43	33	76
2022 January	57	36	93
2021 December	45	27	72
2021 November	40	44	84
2021 October	67	57	124
2021 September	53	44	97
2021 August	64	42	106
2021 July	45	35	80
2021 June	48	34	82
2021 May	58	46	104
2021 April	120	52	172
2021 March	67	17	84
2021 February	53	14	67
2021 January	56	14	70
2020 December	48	10	58
2020 November	58	15	73
2020 October	40	13	53
2020 September	32	11	43
2020 August	55	13	68
2020 July	49	19	68
2020 June	50	22	72
2020 May	57	25	82
2020 April	41	16	57
2020 March	56	18	74
2020 February	53	16	69
2020 January	50	28	78
2019 December	63	22	85
2019 November	65	15	80
2019 October	50	9	59
2019 September	40	9	49
2019 August	56	22	78
2019 July	44	21	65
2019 June	33	20	53
2019 May	74	19	93
2019 April	65	28	93
2019 March	45	22	67
2019 February	47	12	59
2019 January	44	12	56
2018 December	43	15	58
2018 November	96	37	133
2018 October	189	30	219
2018 September	70	18	88
2018 August	2	0	2
2018 July	1	0	1
2018 June	5	0	5
2018 May	3	0	3
2018 April	10	0	10
2018 March	17	0	17
2018 February	14	0	14
2018 January	17	0	17
2017 December	8	0	8
2017 November	13	0	13
2017 October	15	0	15
2017 September	14	0	14
2017 August	13	0	13
2017 July	14	0	14
2017 June	35	13	48
2017 May	21	7	28
2017 April	21	6	27
2017 March	9	5	14
2017 February	8	7	15
2017 January	5	1	6
2016 December	28	6	34
2016 November	20	2	22
2016 October	29	5	34
2016 September	38	7	45
2016 August	30	9	39
2016 July	13	2	15
2016 June	1	0	1
2016 April	1	0	1
2016 March	2	0	2
2016 February	1	0	1
2015 December	8	9	17
2015 November	2	14	16
2015 October	8	9	17
2015 September	0	8	8
2015 August	2	15	17
2015 July	5	14	19

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