Share
array:23 [ "pii" => "S238702061600098X" "issn" => "23870206" "doi" => "10.1016/j.medcle.2016.02.033" "estado" => "S300" "fechaPublicacion" => "2015-10-05" "aid" => "3190" "copyright" => "Elsevier España, S.L.U.. All rights reserved" "copyrightAnyo" => "2015" "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Med Clin. 2015;145:281-7" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 12 "formatos" => array:2 [ "HTML" => 11 "PDF" => 1 ] ] "Traduccion" => array:1 [ "es" => array:19 [ "pii" => "S0025775314008793" "issn" => "00257753" "doi" => "10.1016/j.medcli.2014.11.018" "estado" => "S300" "fechaPublicacion" => "2015-10-05" "aid" => "3190" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Med Clin. 2015;145:281-7" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 26 "formatos" => array:2 [ "HTML" => 18 "PDF" => 8 ] ] "es" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original</span>" "titulo" => "Catepsina K como biomarcador de afectación ósea en la enfermedad de Gaucher tipo 1" "tienePdf" => "es" "tieneTextoCompleto" => "es" "tieneResumen" => array:2 [ 0 => "es" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "281" "paginaFinal" => "287" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Cathepsin K as a biomarker of bone involvement in type 1 Gaucher disease" ] ] "contieneResumen" => array:2 [ "es" => true "en" => true ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1083 "Ancho" => 1632 "Tamanyo" => 122784 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Signos óseos presentes en la población de pacientes con enfermedad de Gaucher tipo 1.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Joaquín Bobillo Lobato, Pilar Durán Parejo, Ramiro J. Núñez Vázquez, Luis M. Jiménez Jiménez" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Joaquín" "apellidos" => "Bobillo Lobato" ] 1 => array:2 [ "nombre" => "Pilar" "apellidos" => "Durán Parejo" ] 2 => array:2 [ "nombre" => "Ramiro J." "apellidos" => "Núñez Vázquez" ] 3 => array:2 [ "nombre" => "Luis M." "apellidos" => "Jiménez Jiménez" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S238702061600098X" "doi" => "10.1016/j.medcle.2016.02.033" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S238702061600098X?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775314008793?idApp=UINPBA00004N" "url" => "/00257753/0000014500000007/v1_201509120059/S0025775314008793/v1_201509120059/es/main.assets" ] ] "itemSiguiente" => array:19 [ "pii" => "S2387020616001042" "issn" => "23870206" "doi" => "10.1016/j.medcle.2016.02.039" "estado" => "S300" "fechaPublicacion" => "2015-10-05" "aid" => "3277" "copyright" => "Elsevier España, S.L.U." "documento" => "article" "crossmark" => 1 "subdocumento" => "fla" "cita" => "Med Clin. 2015;145:288-93" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:2 [ "total" => 7 "HTML" => 7 ] "en" => array:13 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Accuracy in the medication history and reconciliation errors in the emergency department" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "es" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "288" "paginaFinal" => "293" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Adecuación de la historia farmacoterapéutica y errores de conciliación en un servicio de urgencias" ] ] "contieneResumen" => array:2 [ "en" => true "es" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1145 "Ancho" => 1627 "Tamanyo" => 97035 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Types of discrepancies detected between the physician's and pharmacist's medical history.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Ana M. de Andrés-Lázaro, Daniel Sevilla-Sánchez, M. del Mar Ortega-Romero, Carles Codina-Jané, Beatriz Calderón-Hernanz, Miquel Sánchez-Sánchez" "autores" => array:6 [ 0 => array:2 [ "nombre" => "Ana M." "apellidos" => "de Andrés-Lázaro" ] 1 => array:2 [ "nombre" => "Daniel" "apellidos" => "Sevilla-Sánchez" ] 2 => array:2 [ "nombre" => "M. del Mar" "apellidos" => "Ortega-Romero" ] 3 => array:2 [ "nombre" => "Carles" "apellidos" => "Codina-Jané" ] 4 => array:2 [ "nombre" => "Beatriz" "apellidos" => "Calderón-Hernanz" ] 5 => array:2 [ "nombre" => "Miquel" "apellidos" => "Sánchez-Sánchez" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0025775315001839" "doi" => "10.1016/j.medcli.2015.02.024" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => false "ES2" => false "LATM" => false ] "gratuito" => false "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0025775315001839?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2387020616001042?idApp=UINPBA00004N" "url" => "/23870206/0000014500000007/v2_201604010141/S2387020616001042/v2_201604010141/en/main.assets" ] "en" => array:20 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>" "titulo" => "Cathepsin K as a biomarker of bone involvement in type 1 Gaucher disease" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "281" "paginaFinal" => "287" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Joaquín Bobillo Lobato, Pilar Durán Parejo, Ramiro J. Núñez Vázquez, Luis M. Jiménez Jiménez" "autores" => array:4 [ 0 => array:3 [ "nombre" => "Joaquín" "apellidos" => "Bobillo Lobato" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Pilar" "apellidos" => "Durán Parejo" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 2 => array:3 [ "nombre" => "Ramiro J." "apellidos" => "Núñez Vázquez" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 3 => array:4 [ "nombre" => "Luis M." "apellidos" => "Jiménez Jiménez" "email" => array:1 [ 0 => "lmjimenezj@telefonica.net" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Servicio de Bioquímica Clínica, Hospital Universitario Virgen del Rocío, Sevilla, Spain" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Servicio de Hematología, Hospital Universitario Virgen del Rocío, Sevilla, Spain" "etiqueta" => "b" "identificador" => "aff0010" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Catepsina K como biomarcador de afectación ósea en la enfermedad de Gaucher tipo 1" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1646 "Ancho" => 3368 "Tamanyo" => 291312 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">ROC curves in type 1 GD patients with and without bone involvement.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Gaucher disease (GD) is an inherited autosomal recessive disorder, the most common lysosomal storage disease, with an overall prevalence of 1/50,000 individuals.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">1</span></a> It is caused by deficiency of the β-glucocerebrosidase liposomal enzyme activity (EC 3.2.1.45), which catalyzes the degradation of glucosylceramide to ceramide and glucose.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">2</span></a> The deposit of unmetabolized glucosylceramide in macrophages (so-called Gaucher cells), causes modifications in various organs, mainly liver, spleen, lymph nodes and bone marrow.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">3</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The disease has 3 forms of presentation. Type 1 Gaucher disease is the most common. According to the latest data from the International Gaucher Registry (<a id="intr0010" class="elsevierStyleInterRef" href="http://www.gaucherregistry.com/">www.gaucherregistry.com</a>) over 90% of patients are included in this type, with a similar sex ratio and age at diagnosis ranging from 4 to 30, with an average age around 19 years. There is a wide variability in both age of onset and development, severity of symptoms and the number of organs involved. Most patients have fatigue, splenomegaly, anemia, thrombocytopenia, hepatomegaly, and skeletal disorders. This disease does not show changes in the central nervous system.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">4</span></a> This is why it is called non-neuronopathic form as opposed to type 2 GD (acute neuronopathic GD) and type 3 GD (chronic neuronopathic GD), less prevalent forms and with a higher morbidity and mortality.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Although the underlying disorder of type 1 GD is primarily hematologic, bone is the second structure most frequently involved. Over 80% patients have bone disorders (infiltrations, atypical pain, aseptic osteomyelitis, avascular necrosis, inadequate remodeling with bone deformities, pathologic fractures, etc.) responsible for the high morbidity.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">6</span></a> Bone disease in type 1 GD arises directly or indirectly from infiltration of Gaucher cells in the bone marrow, fact reported in almost every patient by biopsy or MRI, performed mainly in lumbar vertebrae and/or femur.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">7</span></a> The variability observed in bone metabolism disorders in GD patients suggests that there might be individual factors playing an important role in these disorders.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">5</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Gaucher cells, which are activated macrophages, secrete various factors directly responsible for local tissue damage.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">8</span></a> Additionally, by selection and activation of proinflammatory macrophages and possibly other cells, multiple cytokines that alter bone tissue homeostasis are secreted from the bone marrow.<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">9–11</span></a> The infiltration of the bone marrow is heterogeneous and its effects on the bone structure involves cortical and trabecular areas, bone vascularization, and the bone marrow's composition and organization.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">12</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Cathepsin K (CATK) is a cysteine protease<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">13</span></a> expressed abundantly and selectively in the lysosome of osteoclasts, in the rough edge of mature osteoclasts and bone resorption area on bone surface.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">14</span></a> It works with either acid or neutral pH and has the ability to degrade most matrix proteins.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">15</span></a> Since this enzyme plays a significant role in the remodeling process, it has been suggested that the determination of serum CATK might provide information complementary to other biomarkers. In a study by Moran et al.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">16</span></a> it has been shown that, in spleen extracts of GD patients, regulation of the gene encoding CATK is activated, causing increasing expression levels.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Several studies have been conducted determining biomarkers of bone remodeling in GD patients with no conclusive results.<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">17–19</span></a> The purpose of this study has been to analyze various markers of bone metabolism, in both synthesis (<span class="elsevierStyleItalic">bone alkaline phosphatase</span> [B-ALP] and <span class="elsevierStyleItalic">amino-terminal propeptide of procollagen type 1</span> [P1NP]) and degradation(<span class="elsevierStyleItalic">β-Cross Laps</span>, <span class="elsevierStyleItalic">carboxy-terminal telopeptide of collagen type 1</span> [CTx] and CATK), and compare their levels with different bone manifestations existing in a group of 20 patients with type 1 GD. The novelty of this paper is the CATK determination, not included in previous studies.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Material and methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Sampling and description of the study subjects</span><p id="par0035" class="elsevierStylePara elsevierViewall">The study lasted 15 months and included a total of 40 patients from Andalusia and Extremadura. On the one hand, a control group (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>20) consisting of healthy subjects aged from 12 to 51 (9 women and 11 men). On the other hand, a group of patients with type 1 GD (n<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>20) consisting of 9 patients with bone involvement and 11 with no bone involvement, with equal sex ratio and age ranging from 7 to 56.</p><p id="par0040" class="elsevierStylePara elsevierViewall">All patients with type 1 GD received enzyme replacement therapy (Cerezyme<span class="elsevierStyleSup">®</span>) established for at least a year, and samples were taken after informed consent, during clinical follow-up visits, extracting 10<span class="elsevierStyleHsp" style=""></span>mL from peripheral blood to obtain serum and plasma (EDTA as anticoagulant). After 3500<span class="elsevierStyleHsp" style=""></span>rpm centrifugation during 5<span class="elsevierStyleHsp" style=""></span>min at 4<span class="elsevierStyleHsp" style=""></span>°C, they were stored at 80<span class="elsevierStyleHsp" style=""></span>°C, until analysis completion.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Previous diagnosis study of patients was performed by quantification of β-glucocerebrosidase enzyme activity in leukocytes isolated from peripheral blood, using 4-methylumbelliferyl-beta-<span class="elsevierStyleSmallCaps">d</span>-glucopyranoside as substrate.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">20</span></a> The plasma chitotriosidase activity, indicative of metabolic control, was analyzed using the method described by Hollack et al.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">21</span></a> using 4-methylumbelliferyl-beta-<span class="elsevierStyleSmallCaps">d</span>-triacetyl chitotriosidase as substrate. The molecular study of the GBA gene mutations, which completes the study of patients, was performed by finding the most frequent mutations N370S, L444P and 84GG by real-time PCR and/or subsequent sequencing of the gene (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">22</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall">The group of bone signs included in the study were: Gaucher cell infiltration in spinal cord, femur infiltration and further signs (disk disease, bone deformities, Erlenmeyer flask deformity of the tibia) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Osteonecrosis (including avascular necrosis and bone infarction) was included despite not being a specific sign of disease activity, since, lacking other evidence, its existence may be due to a bone disease.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Study of bone biomarkers</span><p id="par0055" class="elsevierStylePara elsevierViewall">P1NP and CTx determinations were analyzed by electrochemiluminescence (Total P1NP Rfa. 031141071, and β-CrossLaps/serum Rfa. 11972308 respectively, Roche Diagnostics GmbH) in a Cobas e602 autoanalyzer (Roche Diagnostics). B-ALP and CATK were analyzed by enzymoimmunoassay (MicroVue™ BAP EIA, Rfa. 8012 Quidel Corporation in Triturus autoanalyzer, Grifols-Quest, Inc. and Cathepsin K Rfa. BI-20403 Biomedica Groupe GmbH semiautomatic, with final quantification on Tecan Rainbow microplate reader).</p><p id="par0060" class="elsevierStylePara elsevierViewall">Quantification of each of these markers was performed individually, also calculating the ratio between the markers of bone resorption and formation.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Analysis of results</span><p id="par0065" class="elsevierStylePara elsevierViewall">Statistical analysis of the results was performed using the IBM1 SPSS1 Statistics 20.0.0 statistical software, with <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05 as statistical significance limit. With this software, we proceeded to conduct studies comparing distribution and means, as well as box plot charts and ROC curves.</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><p id="par0070" class="elsevierStylePara elsevierViewall">The results obtained in both groups (type 1 GD patients vs control group) are expressed in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>, respectively.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">Before comparing both groups, Levene's test was performed for homogeneity of variances in order to use the relevant methodologies in comparison studies, considering dispersions around <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span> <<span class="elsevierStyleHsp" style=""></span>0.05. The comparative study obtained significant statistical differences for CATK values and ratios, as well as for CTx/P1NP ratio between patients and controls (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><p id="par0080" class="elsevierStylePara elsevierViewall">It is noteworthy the increased CATK levels in patients with type 1 GD about 3.29 times compared to the average obtained in the healthy control group with statistical significance of <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.019. Furthermore, the ratios where CATK appears versus the biomarkers of bone synthesis, CATK/P1NP and CATK/B-ALP, are also increased by 2.78 and 4.31 times, with <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.01 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.026 statistical significances, respectively.</p><p id="par0085" class="elsevierStylePara elsevierViewall">Considering only the group of type 1 Gaucher patients, we found that 45% of them had at least one bone sign. The main signs were infiltration of Gaucher cells in femur (all patients with bone involvement had this sign) and in lumbar spine (89%) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><p id="par0090" class="elsevierStylePara elsevierViewall">The detailed analysis of this group, with or without bone signs, shows no statistically significant differences in the biomarkers analyzed except for CATK, with mean level 3.01 times higher in patients with bone damage (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.04), and the CATK/P1NP ratio increased 2.86 times, with <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.04 statistical significance (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">The patient population representation, using box plot, facing each biomarker with the presence or absence of bone signs, illustrates the degree of separation and little overlap between the two populations regarding CATK levels, both independently as their corresponding ratios (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0100" class="elsevierStylePara elsevierViewall">The study of ROC curves shows the different capacity of each biomarker to reveal bone involvement. The AUC for CATK is 0.93 and 0.96 and 0.84 for CATK/P1NP and CATK/B-ALP ratios, respectively (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Discussion</span><p id="par0105" class="elsevierStylePara elsevierViewall">Bone involvement is a significant complication in the management of type 1 GD patients. It is studied by imaging; MRI and bone densitometry studies are particularly useful. However, they have major disadvantages such as high cost, waiting lists and some limitations for certain patients (e.g. implants with metal components). Thus, the development of biochemical markers that allow assess bone involvement may be interesting for the understanding and prediction of metabolic changes in bone tissue.</p><p id="par0110" class="elsevierStylePara elsevierViewall">It should be noted that, traditionally, GD has been seen as a chronic inflammatory disorder in which activated macrophages produce inflammatory cytokines that promote bone resorption. This hypothesis has no objective data to confirm it.</p><p id="par0115" class="elsevierStylePara elsevierViewall">Therefore, previous studies in GD patients, either treated (Ciana et al.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">17</span></a>, Mikosch et al.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">23</span></a>) or untreated (Ciana et al.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">18</span></a>, Drugan et al.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">19</span></a>) failed to find a clear relationship between biomarkers of bone remodeling or with chitotriosidase levels (main biomarker for monitoring the disease) or by measuring bone mineral density in patients.</p><p id="par0120" class="elsevierStylePara elsevierViewall">It has been suggested that, for various diseases with involvement of bone tissue, determining CATK might provide additional information on other remodeling biomarkers, also reflecting the number of active osteoclasts and might be interesting as a pharmacological target.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">24</span></a></p><p id="par0125" class="elsevierStylePara elsevierViewall">In our study, in the type 1 GD group patients, the only significant finding was the increased P1NP values in 2 patients aged 7 and 12 years, possibly explained by the processes of bone formation at that age.</p><p id="par0130" class="elsevierStylePara elsevierViewall">Despite the efforts to form homogeneous study groups, and with the limitations of the disease for the selection of patients with type 1 GD, the group of subjects with the disease showed a slightly higher dispersion regarding age compared to the control group. This finding might explain the differences found in the CTx/P1NP ratio between controls and patients, being heavily influenced by age.</p><p id="par0135" class="elsevierStylePara elsevierViewall">Moreover, statistically significant differences between the CATK values and ratios where marker is involved (CATK/P1NP and CATK/B-ALP) are much more significant (3.29 times and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.019; 2.78 times and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.01; 4.31 times and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.026 respectively), which shows evidence of a stronger relationship between bone marker and GD occurrence.</p><p id="par0140" class="elsevierStylePara elsevierViewall">This relationship does not appear to be strong enough, or be pathophysiologically associated with GD, if the specific bone involvement present in these patients is not taken into account. Therefore, the second part of the study was focused exclusively on the group of patients with the disease considering the presence or not of bone signs.</p><p id="par0145" class="elsevierStylePara elsevierViewall">Consistent with previous studies, no statistically significant differences appeared between the various biomarkers analyzed and the presence of bone signs except for the CATK and CATK/P1NP ratio. For the CATK/B-ALP ratio, the lack of correlation might be explained by the very low specificity of B-ALP.</p><p id="par0150" class="elsevierStylePara elsevierViewall">An overlap between the maximum and minimum values for CATK, CATK/P1NP and CATK/B-ALP can also be seen in the box plot chart. However, this same chart allows observe how in the highest and lowest non atypical levels overlap is minimal (CATK/P1NP case) or how it disappears (for CATK and CATK/B-ALP).</p><p id="par0155" class="elsevierStylePara elsevierViewall">Finally, the study of ROC curves (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>) demonstrates the ability of the biomarker to differentiate CATK patients with or without bone involvement, either alone or combined with P1NP and B-ALP formation markers, mainly the ratio including P1NP, possibly due to its higher specificity and sensitivity. Furthermore, analysis of the curve coordinates would allow set potential cutoffs for both ratios, with the combination of sensitivity and specificity values most appropriate. We selected CATK/P1NP<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.3 and CATK/B-ALP<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.545 both with a 88.9% sensitivity and a 90.9% specificity.</p><p id="par0160" class="elsevierStylePara elsevierViewall">The limitation in our study is the lack of information on bone mineral density by densitometry in type 1 GD patients, due to the high cost of the test and for not being available in all the clinical services visited by the patients. Therefore, description of bone signs is reported only in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>.</p><p id="par0165" class="elsevierStylePara elsevierViewall">Thus we can conclude that, although imaging studies are the gold standard for monitoring bone disease in type 1 GD patients, in view of the results, serum CATK should be used as an indicator of the osteoclast/osteoblast imbalance in these patients. In addition, this parameter is useful in monitoring the treatment of bone disease, one of the main factors of disease morbidity.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Conflict of interests</span><p id="par0170" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres624723" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec638077" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres624722" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Fundamento y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec638076" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Material and methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Sampling and description of the study subjects" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Study of bone biomarkers" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Analysis of results" ] ] ] 6 => array:2 [ "identificador" => "sec0030" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0035" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflict of interests" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-08-27" "fechaAceptado" => "2014-11-20" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec638077" "palabras" => array:5 [ 0 => "Gaucher disease" 1 => "Bone remodeling" 2 => "Bone damage" 3 => "Biomarkers" 4 => "Cathepsin K" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec638076" "palabras" => array:5 [ 0 => "Enfermedad de Gaucher" 1 => "Remodelado óseo" 2 => "Daño óseo" 3 => "Biomarcador" 4 => "Catepsina K" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background and objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Gaucher disease is an inherited disorder caused by deficit of acid β-glucocerebrosidase, responsible for the degradation of glucosylceramide to ceramide and glucose. Although the disorder is primarily hematologic, bone is the second most commonly affected structure. Cathepsin K (CATK) is an enzyme involved in bone remodeling process. It has been proposed that determination of its serum concentrations may provide additional information to other biomarkers.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Patients and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The study included 20 control subjects and 20 Gaucher type 1 patients from Andalusia and Extremadura regions. We analyzed the biomarkers of bone remodeling: the bone alkaline phosphatase (B-ALP), the N-terminal propeptide of type 1 procollagen (P1NP), the β carboxyterminal telopeptide of type 1 collagen (CTx) and the CATK through electrochemiluminescence and immunoassay techniques.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">There is an increase in levels of CATK, CATK/P1NP and CATK/B-ALP ratios in type 1 Gaucher patients compared to the control group. Considering the existence of skeletal manifestations in the patient group, the CATK and CATK/P1NP ratio showed higher levels in patients with bone damage compared to those without it.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Although imaging studies are the <span class="elsevierStyleItalic">gold standard</span> for monitoring bone disease in type 1 Gaucher patients, the utility of CATK should be considered as a possible indicator of bone damage in these patients. Furthermore, this parameter can be used in the monitoring of the treatment of bone pathology.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Background and objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Patients and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Fundamento y objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">La enfermedad de Gaucher es un trastorno hereditario, que se origina como consecuencia del déficit de la actividad β-glucocerebrosidasa ácida, responsable de la degradación de glucosilceramida hasta ceramida y glucosa. Aunque el trastorno de base es fundamentalmente hematológico, el hueso es la segunda estructura más frecuentemente afectada. La catepsina K (CATK) es una enzima implicada en el proceso de remodelado óseo, habiéndose propuesto que la determinación de sus concentraciones séricas podría aportar información complementaria a la de otros biomarcadores.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Pacientes y métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Se realizó un estudio en 20 controles sanos y 20 pacientes con enfermedad de Gaucher tipo 1, de las comunidades autónomas de Andalucía y Extremadura. Se determinaron como biomarcadores de remodelado óseo la <span class="elsevierStyleItalic">bone alkaline phosphatase</span> (B-ALP, «fosfatasa alcalina ósea»), el <span class="elsevierStyleItalic">amino-terminal propeptide of procollagen type 1</span> (P1NP, «propéptido aminoterminal del procolágeno 1»), la <span class="elsevierStyleItalic">β-Cross Laps</span>, <span class="elsevierStyleItalic">carboxy-terminal telopeptide of collagen type 1</span> (CTx, «fracción β del colágeno tipo 1») y CATK por técnicas de electroquimioluminiscencia y enzimoinmunoanálisis.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Existe un incremento en los niveles de CATK y las ratios CATK/P1NP y CATK/B-ALP en los pacientes con Gaucher tipo 1 respecto a la media obtenida en el grupo control. Por otro lado, considerando la existencia o no de manifestaciones óseas en el grupo de pacientes, la CATK y la ratio CATK/P1NP muestran niveles medios superiores en aquellos pacientes con daño óseo respecto a los que no lo presentan.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Aunque los estudios radiológicos constituyen el <span class="elsevierStyleItalic">gold-standard</span> para el seguimiento de enfermedad ósea en pacientes con enfermedad de Gaucher tipo 1, debe considerarse la utilidad de la CATK como posible indicador de daño óseo en estos pacientes. Asimismo, este parámetro puede utilizarse en la monitorización del tratamiento de la enfermedad ósea.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Fundamento y objetivo" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Pacientes y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0020">Please cite this article as: Bobillo Lobato J, Durán Parejo P, Núñez Vázquez RJ, Jiménez Jiménez LM. Catepsina K como biomarcador de afectación ósea en la enfermedad de Gaucher tipo 1. Med Clin (Barc). 2015;145:281–287.</p>" ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1080 "Ancho" => 1630 "Tamanyo" => 86434 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Bone signs in the population of patients with type 1 Gaucher disease.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 3193 "Ancho" => 3296 "Tamanyo" => 301729 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Box plot chart of bone remodeling markers in Type 1 Guacher disease patients. The populations with and without bone signs may be differentiated according to the levels of cathepsin K and the ratios in which the biomarker is involved.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1646 "Ancho" => 3368 "Tamanyo" => 291312 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">ROC curves in type 1 GD patients with and without bone involvement.</p>" ] ] 3 => array:7 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "leyenda" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall"><span class="elsevierStyleSup">a</span>Reference values in healthy subjects.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="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">Age \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">Sex \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">Bone involvement \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">Chitotriosidase activity (4–76<span class="elsevierStyleHsp" style=""></span>nmol/mL/h)ª \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">Mutations \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="char" valign="top">1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" 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">M \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="char" valign="top">2445 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N370S/unknown \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" 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">F \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="char" valign="top">3025 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N370S/L444P \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" 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">F \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="char" valign="top">291 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N370S/D409H \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \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="char" valign="top">772 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N370S/R463C \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \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="char" valign="top">640 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">G195W/N370S \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \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="char" valign="top">1018 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N370S/R463C \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" 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">M \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="char" valign="top">2486 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N370S/L444P \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">8 \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="left" valign="top">F \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="char" valign="top">999 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">G195W/N370S \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \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="char" valign="top">818 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N370S/84GG \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \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="char" valign="top">288 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N370S/84GG \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">11 \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="left" valign="top">F \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="char" valign="top">1145 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N370S/L444P \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">12 \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="left" valign="top">F \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="char" valign="top">988 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">G377S/D409H \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><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">40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \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="char" valign="top">2820 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N370S/L444P \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">14 \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="left" valign="top">F \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="char" valign="top">8476 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">G377S/D409H \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">44 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \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="char" valign="top">689 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N370S/L444P \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \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="char" valign="top">895 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N370S/N370S \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">47 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">F \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="char" valign="top">1850 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N370S/L444P \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \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="char" valign="top">256 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N370S/84GG \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \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="char" valign="top">181 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N370S/84GG \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="char" valign="top">20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">M \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="char" valign="top">857 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N370S/L444P \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1024694.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Population of patients with type 1Gaucher disease.</p>" ] ] 4 => array:7 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "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="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Mean \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Standard deviation \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Minimum \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Maximum \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Percentiles</th><th class="td" title="table-head " align="left" valign="top" scope="col">Statistical significance \t\t\t\t\t\t\n \t\t\t\t</th></tr><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="" 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="" 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="" 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="" 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="" 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="center" 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="center" valign="top" scope="col" style="border-bottom: 2px solid black">95 \t\t\t\t\t\t\n \t\t\t\t</th><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></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">P1NP (15–60<span class="elsevierStyleHsp" style=""></span>ng/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Control \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37.30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">58.60 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.08 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">GD 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45.42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18.16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22.90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">89 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">23.06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">88.46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="9" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">B-ALP (35–130<span class="elsevierStyleHsp" style=""></span>U/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Control \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24.35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12 \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">12.10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">37.75 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.69 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">GD 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22.62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17.70 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">79.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.07 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">78.41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="9" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CTx (200–600<span class="elsevierStyleHsp" style=""></span>pg/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Control \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">373.45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">118.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">198 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">612 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">198 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">607.85 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.85 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">GD 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">364.41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">168.87 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">198.80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">695.40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">198.83 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">694.79 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="9" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CATK (1.5–10<span class="elsevierStyleHsp" style=""></span>pmol/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Control \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.74 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">9.57 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.02<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">GD 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14.10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16.94 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">83 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.92 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">79.96 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="9" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CTx/P1NP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Control \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10.56 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.30 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.88 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18.29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.93 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">18.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.03<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">GD 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.99 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12.32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">4.08 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12.28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="9" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CTx/B-ALP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Control \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16.29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.97 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">27.82 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">27.72 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.13 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">GD 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20.86 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.76 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">46.14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">45.91 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="9" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CATK/P1NP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Control \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.12 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.07 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.04 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.04 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.26 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.01<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">**</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">GD 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.33 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="9" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CATK/B-ALP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Control \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.69 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.68 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.03<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">GD 1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.86 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.08 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.09 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.77 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1024692.png" ] ] ] "notaPie" => array:2 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "*" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">With significance <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05.</p>" ] 1 => array:3 [ "identificador" => "tblfn0010" "etiqueta" => "**" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">With significance <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.01.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Comparison between the control group and the population of type 1 Gaucher patients.</p>" ] ] 5 => array:7 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "tabla" => array:2 [ "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="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="" valign="top" scope="col"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Mean \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Standard deviation \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Minimum \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col">Maximum \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Percentiles</th><th class="td" title="table-head " align="left" valign="top" scope="col">Statistical significance \t\t\t\t\t\t\n \t\t\t\t</th></tr><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="" 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="" 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="" 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="" 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="" 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="center" 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="center" valign="top" scope="col" style="border-bottom: 2px solid black">95 \t\t\t\t\t\t\n \t\t\t\t</th><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></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">P1NP (15–60<span class="elsevierStyleHsp" style=""></span>ng/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No bone involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">48.10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22.67 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22.90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">89 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22.90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">89 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.48 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Bone involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">42.16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10.89 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26.95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">54.80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">26.95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">54.80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="9" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">B-ALP (35–130<span class="elsevierStyleHsp" style=""></span>U/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No bone involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22.92 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">19.01 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">79.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">79.05 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.94 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Bone involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22.24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">17.11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">66.20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">66.20 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="9" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CTx (200–600<span class="elsevierStyleHsp" style=""></span>pg/mL) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No bone involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">372.14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">192.41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">198.80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">695.40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">198.80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">695.40 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.82 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Bone involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">354.95 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">145.84 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">199.35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">637.65 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">199.35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">637.65 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="9" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CATK (1.5–10<span class="elsevierStyleHsp" style=""></span>pmol/L) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No bone involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.39 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16.90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16.90 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.04<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Bone involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22.31 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">22.99 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">83 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.35 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">83 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="9" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CTx/P1NP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No bone involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">7.99 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">3.98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.61 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Bone involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">8.46 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.88 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12.32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">6.32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12.32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="9" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CTx/B-ALP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No bone involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">21.37 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12.36 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41.45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">2.54 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">41.45 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.84 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Bone involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">20.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.68 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">46.14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">46.14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="9" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CATK/P1NP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No bone involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.09 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.06 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.32 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.04<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">*</span></a> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Bone involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.52 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.27 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="9" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">CATK/B-ALP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No bone involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.42 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.23 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.08 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.08 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.03 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.08 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Bone involvement \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.41 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.77 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.24 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">5.98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1024693.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0015" "etiqueta" => "*" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">With significance <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Comparative study of patients with type 1 Gaucher disease with and without bone involvement.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:24 [ 0 => array:3 [ "identificador" => "bib0125" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Phenotype, diagnosis and treatment of Gaucher's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "G.A. Grabowski" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S0140-6736(08)61522-6" "Revista" => array:6 [ "tituloSerie" => "Lancet" "fecha" => "2008" "volumen" => "372" "paginaInicial" => "1263" "paginaFinal" => "1271" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19094956" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0130" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Metabolism of glucocerebrosidases. II. Evidence of an enzymatic deficiency in Gaucher's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "R.O. Brady" 1 => "J.N. Kanfer" 2 => "D. Shapiro" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Biochem Biophys Res Commun" "fecha" => "1965" "volumen" => "18" "paginaInicial" => "211" "paginaFinal" => "215" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0135" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Gaucher disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "E. Beutler" 1 => "G. Grabowski" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:7 [ "edicion" => "8th ed." "fecha" => "2001" "paginaInicial" => "3635" "paginaFinal" => "3668" "editores" => "C.R.ScriverW.S.SlyE.D.Valle" "editorial" => "McGraw-Hill" "editorialLocalizacion" => "New York" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0140" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Non neuronopathic Gaucher disease reconsidered. Prevalence of neurological manifestations in Dutch cohort of type I Gaucher disease patients and a systematic review of the literature" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "M. Biegstraaten" 1 => "I.N. van Schaik" 2 => "J.M. Aerts" 3 => "C.E. Hollack" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "J Inherit Metab Dis" "fecha" => "2008" "volumen" => "1" "paginaInicial" => "337" "paginaFinal" => "349" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0145" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Markers of bone turnover in Gaucher disease: modeling the evolution of bone disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. Van Dussen" 1 => "P. Lips" 2 => "V.E. Everts" 3 => "N. Bravenboer" 4 => "I.D.C. Jansen" 5 => "J.E.M. Groener" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1210/jc.2011-0162" "Revista" => array:6 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "2011" "volumen" => "96" "paginaInicial" => "2194" "paginaFinal" => "2205" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/21543432" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0150" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The bone in Gaucher disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "N.J. Weinreb" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Eur Musculoskelet Rev" "fecha" => "2007" "volumen" => "1" "paginaInicial" => "33" "paginaFinal" => "36" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0155" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Quantification of bone involvement in Gaucher disease: MR imaging bone marrow burden score as an alternative to Dixon quantitative chemical MR imaging-initial experience" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. Maas" 1 => "C. van Kuijk" 2 => "J. Stoker" 3 => "C.E. Hollak" 4 => "E.M. Akkerman" 5 => "J.F. Aerts" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1148/radiol.2292020296" "Revista" => array:6 [ "tituloSerie" => "Radiology" "fecha" => "2003" "volumen" => "229" "paginaInicial" => "554" "paginaFinal" => "561" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14526090" "web" => "Medline" ] ] ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0160" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Gaucher cells demonstrate a distinct macrophage phenotype and resemble alternatively activated macrophages" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L.A. Boven" 1 => "M. van Meurs" 2 => "R.G. Boot" 3 => "A. Mehta" 4 => "L. Boon" 5 => "J.M. Aerts" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Am J Clin Pathol" "fecha" => "2004" "volumen" => "122" "paginaInicial" => "356" "paginaFinal" => "369" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0165" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Proinflammatory cytokines and the pathogenesis of Gaucher's disease: increased release of interleukin-6 and interleukin-1" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "M.J. Allen" 1 => "B.J. Myer" 2 => "A.M. Khokher" 3 => "N. Rushton" 4 => "T.M. Cox" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Quart J Med" "fecha" => "1997" "volumen" => "90" "paginaInicial" => "19" "paginaFinal" => "25" ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0170" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "TNF-alpha levels and TNF-alpha gene polymorphism in type 1 Gaucher disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "G. Altarescu" 1 => "A. Zimran" 2 => "H. Michelakakis" 3 => "D. Elstein" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cyto.2005.03.006" "Revista" => array:6 [ "tituloSerie" => "Cytokine" "fecha" => "2005" "volumen" => "31" "paginaInicial" => "149" "paginaFinal" => "152" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15919211" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0175" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Increased plasma macrophage inflammatory protein (MIP)-1alpha and MIP-1beta levels in type 1 Gaucher disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M.J. Van Breemen" 1 => "M. de Fost" 2 => "J.S. Voerman" 3 => "J.D. Laman" 4 => "R.G. Boot" 5 => "M. Maas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.bbadis.2007.04.002" "Revista" => array:6 [ "tituloSerie" => "Biochim Biophys Acta" "fecha" => "2007" "volumen" => "1772" "paginaInicial" => "788" "paginaFinal" => "796" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/17499484" "web" => "Medline" ] ] ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0180" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Skeletal aspect of Gaucher disease: a review" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "R.J. Wenstrup" 1 => "M. Roca-Espiau" 2 => "N.J. Weinreb" 3 => "B. Bembi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1259/bjr.75.suppl_1.750002" "Revista" => array:7 [ "tituloSerie" => "Br J Radiol" "fecha" => "2002" "volumen" => "75" "numero" => "1 (Suppl.)" "paginaInicial" => "A2" "paginaFinal" => "A12" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12036828" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0185" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Human cathepsin K cleaves native type I and II collagens at the N-terminal end of the triple helix" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "W. Kafienah" 1 => "D. Bromme" 2 => "D.J. Buttle" 3 => "L.J. Croucher" 4 => "A.P. Hollander" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Biochem J" "fecha" => "1998" "volumen" => "331" "paginaInicial" => "727" "paginaFinal" => "732" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9560298" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0190" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The role of cathepsin K in normal bone resorption" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "B.R. Troen" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Drug News Perspect" "fecha" => "2004" "volumen" => "17" "paginaInicial" => "19" "paginaFinal" => "28" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/14993931" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0195" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The collagenolytic activity of cathepsin K is unique among mammalian proteinases" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Garnero" 1 => "O. Borel" 2 => "I. Byrjalsen" 3 => "M. Ferreras" 4 => "F.H. Drake" 5 => "M.S. McQueney" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Biol Chem" "fecha" => "1998" "volumen" => "273" "paginaInicial" => "32347" "paginaFinal" => "32352" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/9822715" "web" => "Medline" ] ] ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0200" "etiqueta" => "16" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pathologic gene expression in Gaucher disease: up-regulation of cysteine proteinases including osteoclastic cathepsin K" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "M.T. Moran" 1 => "J.P. Schofield" 2 => "A.R. Hayman" 3 => "G.P. Shi" 4 => "E. Young" 5 => "T.M. Cox" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Blood" "fecha" => "2000" "volumen" => "96" "paginaInicial" => "1969" "paginaFinal" => "1978" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/10961902" "web" => "Medline" ] ] ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0205" "etiqueta" => "17" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Gaucher disease and bone: laboratory and skeletal mineral density variations during a long period of enzyme replacement therapy" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Ciana" 1 => "R. Addobbati" 2 => "G. Tamaro" 3 => "A. Leopaldi" 4 => "M. Nevyjel" 5 => "L. Ronfani" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s10545-005-0032-y" "Revista" => array:6 [ "tituloSerie" => "J Inherit Metab Dis" "fecha" => "2005" "volumen" => "28" "paginaInicial" => "723" "paginaFinal" => "732" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16151904" "web" => "Medline" ] ] ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0210" "etiqueta" => "18" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Bone marker alterations in patients with type 1 Gaucher disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. Ciana" 1 => "C. Martini" 2 => "A. Leopaldi" 3 => "G. Tamaro" 4 => "F. Katouzian" 5 => "L. Ronfani" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00223-001-2072-0" "Revista" => array:6 [ "tituloSerie" => "Calcif Tissue Int" "fecha" => "2003" "volumen" => "72" "paginaInicial" => "185" "paginaFinal" => "189" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12522660" "web" => "Medline" ] ] ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0215" "etiqueta" => "19" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Biochemical markers of bone turnover as tools in the evaluation of skeletal involvement in patients with type 1 Gaucher disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "C. Drugan" 1 => "G. Jebeleanu" 2 => "P. Grigorescu-Sido" 3 => "C. Caillaud" 4 => "A.M. Cracium" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1006/bcmd.2001.0479" "Revista" => array:6 [ "tituloSerie" => "Blood Cells Mol Dis" "fecha" => "2002" "volumen" => "28" "paginaInicial" => "13" "paginaFinal" => "20" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11814307" "web" => "Medline" ] ] ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0220" "etiqueta" => "20" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Biochemical study on beta-glucosidase in individuals with Gaucher's disease and normal subjects" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "K. Michelin" 1 => "A. Wajner" 2 => "L.S. Goulart" 3 => "A.A. Fachel" 4 => "M.L. Pereira" 5 => "A.S. de Mello" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.cccn.2004.01.010" "Revista" => array:6 [ "tituloSerie" => "Clin Chim Acta" "fecha" => "2004" "volumen" => "343" "paginaInicial" => "145" "paginaFinal" => "153" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15115687" "web" => "Medline" ] ] ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0225" "etiqueta" => "21" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Marked elevation of plasma chitotriosidase activity. A novel hallmark of Gaucher disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "C.E. Hollack" 1 => "S. van Weely" 2 => "M.H. van Oers" 3 => "J.M. Aerts" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1172/JCI117084" "Revista" => array:6 [ "tituloSerie" => "J Clin Invest" "fecha" => "1994" "volumen" => "93" "paginaInicial" => "1288" "paginaFinal" => "1292" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8132768" "web" => "Medline" ] ] ] ] ] ] ] ] 21 => array:3 [ "identificador" => "bib0230" "etiqueta" => "22" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Mapping the genetic and clinical characteristics of Gaucher disease in the Iberian Peninsula" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Giraldo" 1 => "P. Alfonso" 2 => "P. Irún" 3 => "L. Gort" 4 => "A. Chabás" 5 => "L. Vilageliu" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/1750-1172-7-17" "Revista" => array:5 [ "tituloSerie" => "Orphanet J Rare Dis" "fecha" => "2012" "volumen" => "7" "paginaInicial" => "17" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/22429443" "web" => "Medline" ] ] ] ] ] ] ] ] 22 => array:3 [ "identificador" => "bib0235" "etiqueta" => "23" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Changes of bone metabolism in seven patients with Gaucher disease treated consecutively with imiglucerase and miglustat" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Mikosch" 1 => "M. Reed" 2 => "R. Baker" 3 => "B. Holloway" 4 => "L. Berger" 5 => "A.B. Metha" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s00223-008-9143-4" "Revista" => array:6 [ "tituloSerie" => "Calcif Tissue Int" "fecha" => "2008" "volumen" => "83" "paginaInicial" => "43" "paginaFinal" => "54" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18553043" "web" => "Medline" ] ] ] ] ] ] ] ] 23 => array:3 [ "identificador" => "bib0240" "etiqueta" => "24" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Assessment of osteoclast number and function: application in the development of new and improved treatment modalities for bone diseases" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "K. Henriksen" 1 => "L.B. Tanko" 2 => "P. Qvist" 3 => "P.D. Delmas" 4 => "C. Christiansen" 5 => "M.A. Karsdal" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:5 [ "tituloSerie" => "Osteopor Int" "fecha" => "2007" "volumen" => "18" "paginaInicial" => "681" "paginaFinal" => "685" ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/23870206/0000014500000007/v2_201604010141/S238702061600098X/v2_201604010141/en/main.assets" "Apartado" => array:4 [ "identificador" => "43310" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23870206/0000014500000007/v2_201604010141/S238702061600098X/v2_201604010141/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S238702061600098X?idApp=UINPBA00004N" ]
