Original Paper
Osteoprotegerin changes in saliva and serum of patients with knee osteoarthritis
Cambios de osteoprotegerina en saliva y suero de pacientes con osteoartritis de rodilla
M.-R. Mirzaii-Dizgaha, M.-H. Mirzaii-Dizgahb, I. Mirzaii-Dizgahc,
, M. Karamid, B. Foroghe
Corresponding author
a Student Research Committee, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
b Student Research Committee, School of Dentistry, Aja University of Medical Sciences, Tehran, Iran
c Dep. of Physiology, School of Medicine, Aja University of Medical Sciences, Tehran, Iran
d Dep. of Biochemistry, School of Medicine, Aja University of Medical Sciences, Tehran, Iran
e Dep. of Physical Medicine and Rehabilitation, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
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"apellidos" => "Mirzaii-Dizgah" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "M.-H." "apellidos" => "Mirzaii-Dizgah" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] ] ] 2 => array:4 [ "nombre" => "I." "apellidos" => "Mirzaii-Dizgah" "email" => array:1 [ 0 => "emirzaii@alumnus.tums.ac.ir" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 3 => array:3 [ "nombre" => "M." "apellidos" => "Karami" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] 4 => array:3 [ "nombre" => "B." "apellidos" => "Forogh" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Student Research Committee, School of Medicine, Iran University of Medical Sciences, Tehran, Iran" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Student Research Committee, School of Dentistry, Aja University of Medical Sciences, Tehran, Iran" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Dep. of Physiology, School of Medicine, Aja University of Medical Sciences, Tehran, Iran" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Dep. of Biochemistry, School of Medicine, Aja University of Medical Sciences, Tehran, Iran" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Dep. of Physical Medicine and Rehabilitation, School of Medicine, Iran University of Medical Sciences, Tehran, Iran" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Cambios de osteoprotegerina en saliva y suero de pacientes con osteoartritis de rodilla" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1515 "Ancho" => 1458 "Tamanyo" => 89044 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">The receiver operating characteristic curve generated from serum OPG levels assessed in knee OA and healthy controls.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Osteoarthritis (OA) or degenerative joint disease is one of the most common chronic degenerative diseases and is one of the important causes of pain and inability worldwide and is associated with increased treatment costs, decreased productivity, and absence from work.<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">1–3</span></a> The prevalence of knee OA is higher among patients with OA.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">4</span></a> The incidence of OA is increasing because of population aging and overweightness <a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">5</span></a>and it is assessed that 10% of men and 18% of women over 60 years of age have OA.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">6</span></a> Accordingly, OA has a noteworthy negative impact on the quality of life of the old and the unseen budgets are high, so it put on a substantial burden on the health care system.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">6</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Osteoprotegerin (OPG), as a controller of osteoclasts differentiation and function, is a growth factor receptor and depends to the tumor necrosis factor receptor family that contacts to receptor activator of nuclear factor-kB ligand (RANKL) subsequently inhibits connection of RANKL to receptor activator of nuclear factor-kB (RANK) and thus have a protecting effect versus bone demolition.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">7</span></a> Comparable osteoblasts, chondrocytes make OPG and RANKL. It has been shown that changes in RANK, RANKL, and OPG levels are linked to basic abnormalities of the joint cartilage in OA.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">8</span></a> Also, overexpressed of RANKL has been shown in OA.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">9</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">OA is today recognized based on radiographic norms and clinical signs.<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">10</span></a> Magnetic resonance imaging (MRI) is a non-invasive technology that can provide images of structural changes in all joint constructions.<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">11</span></a> However, this technique is a time consuming and costly procedure. Earlier studies have recommended certain biomarkers can be used in the diagnosis or the progression of OA. The bioindicator that has been precisely demarcated for OA can be associated with bone, cartilage, and synovium metabolisms or systemic irritation.<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">12</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">It has been shown that saliva as an indicator of oral and systemic health, can offer dependable evidence about the disease. Non-invasive matter, easier gathering and more cost-effective of saliva equated to serum and synovial fluid (SF) has prompted researchers to study about saliva.<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">13,14</span></a> It has been described that serum levels of OPG increases in patients with OA.<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">15,16</span></a> Therefore, in this study, OPG was evaluated in serum and saliva samples of patients with knee OA to evaluate the potential of this marker in the diagnosis and monitoring of the disease.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">In a cross-sectional study, based on the American College of Rheumatology, radiological and clinical criteria for OA of the knee system,<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">17</span></a> 30 patients with a grade 2 or 3 knee OA based on the Kellgren and Lawrence (KL) classification<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">18</span></a> (19 male/11 female; aged 55.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.4 years) who candidate for stem cell therapy of knee joint in Firoozgar Hospital and had no history of gout, knee surgery, joint trauma, and rheumatic disease and had no treatment might interfere with bone metabolisms, and also 30 sex and age-matched healthy individuals (19 male/11 female; aged 54.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.2 years) were enrolled in this study. The healthy participants had no sign of symptomatic and radiological osteoarthritis as evaluated by the clinical examination of the knees by a skilled orthopedist. All of them were healthy without any disease or treatment that might affect bone or joint metabolism, including hormone replacement therapy in postmenopausal women.</p><p id="par0030" class="elsevierStylePara elsevierViewall">This study was approved by the Review Board of the National Institute for Medical Research Development (IR.NIMAD.REC.1396.206) and informed written consent was obtained from all participants.</p><p id="par0035" class="elsevierStylePara elsevierViewall">The Patients’ symptoms and physical disabilities were evaluated using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index.<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">19</span></a> They are each divided on a 5-point Likert scale (none, mild, moderate, severe, and excessive). The WOMAC score ranged between 0 and 96. Patients filled in the WOMAC Persian language questionaries before cell therapy.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Serum and saliva were accomplished from each participant in the morning. Serum and saliva samples were collected as previously described.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">13</span></a> The specimens were centrifuged at 5000<span class="elsevierStyleItalic">g</span> for 10<span class="elsevierStyleHsp" style=""></span>min; the serum and saliva supernatants were stored at −80<span class="elsevierStyleHsp" style=""></span>°C for later measurement of OPG. OPG was assessed by the sandwich ELISA method based on the manufacturer's protocol (BioAssay Technology Laboratory, Shanghai, China). The sensitivity of the ELISA OPG kit was 23<span class="elsevierStyleHsp" style=""></span>pg/ml (0.023<span class="elsevierStyleHsp" style=""></span>ng/ml).</p><p id="par0045" class="elsevierStylePara elsevierViewall">The data are offered as a mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SEM. Assessment of means amongst groups was performed with an unpaired two-tailed student's <span class="elsevierStyleItalic">t</span>-test. The Spearman correlation test was used to confirm the association between the parameters. Receiver operating characteristic (ROC) analysis was used to detect cut-off point for serum and salivary OPG between OA and healthy groups. Analyses were done using SPSS software version 16.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><p id="par0050" class="elsevierStylePara elsevierViewall">There was no significant difference in sex and age between healthy and OA groups (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05). The mean (±SD) WOMAC score of OA group was 37.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.9. There was no significant difference in BMI (mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SEM, kg/m<span class="elsevierStyleSup">2</span>) between healthy (28.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.5) and knee OA (28.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.7) groups (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.636).</p><p id="par0055" class="elsevierStylePara elsevierViewall">The mean serum OPG concentration was lower in OA than that of the healthy group (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.001) (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). However, stimulated and unstimulated salivary concentrations of OPG were not significantly different between OA and control group (<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.317, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.712; respectively).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">WOMAC score negatively correlates with serum OPG level (<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>−0.501; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.000). However, there was no significant correlation between WOMAC score and stimulated saliva OPG level (<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>−0.097; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.361) and also with OPG unstimulated saliva (<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>−0.102; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.470).</p><p id="par0065" class="elsevierStylePara elsevierViewall">The serum level of OPG was not significantly correlated with unstimulated (<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.186; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.188) and stimulated (<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.134; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.366) saliva OPG levels.</p><p id="par0070" class="elsevierStylePara elsevierViewall">The ROC analysis results revealed that the cut-off value of serum OPG for the diagnosis of OA was 237.5<span class="elsevierStyleHsp" style=""></span>pg/m1 (ROC-area under the curve<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.799). With this cut-off, sensitivity was 82%, and specificity was 79% (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discussion</span><p id="par0075" class="elsevierStylePara elsevierViewall">Today, biomarkers, which are applied to evaluate the activity of disease or to screen treatment effectivity in OA depend on MRI outcomes. Relative invasiveness resulting from blood or SF collection is another cause for a need for new simple, cost-effective and non-invasive biomarkers. Saliva can be collected noninvasively, with easy access and the possibility of repeated sampling. Therefore, the saliva represents an attractive diagnostic fluid for distinguishing biomarkers of various pathological conditions.<a class="elsevierStyleCrossRefs" href="#bib0285"><span class="elsevierStyleSup">20–28</span></a> In OA patients, there was a little study about markers in other biofluids apart from plasma and SF. Also, the possibility of measuring these in saliva brings non-invasive techniques and therefore more compliance from patients. This study aimed to analyze OPG in serum and saliva samples of patients with OA. Our results showed that serum OPG was lower in knee OA and negatively correlated with WOMAC. However, stimulated and unstimulated saliva OPG were not differ between two groups and did not correlate with WOMAC.</p><p id="par0080" class="elsevierStylePara elsevierViewall">OA is a degenerative joint disease categorized by the slow destruction of the cartilage matrix and by bone changes.<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">29</span></a> It has been shown that mice lacking both OPG alleles have the more severe degenerative joint disease and administration of OPG in OA mice protects articular cartilage destruction.<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">30,31</span></a> Also, it has been indicated that OPG-deficient mice exhibit thin articular cartilage layers,<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">31</span></a> show hard destruction of growth plate cartilage and show some degree of cartilage destruction with aging.<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">30,31</span></a> They agree with our results that serum OPG level was lower in patients with OA than in healthy individuals and the serum OPG concentration negatively correlated with WOMAC as an indicator of knee OA severity in this study. However, our result is in contrary to Min's et al.<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">15</span></a>and Pilichou et al.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">16</span></a> reports that showed serum OPG level is higher in OA than healthy individuals. The majority of the participants in the mentioned studies were female (female/male<span class="elsevierStyleHsp" style=""></span>≈<span class="elsevierStyleHsp" style=""></span>4), but most were male (female/male<span class="elsevierStyleHsp" style=""></span>≈<span class="elsevierStyleHsp" style=""></span>0.6) in our study. Perhaps this paradox is related to gender which needs further study to prove it.</p><p id="par0085" class="elsevierStylePara elsevierViewall">OPG is a soluble receptor that binds to RANKL and inhibits binding of RANKL to RANK which presents on the membrane of preosteoclast,<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">32</span></a> consequently inhibits osteoclastogenesis.<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">33</span></a> RANKL mRNA expression has been shown to increase in the cartilage of patients with grade 2 OA.<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">34</span></a> RANKL also increases MMP-13 expression in these patients. Studies have shown that overexpression of MMP-13 plays a key role in the destruction of articular cartilage and morphological changes in bone tissue in OA.<a class="elsevierStyleCrossRef" href="#bib0360"><span class="elsevierStyleSup">35</span></a> The RANKL in the deep cartilage region may be distributed from a thin layer of the calcified cartilage into the bone where it can bind to RANK in osteoclastic precursors in the subchondral bone. Also, it has been indicated that RANKL increases in the serum of patients with knee OA.<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">16</span></a> It seems that OPG production reduces and RANKL production increases in knee OA, so MMP-13 overexpressed in these patients which cause cartilage and bone destruction in joints of these patients. In addition, it has been shown that cortisol is higher in OA and associates with WOMAC and glucocorticoids reduce serum OPG.<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">36,37</span></a> It may explain serum OPG reduction in the OA patients.</p><p id="par0090" class="elsevierStylePara elsevierViewall">WOMAC negatively correlated with serum OPG in this study. The ROC analysis indicated a cut-off value of 237.5<span class="elsevierStyleHsp" style=""></span>pg/m1 for serum in the differential diagnosis of OA and normal individuals. These results suggest that OPG may be related to the pathogenesis of OA and is a potential biomarker for OA.</p><p id="par0095" class="elsevierStylePara elsevierViewall">There were no significant differences in saliva OPG between knee OA and healthy individuals. To our best knowledge, this is the first study about the detection of OPG in the saliva of OA patients. It seems that detection of OPG in the saliva is not a potential biomarker for OA.</p><p id="par0100" class="elsevierStylePara elsevierViewall">There were some limitations for this study. As patients with knee OA in grade 2 and 3 were enrolled, we cannot evaluate the association of OPG with the radiological degree of the knee OA. In addition, for accurate calculation of the cutoff point of serum OPG, the sample size was low.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conclusion</span><p id="par0105" class="elsevierStylePara elsevierViewall">Our results showed that as serum OPG was lower in knee OA and negatively correlated with WOMAC, it seems that detection of OPG in serum but not in saliva may be a probable marker to the diagnosis of knee OA.</p><p id="par0110" class="elsevierStylePara elsevierViewall">Level of evidence II.</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Ethical approval</span><p id="par0115" class="elsevierStylePara elsevierViewall">This research was approved by the Ethics Committee of the National Institute for Medical Research Development (NIMAD) with the approval code IR.NIMAD.REC.1396.206.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Funding/support</span><p id="par0120" class="elsevierStylePara elsevierViewall">The research reported in this publication was supported by Elite Researcher Grant Committee under award number 963466 from the National Institute for Medical Research Development (NIMAD), Deputy of Research and Technology, Ministry of Health and Medical Education of Iran.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflict of interest</span><p id="par0125" class="elsevierStylePara elsevierViewall">The authors declare that there is no conflict of interests.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres2129842" "titulo" => "Abstract" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Key messages" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1808745" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres2129843" "titulo" => "Resumen" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Conclusiones" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Mensajes clave" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1808744" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conclusion" ] 9 => array:2 [ "identificador" => "sec0030" "titulo" => "Ethical approval" ] 10 => array:2 [ "identificador" => "sec0035" "titulo" => "Funding/support" ] 11 => array:2 [ "identificador" => "sec0040" "titulo" => "Conflict of interest" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-11-22" "fechaAceptado" => "2021-02-10" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1808745" "palabras" => array:4 [ 0 => "Knee osteoarthritis" 1 => "Osteoprotegerin" 2 => "Saliva" 3 => "Serum" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The scope of this study was to assess salivary and serum osteoprotegerin (OPG) levels in knee osteoarthritis (OA).</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Serum and saliva OPG levels of 30 knee OA and 30 matched healthy controls in this cross-sectional study was assessed by ELISA. Knee pain was assessed by WOMAC. Data were analyzed by Student's <span class="elsevierStyleItalic">t</span>-test, Spearman correlation test and ROC.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">The mean serum but not saliva OPG level was lower in knee OA than that of the healthy group. WOMAC negatively correlated with serum OPG (<span class="elsevierStyleItalic">r</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>−0.501; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.000). The serum OPG cutoff value was 237.5<span class="elsevierStyleHsp" style=""></span>pg/ml for the diagnosis of knee OA.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">As serum OPG was lower in knee OA and negatively correlated with WOMAC, it seems that detection of OPG in serum but not in saliva may be a probable marker to the diagnosis of knee OA.</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Key messages</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Osteoprotegerin decreases in knee osteoarthritis.</p></span>" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] 4 => array:2 [ "identificador" => "abst0025" "titulo" => "Key messages" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Objetivo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">El alcance de este estudio fue evaluar los niveles de osteoprotegerina (OPG) salival y sérica en la osteoartritis de rodilla (OA).</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Métodos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Los niveles de OPG en suero y saliva de 30<span class="elsevierStyleHsp" style=""></span>OA y 30 controles sanos emparejados en este estudio transversal se evaluaron mediante ELISA. El dolor de rodilla fue evaluado por WOMAC. Los datos se analizaron mediante la prueba t de Student, la prueba de correlación de Spearman y ROC.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Resultados</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El nivel medio de OPG en suero, pero no en saliva fue menor en la artrosis de rodilla que en el grupo sano. WOMAC se correlacionó negativamente con la OPG sérica (r<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>−0,501; p<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0,000). El valor de corte de OPG sérico fue de 237,5<span class="elsevierStyleHsp" style=""></span>pg/m1 para el diagnóstico de OA de rodilla.</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conclusiones</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Como la OPG sérica fue más baja en la artrosis de rodilla y se correlacionó negativamente con WOMAC, parece que la detección de OPG en suero, pero no en la saliva puede ser un marcador probable para el diagnóstico de artrosis de rodilla.</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Mensajes clave</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">La osteoprotegerina disminuye en la osteoartritis de rodilla.</p></span>" "secciones" => array:5 [ 0 => array:2 [ "identificador" => "abst0030" "titulo" => "Objetivo" ] 1 => array:2 [ "identificador" => "abst0035" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0040" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0045" "titulo" => "Conclusiones" ] 4 => array:2 [ "identificador" => "abst0050" "titulo" => "Mensajes clave" ] ] ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1530 "Ancho" => 2460 "Tamanyo" => 241081 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Concentrations of osteoprotegerin in serum, unstimulated, and stimulated saliva of patients who suffer knee OA and control individuals. Data are expressed as mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SE and analyzed by unpaired student's <span class="elsevierStyleItalic">t</span>-test. * indicates <span class="elsevierStyleItalic">P</span>-value<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.05.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1515 "Ancho" => 1458 "Tamanyo" => 89044 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">The receiver operating characteristic curve generated from serum OPG levels assessed in knee OA and healthy controls.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:37 [ 0 => array:3 [ "identificador" => "bib0190" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Health economics in the field of osteoarthritis: an expert's consensus paper from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO)" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "M. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 5 | 0 | 5 |
| 2024 October | 24 | 4 | 28 |
| 2024 September | 47 | 6 | 53 |
| 2024 August | 39 | 3 | 42 |
| 2024 July | 23 | 3 | 26 |
| 2024 June | 16 | 4 | 20 |
| 2024 May | 13 | 3 | 16 |
| 2024 April | 9 | 5 | 14 |
| 2024 March | 29 | 6 | 35 |
| 2024 February | 30 | 4 | 34 |
| 2024 January | 28 | 9 | 37 |
| 2023 December | 14 | 5 | 19 |
| 2023 November | 28 | 9 | 37 |
| 2023 October | 41 | 10 | 51 |
| 2023 September | 18 | 1 | 19 |
| 2023 August | 20 | 2 | 22 |
| 2023 July | 11 | 6 | 17 |
| 2023 June | 26 | 1 | 27 |
| 2023 May | 42 | 3 | 45 |
| 2023 April | 38 | 0 | 38 |
| 2023 March | 29 | 5 | 34 |
| 2023 February | 26 | 2 | 28 |
| 2023 January | 7 | 2 | 9 |
| 2022 December | 12 | 6 | 18 |
| 2022 November | 15 | 3 | 18 |
| 2022 October | 13 | 4 | 17 |
| 2022 September | 13 | 8 | 21 |
| 2022 August | 27 | 9 | 36 |
| 2022 July | 15 | 8 | 23 |
| 2022 June | 10 | 6 | 16 |
| 2022 May | 15 | 9 | 24 |
| 2022 April | 33 | 15 | 48 |
| 2022 March | 29 | 17 | 46 |
| 2022 February | 36 | 18 | 54 |
| 2022 January | 1 | 0 | 1 |
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