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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Psoriatic arthritis &#40;PsA&#41; is a complex inflammatory disease with various clinical features including peripheral and axial joint inflammation&#44; enthesitis&#44; dactylitis&#44; nail disease&#44; and psoriasis&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">1</span></a> Progressive bone destruction and abnormal bone growth can be detected throughout PsA&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Patients with PsA show a variety of bone pathologies&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">3</span></a> Bone loss can take place systemically with a reduction of skeletal bone mineral density &#40;BMD&#41; or locally in the form of bone erosion and osteolysis affecting the peripheral joints&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">4</span></a> New bone formation and syndesmophyte formation may also occur&#46; These different bone pathologies can be detected in the same patient&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Four candidate bone-turnover markers in PsA were identified by a systematic literature review of serum-soluble bone and cartilage-turnover markers in PsA and psoriatic spondyloarthritis &#40;PsSpA&#41;&#58; Dickkopf 1 &#40;DKK-1&#41;&#44; which inhibits Wnt-mediated bone formation&#59; osteoprotegerin &#40;OPG&#41;&#44; which inhibits RANK-mediated bone resorption&#59; and matrix metalloproteinase 3 &#40;MMP-3&#41;&#44; which degrades the extra-cellular matrix of bone and cartilage&#44; causing bone erosion and narrowing of the joint space&#59; and macrophage colony stimulating factor &#40;M-CSF&#41;&#44; which encourages bone resorption&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">6</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The balance between the osteoclast and osteoblast activities mainly depends on the regulation of the Wnt pathway&#44; which is done by inhibitors as DKK-1 and sclerostin&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">The serum level of DKK-1 in PsA patients is controversial&#46; The aim of this study was to investigate the serum level of DKK-1 and its association with disease activity and enthesopathy in PsA patients&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Patients and methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">It&#39;s a case&#8211;control study conducted at a single center&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Setting</span><p id="par0035" class="elsevierStylePara elsevierViewall">Patients were recruited from the outpatient clinic of Rheumatology and Rehabilitation Department&#44; Tanta University Hospitals&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Patients</span><p id="par0040" class="elsevierStylePara elsevierViewall">The study included 50 patients who met CASPAR<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">8</span></a> criteria for PsA&#44; and 50 healthy volunteers matched for age and gender&#46; Patients who have used drugs affecting bone metabolism such as bisphosphonates&#44; glucocorticoids&#44; or vitamin D in the past six months&#44; as well as those who are pregnant or who have cancers such as osteosarcoma&#44; prostate cancer&#44; or multiple myeloma were excluded from the study&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Duration of the study&#58; 15 months &#40;from March 2021 to May 2022&#41;&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Ethics approval and consent to participate</span><p id="par0050" class="elsevierStylePara elsevierViewall">This study has been approved by the institution&#39;s ethics board with permission number 34483&#47;2&#47;21 and is in accordance with the Declaration of Helsinki&#39;s ethical principles as well as the ethical standards of the Tanta Faculty of Medicine&#46; According to the local ethical commission&#44; informed consent was received from each patient&#46; Every patient file included a code number that incorporated the results of all investigations&#44; ensuring the privacy of all patient data&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Clinical assessment</span><p id="par0055" class="elsevierStylePara elsevierViewall">Demographic information and a thorough medication history were recorded&#46; The Spondyloarthritis Research Consortium of Canada &#40;SPARCC&#41; Enthesitis Index<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">9</span></a> was used to assess the enthesitis clinically&#46; This index measures the tenderness at 16 enthesitis sites&#44; including&#58; bilateral greater trochanter&#44; quadriceps tendon insertion into the patella&#44; patellar ligament insertion into the patella and tibial tuberosity&#44; Achilles tendon insertion&#44; plantar fascia insertion&#44; medial&#44; and lateral epicondyles and the supraspinatus insertion&#46; Each site&#39;s tenderness was graded using the following scale&#58; 0 for non-tender and 1 for tender&#46; PSA activity was estimated using the Disease Activity Index for Psoriatic Arthritis &#40;DAPSA&#41; score<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">10</span></a> which is numerical summation of 66 swollen and 68 tender joint counts&#44; pain&#44; patient global assessment &#40;PGA&#41;&#44; and C-reactive protein &#40;CRP&#41; &#40;mg&#47;dL&#41;&#46; Levels of disease activity were divided into four categories&#58; remission &#40;0&#8211;4&#41;&#44; low disease activity &#40;5&#8211;14&#41;&#44; moderate disease activity &#40;15&#8211;28&#41;&#44; and high disease activity &#40;&#62;28&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The Psoriasis Area and Severity Index &#40;PASI&#41; score was used to determine the extent and severity of psoriasis&#59; a representative area of psoriasis is selected for each body region&#46; The severity of the psoriasis&#8217; redness&#44; thickness&#44; and scaling is graded as none &#40;0&#41;&#44; mild &#40;1&#41;&#44; moderate &#40;2&#41;&#44; severe &#40;3&#41;&#44; or extremely severe &#40;4&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">11</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Laboratory assessment</span><p id="par0065" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#8226;</span><p id="par0070" class="elsevierStylePara elsevierViewall">Routine laboratory assessment&#58; erythrocyte sedimentation rate &#40;ESR&#41; by Westergren method and CRP&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#8226;</span><p id="par0075" class="elsevierStylePara elsevierViewall">Venous blood samples &#40;10<span class="elsevierStyleHsp" style=""></span>mL&#41; were taken from all individuals after 10<span class="elsevierStyleHsp" style=""></span>h of overnight fasting into sodium citrate and plain plastic tubes&#46; The latter was allowed to clot and centrifuged at 2000<span class="elsevierStyleHsp" style=""></span>rpm for 10<span class="elsevierStyleHsp" style=""></span>min to separate the serum&#46; The collected sera were stored in aliquots at &#8722;80<span class="elsevierStyleHsp" style=""></span>&#176;C until used&#46; A citrated blood for erythrocyte sedimentation rate &#40;ESR&#41; by Westergren method&#44; one of the aliquots used for measuring CRP &#40;Thermo Fisher Scientific Inc&#46; Konelab&#8482;&#47;T Series CRP Plus 981794&#41; and the other aliquot used for measuring DKK-1 by ELISA &#40;cat no &#35; Dl&#95;DKk1-Hu&#41;&#46;</p></li></ul></p><p id="par0080" class="elsevierStylePara elsevierViewall">DKK-1 was detected in serum by Enzyme Linked Immunosorbent Assay &#40;ELISA&#41;&#58; Reagent and sample preparation&#44; and assay procedure were performed following the instructions of manufacturer&#46; The ELISA kit used sandwich ELISA as method&#46; The microelisa strip plate provided in this kit had been precoated with an antibody specific to DKK-1&#46; Standard or samples were added to appropriate microelisa stripplate wells and combined to specific antibody&#46; The horseradish peroxidase &#40;HRP&#41;-conjugated antibody specific for DKK-1 was added to each microelisa strip plate well and incubated&#46; The free component was washed away&#46; The tetramethyl benzidine substrate solution was added to each well&#46; Only those wells that contain DKK-1&#38; HRP conjugated DKK-1 appeared blue in color then turned yellow after the addition of stop solution&#46; The optical density was measured spectrophotometrically at wavelength of 450<span class="elsevierStyleHsp" style=""></span>mm&#46; The optical density value was proportional to the concentration of DKK-1&#46; The concentration of DKK-1 was calculated by comparing the optical density of the sample to the standard curve&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Ultrasonographic assessment</span><p id="par0085" class="elsevierStylePara elsevierViewall">According to the Madrid Sonographic Enthesitis Index &#40;MASEI&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">12</span></a> bilateral ultrasonographic evaluations of the brachial triceps tendons&#44; proximal plantar fascia&#44; distal Achilles tendon&#44; proximal and distal patellar ligaments&#44; and distal quadriceps&#46; Musculoskeletal ultrasonographic &#40;MSUS&#41; examination was conducted using &#40;SAMSUNG MEDISON&#44; UGEO&#41; with linear array transducers &#40;9&#8211;13<span class="elsevierStyleHsp" style=""></span>MHz&#41;&#46; The ultrasound examination assessed the following fundamental enthesis lesions at each location&#58; structure&#44; thickness&#44; calcifications&#44; erosions&#44; bursae&#44; and power doppler signal in bursa or enthesis full tendon&#46; The total MASEI score was further divided into the following&#58; chronic damage&#44; including enthesophytes&#44; calcifications&#44; and erosions &#40;MASEI damage&#41;&#59; and inflammatory changes including entheseal structural changes&#59; thickening&#59; bursitis and vascularization &#40;MASEI-inflammatory&#41;&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Assessment of patients was performed by a rheumatologist experienced in MSUS imaging on the same day of the clinical and laboratory evaluation&#46; Inter-observer reliability&#58; Two physicians who were blind to the clinical and laboratory results independently read every image&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Statistical analysis</span><p id="par0095" class="elsevierStylePara elsevierViewall">Data were statistically analyzed using SPSS version 20&#46; Qualitative data were described using numbers and percentages&#46; The Kolmogorov&#8211;Smirnov &#38; Shapiro&#8211;Wilk test was used to verify the normality of distribution&#46; Quantitative data were described using mean&#44; standard deviation&#44; median and interquartile range &#40;IQR&#41;&#46; Chi-square test was used for comparing categorical data&#46; Student&#39;s <span class="elsevierStyleItalic">t</span>-test was used for normally distributed quantitative variables&#44; to compare between two studied groups&#46; Mann&#8211;Whitney test was used for abnormally distributed quantitative variables&#44; to compare between two studied groups&#46; Correlation between two distributed abnormally quantitative variables was done using Spearman coefficient&#46; <span class="elsevierStyleItalic">p</span> values less than 0&#46;05 was considered statistically significant&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a></p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Results</span><p id="par0100" class="elsevierStylePara elsevierViewall">There was no significant difference between patients and controls regarding age and sex&#46; The mean duration of psoriasis was 6&#46;24<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>6&#46;27 years while the mean duration of PsA was 2&#46;33<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;19 years&#46; 31 patients were on conventional synthetic disease modifying antirheumatic drugs &#40;csDMARDs&#41;&#44; while 19 patients were receiving biological therapy&#46; Demographic data are summarized in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">The mean value of SPARCC index was 6&#46;74<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;58&#46; The mean value of DAPSA score was 33&#46;24<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#46;26&#59; 3 patients had low disease activity&#44; and 23 patients had moderate disease activity&#44; while 24 patients had severe disease activity&#46; The mean value of PASI score was 8&#46;35<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;93&#46; There was significant difference between patients and controls regarding the serum levels of DKK-1 and MASEI score &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> summarizes clinical&#44; laboratory&#44; and radiological data&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">There was a significant lower level of DKK-1 in PsA patients treated with bDMARDS &#40;2180&#46;52<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1206&#46;53<span class="elsevierStyleHsp" style=""></span>pg&#47;mL&#41; when compared to those treated with csDMARDS &#40;3575&#46;58<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1734&#46;53&#41; &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;005&#41;&#46; There was no statistically significant difference regarding DAPSA&#44; total MASEI&#44; MASEI inflammatory and MASEI damage between patients treated with csDMARDs and those treated with bDMARDs&#46; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;405&#44; 0&#46;565&#44; 0&#46;642&#44; 0&#46;588&#44; respectively&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">There was a statistically significant positive correlation between serum DKK-1 and MASEI &#40;<span class="elsevierStyleItalic">r</span>&#58; 0&#46;43527&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;00158&#41;&#44; MASEI inflammatory &#40;<span class="elsevierStyleItalic">r</span>&#58; 0&#46;37958&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;00655&#41; and MASEI damage scores &#40;<span class="elsevierStyleItalic">r</span>&#58; 0&#46;38384&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;00593&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> summarizes correlations between DKK-1 and different parameters&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Discussion</span><p id="par0120" class="elsevierStylePara elsevierViewall">Psoriatic arthritis &#40;PsA&#41; is a chronic systemic immune condition&#44; affecting peripheral and&#47;or axial joints&#46; The purpose of this study was to evaluate the serum level of DKK-1 in PsA patients and their relationship to disease activity and enthesopathy&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Psoriatic arthritis patients showed a higher level of DKK-1 than the control group&#46; Serum level of DKK-1 was correlated with total MASEI score&#44; MASEI inflammatory&#44; and MASEI damage scores&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">According to Dalbeth N et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a> PsA patients with or without erosion had higher levels of DKK-1 than psoriatic controls&#44; and there was no correlation between the level of DKK-1 and the pattern of bone disease in PsA patients&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">Jadon DR et al&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a> found that DKK-1 concentrations were significantly higher in PsA patients with radiographic axial affection compared with patients without axial affection&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Furthermore&#44; Chung Y et al&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a> reported that the level of serum DKK-1 in PsA was higher compared with patients with rheumatoid arthritis patients and healthy controls and that increased level of DKK-1 was correlated with swollen joint count&#46; There is no difference between PsA patients with elevated DKK-1 and those with normal DKK-1 levels regarding the duration of arthritis&#47;psoriasis&#44; the number of tender joints&#44; the frequency of nail psoriasis&#44; dactylitis&#44; and enthesitis&#46; However&#44; PsA patients with elevated DKK-1 have a higher swollen joint count&#44; sacroiliitis&#44; and bone erosion&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">Sungsin Jo et al&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a> reported that DKK-1 directly promoted bone formation in enthesis in ankylosing spondylitis patients&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">On the other hand&#44; Fassio A et al&#46; showed that PsA patients had lower levels of DKK-1 than those with rheumatoid arthritis and the control groups&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">18</span></a> Additionally&#44; Daoussis et al&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a> observed that DKK-1 did not differ between PsA patients and controls&#44; and no correlation was found between DKK-1 and acute phase reactant &#40;ESR and CRP&#41; indicating that expression of Wnt antagonist isn&#8217;t linked to acute phase response&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Enthesitis is characterized by a strong tissue reaction&#44; which is an early sign of diseases like PsA&#46; Enthesitis then leads to consequences including enthesophytes&#44; calcaneal spurs&#44; and plantar fasciitis&#46; Resident mesenchymal cells&#44; which have the capacity for proliferation and differentiation inside the chondroblasts and the osteoblasts to produce cartilage and bone&#44; are likely the source of these new bone forms&#46; PGE2 plays a significant role in promoting osteoblast differentiation&#46; Similarly&#44; Wnt proteins coupled with their inhibitors&#44; DKK-1 and sclerostin&#44; are effector molecules that enhance the activity of osteoblasts for the apposition of new bone in the entheses&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">20&#44;21</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">DKK-1 acts as an endogenous inhibitor of the Wnt&#47;&#946;-catenin signaling pathways&#46; Wnt-1 protein can signal proliferation via &#946;-catenin after binding to low-density lipoprotein receptor-related protein-5&#47;6 &#40;LRP5&#47;6&#41; and the frizzled receptor&#46; DKK-1 binds to LRP5&#47;6 and prevents binding between LRP5&#47;6 and Wnt-1&#44; causing degradation of &#946;-catenin which blocks the formation and differentiation of osteoblasts and stimulates the apoptosis of immature osteoblasts&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">22&#44;23</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">Because DKK-1 is an inhibitor of the Wnt pathway&#44; which stimulates osteoblastogenesis and the synthesis of new bone&#44; one may assume that DKK-1 levels would decrease over the course of a spectrum of diseases with increasing new bone formation&#46; However&#44; in line with many previous studies&#44; DKK-1 levels in SpA may be higher because DKK-1 is pathologically dysfunctional&#46; According to Daoussis et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a> DKK-1 is dysfunctional in AS even though serum total DKK-1 levels are higher in patients with AS compared to those with healthy controls or PsA&#59; they reported reduced binding of DKK-1 to its receptor in AS may lead to unopposed stimulation of Wnt signaling pathway&#46; According to Yucong et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a> functional DKK-1 levels in serum were observed to be lower in AS patients compared to healthy controls since DKK-1 binds less strongly to its receptor LRP6&#46; According to Heiland GR et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">25</span></a> an absence of syndesmophyte development in AS patients is associated with elevated serum levels of functional DKK-1 binding to its receptor LRP-6&#46; This could explain the elevated DKK-1 levels in our patients as an attempt to compensate for dysfunctional DKK-1&#46; The osteoproliferative phenotype of SpA may be explained by inadequate Wnt-pathway inhibition caused by dysfunctional DKK-1&#44; which stimulates unlimited bone formation&#46; Another theory is that the serum of PsA patients has soluble DKK-1 inhibitors&#44; such as autoantibodies against DKK-1 or soluble receptors&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Previous studies have suggested that DKK-1 participates in osteoblast development in a dual stage-dependent manner&#46; DKK-1 is involved in physiological changes associated with mineralization because research has shown that it is decreased during extra-cellular matrix maturation but increases during the mineralization stage of osteoblast differentiation&#46;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">26&#44;27</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">The level of DKK-1 was lower in PsA patients treated with bDMARDS when compared to those treated with csDMARDS&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">It was reported that after 12 months of anti-TNF treatment&#44; DKK-1 level was lower in PsA patients when compared to rheumatoid arthritis patients&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">28</span></a> Also&#44; treatment with secukinumab may influence WNT inhibitors &#40;DKK-1 and sclerostin&#41; as DKK-1 and sclerostin show significant increase after treatment with secukinumab&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">29</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">DKK-1 has been linked to structural damage pathogenesis&#44; syndesmophyte production&#44; and new bone formation in SpA&#44; however most of the results are contradictory&#46;<a class="elsevierStyleCrossRefs" href="#bib0245"><span class="elsevierStyleSup">19&#44;23</span></a> Serum levels of DKK-1 were further elevated in AS patients receiving anti-TNF treatment&#44;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a> The authors proposed that the greater levels of DKK-1 may represent a compensatory mechanism to reduce Wnt signaling&#44; which is activated after the treatment-induced reduction in inflammation&#46; On the other hand&#44; according to a different study&#44; circulation levels of DKK-1 were lower in AS patients compared to healthy controls and remained unchanged after anti-TNF therapy&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a> According to a prospective study on SpA patients found that treatment with TNF blockers caused a significant decrease in DKK-1 level&#46; This decrease was correlated with the reduction of MRI bone marrow edema of the sacroiliac joint and spine&#46; The reduction of DKK-1 by anti-TNF agents may be related to the inhibitory effects of these drugs on new bone formation in SpA&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">To our knowledge&#44; this is few studies that evaluated the levels of DKK-1 in PsA patients in relation to enthesopathy which is a common feature in PsA patients and in this study musculoskeletal ultrasonography was used to evaluate enthesopathy using MASEI score which is more sensitive in evaluation of enthesopathy than clinical assessment&#46; There were some limitations in this study as this is single-centered study&#44; it was better if it was a multicenter study also it was better if the participants were a larger number&#46; Our study is a cross-sectional study&#44; future longitudinal studies are needed to assess if serum level of DKK-1 decreases overtime also future studies needed to assess the level of functional DKK-1 in PsA patients&#46;</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conclusion</span><p id="par0195" class="elsevierStylePara elsevierViewall">Serum DKK-1 levels were elevated in PsA patients and were found to be correlated with MASEI score for enthesopathy so&#44; it may be involved in enthesopathy formation in PsA&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Authors&#8217; contributions</span><p id="par0200" class="elsevierStylePara elsevierViewall">MAWA and SAT conceived the idea for the study and in conjunction with NME designed the study and wrote the analysis plan&#46; MAWA and SAT undertook data analysis and interpretation&#44; supported RME&#46; The initial draft of manuscript was written by SAT and RME&#44; with contribution from MAWA&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">All authors contributed in the study methodology&#44; analysis&#44; and interpretation of the data and outcomes as well as the manuscript writing&#44; reading&#44; and approval of the final version&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Authorship</span><p id="par0210" class="elsevierStylePara elsevierViewall">All named authors meet the International Committee of Medical Journal Editors &#40;ICMJE&#41; criteria for authorship for this article&#44; take responsibility for the integrity of the work as a whole&#44; and have given their approval for this version to be published&#46;</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Compliance with ethics guidelines</span><p id="par0215" class="elsevierStylePara elsevierViewall">This study has been approved by the institution&#39;s ethics board with permission number 34483&#47;2&#47;21 and is in accordance with the Declaration of Helsinki&#39;s ethical principles as well as the ethical standards of the Tanta Faculty of Medicine&#46; According to the local ethical commission&#44; informed consent was received from each patient&#46; Every patient file included a code number that incorporated the results of all investigations&#44; ensuring the privacy of all patient data&#46;</p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Compliance with ethical standards</span><p id="par0220" class="elsevierStylePara elsevierViewall">All steps are performed according to the revised ethical principles of the Declaration of Helsinki in 2000&#44; and local ethical and methodological protocols for approval of the study were followed&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Data availability</span><p id="par0225" class="elsevierStylePara elsevierViewall">The datasets generated during and&#47;or analyzed during the current study are available from the corresponding author on reasonable request&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Consent for publication</span><p id="par0230" class="elsevierStylePara elsevierViewall">The final manuscript has been seen and approved by all the authors&#44; and they have obtained the required ethical approvals&#44; and they have given the necessary attention to ensure the integrity of the work and agree to publish this work&#46;</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Ethics approval and consent to participate</span><p id="par0235" class="elsevierStylePara elsevierViewall">This study is in agreement with the ethical guidelines of the Declaration of Helsinki and it follows the ethical standards of Tanta Faculty of Medicine&#44; with the institution&#39;s ethics board approval number 34483&#47;2&#47;21&#46; Informed consent from all patients was obtained in accordance with the local ethical committee&#46; Privacy of all patients&#8217; data was granted as there was a code number for every patient file that included all investigations&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Funding</span><p id="par0240" class="elsevierStylePara elsevierViewall">No funding or sponsorship was received for this study or publication of this article&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Conflict of interest</span><p id="par0245" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest&#46;</p></span></span>"
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          "titulo" => "Authorship"
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          "identificador" => "sec0075"
          "titulo" => "Compliance with ethics guidelines"
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          "identificador" => "sec0080"
          "titulo" => "Compliance with ethical standards"
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        13 => array:2 [
          "identificador" => "sec0085"
          "titulo" => "Data availability"
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          "titulo" => "Ethics approval and consent to participate"
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          "identificador" => "sec0105"
          "titulo" => "Conflict of interest"
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        18 => array:2 [
          "identificador" => "xack722591"
          "titulo" => "Acknowledgments"
        ]
        19 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2023-04-17"
    "fechaAceptado" => "2023-06-08"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1769934"
          "palabras" => array:4 [
            0 => "Psoriatic arthritis"
            1 => "DKK-1"
            2 => "Enthesopathy"
            3 => "Disease activity"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
          "identificador" => "xpalclavsec1769933"
          "palabras" => array:4 [
            0 => "Artritis psori&#225;sica"
            1 => "DKK-1"
            2 => "Entesopat&#237;a"
            3 => "Actividad de la enfermedad"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Background</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Psoriatic arthritis &#40;PsA&#41; is a complex inflammatory disease with varied clinical characteristics&#46; A pathognomonic characteristic of PsA is enthesitis&#46; Entheseal inflammation ultimately leads to the production of new bone &#40;enthesophytes&#41;&#46; Dickkopf-related protein-1 &#40;DKK-1&#41; is a wingless &#40;Wnt&#41; inhibitor that inhibits osteoblast function&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Assessment of the serum level of DKK-1 and its association with disease activity and enthesopathy in PsA patients&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">This observational case&#8211;control study included 50 PsA patients and 50 healthy volunteers matched for age and gender&#46; All participants were subjected to full medical history&#44; clinical assessment&#44; PSA activity using Disease Activity Index for Psoriatic Arthritis &#40;DAPSA&#41; score&#44; the severity and extent of psoriasis were determined by the Psoriasis Area and Severity Index &#40;PASI&#41;&#46; Ultrasonographic assessment of the entheses was done in accordance with the Madrid Sonographic Enthesitis Index &#40;MASEI&#41;&#46; Serum level of DKK-1 and correlation with disease activity and enthesopathy in PsA patients were assessed&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">There was no significant difference between patients and controls regarding age and sex&#46; The mean value of SPARCC index&#44; DAPSA score and PASI score were 6&#46;74<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;58&#44; 33&#46;24<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#46;26&#44; and 8&#46;35<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#46;93&#44; respectively&#46; There was significant difference between patients and controls regarding the serum levels of DKK-1 and MASEI score &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0001&#41;&#46; There was a significant positive correlation between serum DKK-1 and MASEI &#40;<span class="elsevierStyleItalic">r</span>&#58; 0&#46;43527&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;00158&#41;&#44; MASEI inflammatory &#40;<span class="elsevierStyleItalic">r</span>&#58; 0&#46;37958&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;00655&#41;&#44; and MASEI damage &#40;<span class="elsevierStyleItalic">r</span>&#58; 0&#46;38384&#44; <span class="elsevierStyleItalic">p</span>&#58; 0&#46;00593&#41;&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Serum DKK-1 levels were elevated in PsA patients and were found to be correlated with MASEI score for enthesopathy&#46;</p></span>"
        "secciones" => array:5 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Background"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Objectives"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Methods"
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          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Results"
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          4 => array:2 [
            "identificador" => "abst0025"
            "titulo" => "Conclusions"
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      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Antecedentes</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">La artritis psori&#225;sica &#40;APs&#41; es una enfermedad inflamatoria compleja con caracter&#237;sticas cl&#237;nicas variadas&#46; Una caracter&#237;stica patognom&#243;nica de la artritis psori&#225;sica es la entesitis&#46; La inflamaci&#243;n entes&#243;fila finalmente conduce a la producci&#243;n de hueso nuevo &#40;entes&#243;fitos&#41;&#46; La prote&#237;na 1 relacionada con dickkopf &#40;DKK-1&#41; es un inhibidor sin alas &#40;Wnt&#41; que inhibe la funci&#243;n de los osteoblastos&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Evaluaci&#243;n del nivel s&#233;rico de DKK-1 y su asociaci&#243;n con la actividad de la enfermedad y la entesopat&#237;a en pacientes con APs&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Este estudio observacional de casos y controles&#59; incluy&#243; a 50 pacientes con artritis psori&#225;sica y 50 voluntarios sanos emparejados por edad y sexo&#46; Todos los participantes fueron sometidos a historia cl&#237;nica completa&#44; evaluaci&#243;n cl&#237;nica&#44; actividad de APs utilizando la puntuaci&#243;n del &#205;ndice de Actividad de la Enfermedad para la Artritis Psori&#225;sica &#40;DAPSA&#41;&#44; la gravedad y la extensi&#243;n de la psoriasis fueron determinadas por el &#225;rea de psoriasis y el &#237;ndice de gravedad &#40;PASI&#41;&#46; La evaluaci&#243;n ultrasonogr&#225;fica de las entesis se realiz&#243; de acuerdo con el &#237;ndice de entesitis sonogr&#225;fica de Madrid &#40;MASEI&#41;&#46; Se evalu&#243; el nivel s&#233;rico de DKK-1 y la correlaci&#243;n con la actividad de la enfermedad y la entesopat&#237;a en pacientes con artritis psori&#225;sica&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">No hubo diferencias significativas entre los pacientes y los controles con respecto a la edad y el sexo&#46; El valor medio del &#237;ndice SPARCC&#44; la puntuaci&#243;n DAPSA y la puntuaci&#243;n PASI fueron 6&#44;74<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#44;58&#44; 33&#44;24<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#44;26 y 8&#44;35<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>10&#44;93 respectivamente&#46; Hubo diferencia significativa entre pacientes y controles con respecto a los niveles s&#233;ricos de DKK-1 y la puntuaci&#243;n MASEI &#40;p &#60;<span class="elsevierStyleHsp" style=""></span>0&#44;0001&#41;&#46; Hubo correlaci&#243;n positiva significativa entre DKK-1 s&#233;rico y MASEI &#40;r&#58; 0&#44;43527&#44; p &#61; 0&#44;00158&#41;&#44; y da&#241;o MASEI &#40;r&#58; 0&#46;38384&#44; p &#61; 0&#44;00593&#41;&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Los niveles s&#233;ricos de DKK-1 se elevaron en pacientes con APs y se encontr&#243; que estaban correlacionados con la puntuaci&#243;n MASEI para la entesopat&#237;a&#46;</p></span>"
        "secciones" => array:5 [
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            "identificador" => "abst0030"
            "titulo" => "Antecedentes"
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          1 => array:2 [
            "identificador" => "abst0035"
            "titulo" => "Objetivos"
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          2 => array:2 [
            "identificador" => "abst0040"
            "titulo" => "M&#233;todos"
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          3 => array:2 [
            "identificador" => "abst0045"
            "titulo" => "Resultados"
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          4 => array:2 [
            "identificador" => "abst0050"
            "titulo" => "Conclusiones"
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          "leyenda" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">BMI&#44; body mass index&#59; csDMARDs&#44; convential synthetic disease modifying antirheumatic drugs&#59; bDMARDs&#44; biologic disease modifying antirheumatic drugs&#46;</p><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Significant <span class="elsevierStyleItalic">p</span> value if &#60;0&#46;05&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PSA patients &#40;50&#41;&nbsp;\t\t\t\t\t\t\n
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