The Clinical Significance Of Dickkopf-1 Detection In The Diagnosis Of Menopausal Women With Rheumatoid Arthritis And Osteoporosis

Background:Rheumatoid arthritis(RA)is a chronic progressive autoimmune disease ch aracterized by proliferative aggressive synovitis,which can cause joint destructi on,cartilage and bone erosion,and even disability and death.However,long-te rm use of high-dose or even low-dose glucocorticoids can cause bone loss,red uce bone quality,and even increase the risk of fractures.Therefore,whether th e occurrence of secondary osteoporosis(OP)is caused by the RA disease itself or other related factors,such as steroid hormone therapy and hormone metabo lism disorders in elderly and menopausal women,the etiology is still unclear.RA is often accompanied by periarticular or systemic bone loss and even OP.However,whether RA induces secondary OP is still controversial.Recent studi es have shown that Dickkopf-1(DKK1)is an inhibitor of the wingless signali ng pathway(Wnt)and is involved in the regulation of bone homeostasis.The overexpression of DKK1 is related to the destruction of RA bone and the loss of bone mass throughout the body.DKK1 relies on the co-receptor low-densit y lipoprotein receptor-related protein 5(LRP5)of the Wnt signaling pathway.LRP5 regulates osteoblast production and osteoclast activation through the expr ession of bone cells.If this mutant functional area is activated,it will lead to a high phenotype.The combination of DKK1 and LRP5 can cause the loss o f this functional mutation area to lead to the occurrence of OP.DKK1 is incre ased in both RA and OP patients.The purpose of this study is to further expl ore DKK1 in menopausal women with RA and OP(RAO)The detection level of patients and each control group and related research.Objective:To explore the detection level and clinical diagnostic significance of dickkop f-1 in menopausal women with RAO.Methods:Collect 50 cases of RAO,105 cases of RA menopausal women(RA)and 45 cases of OP menopausal women(OP)diagnosed in the Second Affiliated Ho spital of Nanchang University from April 2019 to November 2020,and healthy controls(HC)for 40 menopausal women in the hospital during the same perio d.Serum DKK1,anti-cyclic citrulline peptide antibody(anti-CCP)and anti-muta nt citrulline vimentin antibody(anti-MCV)were detected by ELISA,erythrocyte sedimentation rate(ESR)was detected by capillary method,C-reactive protein(CRP)and rheumatoid factor(RF)using rate scattering turbidimetric method,bo ne metabolism index,for example parathyroid hormone(PTH),type I collagen C-terminal peptide(CTx),25-hydroxyvitamin D3(250HD3),type I pre-collage n N-terminal peptide(PINP)and osteocalcin(OC)are detected by electrochemi luminescence,and bone alkaline phosphatase(BALP)was detected by chromat ography,etc.Using Lunar Prodigy dual-energy X-ray(DXA)was to detect bon e mineral density(BMD)in all patients including the total hip and lumbar spi ne L1～4.Results:①Results Analysis of DKK1,PTH,CTx,25OHD3,PINP,BALP,OC,ESR,CRP,BMI,fracture history,total hip BMD,total hip T score,RAO,RA,OP and HC groups among the four groups Lumbar spine L1～4 BMD,lumbar spine L1～4 T score and other indicators.Among them,DKK1,PTH,25OHD3,ESR,CRP,BMI,fracture history,total hip T score,total hip T score,lumbar spine L1～4 BMD,lumbar spine L1～4 T score and other indicators have statistically si gnificant differences between groups(P<0.01).There are statistically significa nt differences in DKK1 between the RAO group and the RA,OP and HC gro ups,respectively(P<0.01).The levels of DKK1 in each group were 10.94±2.6μg/L,6.91 ± 1.91μg/L,9.84±2.24μg/L and 5.63±1.65μg/L.There are statistically significant differences in DKK1 between the RAO and RA,OP or HC group,respectively(P<0.01).②Comparison of the detection methods between DK K1(ELISA)and bone metabolism indexes(electrochemiluminescence and chro matography)and BMD-related indexes(dual energy X-ray).The results show t hat the two index detection methods are different and have statistical significan ce.③Bivariate correlation analysis between DKK1 and various indicators.Seru m DKK1 was positively correlated with CRP,fracture history and PINP(P<0.05),and was positively correlated with BMI,total hip BMD,total hip T score,lumbar spine L1～4 BMD,and lumbar spine L1～4 T score(P<0.05).Subsequ ent multiple linear regression analysis was performed and it was found that D KK1 was independently positively correlated with fracture history and PINP(β=0.145,P=0.016 and β=0.178,P=0.014),and independently negatively corr elated with total hip T score(β=-0.374,P=0.000).④ROC curve analysis wa s performed in the RAO group with the RA,OP and HC groups.Compared with the RA group,its specificity(Spe)and negative predictive value(NPV-)clinical diagnostic efficiency were 86%and 90.3%,respectively better than OP group.Compared with the HC group,the area under the curve(AUC),sensiti vity(Sen),Youden index(YDI)and positive predictive value(PPV+)had the highest clinical diagnostic efficacy of 0.95,94%,0.777,and 93%,respectively and were better than those in OP group,suggesting that DKK1 has good clini cal diagnostic efficiency and diagnostic value in menopausal women with RAO⑤Whether OP occurs in RA patients(combined OP=1,not combined OP=0)as the dependent variable,DKK1,PTH,25OHD3,ESR,CRP,BMI,fracture,D AS28(ESR),anti-CCP,anti-MCV and RF are independent variables.Logistic r egression analysis is used to explore the risk factors of RAO patients.The res ults show that DKK1,CRP,RF,DAS28(ESR),25OHD3 are risk factors for R AO.But BMI and PTH are protections for RAO sexual factors.However,multi variate logistic regression analysis in univariate analysis(P<0.05)found that on ly DKK1 was an independent risk factor for RAO.Conclusion:Compared with the RA group,OP group,and HC group,the RAO group has the highest detection level of serum DKK1 in menopausal women with R AO.Compared with other disease groups and HC group,DKK1 has better cli nical results in the RAO group and the RA group Diagnostic value.Menopaus al women are a high-risk group of patients with RAO,and high levels of DK K1,advanced age,inflammation,high BMI,high activity score DAS28(ESR),low levels of 25OHD3,etc.are also risk factors for RAO.DKK1 affects bon e metabolism in RA patients and participates in the process of RAO.Therefor e,DKK1,bone transformation markers(BTMs)and BMD related other indicat ors should be screened and tested regularly.Attention should be paid to variou s related risk factors,and the occurrence of OP should be detected early and early treatment should be carried out to reduce the incidence of OP and the in cidence of fractures.In menopausal women with RA who have not yet underg one OP,the changes in DKK1 may not be significantly coupled with their bon e erosion.At this time,active treatment measures should be taken to control t he level of DKK1(such as DKK1 monoclonal antibody,etc.)to prevent the lo ng-term course of the disease,due to the increase of DKK1,the occurrence an d development of bone erosion laterly.