AUTHOR=Maharavi Bawatharani , Mahendra Jaideep , Ponnaiyan Deepa , Rajaram Vijayalakshmi , Gyanchand Pragya , Rughwani Roshan R. , Thakare Kaustubh Suresh , Kumar Gayathri , Patil Gauri 

TITLE=Evaluating Dickkopf-1 as a biomarker: insights into periodontitis, rheumatoid arthritis, and their comorbidity—a systematic review and meta-analysis

JOURNAL=Frontiers in Dental Medicine

VOLUME=Volume 6 - 2025

YEAR=2025

URL=https://www.frontiersin.org/journals/dental-medicine/articles/10.3389/fdmed.2025.1593218

DOI=10.3389/fdmed.2025.1593218

ISSN=2673-4915

ABSTRACT=BackgroundDickkopf-1 is a glycoprotein that inhibits Wingless-related integration site signaling, impairing osteoblast and osteoclast functions, leading to bone loss and systemic inflammation linked to periodontitis and rheumatoid arthritis. Porphyromonas gingivalis exacerbates rheumatoid arthritis through citrullination and inflammation, highlighting their bidirectional relationship. To date no meta-analysis has examined the role of Dickkopf-1 in periodontitis, rheumatoid arthritis, and their comorbidity. Therefore, we conducted this meta-analysis to investigate the association and role of Dickkopf-1 in these comorbid conditions.MethodsThe present study was conducted in accordance with the guidelines of Transparent Reporting of Systematic Reviews and Meta-Analyses PRISMA statement (registered at PROSPERO under the number CRD42025643227). A total of 15 studies (14 case–control and 1 cross-sectional) were selected out of 386 using databases like PubMed and Google Scholar (by BM, JM, and DP). A random-effects model evaluated Dickkopf-1 levels in serum/gingival crevicular fluid in periodontitis and rheumatoid arthritis via standardized mean difference (SMD) and 95% confidence intervals (CI). Heterogeneity and publication bias were assessed using statistical metrics, forest plots, funnel plots, Begg's test, and Egger's regression.ResultsA total of 386 studies were retrieved and 15 were included in the meta-analysis, encompassing 4,438 participants (2,190 cases and 2,248 controls). The pooled SMD of 2.694 (p = 0.02; 95% CI: 1.170–6.203) indicated a significant association of Dickkopf-1 with periodontitis and/or rheumatoid arthritis compared to healthy controls. However, Egger's test revealed a t-value of 3.05 (p = 0.009), indicating significant publication bias.ConclusionElevated Dickkopf-1 levels in rheumatoid arthritis and periodontitis patients suggest its critical role in the pathogenesis of both conditions. Hence, Dickkopf-1 holds therapeutic potential for managing interconnected inflammatory and bone disorders and may serve as a biomarker for diagnosing these diseases.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPERO/search, PROSPERO CRD42025643227.