{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T13:00:45Z","timestamp":1784638845245,"version":"3.55.0"},"reference-count":61,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T00:00:00Z","timestamp":1753056000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Dent. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Dickkopf-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. <jats:italic>Porphyromonas gingivalis<\/jats:italic> 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The 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\u2013control 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A 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 (<jats:italic>p<\/jats:italic>\u2009=\u20090.02; 95% CI: 1.170\u20136.203) 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 (<jats:italic>p<\/jats:italic>\u2009=\u20090.009), indicating significant publication bias.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Elevated 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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Systematic Review Registration<\/jats:title><jats:p><jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/search<\/jats:ext-link>, PROSPERO CRD42025643227.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fdmed.2025.1593218","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T05:22:28Z","timestamp":1753075348000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Evaluating Dickkopf-1 as a biomarker: insights into periodontitis, rheumatoid arthritis, and their comorbidity\u2014a systematic review and meta-analysis"],"prefix":"10.3389","volume":"6","author":[{"given":"Bawatharani","family":"Maharavi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaideep","family":"Mahendra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepa","family":"Ponnaiyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vijayalakshmi","family":"Rajaram","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pragya","family":"Gyanchand","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roshan R.","family":"Rughwani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaustubh 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