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. 2025 Jul 21:6:1593218.
doi: 10.3389/fdmed.2025.1593218. eCollection 2025.

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

Bawatharani Maharavi  1 , Jaideep Mahendra  1 , Deepa Ponnaiyan  2 , Vijayalakshmi Rajaram  1 , Pragya Gyanchand  1 , Roshan R Rughwani  3 , Kaustubh Suresh Thakare  4 , Gayathri Kumar  5 , Gauri Patil  1
Affiliations

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

Bawatharani Maharavi et al. Front Dent Med. .

Abstract

Background: 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. 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.

Methods: 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-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.

Results: 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 (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.

Conclusion: 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.

Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/search, PROSPERO CRD42025643227.

Keywords: Dickkopf-1 (DKK-1); Wnt signaling pathway; bone remodeling; periodontitis; pro-inflammatory biomarker; rheumatoid arthritis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
PRISMA flowchart of literature retrieval and study selection process.
Figure 2
Figure 2
Flowchart of literature retrieval and study selection process.
Figure 3
Figure 3
Funnel plot symmetry analysis for included studies.
See this image and copyright information in PMC

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