Effect of anti-rheumatic agents on periodontal parameters and biomarkers of inflammation: a systematic review and meta-analysis

Ji Young Han, Mark A Reynolds, Ji Young Han, Mark A Reynolds

Abstract

Purpose: Anti-rheumatic agents target common molecular pathways of inflammation in rheumatoid arthritis (RA) and periodontitis. The purpose of this study was to determine the relative effect of anti-rheumatic agents on the levels of inflammatory biomarkers and periodontal inflammation in RA patients with periodontitis.

Methods: A systematic review and meta-analysis were conducted of studies comparing periodontal parameters of inflammation, such as bleeding on probing, and biomarkers of inflammation in RA patients with periodontitis and healthy adults with and without periodontitis. The search included the electronic databases MEDLINE, Cochrane Database of Systematic Reviews, and Google Scholar, inclusive through October 2011, with no language restrictions. Hand searches were conducted of the bibliographies of related journals and systematic reviews. Observational and interventional studies assessing the effects of antirheumatic therapy qualified for inclusion. Two reviewers performed independent data extraction and risk-of-bias assessment. Of the 187 identified publications, 13 studies fulfilled the inclusion criteria.

Results: When compared to healthy adults without periodontitis, RA subjects were found to have significantly higher levels of bleeding on probing and limited evidence of higher levels of interleukin-1β and tumor necrosis factor-α (TNF-α) in gingival crevicular fluid and saliva. No consistent differences were found in periodontal parameters and inflammatory biomarkers between RA subjects and adults with periodontitis. Studies evaluating the effect of anti-TNF-α therapy in RA subjects with periodontitis have yielded inconsistent results.

Conclusions: There are limited data, however, to suggest that anti-TNF-α agents can reduce local production of inflammatory cytokines and periodontal inflammation in RA patients with periodontitis.

Keywords: Periodontitis; Rheumatoid arthritis; Tumor necrosis factor-alpha.

Conflict of interest statement

No potential conflict of interest relevant to this article was reported.

Figures

Figure 1
Figure 1
Flowchart of literature identification, screening, eligibility, and inclusion process. RA: rheumatoid arthritis, PO: periodontitis, TNF-α: tumor necrosis factor-α.

References

    1. Symmons DP. Epidemiology of rheumatoid arthritis: determinants of onset, persistence and outcome. Best Pract Res Clin Rheumatol. 2002;16:707–722.
    1. Bartold PM, Marshall RI, Haynes DR. Periodontitis and rheumatoid arthritis: a review. J Periodontol. 2005;76(11 Suppl):2066–2074.
    1. Pejcic A, Kesic LJ, Milasin J. C-reactive protein as a systemic marker of inflammation in periodontitis. Eur J Clin Microbiol Infect Dis. 2011;30:407–414.
    1. Greenwald RA, Kirkwood K. Adult periodontitis as a model for rheumatoid arthritis (with emphasis on treatment strategies) J Rheumatol. 1999;26:1650–1653.
    1. Liao F, Li Z, Wang Y, Shi B, Gong Z, Cheng X. Porphyromonas gingivalis may play an important role in the pathogenesis of periodontitis-associated rheumatoid arthritis. Med Hypotheses. 2009;72:732–735.
    1. Birkedal-Hansen H. Role of cytokines and inflammatory mediators in tissue destruction. J Periodontal Res. 1993;28(6 Pt 2):500–510.
    1. Mercado F, Marshall RI, Klestov AC, Bartold PM. Is there a relationship between rheumatoid arthritis and periodontal disease? J Clin Periodontol. 2000;27:267–272.
    1. Pischon N, Pischon T, Kröger J, Gülmez E, Kleber BM, Bernimoulin JP, et al. Association among rheumatoid arthritis, oral hygiene, and periodontitis. J Periodontol. 2008;79:979–986.
    1. Moen K, Brun JG, Valen M, Skartveit L, Eribe EK, Olsen I, et al. Synovial inflammation in active rheumatoid arthritis and psoriatic arthritis facilitates trapping of a variety of oral bacterial DNAs. Clin Exp Rheumatol. 2006;24:656–663.
    1. Saal JG, Krimmel M, Steidle M, Gerneth F, Wagner S, Fritz P, et al. Synovial Epstein-Barr virus infection increases the risk of rheumatoid arthritis in individuals with the shared HLA-DR4 epitope. Arthritis Rheum. 1999;42:1485–1496.
    1. Slots J. Herpesviruses in periodontal diseases. Periodontol 2000. 2005;38:33–62.
    1. Vincent C, de Keyser F, Masson-Bessière C, Sebbag M, Veys EM, Serre G. Anti-perinuclear factor compared with the so called "antikeratin" antibodies and antibodies to human epidermis filaggrin, in the diagnosis of arthritides. Ann Rheum Dis. 1999;58:42–48.
    1. van Venrooij WJ, Pruijn GJ. Citrullination: a small change for a protein with great consequences for rheumatoid arthritis. Arthritis Res. 2000;2:249–251.
    1. Moher D, Liberati A, Tetzlaff J, Altman DG PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009;6:e1000097.
    1. Kobayashi T, Murasawa A, Komatsu Y, Yokoyama T, Ishida K, Abe A, et al. Serum cytokine and periodontal profiles in relation to disease activity of rheumatoid arthritis in Japanese adults. J Periodontol. 2010;81:650–657.
    1. Mayer Y, Balbir-Gurman A, Machtei EE. Anti-tumor necrosis factor-alpha therapy and periodontal parameters in patients with rheumatoid arthritis. J Periodontol. 2009;80:1414–1420.
    1. Miranda LA, Islabão AG, Fischer RG, Figueredo CM, Oppermann RV, Gustafsson A. Decreased interleukin-1beta and elastase in the gingival crevicular fluid of individuals undergoing anti-inflammatory treatment for rheumatoid arthritis. J Periodontol. 2007;78:1612–1619.
    1. Nilsson M, Kopp S. Gingivitis and periodontitis are related to repeated high levels of circulating tumor necrosis factor-alpha in patients with rheumatoid arthritis. J Periodontol. 2008;79:1689–1696.
    1. Biyikoğlu B, Buduneli N, Kardeşler L, Aksu K, Oder G, Kütükçüler N. Evaluation of t-PA, PAI-2, IL-1beta and PGE(2) in gingival crevicular fluid of rheumatoid arthritis patients with periodontal disease. J Clin Periodontol. 2006;33:605–611.
    1. Biyikoğlu B, Buduneli N, Kardeşler L, Aksu K, Pitkala M, Sorsa T. Gingival crevicular fluid MMP-8 and -13 and TIMP-1 levels in patients with rheumatoid arthritis and inflammatory periodontal disease. J Periodontol. 2009;80:1307–1314.
    1. Bozkurt FY, Berker E, Akkuş S, Bulut S. Relationship between interleukin-6 levels in gingival crevicular fluid and periodontal status in patients with rheumatoid arthritis and adult periodontitis. J Periodontol. 2000;71:1756–1760.
    1. Bozkurt FY, Yetkin Ay Z, Berker E, Tepe E, Akkuş S. Anti-inflammatory cytokines in gingival crevicular fluid in patients with periodontitis and rheumatoid arthritis: a preliminary report. Cytokine. 2006;35:180–185.
    1. Havemose-Poulsen A, Sørensen LK, Stoltze K, Bendtzen K, Holmstrup P. Cytokine profiles in peripheral blood and whole blood cell cultures associated with aggressive periodontitis, juvenile idiopathic arthritis, and rheumatoid arthritis. J Periodontol. 2005;76:2276–2285.
    1. Havemose-Poulsen A, Westergaard J, Stoltze K, Skjødt H, Danneskiold-Samsøe B, Locht H, et al. Periodontal and hematological characteristics associated with aggressive periodontitis, juvenile idiopathic arthritis, and rheumatoid arthritis. J Periodontol. 2006;77:280–288.
    1. Mirrielees J, Crofford LJ, Lin Y, Kryscio RJ, Dawson DR, 3rd, Ebersole JL, et al. Rheumatoid arthritis and salivary biomarkers of periodontal disease. J Clin Periodontol. 2010;37:1068–1074.
    1. Ortiz P, Bissada NF, Palomo L, Han YW, Al-Zahrani MS, Panneerselvam A, et al. Periodontal therapy reduces the severity of active rheumatoid arthritis in patients treated with or without tumor necrosis factor inhibitors. J Periodontol. 2009;80:535–540.
    1. Pers JO, Saraux A, Pierre R, Youinou P. Anti-TNF-alpha immunotherapy is associated with increased gingival inflammation without clinical attachment loss in subjects with rheumatoid arthritis. J Periodontol. 2008;79:1645–1651.
    1. Berthelot JM, Le Goff B. Rheumatoid arthritis and periodontal disease. Joint Bone Spine. 2010;77:537–541.
    1. Ramamurthy NS, Greenwald RA, Celiker MY, Shi EY. Experimental arthritis in rats induces biomarkers of periodontitis which are ameliorated by gene therapy with tissue inhibitor of matrix metalloproteinases. J Periodontol. 2005;76:229–233.
    1. Cantley MD, Haynes DR, Marino V, Bartold PM. Pre-existing periodontitis exacerbates experimental arthritis in a mouse model. J Clin Periodontol. 2011;38:532–541.
    1. Hart FD, Huskisson EC. Non-steroidal anti-inflammatory drugs. Current status and rational therapeutic use. Drugs. 1984;27:232–255.
    1. Reddy MS, Geurs NC, Gunsolley JC. Periodontal host modulation with antiproteinase, anti-inflammatory, and bone-sparing agents. A systematic review. Ann Periodontol. 2003;8:12–37.
    1. Curtis JR, Singh JA. Use of biologics in rheumatoid arthritis: current and emerging paradigms of care. Clin Ther. 2011;33:679–707.
    1. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum. 1988;31:315–324.
    1. Culshaw S, McInnes IB, Liew FY. What can the periodontal community learn from the pathophysiology of rheumatoid arthritis? J Clin Periodontol. 2011;38(Suppl 11):106–113.
    1. Feldmann M, Maini RN. Lasker Clinical Medical Research Award. TNF defined as a therapeutic target for rheumatoid arthritis and other autoimmune diseases. Nat Med. 2003;9:1245–1250.
    1. Bartold PM, Cantley MD, Haynes DR. Mechanisms and control of pathologic bone loss in periodontitis. Periodontol 2000. 2010;53:55–69.
    1. Bergström J. Tobacco smoking and chronic destructive periodontal disease. Odontology. 2004;92:1–8.
    1. Sugiyama D, Nishimura K, Tamaki K, Tsuji G, Nakazawa T, Morinobu A, et al. Impact of smoking as a risk factor for developing rheumatoid arthritis: a meta-analysis of observational studies. Ann Rheum Dis. 2010;69:70–81.
    1. Zambon JJ, Grossi SG, Machtei EE, Ho AW, Dunford R, Genco RJ. Cigarette smoking increases the risk for subgingival infection with periodontal pathogens. J Periodontol. 1996;67(10 Suppl):1050–1054.

Source: PubMed

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