Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Adjunctive use of locally delivered host-modulators in intra-bony defects as part of step 2 periodontal therapy: systematic review, meta-analysis and trial sequential analysis

Evidence-Based Dentistry volume 24, pages 91–92 (2023)Cite this article

Subjects

Abstract

Background

This systematic review and meta-analysis aimed at investigate the role of locally delivered host-modulators in combination with step 2 of periodontal therapy in reducing probing pocket depth, improving clinical attachment level and reducing bone defect depth in intra-bony defects.

Highlight

RCT with at least 6 months follow-up were included in this study. Risk of bias assessment was performed with Cochrane collaboration tool and Grade GRADEpro. In addition, meta-analysis and trial sequential analysis were used to aggregate the available evidence. 22 studies met the inclusion criteria and were included in this systematic review. At 6 months locally delivered host-modulators significantly improved PD and CAL and bone defect depth.

Conclusion

Considering the emerging role of host-inflammatory response in the treatment of periodontitis, several studies are exploring the role of locally delivered host modulators as an adjunct to step 2 of periodontal therapy.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: PRISMA flow chart.
Fig. 2: Risk of bias evaluation.
Fig. 3: Effect of Statins on Probing Depth (PD), Clinical Attachment Level (CAL) and Bone Defect Depth.
Fig. 4: Diagram showing results of Trial sequential analysis of the adjunct of Statins.
Fig. 5: Effect of metformin on probing depth (PD), clinical attachment level (CAL) and bone defect depth.
Fig. 6: Effect of bisphosphonates on probing depth (PD), clinical attachment level (CAL), and bone defect depth.
Fig. 7: Diagram showing results of trial sequential analysis of the adjunct of metformin.

Similar content being viewed by others

References

  1. Tonetti MS, Greenwell H, Kornman KS. Staging and grading of periodontitis: framework and proposal of a new classification and case definition. J Periodontol. 2018;89:S159–S72.

    Article  PubMed  Google Scholar 

  2. Haffajee AD, Socransky SS. Microbial etiological agents of destructive periodontal diseases. Periodontol 2000. 1994;5:78–111.

    Article  PubMed  Google Scholar 

  3. Papapanou PN, Wennstrom JL. The angular bony defect as indicator of further alveolar bone loss. J Clin Periodontol. 1991;18:317–22.

    Article  PubMed  Google Scholar 

  4. Umeda M, Takeuchi Y, Noguchi K, Huang Y, Koshy G, Ishikawa I. Effects of nonsurgical periodontal therapy on the microbiota. Periodontol 2000. 2004;36:98–120.

    Article  PubMed  Google Scholar 

  5. Cortellini P, Tonetti MS. Focus on intrabony defects: guided tissue regeneration. Periodontol 2000. 2000;22:104–32.

    Article  PubMed  Google Scholar 

  6. Van Dyke TE. Pro-resolving mediators in the regulation of periodontal disease. Mol Aspects Med. 2017;58:21–36.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Greenstein G, Polson A. The role of local drug delivery in the management of periodontal diseases: a comprehensive review. J Periodontol. 1998;69:507–20.

    Article  PubMed  Google Scholar 

  8. Goodson JM, Hogan PE, Dunham SL. Clinical responses following periodontal treatment by local drug delivery. J Periodontol. 1985;56:81–7.

    Article  PubMed  Google Scholar 

  9. Higgins JP, Thomas, J, Chandler, J, Cumpston, M, Li, T, Page, MJ, et al. Cochrane Handbook for Systematic Reviews of Interventions. 2. Wiley-Blackwell. 2020.

  10. Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, et al. The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ. 2011;343:d5928.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Morgan RL, Whaley P, Thayer KA, Schunemann HJ. Identifying the PECO: a framework for formulating good questions to explore the association of environmental and other exposures with health outcomes. Environ Int. 2018;121:1027–31.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Sterne JAC, Savovic J, Page MJ, Elbers RG, Blencowe NS, Boutron I, et al. RoB 2: a revised tool for assessing risk of bias in randomised trials. BMJ. 2019;366:l4898.

    Article  PubMed  Google Scholar 

  13. Higgins JP, Thompson SG, Deeks JJ, Altman DG. Measuring inconsistency in meta-analyses. BMJ. 2003;327:557–60.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Elbourne DR, Altman DG, Higgins JP, Curtin F, Worthington HV, Vail A. Meta-analyses involving cross-over trials: methodological issues. Int J Epidemiol. 2002;31:140–9.

    Article  PubMed  Google Scholar 

  15. Lesaffre E, Garcia Zattera MJ, Redmond C, Huber H, Needleman I. Dentistry ISo. Reported methodological quality of split-mouth studies. J Clin Periodontol. 2007;34:756–61.

    Article  PubMed  Google Scholar 

  16. Lesaffre E, Philstrom B, Needleman I, Worthington H. The design and analysis of split-mouth studies: what statisticians and clinicians should know. Stat Med. 2009;28:3470–82.

    Article  PubMed  Google Scholar 

  17. Guida L, Bressan E, Cecoro G, Volpe AD, Del Fabbro M, Annunziata M. Short versus longer implants in sites without the need for bone augmentation: a systematic review and meta-analysis of randomized controlled trials. Materials (Basel). 2022;15:3138.

    Article  PubMed  Google Scholar 

  18. Patil KS, Mahajani M, Choudhary SH, Aldhuwayhi SD, Thakare A, Mustafa MZ. Efficacy of 1.5% metformin gel as an adjuvant to scaling, root planing, and curettage for the treatment of infrabony defects in chronic periodontitis patients. Contemp Clin Dent. 2022;13:18–23.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Shirke PY, Kolte AP, Kolte RA, Bawanakar PV. Evaluation of the clinical efficacy of 1.2% atorvastatin in the treatment of periodontal intraosseous defects by CBCT: A randomized controlled clinical trial. J Dent Res Dent Clin Dent Prospects. 2019;13:183–91.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Gonde NP, Rathod SR, Kolte AP. Comparative evaluation of 1% melatonin gel in the treatment of intrabony defect: a randomized controlled clinical trial. J Periodontol. 2022;93:1878–88.

    Article  PubMed  Google Scholar 

  21. Gupta A, Govila V, Pant VA, Gupta R, Verma UP, Ahmad H, et al. A randomized controlled clinical trial evaluating the efficacy of zoledronate gel as a local drug delivery system in the treatment of chronic periodontitis: A clinical and radiological correlation. Natl J Maxillofac Surg. 2018;9:22–32.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Kurian IG, Dileep P, Ipshita S, Pradeep AR. Comparative evaluation of subgingivally-delivered 1% metformin and Aloe vera gel in the treatment of intrabony defects in chronic periodontitis patients: a randomized, controlled clinical trial. J Investig Clin Dent. 2018;9:e12324.

    Article  PubMed  Google Scholar 

  23. Pankaj D, Sahu I, Kurian IG, Pradeep AR. Comparative evaluation of subgingivally delivered 1.2% rosuvastatin and 1% metformin gel in treatment of intrabony defects in chronic periodontitis: a randomized controlled clinical trial. J Periodontol. 2018;89:1318–25.

    Article  PubMed  Google Scholar 

  24. Kanoriya D, Singhal S, Garg V, Pradeep AR, Garg S, Kumar A Clinical efficacy of subgingivally-delivered 0.75% boric acid gel as an adjunct to mechanotherapy in chronic periodontitis: a randomized, controlled clinical trial. J Investig Clin Dent. 2018;9:e12271. https://doi.org/10.1111/jicd.12271.

  25. Pradeep AR, Patnaik K, Nagpal K, Karvekar S, Ramamurthy BL, Naik SB, et al. Efficacy of locally-delivered 1% metformin gel in the treatment of intrabony defects in patients with chronic periodontitis: a randomized, controlled clinical trial. J Investig Clin Dent. 2016;7:239–45.

    Article  PubMed  Google Scholar 

  26. Priyanka N, Abhilash A, Saquib S, Malgaonkar N, Kudyar N, Gupta A, et al. Clinical efficacy of subgingivally delivered 1.2 mg simvastatin in the treatment of patients with aggressive periodontitis: a randomized controlled clinical trial. Int J Periodontics Restorative Dent. 2017;37:e135–e41.

    Article  Google Scholar 

  27. Martande SK M, Pradeep AR, Singh SP, Suke DK. Comparative evaluation of efficacy of subgingivally delivered 1.2% Atorvastatin and 1.2% Simvastatin in the treatment of intrabony defects in chronic periodontitis: a randomized controlled trial. J Dental Res Dental Clinics Dental Prospects. 2016;11:18–25.

    Article  Google Scholar 

  28. Sharma A, Raman A, Pradeep AR. Role of 1% alendronate gel as adjunct to mechanical therapy in the treatment of chronic periodontitis among smokers. J Appl Oral Sci. 2017;25:243–9.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Pradeep AR, Kanoriya D, Singhal S, Garg V, Manohar B, Chatterjee A Comparative evaluation of subgingivally delivered 1% alendronate versus 1.2% atorvastatin gel in treatment of chronic periodontitis: a randomized placebo-controlled clinical trial. J Investig Clin Dent.2017;8. https://doi.org/10.1111/jicd.12215.

  30. Kumari M, Martande SS, Pradeep AR Subgingivally delivered 1.2% atorvastatin in the treatment of chronic periodontitis among smokers: a randomized, controlled clinical trial. J Investig Clin Dent. 2017;8. https://doi.org/10.1111/jicd.12213.

  31. Pradeep AR, Garg V, Kanoriya D, Singhal S. 1.2% rosuvastatin versus 1.2% atorvastatin gel local drug delivery and redelivery in treatment of intrabony defects in chronic periodontitis: a randomized placebo-controlled clinical trial. J Periodontol. 2016;87:756–62.

    Article  PubMed  Google Scholar 

  32. Pradeep AR, Karvekar S, Nagpal K, Patnaik K, Guruprasad CN, Kumaraswamy KM. Efficacy of locally delivered 1.2% rosuvastatin gel to non-surgical treatment of patients with chronic periodontitis: a randomized, placebo-controlled clinical trial. J Periodontol. 2015;86:738–45.

    Article  PubMed  Google Scholar 

  33. Rao NS, Pradeep AR, Bajaj P, Kumari M, Naik SB. Simvastatin local drug delivery in smokers with chronic periodontitis: a randomized controlled clinical trial. Aust Dent J. 2013;58:156–62.

    Article  PubMed  Google Scholar 

  34. Rao NS, Pradeep AR, Kumari M, Naik SB. Locally delivered 1% metformin gel in the treatment of smokers with chronic periodontitis: a randomized controlled clinical trial. J Periodontol. 2013;84:1165–71.

    Article  PubMed  Google Scholar 

  35. Pradeep AR, Kumari M, Rao NS, Martande SS, Naik SB. Clinical efficacy of subgingivally delivered 1.2% atorvastatin in chronic periodontitis: a randomized controlled clinical trial. J Periodontol. 2013;84:871–9.

    Article  PubMed  Google Scholar 

  36. Pradeep AR, Rao NS, Naik SB, Kumari M. Efficacy of varying concentrations of subgingivally delivered metformin in the treatment of chronic periodontitis: a randomized controlled clinical trial. J Periodontol. 2013;84:212–20.

    Article  PubMed  Google Scholar 

  37. Sharma A, Pradeep AR. Clinical efficacy of 1% alendronate gel as a local drug delivery system in the treatment of chronic periodontitis: a randomized, controlled clinical trial. J Periodontol. 2012;83:11–8.

    Article  PubMed  Google Scholar 

  38. Sharma A, Pradeep AR. Clinical efficacy of 1% alendronate gel in adjunct to mechanotherapy in the treatment of aggressive periodontitis: a randomized controlled clinical trial. J Periodontol. 2012;83:19–26.

    Article  PubMed  Google Scholar 

  39. Pradeep AR, Thorat MS. Clinical effect of subgingivally delivered simvastatin in the treatment of patients with chronic periodontitis: a randomized clinical trial. J Periodontol. 2010;81:214–22.

    Article  PubMed  Google Scholar 

  40. Pradeep AR, Patnaik K, Nagpal K, Karvekar S, Guruprasad CN, Kumaraswamy KM. Efficacy of 1% metformin gel in patients with moderate and severe chronic periodontitis: a randomized controlled clinical trial. J Periodontol. 2017;88:1023–9.

    Article  PubMed  Google Scholar 

  41. Pradeep AR, Nagpal K, Karvekar S, Patnaik K, Naik SB, Guruprasad CN. Platelet-rich fibrin with 1% metformin for the treatment of intrabony defects in chronic periodontitis: a randomized controlled clinical trial. J Periodontol. 2015;86:729–37.

    Article  PubMed  Google Scholar 

  42. Hunninghake DB. Therapeutic efficacy of the lipid-lowering armamentarium: the clinical benefits of aggressive lipid-lowering therapy. Am J Med. 1998;104:9S–13S.

    Article  PubMed  Google Scholar 

  43. Garrett IR, Gutierrez G, Mundy GR. Statins and bone formation. Curr Pharm Des. 2001;7:715–36.

    Article  PubMed  Google Scholar 

  44. Scarpello JH, Howlett HC. Metformin therapy and clinical uses. Diab Vasc Dis Res. 2008;5:157–67.

    Article  PubMed  Google Scholar 

  45. Viollet B, Guigas B, Sanz Garcia N, Leclerc J, Foretz M, Andreelli F. Cellular and molecular mechanisms of metformin: an overview. Clin Sci (Lond). 2012;122:253–70.

    Article  PubMed  Google Scholar 

  46. Fleisch H. Bisphosphonates: mechanisms of action and clinical use in osteoporosis-an update. Horm Metab Res. 1997;29:145–50.

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

This review utilised only publicly available and published data thus formal ethical approval was not required.

Author information

Authors and Affiliations

  1. Department of Mental and Physical Health and Preventive Medicine, University of Campania “Luigi Vanvitelli”, 80121, Naples, Italy

    Claudia Arena

  2. Multidisciplinary Department of Medical-Surgical and Odontostomatological Specialties, University of Campania “Luigi Vanvitelli”, 80121, Naples, Italy

    Pierluigi Mariani, Diana Russo & Luigi Laino

  3. Department of Clinical and Experimental Medicine, University of Foggia, Via Rovelli 50, 71122, Foggia, Italy

    Khrystyna Zhurakivska

Authors
  1. Claudia Arena
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pierluigi Mariani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Diana Russo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Khrystyna Zhurakivska
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Luigi Laino
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

CA conceptualized the study; CA and PM elaborated the methods of the study; CA, DR and PM extracted and analysed the data; CA and KZ wrote the first draft of the manuscript; CA, LL and PM revised and prepared the final version for submission. All authors have read and agreed to the published version of the manuscript. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Claudia Arena.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Arena, C., Mariani, P., Russo, D. et al. Adjunctive use of locally delivered host-modulators in intra-bony defects as part of step 2 periodontal therapy: systematic review, meta-analysis and trial sequential analysis. Evid Based Dent 24, 91–92 (2023). https://doi.org/10.1038/s41432-023-00877-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41432-023-00877-5

Search

Advanced search

Quick links