Promising approaches for the pathogenetic treatment of periodontitis
https://doi.org/10.35401/2541-9897-2025-10-3-113-118
Abstract
Background: Periodontitis, a prevalent chronic inflammatory disease, can lead to severe dental complications, including secondary adentia. It is closely associated with numerous life-threatening pathologies, including atherosclerosis, type 2 diabetes mellitus, and Alzheimer’s disease. A promising direction for developing new treatments for periodontitis is the implementation of approaches successfully used in other fields of medicine in dental practice.
Objective: To analyze and summarize the results of preclinical studies, observational research, and randomized controlled trials of drugs with pleiotropic effects that may positively influence disease mechanisms. Among the potential therapeutic approaches considered are anti-inflammatory agents (monoclonal antibodies, kinase inhibitors, proteasome inhibitors), as well as drugs used ininternal medicine that possess anti-inflammatory, immunomodulatory, antibacterial, antibiofilm, and osteoprotective properties (e.g., metformin, incretinmimetics, pirfenidone, and statins).
About the Authors
S. A. Zanin
Kuban State Medical University
Russian Federation
Russian Federation
Sergey A. Zanin, Cand. Sci (Med), Associate Professor, Acting Head of the Department of General and Clinical Pathologic Physiology
ulitsa Mitrofana Sedina 4, Krasnodar, 350063
D. A. Naumenko
Kuban State Medical University
Russian Federation
Russian Federation
Daria A. Naumenko, 3rd year student, Faculty of General Medicine
ulitsa Mitrofana Sedina 4, Krasnodar, 350063
P. S. Ezheleva
Kuban State Medical University
Russian Federation
Russian Federation
Polina S. Ezheleva, 3rd year student, Faculty of General Medicine
ulitsa Mitrofana Sedina 4, Krasnodar, 350063
S. D. Morenko
Kuban State Medical University
Russian Federation
Russian Federation
Sergei D. Morenko, 4th year student, Faculty of Dentistry
ulitsa Mitrofana Sedina 4, Krasnodar, 350063
P. P.
Kuban State Medical University
Russian Federation
Russian Federation
Pavel P. Polyakov, Cand. Sci. (Med), Associate Professor, Department of General and Clinical Pathological Physiology
ulitsa Mitrofana Sedina 4, Krasnodar, 350063
O. V. Tsymbalov
Kuban State Medical University
Russian Federation
Russian Federation
Oleg V. Tsymbalov, Dr. Sci (Med), Professor, Department of Surgical Dentistry and Maxillofacial Surgery
ulitsa Mitrofana Sedina 4, Krasnodar, 350063
References
1. Aquino-Martinez R, Khosla S, Farr JN, Monroe DG. Periodontal Disease and Senescent Cells: New Players for an Old Oral Health Problem?. Int J Mol Sci. 2020;21(20):7441. PMID: 33050175. PMCID: PMC7587987. https://doi.org/10.3390/ijms21207441
2. Cheng R, Wu Z, Li M, Shao M, Hu T. Interleukin-1β is a potential therapeutic target for periodontitis: a narrative review. Int J Oral Sci. 2020;12(1):2. PMID: 31900383. PMCID: PMC6949296. https://doi.org/10.1038/s41368-019-0068-8
3. Kim JH, Kim AR, Choi YH, et al. Tumor necrosis factor-α antagonist diminishes osteocytic RANKL and sclerostin expression in diabetes rats with periodontitis. PLoS One. 2017;12(12):e0189702. PMID: 29240821. PMCID: PMC5730195. https://doi.org/10.1371/journal.pone.0189702
4. Tar I, Végh E, Martos R, Soós B, Márton I, Szekanecz Z. Six-Month Follow-Up of Periodontal Condition in Rheumatoid Arthritis and Ankylosing Spondylitis Arthritis Patients Undergoing Anti-Tumour Necrosis Factor-α Therapy. J Clin Med. 2024;13(2):448. PMID: 38256582. PMCID: PMC10816203. https://doi.org/10.3390/jcm13020448
5. Majdi Abunemer R, Saifuddin Shaheen R, Abudullah Alghamdi R. Correlation of anti-TNF-a biological therapy with periodontal conditions and osteonecrosis in autoimmune patients: A systematic review. Saudi Dent J. 2023;35(7):785-796. PMID: 38025596. PMCID: PMC10658390. https://doi.org/10.1016/j.sdentj.2023.07.006
6. Zhang J, Xu C, Gao L, Zhang D, Li C, Liu J. Influence of anti-rheumatic agents on the periodontal condition of patients with rheumatoid arthritis and periodontitis: A systematic review and meta-analysis. J Periodontal Res. 2021;56(6):1099-1115. PMID: 34514591. https://doi.org/10.1111/jre.12925
7. Brijs K, Miclotte I, Vermeire S, Darche V, Politis C. Osteonecrosis of the jaw in patients with inflammatory bowel disease treated with tumour necrosis factor alpha inhibitors. Int J Oral Maxillofac Surg. 2020;49(3):317-324. PMID: 31466830. https:// doi.org/10.1016/j.ijom.2019.08.007
8. Olofsson R, Korytowska M, Almhöjd U, Almståhl A, Cevik-Aras H. Oral health, dental treatment, and medication related osteonecrosis of the jaw in multiple myeloma – a longitudinal cohort study. BMC Oral Health. 2024;24(1):184. PMID: 38317122. PMCID: PMC10840162. https://doi.org/10.1186/s12903-024-03943-1
9. Zhang Z, Song J, Kwon SH, et al. Pirfenidone Inhibits Alveolar Bone Loss in Ligature-Induced Periodontitis by Suppressing the NF-κB Signaling Pathway in Mice. Int J Mol Sci. 2023;24(10):8682. PMID: 37240020. PMCID: PMC10218211. https://doi.org/10.3390/ijms24108682
10. Tseng CH. Metformin and risk of gingival/periodontal diseases in diabetes patients: A retrospective cohort study. Front Endocrinol (Lausanne). 2022;13:1036885. PMID: 36277720. PMCID: PMC9583654. https://doi.org/10.3389/fendo.2022.1036885
11. Araújo AA, Pereira ASBF, Medeiros CACX, et al. Effects of metformin on inflammation, oxidative stress, and bone loss in a rat model of periodontitis. PLoS One. 2017;12(8):e0183506. PMID: 28847008. PMCID: PMC5573680. https://doi.org/10.1371/journal.pone.0183506
12. Xiang M, Liu Y, Guo Q, et al. Metformin enhances the therapeutic effects of extracellular vesicles derived from human periodontal ligament stem cells on periodontitis. Scientific Reports. 2024;14(1):19940. https://doi.org/10.1038/s41598-024-70688-w
13. Nicolini AC, Grisa TA, Muniz FWMG, Rösing CK, Cavagni J. Effect of adjuvant use of metformin on periodontal treatment: a systematic review and meta-analysis. Clin Oral Investig. 2019;23(6):2659-2666. PMID: 30327951. https://doi.org/10.1007/s00784-018-2666-9
14. Zhang Y, Yuan X, Wu Y, et al. Liraglutide regulates bone destruction and exhibits anti-inflammatory effects in periodontitis in vitro and in vivo. J Dent. 2020;94:103310. PMID: 32119967. https://doi.org/10.1016/j.jdent.2020.103310
15. Gheonea TC, Șurlin P, Nicolae FM, Gheorghe DN, Popescu DM, Rogoveanu I. Dipeptidyl-Peptidase-4 and Glucagon-like-Peptide-1, a Link in the Connection between Periodontitis and Diabetes Mellitus-What Do We Know So Far?-A Scoping Review. J Clin Med. 2024;13(3):903. PMID: 38337597. PMCID: PMC10856081. https://doi.org/10.3390/jcm13030903
16. González-Quintanilla D, Abásolo N, Astudillo P. WNT signaling in periodontal disease. Frontiers in Dental Medicine. 2021;2. https://doi.org/10.3389/fdmed.2021.763308
17. de Carvalho RDP, Casarin RCV, de Lima PO, Cogo-Müller K. Statins with potential to control periodontitis: From biological mechanisms to clinical studies. J Oral Biosci. 2021;63(3):232-244. PMID: 34146687. https://doi.org/10.1016/j.job.2021.06.002
18. de Araújo Júnior RF, Souza TO, de Moura LM, et al. Atorvastatin decreases bone loss, inflammation and oxidative stress in experimental periodontitis. PLoS One. 2013;8(10):e75322.PMID: 24130702. PMCID: PMC3794930. https://doi.org/10.1371/journal.pone.0075322
19. Dalcico R, de Menezes AM, Deocleciano OB, et al. Protective mechanisms of simvastatin in experimental periodontal disease. J Periodontol. 2013;84(8):1145-1157. PMID: 23181416. https://doi.org/10.1902/jop.2012.120114
20. Parolina de Carvalho RD, de Andrade Moreno J, Roque SM, et al. Statins and oral biofilm: Simvastatin as a promising drug to control periodontal dysbiosis. Oral Dis. 2024;30(2):669-680. PMID: 36416468. https://doi.org/10.1111/odi.14446
21. Radbakhsh S, Katsiki N, Santos RD, Mikhailidis DP, Mantzoros CS, Sahebkar A. Effects of statins on specialized pro-resolving mediators: An additional pathway leading to resolution of inflammation. Metabolism. 2022;132:155211. PMID: 35533891. https://doi.org/10.1016/j.metabol.2022.155211
22. Kwon MJ, Byun SH, Kim JH, et al. Longitudinal follow-up study of the association between statin use and chronic periodontitis using national health screening cohort of Korean population. Sci Rep. 2022;12(1):5504. PMID: 35365732. PMCID: PMC8976040. https://doi.org/10.1038/s41598-022-09540-y
23. Wang AY, Lin GL, Keller JJ, Wang LH. Association between antihyperlipidemic agents and the risk of chronic periodontitis in patients with hyperlipidemia: A population-based retrospective cohort study in Taiwan. J Periodontol. 2024;95(5):483-493. PMID: 37793052. https://doi.org/10.1002/jper.23-0166
24. Cecoro G, Piccirillo A, Martuscelli G, Del Fabbro M, Annunziata M, Guida L. Efficacy of locally delivered statins as an adjunct to scaling and root planning in the treatment of periodontitis: a systematic review and meta-analysis. Eur Rev Med Pharmacol Sci. 2021;25(18):5737-5754. PMID: 34604965. https://doi.org/10.26355/eurrev_202109_26792
25. Gegout PY, Stutz C, Huck O. Gels as adjuvant to nonsurgical periodontal therapy: A systematic review and metaanalysis. Heliyon. 2023;9(7):e17789. PMID: 37455970. PMCID: PMC10345361. https://doi.org/10.1016/j.heliyon.2023.e17789
26. Greethurst AR, Galletti C, Lo Giudice R, et al. The Use of Statins as an Adjunctive Periodontal Disease Treatment: Systematic Review and Meta-Analysis. Dent J (Basel). 2024;12(6):150. PMID: 38920851. PMCID: PMC11202911. https://doi.org/10.3390/dj12060150
27. Bertl K, Parllaku A, Pandis N, Buhlin K, Klinge B, Stavropoulos A. The effect of local and systemic statin use as an adjunct to non-surgical and surgical periodontal therapy-A systematic review and meta-analysis. J Dent. 2017;67:18-28. PMID: 28855141. https://doi.org/10.1016/j.jdent.2017.08.011
28. Subramanian S, Emami H, Vucic E, et al. High-dose atorvastatin reduces periodontal inflammation: a novel pleiotropic effect of statins. J Am Coll Cardiol. 2013;62(25):2382-2391. PMID: 24070911. PMCID: PMC6849694. https://doi.org/10.1016/j.jacc.2013.08.1627
29. Ma W, Zou Z, Yang L, et al. Exploring the bi-directional relationship between periodontitis and dyslipidemia: a comprehensive systematic review and meta-analysis. BMC Oral Health. 2024;24(1):508. PMID: 38684998. PMCID: PMC11059608. https://doi.org/10.1186/s12903-023-03668-7
30. Pérez-Carrillo L, Aragón-Herrera A, Giménez-Escamilla I, et al. Cardiac Sodium/Hydrogen Exchanger (NHE11) as a Novel Potential Target for SGLT2i in Heart Failure: A Preliminary Study. Pharmaceutics. 2022;14(10):1996. PMID: 36297433. PMCID: PMC9608584. https://doi.org/10.3390/pharmaceutics14101996
31. Mo C, Ke J, Zhao D, Zhang B. Role of the renin-angiotensin-aldosterone system in bone metabolism. J Bone Miner Metab. 2020;38(6):772-779. PMID: 32734523. https://doi.org/10.1007/s00774-020-01132-y
32. Grauballe MC, Bentzen BH, Björnsson M, et al. The effect of spironolactone on experimental periodontitis in rats. J Periodontal Res. 2005;40(3):212-217. PMID: 15853966. https://doi.org/10.1111/j.1600-0765.2005.00792.x
Review
For citations:
Zanin S.A., Naumenko D.A., Ezheleva P.S., Morenko S.D., P. P., Tsymbalov O.V. Promising approaches for the pathogenetic treatment of periodontitis. Innovative Medicine of Kuban. 2025;10(3):113-118. (In Russ.) https://doi.org/10.35401/2541-9897-2025-10-3-113-118
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