inovmedИнновационная медицина КубаниInnovative Medicine of Kuban2541-9897Scientific Research Institute – Ochapovsky Regional Clinical Hospital No. 110.35401/2541-9897-2025-10-3-113-118inovmed-1281Research ArticleОБЗОРЫREVIEWSПерспективы патогенетического лечения пародонтитаPromising approaches for the pathogenetic treatment of periodontitishttps://orcid.org/0000-0002-5667-0623ЗанинС. А.ZaninS. A.

Занин Сергей Александрович, к. м. н., доцент, и.о. заведующего кафедрой общей и клинической патологической физиологии

350063, Краснодар, ул. Митрофана Седина 4

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

https://orcid.org/0009-0005-7731-4520НауменкоД А.NaumenkoD. A.

Науменко Дарья Антоновна, студент 3-го курса лечебного факультета

350063, Краснодар, ул. Митрофана Седина 4

Daria A. Naumenko, 3rd year student, Faculty of General Medicine

ulitsa Mitrofana Sedina 4, Krasnodar, 350063

https://orcid.org/0009-0005-5556-6217ЕжелеваП. С.EzhelevaP. S.

Ежелева Полина Сергеевна, студент 3-го курса лечебного факультета

350063, Краснодар, ул. Митрофана Седина 4

Polina S. Ezheleva, 3rd year student, Faculty of General Medicine

ulitsa Mitrofana Sedina 4, Krasnodar, 350063

https://orcid.org/0000-0001-9697-8457МоренкоС. Д.MorenkoS. D.

Моренко Сергей Дмитриевич, студент 4-го курса стоматологического факультета

350063, Краснодар, ул. Митрофана Седина 4

Sergei D. Morenko, 4th year student, Faculty of Dentistry

ulitsa Mitrofana Sedina 4, Krasnodar, 350063

https://orcid.org/0000-0002-9532-0626ПоляковП. П.P.P.

Поляков Павел Павлович, к. м. н., доцент кафедры общей и клинической патологической физиологии

350063, Краснодар, ул. Митрофана Седина 4

Pavel P. Polyakov, Cand. Sci. (Med), Associate Professor, Department of General and Clinical Pathological Physiology

ulitsa Mitrofana Sedina 4, Krasnodar, 350063

palpal.p@yandex.ruhttps://orcid.org/0000-0002-6203-9272ЦымбаловО. В.TsymbalovO. V.

Цымбалов Олег Владимирович, д. м. н., профессор кафедры хирургической стоматологии и челюстно-лицевой хирургии

350063, Краснодар, ул. Митрофана Седина 4

Oleg V. Tsymbalov, Dr. Sci (Med), Professor, Department of Surgical Dentistry and Maxillofacial Surgery

ulitsa Mitrofana Sedina 4, Krasnodar, 350063

Кубанский государственный медицинский университетРоссияKuban State Medical UniversityRussian Federation202530092025103113118Copyright © Занин С.А., Науменко Д.А., Ежелева П.С., Моренко С.Д., Поляков П.П., Цымбалов О.В., 20252025Занин С.А., Науменко Д.А., Ежелева П.С., Моренко С.Д., Поляков П.П., Цымбалов О.В.Zanin S.A., Naumenko D.A., Ezheleva P.S., Morenko S.D., P. P., Tsymbalov O.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.innovmedkub.ru/jour/article/view/1281

Актуальность: Пародонтит – одно из наиболее распространенных хронических воспалительных заболеваний человека и является причиной тяжелых стоматологических осложнений, вплоть до вторичной адентии, тесно связан с патогенезом многих опасных для жизни заболеваний различных систем, таких как атеросклероз, сахарный диабет 2-го типа и болезнь Альцгеймера. Перспективным направлением поиска новых методов лечения пародонтита является внедрение в стоматологическую практику подходов, успешно применяемых в других областях медицины.Цель: Анализ и обобщение результатов некоторых преклинических работ, обсервационных исследований и рандомизированных контролируемых испытаний препаратов, плейотропные эффекты которых могут положительно влиять на механизмы развития заболевания. Среди возможных подходов такой терапии рассматриваются воздействие на воспаление (моноклональные антитела, киназные ингибиторы, протеосомные ингибиторы) и применение препаратов, заимствованных из практики интерниста, обладающих антивоспалительными, иммуномодулирующими, антибактериальными, антибиопленочными и остеопротективными эффектами (метформин, инкретиномиметики, пирфенидон, статины).

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).

пародонтитNF-κBметформинагонисты рецепторов глюкагоноподобного пептида 1статиныperiodontitisNF-κBmetforminglucagon-like peptide-1 receptor agonistsstatinsReferencesAquino-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/ijms21207441Aquino-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/ijms21207441Cheng 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/s41368-019-0068-8Cheng 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/s41368-019-0068-8Kim 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.0189702Kim 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.0189702Tar 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/jcm13020448Tar 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/jcm13020448Majdi 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.2023.07.006Majdi 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.2023.07.006Zhang 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.12925Zhang 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.12925Brijs 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.2019.08.007Brijs 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.2019.08.007Olofsson 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/s12903-024-03943-1Olofsson 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/s12903-024-03943-1Zhang 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/ijms24108682Zhang 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/ijms24108682Tseng 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.2022.1036885Tseng 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.2022.1036885Araújo 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.0183506Araújo 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.0183506Xiang 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-wXiang 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-wNicolini 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/s00784-018-2666-9Nicolini 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/s00784-018-2666-9Zhang 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.2020.103310Zhang 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.2020.103310Gheonea 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/jcm13030903Gheonea 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/jcm13030903González-Quintanilla D, Abásolo N, Astudillo P. WNT signaling in periodontal disease. Frontiers in Dental Medicine. 2021;2. https://doi.org/10.3389/fdmed.2021.763308González-Quintanilla D, Abásolo N, Astudillo P. WNT signaling in periodontal disease. Frontiers in Dental Medicine. 2021;2. https://doi.org/10.3389/fdmed.2021.763308de 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.2021.06.002de 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.2021.06.002de 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.0075322de 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.0075322Dalcico 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.2012.120114Dalcico 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.2012.120114Parolina 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.14446Parolina 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.14446Radbakhsh 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.2022.155211Radbakhsh 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.2022.155211Kwon 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-yKwon 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-yWang 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.23-0166Wang 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.23-0166Cecoro 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_26792Cecoro 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_26792Gegout 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.e17789Gegout 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.e17789Greethurst 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/dj12060150Greethurst 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/dj12060150Bertl 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.2017.08.011Bertl 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.2017.08.011Subramanian 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.2013.08.1627Subramanian 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.2013.08.1627Ma 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/s12903-023-03668-7Ma 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/s12903-023-03668-7Pérez-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/pharmaceutics14101996Pérez-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/pharmaceutics14101996Mo 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-yMo 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-yGrauballe 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.xGrauballe 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

The authors declare that there are no conflicts of interest present.