Efficacy of Minocycline Hydrochloride Combined with Tinidazole in the Treatment of Chronic Periodontitis and Its Impact on Inflammatory Cytokine Levels
Abstract
The aim of this study was to evaluate the clinical and inflammatory outcomes of minocycline hydrochloride combined with tinidazole in patients with chronic periodontitis.
PubMed, Cochrane Library, Embase, CNKI, WanFang Data, and VIP were searched through December 2025 for randomized and nonrandomized controlled studies. Randomized trials were assessed using the Cochrane Risk of Bias tool, while the cohort study was assessed using ROBINS-I. Meta-analysis was conducted using RevMan 5.3. Random-effects models were applied when substantial heterogeneity was present, and sensitivity analyses were performed by excluding the cohort study.
Fourteen studies were included. Compared with the control treatment, combination therapy was associated with greater improvements in gingival index (MD=−0.71; 95% CI, −0.77 to −0.65), probing pocket depth (MD=−0.87; 95% CI, −1.07 to −0.66), clinical attachment level (MD=−0.77; 95% CI, −1.06 to −0.49), plaque index (MD=−0.38; 95% CI, −0.45 to −0.32), and sulcus bleeding index (MD=−0.68; 95% CI, −0.96 to −0.40). Changes were also observed in several inflammatory and immune-related indicators, whereas CRP did not differ significantly between the groups. Substantial heterogeneity was present for most outcomes.
Overall, minocycline hydrochloride combined with tinidazole may provide additional short-term benefits for patients with chronic periodontitis. Nevertheless, these findings should be interpreted cautiously because of methodological limitations, substantial heterogeneity, incomplete safety reporting, and short follow-up periods.
1. Sethi G, Grover V, Gupta J, Jain A. Response to adjunctive antibiotic therapy along with nonsurgical periodontal therapy in the treatment of peri-implantitis and chronic periodontitis patients: An exploratory review. Journal of Indian Society of Periodontology. 2024;28(4):393-406.
2. Wielento A, Lagosz-Cwik KB, Potempa J, Grabiec AM. The Role of Gingival Fibroblasts in the Pathogenesis of Periodontitis. J Dent Res. 2023;102(5):489-96.
3. Cardoso EM, Reis C, Manzanares-Céspedes MC. Chronic periodontitis, inflammatory cytokines, and interrelationship with other chronic diseases. Postgrad Med. 2018;130(1):98-104.
4. Carvalho-Filho PC, Gomes-Filho IS, Meyer R, Olczak T, Xavier MT, Trindade SC. Role of Porphyromonas gingivalis HmuY in Immunopathogenesis of Chronic Periodontitis. Mediat Inflamm. 2016;2016:7465852.
5. He S, Wei S, Wang J, Ji P. Chronic periodontitis and oral health-related quality of life in Chinese adults: A population-based, cross-sectional study. J Periodontol. 2018;89(3):275-84.
6. Akram Z, Abduljabbar T, Abu Hassan MI, Javed F, Vohra F. Cytokine Profile in Chronic Periodontitis Patients with and without Obesity: A Systematic Review and Meta-Analysis. Dis Markers. 2016;2016:4801418.
7. Zhang D, Liu W, Miao R, Wang L, Zhou X, Wang H, et al. Chronic Periodontitis is a Risk Factor of Renal Dysfunction in Patients with Type 2 Diabetes. Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association. 2021;129(6):407-12.
8. Bullon P, Newman HN, Battino M. Obesity, diabetes mellitus, atherosclerosis and chronic periodontitis: a shared pathology via oxidative stress and mitochondrial dysfunction? Periodontol 2000. 2014;64(1):139-53.
9. Lei D, Zhou Y, Tang S, Li Y. Effect of chronic periodontitis on quality of life and severity in patients with bronchiectasis. Shanghai Kou Qiang Yi Xue = Shanghai Journal of Stomatology. 2024;33(2):186-9.
10. Mkrtchyan S, Dunamalyan R, Sakanyan G, Varuzhanyan H, Hambardzumyan S, Mardiyan M. EFFECT OF CHRONIC PERIODONTITIS ON HEALTH-RELATED QUALITY OF LIFE AND ANXIETY AMONG PATIENTS IN YEREVAN, ARMENIA. Georgian Medical News. 2023;(335):36-40.
11. Mlachkova A, Popova C, Doseva V. Presence of IL-8 Gene Polymorphism and IL-8 Serum Levels in Patients with Chronic Periodontitis - Literature Review. Folia Medica. 2020;62(2):253-7.
12. Dosseva-Panova VT, Popova CL, Panov VE. Subgingival microbial profile and production of proinflammatory cytokines in chronic periodontitis. Folia Medica. 2014;56(3):152-60.
13. Wu Q, Cao Z, Wu S. Study on the Clinical Efficacy of Combined Therapy with Minocycline Hydrochloride Ointment and Tinidazole for Chronic Periodontitis: Retrospective Study. J Inflamm Res. 2025;18:4641-9.
14. Jervøe-Storm P, Bunke J, Worthington HV, Needleman I, Cosgarea R, MacDonald L, et al. Adjunctive antimicrobial photodynamic therapy for treating periodontal and peri-implant diseases. Cochrane Db Syst Rev. 2024;7(7):CD011778.
15. Abdullah AN, Al-Habib OAM, Mohammed SA. Changes in the level of cytokines in the saliva of hypertensive patients with chronic periodontitis after scaling and root planning. Prostag Oth Lipid M. 2023;169:106765.
16. Singh A, Vasudevan S, Palle AR, Atchuta A, Bhadauriya S. Comparative Evaluation of Scaling and Root Planing with and without Oxygen-releasing Gel in the Treatment of Chronic Periodontitis: A Split-mouth Study. The Journal of Contemporary Dental Practice. 2024;25(5):445-52.
17. van Steenberghe D, Bercy P, Kohl J, De Boever J, Adriaens P, Vanderfaeillie A, et al. Subgingival minocycline hydrochloride ointment in moderate to severe chronic adult periodontitis: a randomized, double-blind, vehicle-controlled, multicenter study. J Periodontol. 1993;64(7):637-44.
18. Yuan Y, Xu J. Application analysis of minocycline hydrochloride ointment combined with tinidazole in the treatment of chronic periodontitis. Minerva Surg. 2024;79(1):123-5.
19. Yan Q. Effect of minocycline hydrochloride ointment in the treatment of chronic periodontitis. Proceeding of Clinical Medicine 2024;33(10):742-4. DOI: 10.16047/j.cnki.cn14-1300/r.2024.10.019.
20. Wang H Y. Clinical effect and safety study of tinidazole tablets combined with minocycline hydrochloride ointment in the treatment of chronic periodontitis. Chinese Journal of Modern Drug Application 2023;17(19):124-6. DOI: 10.14164/j.cnki.cn11-5581/r.2023.19.033.
21. Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ (Clinical Research Ed.). 2011;343:d5928.
22. Chen H, Ma S, Liu X, et al. Clinical study on minocycline combined with tinidazole in the treatment of patients with severe chronic periodontitis. Chinese Journal of Clinical Pharmacology 2025;41(10):1373-8. DOI: 10.13699/j.cnki.1001-6821.2025.10.005.
23. Liu C X. Clinical effect of minocycline hydrochloride ointment combined with tinidazole in the treatment of patients with chronic periodontitis. Tianjin Pharmacy 2023;35(04):47-50.
24. He D W, Sun J. Clinical value of minocycline hydrochloride combined with tinidazole in the treatment of patients with chronic periodontitis. Guide of China Medicine 2022;20(05):100-102+106. DOI: 10.15912/j.cnki.gocm.2022.05.029.
25. Liu H Y. Safety analysis of minocycline hydrochloride ointment combined with tinidazole in the treatment of chronic periodontitis. Journal of North Pharmacy 2023;20(11):118-20.
26. Xia T, Zhang T J, Dong P. Efficacy of minocycline hydrochloride ointment combined with tinidazole in the treatment of periodontitis and its influence on periodontal indexes of patients. Clinical Rational Drug Use 2023;16(13):19-21+26. DOI: 10.15887/j.cnki.13-1389/r.2023.13.006.
27. Xu C P, Tao Y. Clinical efficacy observation of minocycline hydrochloride ointment combined with tinidazole in the treatment of chronic periodontitis. Journal of Modern Medicine & Health Research 2022;6(21):59-62.
28. Ou S Z, Xu Y X. Clinical efficacy of minocycline hydrochloride ointment combined with tinidazole tablets in the treatment of chronic periodontitis. Journal of Clinical Rational Drug Use 2022;15(03):124-6. DOI: 10.15887/j.cnki.13-1389/r.2022.03.037.
29. Yan Z G. Effects of minocycline hydrochloride ointment combined with tinidazole on oxidative stress response and inflammatory factor levels in gingival crevicular fluid of patients with chronic periodontitis. China Medical Herald 2021;18(30):121-4. DOI: 10.20047/j.issn1673-7210.2021.30.030.
30. Liu Q Z, Pang Z Z, Li Y. Effects of minocycline hydrochloride ointment combined with tinidazole on IL-10, TGF-β levels in gingival crevicular fluid and Th17, Treg levels in peripheral blood of patients with chronic periodontitis. Journal of Clinical and Experimental Medicine 2019;18(09):966-9.
31. Jiang X X. Clinical effect analysis of minocycline hydrochloride combined with tinidazole in the treatment of severe chronic periodontitis. Clinical Medical Engineering 2020;27(03):321-2.
32. Zhang Z B, Zhang Y, Huang W L, et al. Clinical study on tinidazole tablets combined with minocycline hydrochloride ointment in the treatment of chronic periodontitis. Chinese Journal of Clinical Pharmacology 2018;34(03):248-50. DOI: 10.13699/j.cnki.1001-6821.2018.03.017.
33. Guo L, Lin T, Feng Y. Comparison of efficacy and safety of minocycline hydrochloride combined with metronidazole or tinidazole in the treatment of chronic periodontitis. Drug Evaluation Research 2017;40(09):1294-6.
2. Wielento A, Lagosz-Cwik KB, Potempa J, Grabiec AM. The Role of Gingival Fibroblasts in the Pathogenesis of Periodontitis. J Dent Res. 2023;102(5):489-96.
3. Cardoso EM, Reis C, Manzanares-Céspedes MC. Chronic periodontitis, inflammatory cytokines, and interrelationship with other chronic diseases. Postgrad Med. 2018;130(1):98-104.
4. Carvalho-Filho PC, Gomes-Filho IS, Meyer R, Olczak T, Xavier MT, Trindade SC. Role of Porphyromonas gingivalis HmuY in Immunopathogenesis of Chronic Periodontitis. Mediat Inflamm. 2016;2016:7465852.
5. He S, Wei S, Wang J, Ji P. Chronic periodontitis and oral health-related quality of life in Chinese adults: A population-based, cross-sectional study. J Periodontol. 2018;89(3):275-84.
6. Akram Z, Abduljabbar T, Abu Hassan MI, Javed F, Vohra F. Cytokine Profile in Chronic Periodontitis Patients with and without Obesity: A Systematic Review and Meta-Analysis. Dis Markers. 2016;2016:4801418.
7. Zhang D, Liu W, Miao R, Wang L, Zhou X, Wang H, et al. Chronic Periodontitis is a Risk Factor of Renal Dysfunction in Patients with Type 2 Diabetes. Experimental and Clinical Endocrinology & Diabetes : Official Journal, German Society of Endocrinology [and] German Diabetes Association. 2021;129(6):407-12.
8. Bullon P, Newman HN, Battino M. Obesity, diabetes mellitus, atherosclerosis and chronic periodontitis: a shared pathology via oxidative stress and mitochondrial dysfunction? Periodontol 2000. 2014;64(1):139-53.
9. Lei D, Zhou Y, Tang S, Li Y. Effect of chronic periodontitis on quality of life and severity in patients with bronchiectasis. Shanghai Kou Qiang Yi Xue = Shanghai Journal of Stomatology. 2024;33(2):186-9.
10. Mkrtchyan S, Dunamalyan R, Sakanyan G, Varuzhanyan H, Hambardzumyan S, Mardiyan M. EFFECT OF CHRONIC PERIODONTITIS ON HEALTH-RELATED QUALITY OF LIFE AND ANXIETY AMONG PATIENTS IN YEREVAN, ARMENIA. Georgian Medical News. 2023;(335):36-40.
11. Mlachkova A, Popova C, Doseva V. Presence of IL-8 Gene Polymorphism and IL-8 Serum Levels in Patients with Chronic Periodontitis - Literature Review. Folia Medica. 2020;62(2):253-7.
12. Dosseva-Panova VT, Popova CL, Panov VE. Subgingival microbial profile and production of proinflammatory cytokines in chronic periodontitis. Folia Medica. 2014;56(3):152-60.
13. Wu Q, Cao Z, Wu S. Study on the Clinical Efficacy of Combined Therapy with Minocycline Hydrochloride Ointment and Tinidazole for Chronic Periodontitis: Retrospective Study. J Inflamm Res. 2025;18:4641-9.
14. Jervøe-Storm P, Bunke J, Worthington HV, Needleman I, Cosgarea R, MacDonald L, et al. Adjunctive antimicrobial photodynamic therapy for treating periodontal and peri-implant diseases. Cochrane Db Syst Rev. 2024;7(7):CD011778.
15. Abdullah AN, Al-Habib OAM, Mohammed SA. Changes in the level of cytokines in the saliva of hypertensive patients with chronic periodontitis after scaling and root planning. Prostag Oth Lipid M. 2023;169:106765.
16. Singh A, Vasudevan S, Palle AR, Atchuta A, Bhadauriya S. Comparative Evaluation of Scaling and Root Planing with and without Oxygen-releasing Gel in the Treatment of Chronic Periodontitis: A Split-mouth Study. The Journal of Contemporary Dental Practice. 2024;25(5):445-52.
17. van Steenberghe D, Bercy P, Kohl J, De Boever J, Adriaens P, Vanderfaeillie A, et al. Subgingival minocycline hydrochloride ointment in moderate to severe chronic adult periodontitis: a randomized, double-blind, vehicle-controlled, multicenter study. J Periodontol. 1993;64(7):637-44.
18. Yuan Y, Xu J. Application analysis of minocycline hydrochloride ointment combined with tinidazole in the treatment of chronic periodontitis. Minerva Surg. 2024;79(1):123-5.
19. Yan Q. Effect of minocycline hydrochloride ointment in the treatment of chronic periodontitis. Proceeding of Clinical Medicine 2024;33(10):742-4. DOI: 10.16047/j.cnki.cn14-1300/r.2024.10.019.
20. Wang H Y. Clinical effect and safety study of tinidazole tablets combined with minocycline hydrochloride ointment in the treatment of chronic periodontitis. Chinese Journal of Modern Drug Application 2023;17(19):124-6. DOI: 10.14164/j.cnki.cn11-5581/r.2023.19.033.
21. Higgins JPT, Altman DG, Gøtzsche PC, Jüni P, Moher D, Oxman AD, et al. The Cochrane Collaboration's tool for assessing risk of bias in randomised trials. BMJ (Clinical Research Ed.). 2011;343:d5928.
22. Chen H, Ma S, Liu X, et al. Clinical study on minocycline combined with tinidazole in the treatment of patients with severe chronic periodontitis. Chinese Journal of Clinical Pharmacology 2025;41(10):1373-8. DOI: 10.13699/j.cnki.1001-6821.2025.10.005.
23. Liu C X. Clinical effect of minocycline hydrochloride ointment combined with tinidazole in the treatment of patients with chronic periodontitis. Tianjin Pharmacy 2023;35(04):47-50.
24. He D W, Sun J. Clinical value of minocycline hydrochloride combined with tinidazole in the treatment of patients with chronic periodontitis. Guide of China Medicine 2022;20(05):100-102+106. DOI: 10.15912/j.cnki.gocm.2022.05.029.
25. Liu H Y. Safety analysis of minocycline hydrochloride ointment combined with tinidazole in the treatment of chronic periodontitis. Journal of North Pharmacy 2023;20(11):118-20.
26. Xia T, Zhang T J, Dong P. Efficacy of minocycline hydrochloride ointment combined with tinidazole in the treatment of periodontitis and its influence on periodontal indexes of patients. Clinical Rational Drug Use 2023;16(13):19-21+26. DOI: 10.15887/j.cnki.13-1389/r.2023.13.006.
27. Xu C P, Tao Y. Clinical efficacy observation of minocycline hydrochloride ointment combined with tinidazole in the treatment of chronic periodontitis. Journal of Modern Medicine & Health Research 2022;6(21):59-62.
28. Ou S Z, Xu Y X. Clinical efficacy of minocycline hydrochloride ointment combined with tinidazole tablets in the treatment of chronic periodontitis. Journal of Clinical Rational Drug Use 2022;15(03):124-6. DOI: 10.15887/j.cnki.13-1389/r.2022.03.037.
29. Yan Z G. Effects of minocycline hydrochloride ointment combined with tinidazole on oxidative stress response and inflammatory factor levels in gingival crevicular fluid of patients with chronic periodontitis. China Medical Herald 2021;18(30):121-4. DOI: 10.20047/j.issn1673-7210.2021.30.030.
30. Liu Q Z, Pang Z Z, Li Y. Effects of minocycline hydrochloride ointment combined with tinidazole on IL-10, TGF-β levels in gingival crevicular fluid and Th17, Treg levels in peripheral blood of patients with chronic periodontitis. Journal of Clinical and Experimental Medicine 2019;18(09):966-9.
31. Jiang X X. Clinical effect analysis of minocycline hydrochloride combined with tinidazole in the treatment of severe chronic periodontitis. Clinical Medical Engineering 2020;27(03):321-2.
32. Zhang Z B, Zhang Y, Huang W L, et al. Clinical study on tinidazole tablets combined with minocycline hydrochloride ointment in the treatment of chronic periodontitis. Chinese Journal of Clinical Pharmacology 2018;34(03):248-50. DOI: 10.13699/j.cnki.1001-6821.2018.03.017.
33. Guo L, Lin T, Feng Y. Comparison of efficacy and safety of minocycline hydrochloride combined with metronidazole or tinidazole in the treatment of chronic periodontitis. Drug Evaluation Research 2017;40(09):1294-6.
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| Issue | Articles in Press | |
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| Keywords | ||
| Combination Cytokines Drug therapy Minocycline Tinidazole Tinidazole chronic periodontitis | ||
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How to Cite
1.
Chen M, Chen K, Zhong S, Shen C. Efficacy of Minocycline Hydrochloride Combined with Tinidazole in the Treatment of Chronic Periodontitis and Its Impact on Inflammatory Cytokine Levels. Iran J Allergy Asthma Immunol. 2026;:1-18.
