Comparative Assessment of Impact of Interleukins on Orthodontic Miniscrew Stability, Insights to Osseointegration and its Failure Rates: A Systematic Review and Meta-Analysis

Authors

  • Ayesha Imtiaz Baqai Medical University, Karachi, Pakistan.
  • Sadia Nazir Shahida Islam Dental College, Lodhran ,Pakistan.
  • Amna Farrukh Hamdard University Dental Hospital, Karachi, Pakistan.
  • Farah Tasleem Isra Dental College ,Isra university Hyderabad ,Sindh, Pakistan
  • Ejaz Ahmed International Max Planck Research Institute, Berlin, Germany. https://orcid.org/0009-0003-6230-4288

DOI:

https://doi.org/10.36283/ziun-pjmd14-3/071

Keywords:

Interleukins, Orthodontic Anchorage Procedures, Osseointegration, Mini-Implants, Inflammation Mediators

Abstract

Background: The immune system functions under the influence of interleukins because these cytokines affect bone metabolism and the process of osseointegration while determining orthodontic miniscrew stability. This systematic review and meta-analysis served to determine the influence of interleukins on the operations of orthodontic miniscrew stability, osseointegration, and precession outcomes.

Methods: The research included a systematic review and meta-analysis with references to the PRISMA 2020 criteria. Until March of 2025, the electronic databases were searched to find the studies referring to the interleukin levels according to the orthodontic miniscrews or implants. Studies were eligible in cases of RCTs, observational, and retrospective. Risk of bias was assessed using the Cochrane Risk of Bias Tool for RCTs and the Newcastle-Ottawa Scale (NOS) for observational studies. The GRADE framework was used to evaluate the certainty of evidence for the included outcomes. The analysis of the comparison was performed with RevMan 5.4.1, which was done using the inverse variance model and the random-effects model.

Results: Nine publications that used 179 participants were selected. There was a significant increase in the interleukin levels in the study groups as contrasted to the controls (SMD: 1.47; 95% CI: 0.18-2.75; p < 0.05). There was a high heterogeneity (I2 = 88%). Subgroup analyses showed higher IL-1β and IL-17 at unsuccessful or inflamed miniscrew sites.  

Discussion: Higher levels of interleukin, mainly IL-1β and IL-17, are linked to miniscrew instability and peri-implant inflammation, which identifies the diagnostic and prognostic possibilities. Generalizability is limited by small sample size and disparity. These results advocate the use of cytokine profiling as a means by which the success of such implants can be determined.

Author Biographies

  • Ayesha Imtiaz, Baqai Medical University, Karachi, Pakistan.

    Department of Science of Dental Materials,

  • Sadia Nazir, Shahida Islam Dental College, Lodhran ,Pakistan.

    Department of Orthodontics, 

  • Amna Farrukh, Hamdard University Dental Hospital, Karachi, Pakistan.

    Department of Orthodontics,

  • Farah Tasleem, Isra Dental College ,Isra university Hyderabad ,Sindh, Pakistan


    Department of Dental Materials,

  • Ejaz Ahmed, International Max Planck Research Institute, Berlin, Germany.

    School of Pathology,

References

1. Fontes J, Martin VZ, Resende M, Colaço B, Gomes PdS, Amarante JM. Effect of splinting on orthodontic mini-implant tipping and bone histomorphometric parameters: An in vivo animal model study. J Funct Biomater. 2023 Oct;14(5):239. doi:10.3390/jfb14050239.

2. Yilanci H, Gezer P. Effects of common surface modifications on the mechanical properties of miniscrews: A systematic review. Appl Sci. 2024 Feb;14(3):1314. doi:10.3390/app14031314.

3. Cooper LF, Shirazi S. Osseointegration—the biological reality of successful dental implant therapy: A narrative review. Front Oral Maxillofac Med. 2022;4. doi:10.21037/fomm-21-77.

4. Kozak M, Poniewierska-Baran A, Czerewaty M, Łuczkowska K, Safranow K, Mazurek-Mochol M, et al. Effect of adiponectin on the expression of selected cytokines in periodontal ligament cells. Biology (Basel). 2025 Apr;14(4):321. doi:10.3390/biology14040321.

5. Chen Z, Wang Y, Yang R, Liu X, Zhang G, Lu Q, et al. Harnessing osteoimmunity to treat peri-implant inflammatory osteolysis. Mater Adv. 2024;5(8):3113-3134. doi:10.1039/D3MA00733B.

6. Inchingolo F, Inchingolo AM, Malcangi G, Ferrante L, Trilli I, Di Noia A, et al. The interaction of cytokines in orthodontics: A systematic review. Appl Sci. 2024 Jun;14(12):5133. doi:10.3390/app14125133.

7. Kaur A, Kharbanda OP, Kapoor P, Kalyanasundaram D. A review of biomarkers in peri-miniscrew implant crevicular fluid (PMICF). Prog Orthod. 2017 Dec;18(1):42. doi:10.1186/s40510-017-0195-8.

8. Danz JC, Degen M. Selective modulation of the bone remodeling regulatory system through orthodontic tooth movement—A review. Front Oral Health. 2025;6:1472711. doi:10.3389/froh.2025.1472711.

9. Gonçalves A, Mathelié-Guinlet Q, Ramires F, Monteiro F, Carvalho Ó, Silva FS, et al. Biological alterations associated with the orthodontic treatment with conventional appliances and aligners: A systematic review of clinical and preclinical evidence. Heliyon. 2024 Jun;10(12):e32873. doi:10.1016/j.heliyon.2024.e32873.

10. Zhang R, Jo J, Tsuda S, Li R, Nishiura A, Honda Y, et al. Sustained fisetin release prevents orthodontic Ti-6Al-4V screw failure by suppressing peri-implantitis and alveolar bone resorption. ACS Biomater Sci Eng. 2025 Mar;11(3):1472-1485. doi:10.1021/acsbiomaterials.4c01818.

11. Tibbs TN, Lopez LR, Arthur JC. The influence of the microbiota on immune development, chronic inflammation, and cancer in the context of aging. Microb Cell. 2019 Aug;6(8):324-334. doi:10.15698/mic2019.08.685.

12. Jain N. The early life education of the immune system: Moms, microbes and (missed) opportunities. Gut Microbes. 2020 Oct;12(1):1824564. doi:10.1080/19490976.2020.1824564.

13. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021 Mar 29;372:n71. doi: 10.1136/bmj.n71.

14. Spitz A, Teles RP, Nojima LI. Influence of orthodontic loading on biomarker levels around miniscrews. Arch Oral Biol. 2020 Apr;112:104668. doi:10.1016/j.archoralbio.2020.104668.

15. Talib EQ, Taha GI. Involvement of interlukin-17A (IL-17A) gene polymorphism and interlukin-23 (IL-23) level in the development of peri-implantitis. BDJ Open. 2024 Jan;10(1):1-8. doi:10.1038/s41405-024-00193-9.

16. Monga N, Chaurasia S, Kharbanda OP, Duggal R, Rajeswari MR. A study of interleukin 1β levels in peri-miniscrew crevicular fluid (PMCF). Prog Orthod. 2014 Dec;15(1):30. doi:10.1186/s40510-014-0030-4.

17. Andrucioli MCD, Matsumoto MAN, Fukada SY, Saraiva MCP, Bergamo AZN, Romano FL, et al. Quantification of pro-inflammatory cytokines and osteoclastogenesis markers in successful and failed orthodontic mini-implants. J Appl Oral Sci. 2019;27:e20180476. doi:10.1590/1678-7757-2018-0476.

18. Farhad SZ, Rezazadeh F, Mohammadi M. Interleukin—17 and Interleukin-10 as inflammatory and prevention biomarkers in periimplant diseases. Int J Prev Med. 2019;10:137. doi:10.4103/ijpvm.IJPVM_27_19.

19. Afacan B, Öztürk VÖ, Geçgelen Cesur M, Köse T, Bostanci N. Effect of orthodontic force magnitude on cytokine networks in gingival crevicular fluid: A longitudinal randomized split-mouth study. Eur J Orthod. 2019 Apr;41(2):214-222. doi:10.1093/ejo/cjy068.

20. Lee JK, Jha N, Kim YJ, Lee DY. Survival analysis of orthodontic micro-implants: A retrospective study on the effects of patient-related factors on micro-implant success. Appl Sci. 2022 Nov 16;12(22):11655. doi:10.3390/app122211655.

21. Nowzari H, Phamduong S, Botero JE, Villacres MC, Rich SK. The profile of inflammatory cytokines in gingival crevicular fluid around healthy osseointegrated implants. Clin Implant Dent Relat Res. 2012 Aug;14(4):546-552. doi:10.1111/j.1708-8208.2010.00299.x.

22. Wankhede AN, Dhadse PV. Interleukin-17 levels in gingival crevicular fluid of aggressive periodontitis and chronic periodontitis patients. J Indian Soc Periodontol. 2022 Nov-Dec;26(6):552-556. doi:10.4103/jisp.jisp_47_21.

23. He W, Zhu H, Liu C. Profiles of inflammation factors and inflammatory pathways around the peri-miniscrew implant. Histol Histopathol. 2021 Sep;36(9):899-906. doi:10.14670/HH-18-336.

24. Reichow AM, Melo AC, Souza CM de, Castilhos BB, Olandoski M, Alvim-Pereira CCK, et al. Outcome of orthodontic mini-implant loss in relation to interleukin 6 polymorphisms. Int J Oral Maxillofac Surg. 2016 May;45(5):649-657. doi:10.1016/j.ijom.2015.11.012.

25. Liu F, Wang X, He Y, Han R, Wang T, Guo Y. Jaw osteoporosis: Challenges to oral health and emerging perspectives of treatment. Biomed Pharmacother. 2024 Jun;177:116995. doi:10.1016/j.biopha.2024.116995.

26. Jeon HH, Huang X, Rojas Cortez L, Sripinun P, Lee J, Hong JJ, et al. Inflammation and mechanical force-induced bone remodeling. Periodontol 2000. doi:10.1111/prd.12619.

27. Y R, H H, B de H, N Q, P de V. Cytokine profiles in crevicular fluid during orthodontic tooth movement of short and long durations. J Periodontol. 2007 Mar;78(3). doi:10.1902/jop.2007.060261.

28. Kapoor P, Kharbanda OP, Monga N, Miglani R, Kapila S. Effect of orthodontic forces on cytokine and receptor levels in gingival crevicular fluid: A systematic review. Prog Orthod. 2014 Dec;15(1):65. doi:10.1186/s40510-014-0065-6.

29. Luchian I, Surlari Z, Goriuc A, Ioanid N, Zetu I, Butnaru O, et al. The influence of orthodontic treatment on periodontal health between challenge and synergy: A narrative review. Dent J. 2024 Apr;12(4):112. doi:10.3390/dj12040112.

30. Wilharm A, Binz C, Sandrock I, Rampoldi F, Lienenklaus S, Blank E, et al. Interleukin-17 is disease promoting in early stages and protective in late stages of experimental periodontitis. PLoS One. 2022;17(3):e0265486. doi:10.1371/journal.pone.0265486.

31. Lee Y. The role of interleukin-17 in bone metabolism and inflammatory skeletal diseases. BMB Rep. 2013 Oct;46(10):479-483. doi:10.5483/BMBRep.2013.46.10.141.

32. McGeachy MJ, Cua DJ, Gaffen SL. The IL-17 family of cytokines in health and disease. Immunity. 2019 Apr;50(4):892-906. doi:10.1016/j.immuni.2019.03.021.

33. Tan K, Minejima E, Lou M, Mack WJ, Nieberg P, Wong-Beringer A. Cytokine measurements add value to clinical variables in predicting outcomes for Staphylococcus aureus bacteremia. BMC Infect Dis. 2021 Apr;21:317. doi:10.1186/s12879-021-06010-0.

34. Liu C, Chu D, Kalantar-Zadeh K, George J, Young HA, Liu G. Cytokines: From clinical significance to quantification. Adv Sci. 2021 Aug;8(15):2004433. doi:10.1002/advs.202004433.

35. Chen J, Liao M, Gao X, Zhong Q, Tang T, Yu X, et al. IL-17A induces pro-inflammatory cytokines production in macrophages via MAPKinases, NF-κB and AP-1. Cell Physiol Biochem. 2013;32(5):1265-1274. doi:10.1159/000354525.

36. Milinkovic I, Djinic Krasavcevic A, Nikolic N, Aleksic Z, Carkic J, Jezdic M, et al. Notch down-regulation and inflammatory cytokines and RANKL overexpression involvement in peri-implant mucositis and peri-implantitis: A cross-sectional study. Clin Oral Implants Res. 2021 Dec;32(12):1496-1505. doi:10.1111/clr.13850.

37. Song L, Tan J, Wang Z, Ding P, Tang Q, Xia M, et al. Interleukin-17A facilitates osteoclast differentiation and bone resorption via activation of autophagy in mouse bone marrow macrophages. Mol Med Rep. 2019 Jun;19(6):4743-4752. doi:10.3892/mmr.2019.10155.

38. Le Goff B, Bouvard B, Lequerre T, Lespessailles E, Marotte H, Pers Y-M, et al. Implication of IL-17 in bone loss and structural damage in inflammatory rheumatic diseases. Med Inflamm. 2019;2019:8659302. doi:10.1155/2019/8659302.

39. Riekert M, Almanzar G, Schmalzing M, Tony HP, Neumann E, Hofmann S, et al. Mesenchymal stem cells modulate IL-17 and IL-9 production induced by Th17-inducing cytokine conditions in autoimmune arthritis: An explorative analysis. Adv Rheumatol. 2023;63:37. doi:10.1186/s42358-023-00317-z.

40. Yi F, Zheng C, Tu SQ, Wei JM, Hou YL, Kuang ZL, et al. Role of interleukin-17A in the pathomechanisms of periodontitis and related systemic chronic inflammatory diseases. Front Immunol. 2022;13:862415. doi:10.3389/fimmu.2022.862415.

Downloads

Published

2025-07-21

Metrics

How to Cite

1.
Imtiaz A, Nazir S, Farrukh A, Tasleem F, Ahmed E. Comparative Assessment of Impact of Interleukins on Orthodontic Miniscrew Stability, Insights to Osseointegration and its Failure Rates: A Systematic Review and Meta-Analysis. PJMD [Internet]. 2025 Jul. 21 [cited 2026 Jun. 3];14(3):539-48. Available from: https://ojs.zu.edu.pk/pjmd/article/view/3775

Similar Articles

1-10 of 141

You may also start an advanced similarity search for this article.

Most read articles by the same author(s)

1 2 > >>