Melatonin Effect on Immediate Dental Implants in the Posterior Mandible: A Pilot Study

Summary

This pilot randomized controlled clinical trial aims to evaluate the feasibility, clinical safety, and preliminary radiographic osteogenic effects of applying topical 1% w/w melatonin gel during immediate implant placement in the posterior mandible. The study assesses surgical feasibility, soft-tissue healing, bone density, buccal bone thickness, and implant stability to provide preliminary effect size and variance estimates to inform future definitive clinical trials.

Timeline

Start

2025-11-06

Primary completion

2027-06

Completion

2027-06

Publications

• Background Chen ST, Wilson TG Jr, Hammerle CH. Immediate or early placement of implants following tooth extraction: review of biologic basis, clinical procedures, and outcomes. Int J Oral Maxillofac Implants. 2004;19 Suppl:12-25.
• Background S DS, Kamath D, Sinha A, Kamath D. Melatonin: The potential avenues in dentistry. F1000Res. 2025 Jan 14;14:77. doi: 10.12688/f1000research.159942.1. eCollection 2025.
• Background Hosseinzadeh A, Bagherifard A, Sheibani M, Karimi-Behnagh A, Reiter RJ, Mehrzadi S. Significant Interaction between Melatonin and Titanium Bone Implants: Available Evidence and Future Research Directions. Curr Pharm Biotechnol. 2025;26(9):1258-1270. doi: 10.2174/0113892010300967240610111644.
• Background Ravi Kiran S, Bammidi N, Kumar AK, Kumar PS, Karnam Y. Evaluation of the Effect of Topical Melatonin Application on Immediately Placed Dental Implants Using Cone Beam Computed Tomography (CBCT). Cureus. 2022 May 23;14(5):e25233. doi: 10.7759/cureus.25233. eCollection 2022 May.
• Background El-Gammal MY, Salem AS, Anees MM, Tawfik MA. Clinical and Radiographic Evaluation of Immediate Loaded Dental Implants With Local Application of Melatonin: A Preliminary Randomized Controlled Clinical Trial. J Oral Implantol. 2016 Apr;42(2):119-25. doi: 10.1563/aaid-joi-D-14-00277. Epub 2015 Jun 23.
• Background Yan W, Li C, Song X, Zhou W, Chen Z. Prophylactic melatonin for delirium in critically ill patients: A systematic review and meta-analysis with trial sequential analysis. Medicine (Baltimore). 2022 Oct 28;101(43):e31411. doi: 10.1097/MD.0000000000031411.
• Background Zhao Y, Shao G, Liu X, Li Z. Assessment of the Therapeutic Potential of Melatonin for the Treatment of Osteoporosis Through a Narrative Review of Its Signaling and Preclinical and Clinical Studies. Front Pharmacol. 2022 May 11;13:866625. doi: 10.3389/fphar.2022.866625. eCollection 2022.
• Background Huang X, Chen W, Gu C, Liu H, Hou M, Qin W, Zhu X, Chen X, Liu T, Yang H, He F. Melatonin suppresses bone marrow adiposity in ovariectomized rats by rescuing the imbalance between osteogenesis and adipogenesis through SIRT1 activation. J Orthop Translat. 2022 Oct 27;38:84-97. doi: 10.1016/j.jot.2022.10.002. eCollection 2023 Jan.
• Background Maria S, Samsonraj RM, Munmun F, Glas J, Silvestros M, Kotlarczyk MP, Rylands R, Dudakovic A, van Wijnen AJ, Enderby LT, Lassila H, Dodda B, Davis VL, Balk J, Burow M, Bunnell BA, Witt-Enderby PA. Biological effects of melatonin on osteoblast/osteoclast cocultures, bone, and quality of life: Implications of a role for MT2 melatonin receptors, MEK1/2, and MEK5 in melatonin-mediated osteoblastogenesis. J Pineal Res. 2018 Apr;64(3):10.1111/jpi.12465. doi: 10.1111/jpi.12465. Epub 2018 Jan 17.
• Background Vaseenon S, Chattipakorn N, Chattipakorn SC. Effects of melatonin in wound healing of dental pulp and periodontium: Evidence from in vitro, in vivo and clinical studies. Arch Oral Biol. 2021 Mar;123:105037. doi: 10.1016/j.archoralbio.2020.105037. Epub 2021 Jan 6.
• Background Hardeland R, Pandi-Perumal SR. Melatonin, a potent agent in antioxidative defense: actions as a natural food constituent, gastrointestinal factor, drug and prodrug. Nutr Metab (Lond). 2005 Sep 10;2:22. doi: 10.1186/1743-7075-2-22.
• Background Tian Y, Ming J. Melatonin inhibits osteoclastogenesis via RANKL/OPG suppression mediated by Rev-Erbalpha in osteoblasts. J Cell Mol Med. 2022 Jul;26(14):4032-4047. doi: 10.1111/jcmm.17440. Epub 2022 Jun 21.
• Background Hu W, Deng C, Ma Z, Wang D, Fan C, Li T, Di S, Gong B, Reiter RJ, Yang Y. Utilizing melatonin to combat bacterial infections and septic injury. Br J Pharmacol. 2017 May;174(9):754-768. doi: 10.1111/bph.13751. Epub 2017 Mar 21.
• Background Favero G, Franceschetti L, Bonomini F, Rodella LF, Rezzani R. Melatonin as an Anti-Inflammatory Agent Modulating Inflammasome Activation. Int J Endocrinol. 2017;2017:1835195. doi: 10.1155/2017/1835195. Epub 2017 Oct 1.
• Background Cuzzocrea S, Reiter RJ. Pharmacological actions of melatonin in acute and chronic inflammation. Curr Top Med Chem. 2002 Feb;2(2):153-65. doi: 10.2174/1568026023394425.
• Background Permuy M, Lopez-Pena M, Gonzalez-Cantalapiedra A, Munoz F. Melatonin: A Review of Its Potential Functions and Effects on Dental Diseases. Int J Mol Sci. 2017 Apr 19;18(4):865. doi: 10.3390/ijms18040865.
• Background Sola-Ruiz MF, Perez-Martinez C, Labaig-Rueda C, Carda C, Martin De Llano JJ. Behavior of Human Osteoblast Cells Cultured on Titanium Discs in Relation to Surface Roughness and Presence of Melatonin. Int J Mol Sci. 2017 Apr 13;18(4):823. doi: 10.3390/ijms18040823.
• Background Gomez-Moreno G, Aguilar-Salvatierra A, Boquete-Castro A, Guardia J, Piattelli A, Perrotti V, Delgado-Ruiz RA, Calvo-Guirado JL. Outcomes of topical applications of melatonin in implant dentistry: a systematic review. Implant Dent. 2015 Feb;24(1):25-30. doi: 10.1097/ID.0000000000000186.
• Background Roth JA, Kim BG, Lin WL, Cho MI. Melatonin promotes osteoblast differentiation and bone formation. J Biol Chem. 1999 Jul 30;274(31):22041-7. doi: 10.1074/jbc.274.31.22041.
• Background Cardinali DP, Ladizesky MG, Boggio V, Cutrera RA, Mautalen C. Melatonin effects on bone: experimental facts and clinical perspectives. J Pineal Res. 2003 Mar;34(2):81-7. doi: 10.1034/j.1600-079x.2003.00028.x.
• Background Cutando A, Gomez-Moreno G, Arana C, Munoz F, Lopez-Pena M, Stephenson J, Reiter RJ. Melatonin stimulates osteointegration of dental implants. J Pineal Res. 2008 Sep;45(2):174-9. doi: 10.1111/j.1600-079X.2008.00573.x. Epub 2008 Feb 19.
• Background Botticelli D, Berglundh T, Buser D, Lindhe J. The jumping distance revisited: An experimental study in the dog. Clin Oral Implants Res. 2003 Feb;14(1):35-42. doi: 10.1034/j.1600-0501.2003.140105.x.
• Background Albrektsson T, Branemark PI, Hansson HA, Lindstrom J. Osseointegrated titanium implants. Requirements for ensuring a long-lasting, direct bone-to-implant anchorage in man. Acta Orthop Scand. 1981;52(2):155-70. doi: 10.3109/17453678108991776.

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Indications