Orthodontic tooth movement (OTM) is achieved by the simultaneous activation of bone resorption by osteoclasts and bone formation by osteoblasts. When orthodontic forces are applied, osteoclast-mediated bone resorption occurs in the alveolar bone on the compression side, creating space for tooth movement. Therefore, controlling osteoclastogenesis is the fundamental tenet of orthodontic treatment. Orthodontic forces are sensed by osteoblast lineage cells such as periodontal ligament (PDL) cells and osteocytes. Of several cytokines produced by these cells, the most important cytokine promoting osteoclastogenesis is the receptor activator of nuclear factor-κB ligand (RANKL), which is mainly supplied by osteoblasts. Additionally, osteocytes embedded within the bone matrix, T lymphocytes in inflammatory conditions, and PDL cells produce RANKL. Besides RANKL, inflammatory cytokines, such as interleukin-1, tumor necrosis factor-α, and prostaglandin E2 promote osteoclastogenesis under OTM. On the downside, excessive osteoclastogenesis activation triggers orthodontically-induced external root resorption (ERR) through pro-osteoclastic inflammatory cytokines. Therefore, understanding the mechanisms of osteoclastogenesis during OTM is essential in reducing the adverse effects of orthodontic treatment. Here, we review the current concepts of the mechanisms underlying osteoclastogenesis in OTM and orthodontically induced ERR.
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1. Decellularized porcine pericardium supports periodontal ligament tissue regeneration and attenuates root resorption in a tooth replantation model Mingyuan HSIAO, Tsuyoshi KIMURA, Mika SUZUKI, Yoshihide HASHIMOTO, Masahiro YAMADA, Yusoon KIM, Yousuke HARAZONO, Hiroyuki YOSHITAKE, Masahiko TERAUCHI, Akio KISHIDA, Tetsuya YODA Dental Materials Journal.2026; 45(1): 72. CrossRef
2. Development of an AQbD driven HPLC method for the simultaneous estimation of caffeine and misoprostol in nanoparticle formulations Nitasha Chauhan, Shiv Kumar, Shailendra Singh Rana, Shruti Chopra, Amit Bhatia Analytical Methods.2026; 18(2): 389. CrossRef
3. Three pharmacological agents for acceleratory orthodontic tooth movement and subsequent relapse: A randomized controlled animal study Samar Ali Hamed, Mohammad Hasan Mohammad, Mohamed E. Grawish, Ahmed Maher Fouda, Mona Abdelaziz Montasser International Orthodontics.2026; 24(2): 101112. CrossRef
4. Clinical Soft Tissue Adaptation to Biomechanical Modulation with the Bone Protection System (BPS): A Two-Case Report in Thin-Biotype Patients Anna Ewa Kuc, Jacek Kotuła, Kamil Sybilski, Grzegorz Hajduk, Joanna Lis, Beata Kawala, Michał Sarul, Magdalena Sulewska Journal of Clinical Medicine.2026; 15(2): 721. CrossRef
5. COMPARATIVE ANALYSIS OF MACROSCOPIC VS MICROSCOPIC MEASUREMENT CRITERIA OF INDUCED TOOTH MOVEMENT José Roberto Alves Moreira, Osmar Aparecido Cuoghi, Marcos Rogério De Mendonça, Alberto Consolaro, Maria Fernanda Martins-Ortiz, Henrique Barcelos Brandão, Luiz Gonzaga Gandini Junior, Ary dos Santos Pinto LUMEN ET VIRTUS.2026; 17(56): e11680. CrossRef
6. Molecular Investigation of the Effects of Two Antiepileptic Drugs (Valproic Acid and Levetiracetam) on Alveolar Bone Under Orthodontic Force Nurhan Bayindir-Durna, Metin Uckan, Seyma Aydin, Selcuk Ozdemir Medicina.2026; 62(1): 178. CrossRef
7. Tension-Dominant Orthodontic Loading and Buccal Periodontal Phenotype Preservation: An Integrative Mechanobiological Model Supported by FEM and a Proof-of-Concept CBCT Anna Ewa Kuc, Jacek Kotuła, Kamil Sybilski, Szymon Saternus, Jerzy Małachowski, Natalia Kuc, Grzegorz Hajduk, Joanna Lis, Beata Kawala, Michał Sarul, Magdalena Sulewska Journal of Functional Biomaterials.2026; 17(1): 47. CrossRef
8. Rapid maxillary expansion related sutural and dentoalveolar changes provoke early-term oxidative stress Tuba Kose, Ali Kiki, Oguz Kose, Ozge Nur Turkeri BMC Oral Health.2026;[Epub] CrossRef
9. Mechanical forces orchestrate the epigenetic landscape of oral mesenchymal stem/progenitor cell fate in dental and periodontal tissues Yikun Zhou, Gengming Zhang, Hong He Frontiers in Cell and Developmental Biology.2026;[Epub] CrossRef
10. Exacerbating orthodontic tooth movement in mice with salt-sensitive hypertension Ziqiu Fan, Hideki Kitaura, Takahiro Noguchi, Fumitoshi Ohori, Aseel Marahleh, Jinghan Ma, Jiayi Ren, Angyi Lin, Kohei Narita, Itaru Mizoguchi Journal of Dental Sciences.2025; 20(2): 764. CrossRef
11. Biomechanically induced regulation of Damage-Regulated Autophagy Modulator 1 in periodontal cells and tissues Anemone Mannes, Andressa Nogueira, Annika Both, Alexandra Mayr, Jana Marciniak, Erika Calvano Küchler, Fazilet Bekbulat, Joni A. Cirelli, Christian Kirschneck, Christian Behl, James Deschner, Andreas Jäger, Svenja Beisel-Memmert Biochemical and Biophysical Research Communications.2025; 742: 151131. CrossRef
12. Periodontal response to nonsurgical accelerated orthodontic tooth movement Fatma Oner, Alpdogan Kantarci Periodontology 2000.2025;[Epub] CrossRef
13. Does the Phase-One Functional Therapy Increase the Risk of an External Apical Root Resorption Following the Phase-Two Fixed Orthodontic Treatment? A Pilot Study Sara Eslami, Jakob Stuhlfelder, Suh-In Rhie, Sarah Bühling, Mauricio Gonzalez Balut, Ludovica Nucci, Abdolreza Jamilian, Babak Sayahpour Dentistry Journal.2025; 13(3): 95. CrossRef
14. Metformin reverses periodontal destruction caused by experimental periodontitis by inhibiting interleukin‐1β activity Zhao Wang, Ju Han Song, Jung‐Woo Kim, Seung‐Hee Kwon, Xianyu Piao, Sin‐Hye Oh, Suk‐Gyun Park, Sun‐Hun Kim, Je‐Hwang Ryu, Ok‐Su Kim, Jeong‐Tae Koh Journal of Periodontology.2025; 96(11): 1257. CrossRef
15. miR‐223‐3p Mitigates Mitochondrial Dysfunction and Cementoblast Apoptosis in Orthodontic Root Resorption via FoxO3 Wei He, Lei Xu, Wei Jiang, Song Yao, Yu Fu, Zishuo Cheng, Danlan Zhang, Lan Huang Journal of Periodontal Research.2025; 60(9): 923. CrossRef
16. Role of Masticatory Force in Modulating Jawbone Immunity and Bone Homeostasis: A Review Yue Song, Yao Jiao, Yitong Liu, Lijia Guo International Journal of Molecular Sciences.2025; 26(10): 4478. CrossRef
17. Bidirectional substance P signaling between periodontal ligament fibroblasts and sensory neurons under mechanical stress Judit Symmank, Lara Löffler, Ulrike Schulze-Späte, Collin Jacobs Frontiers in Molecular Neuroscience.2025;[Epub] CrossRef
18. Single-Cell Atlas of Immune Microenvironment in Orthodontic Tooth Movement J. Wang, C. Tao, H. Liu, Y. Yang, Y. Zhao, K. Tan, F. Chen, E. Yang, Y. Huang, W. Li Journal of Dental Research.2025; 104(12): 1361. CrossRef
19. Taurine up-regulated 1: A dual regulator in immune cell-mediated pathogenesis of human diseases Xin Lan, Shuwen Zhang, Lu Yang Progress in Biophysics and Molecular Biology.2025; 197: 84. CrossRef
20. Evaluation of Efficacy of Advanced Platelet-rich Fibrin in Premolar Extraction Sockets as an Aid to Accelerate Orthodontic Tooth Movement and Wound Healing: A Split-mouth In Vivo Study Divya Mareddy, Marimallappa TR, Mahesh Kumar Ranghnath, Ashok Kumar KR, Jambukeshwar Kumar B, Supriyo Pal International Journal of Clinical Pediatric Dentistry.2025; 18(7): 838. CrossRef
21. Local abaloparatide administration promotes in situ alveolar bone augmentation via FAK-mediated periosteal osteogenesis Ruyi Wang, Yuan Li, Bowen Tan, Shijia Li, Yanting Wu, Yao Chen, Yuran Qian, Haochen Wang, Bo Li, Zhihe Zhao, Quan Yuan, Yu Li International Journal of Oral Science.2025;[Epub] CrossRef
22. Navigating the Complex Landscape of Osteoclastogenesis in Orthodontics Sandra Sagar, Genickson Jeyaraj, Pratibha Ramani Journal of Bone Metabolism.2025; 32(3): 244. CrossRef
23. Recent Advances in the Role of Osteocytes in Orthodontic Tooth Movement Aseel Marahleh, Fumitoshi Ohori, Jinghan Ma, Ziqiu Fan, Angyi Lin, Kohei Narita, Kou Murakami, Hideki Kitaura International Journal of Molecular Sciences.2025; 26(19): 9396. CrossRef
24. Biological Regulatory Mechanisms of Orthodontic Tooth Movement: Potential Analysis of Cordycepin and Other Natural Products 美彤 刘 Advances in Clinical Medicine.2025; 15(10): 803. CrossRef
25. Photobiomodulation Meets Mechanotransduction: Immune-Stromal Crosstalk in Orthodontic Remodeling Jovan Marković, Miodrag Čolić Biomedicines.2025; 13(10): 2495. CrossRef
26. Salivary Albumin and Alkaline Phosphatase in Infants: Exploring the Link Between Early Dental Development and Biomarkers Sindy Cornelia Nelwan, Udijanto Tedjosasongko, Tania Saskianti, Ardianti Maartrina Dewi, Erika Setyowati, Sofia Tandya Putri, Nunthawan Nowwarote European Journal of Dentistry.2025;[Epub] CrossRef
27. Three-Dimensional Finite-Element Study into the Biomechanical Comparison of Force Distribution in Self-Ligating and Conventional Brackets Aulia Ayub, Ananto Ali Alhasyimi Odovtos - International Journal of Dental Sciences.2025; (00): 403. CrossRef
28. C‐reactive protein interactive with IL‐6 mediates alveolar bone remodeling imbalance during orthodontic tooth movement with periodontitis Qin Xue, Xuyang Zhang, Mei Hu, Yao He Journal of Periodontology.2025;[Epub] CrossRef
29. Corticotomy Depth as a Modulator of Orthodontic Tooth Movement and PDL Stress—A Finite Element Study Anna Ewa Kuc, Kamil Sybilski, Jacek Kotuła, Grzegorz Hajduk, Magdalena Sulewska, Szymon Saternus, Justyna Ewa Kulikowska-Kulesza, Małgorzata Kotarska, Beata Kawala, Jerzy Małachowski, Michał Sarul Materials.2025; 18(23): 5290. CrossRef
30. Predicting the Effects of Medication and Nutrients on Orthodontic Tooth Movement via the Receptor Activator of Nuclear Factor kappa-B Ligand/ Osteoprotegerin (RANKL/OPG) Ratio in Cultured Human Periodontal Ligament Fibroblasts
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31. Mechanistic Model of Periodontal Inflammation and Orthodontic Force Interactions Olivia S. Brown, Ahmad F. Rahman, Ahmed K. El Sherif Asian Journal of Periodontics and Orthodontics.2025; 5(1): 298. CrossRef
32. Exploring the role of innate lymphoid cells in the periodontium: insights into immunological dynamics during orthodontic tooth movement Eva Pastille, Anna Konermann Frontiers in Immunology.2024;[Epub] CrossRef
33. The Role of Bone and Root Resorption on the Biomechanical Behavior of Mandibular Anterior Teeth Subjected to Orthodontic Forces: A Finite Element Approach Jana Flatten, Thomasz Gedrange, Christoph Bourauel, Ludger Keilig, Anna Konermann Biomedicines.2024; 12(9): 1959. CrossRef
34. Investigating the Role of Primary Cilia and Bone Morphogenetic Protein Signaling in Periodontal Ligament Response to Orthodontic Strain In Vivo and In Vitro: A Pilot Study Emily R. Moore, Anna Konermann International Journal of Molecular Sciences.2024; 25(23): 12648. CrossRef
35. Thermogenic preworkout supplement induces alveolar bone loss in a rat model of tooth movement via RANK/RANKL/OPG pathway Gurgiane Rodrigues Gurgel CAVALCANTE, Mariana Cabral MORENO, Flavia Queiroz PIRIH, Vanessa de Paula SOARES, Éricka Janine Dantas da SILVEIRA, José Sandro Pereira da SILVA, Hallissa Simplício Gomes PEREIRA, Katherine Pennington KLEIN, Maria Luiza Diniz de Brazilian Oral Research.2024;[Epub] CrossRef
37. Cytokine and Chemokine Profiles in Orthodontic Treatment with Reduced Periodontal Support Daniel R. Miller, Sophie L. Grant, Michael J. Patel, Hannah K. Brooks Asian Journal of Periodontics and Orthodontics.2024; 4(1): 285. CrossRef
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