{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T15:06:40Z","timestamp":1780067200775,"version":"3.54.0"},"reference-count":36,"publisher":"The Angle Orthodontist (EH Angle Education & Research Foundation)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the effectiveness of early and short-term administration of lithium (Li) during orthodontic force application (OFA) in preventing orthodontically induced root resorption (OIRR) and verify the importance of the early phase of OFA in the induction of OIRR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>Bilateral maxillary first molars of 10-week-old male Wistar rats were moved for 14 days using a closed coil spring inserted between the first molar and the incisor. The rats were randomly grouped into three groups: a group receiving Li for the first 4 days, a group receiving Li daily for 14 days, and a control group receiving a vehicle (saline). Orthodontic tooth movement (OTM) was measured using microcomputed tomography on day 14. The OIRR, osteoclasts, and odontoclasts were evaluated via histological analysis. Immunohistochemical staining for the receptor-activated NF-kB ligand and osteoprotegerin was also performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The OTM distance did not differ among the three groups, and the pattern of OTM changed from tipping to bodily movement for both Li groups. Early and short-term administration of Li suppressed OIRR on day 14 as effectively as long-term administration for 14 days. The observed odontoclasts on days 4 and 14 were significantly reduced in both Li groups. Osteoprotegerin expression was significantly increased on day 14 in both groups receiving Li relative to the vehicle group.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Early and short-term Li administration effectively suppressed OIRR. This suggests that the early phase of OFA plays an important role in the induction of OIRR.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2319\/060324-433.1","type":"journal-article","created":{"date-parts":[[2025,2,5]],"date-time":"2025-02-05T19:00:56Z","timestamp":1738782056000},"page":"323-331","source":"Crossref","is-referenced-by-count":1,"title":["Importance of the early phase of orthodontic force application in the induction of root resorption"],"prefix":"10.2319","volume":"95","author":[{"given":"Mariko","family":"Funaki-Dohi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuka","family":"Hotokezaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitoshi","family":"Hotokezaka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukako","family":"Nashiro-Oyakawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Moriishi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mizuki","family":"Ohama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yosuke","family":"Iuchi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuya","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kie","family":"Nishioka-Sakamoto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noriaki","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1164","reference":[{"key":"i1945-7103-95-3-323-b01","series-title":"Am J Orthod Dentofacial Orthop","first-page":"462","article-title":"Root resorption associated with orthodontic tooth movement: a systematic review","volume":"137","author":"Weltman","year":"2010","unstructured":"Weltman B,\nVig KWL,\nFields HW,\nShanker S,\nKaizar EE. Root resorption associated with orthodontic tooth movement: a systematic review. Am J Orthod Dentofacial Orthop. 2010;137:462\u2013476."},{"key":"i1945-7103-95-3-323-b02","series-title":"Eur J Orthod","first-page":"350","article-title":"Association between root resorption incident to orthodontic treatment and treatment factors","volume":"34","author":"Motokawa","year":"2012","unstructured":"Motokawa M,\nSasamoto T,\nKaku M, et al. Association between root resorption incident to orthodontic treatment and treatment factors. Eur J Orthod. 2012;34:350\u2013356."},{"key":"i1945-7103-95-3-323-b03","series-title":"Angle Orthod","first-page":"502","article-title":"Force magnitude and duration effects on amount of tooth movement and root resorption in the rat molar","volume":"78","author":"Gonzales","year":"2008","unstructured":"Gonzales C,\nHotokezaka H,\nYoshimatsu M,\nYozgatian JH,\nDarendeliler MA,\nYoshida N. Force magnitude and duration effects on amount of tooth movement and root resorption in the rat molar. Angle Orthod. 2008;78:502\u2013509."},{"key":"i1945-7103-95-3-323-b04","series-title":"Am J Orthod Dentofacial Orthop","first-page":"610","article-title":"Association of orthodontic force system and root resorption: a systematic review","volume":"147","author":"Roscoe","year":"2015","unstructured":"Roscoe MG,\nMeira JB,\nCattaneo PM. Association of orthodontic force system and root resorption: a systematic review. Am J Orthod Dentofacial Orthop. 2015;147:610\u2013626."},{"key":"i1945-7103-95-3-323-b05","series-title":"Angle Orthod","first-page":"235","article-title":"Root resorption in bicuspid intrusion. A scanning electron microscope study","volume":"52","author":"Harry","year":"1982","unstructured":"Harry MR,\nSims MR. Root resorption in bicuspid intrusion. A scanning electron microscope study. Angle Orthod. 1982;52:235\u2013258."},{"key":"i1945-7103-95-3-323-b06","series-title":"Eur J Orthod","first-page":"346","article-title":"Effects of systemic medication on root resorption associated with orthodontic tooth movement: a systematic review of animal studies","volume":"41","author":"Makrygiannakis","year":"2019","unstructured":"Makrygiannakis MA,\nKaklamanos EG,\nAthanasiou AE. Effects of systemic medication on root resorption associated with orthodontic tooth movement: a systematic review of animal studies. Eur J Orthod. 2019;41:346\u2013359."},{"key":"i1945-7103-95-3-323-b07","series-title":"Nordisk Tandl\u00e4kare Tidskrift","first-page":"236","article-title":"Einige Beitrage zur Theorie der Zahnregulierung","volume":"5","author":"Sandstedt","year":"1904","unstructured":"Sandstedt C. Einige Beitrage zur Theorie der Zahnregulierung. Nordisk Tandl\u00e4kare Tidskrift. 1904;5:236\u2013256."},{"key":"i1945-7103-95-3-323-b08","series-title":"Eur J Orthod","first-page":"249","article-title":"The initial phase of orthodontic root resorption incident to local compression of the periodontal ligament","volume":"15","author":"Brudvik","year":"1993","unstructured":"Brudvik P,\nRygh P. The initial phase of orthodontic root resorption incident to local compression of the periodontal ligament. Eur J Orthod. 1993;15:249\u2013263."},{"key":"i1945-7103-95-3-323-b09","series-title":"Eur J Orthod","first-page":"249","article-title":"Root resorption beneath the main hyalinized zone","volume":"16","author":"Brudvik","year":"1994","unstructured":"Brudvik P,\nRygh P. Root resorption beneath the main hyalinized zone. Eur J Orthod. 1994;16:249\u2013263."},{"key":"i1945-7103-95-3-323-b10","series-title":"Angle Orthod","first-page":"547","article-title":"Lithium reduces orthodontically induced root resorption by suppressing cell death, hyalinization, and odontoclast formation in rats","volume":"92","author":"Ueda-Ichinose","year":"2022","unstructured":"Ueda-Ichinose Y,\nHotokezaka H,\nMiyazaki T, et al. Lithium reduces orthodontically induced root resorption by suppressing cell death, hyalinization, and odontoclast formation in rats. Angle Orthod. 2022;92:547\u2013554."},{"key":"i1945-7103-95-3-323-b11","series-title":"Angle Orthod","first-page":"240","article-title":"Early-stage periodontal ligament compression predicts orthodontically induced root resorption in rats","volume":"94","author":"Nakamura","year":"2024","unstructured":"Nakamura T,\nHotokezaka Y,\nKaradeniz C, et al. Early-stage periodontal ligament compression predicts orthodontically induced root resorption in rats. Angle Orthod. 2024;94:240\u2013246."},{"key":"i1945-7103-95-3-323-b12","series-title":"Angle Orthod","first-page":"474","article-title":"Lithium chloride reduces orthodontically induced root resorption and affects tooth root movement in rats","volume":"88","author":"Ino-Kondo","year":"2018","unstructured":"Ino-Kondo A,\nHotokezaka H,\nKondo T, et al. Lithium chloride reduces orthodontically induced root resorption and affects tooth root movement in rats. Angle Orthod. 2018;88:474\u2013482."},{"key":"i1945-7103-95-3-323-b13","series-title":"Exp Ther Med","first-page":"468","article-title":"Lithium chloride attenuates root resorption during orthodontic tooth movement in rats","volume":"7","author":"Wang","year":"2014","unstructured":"Wang Y,\nGao S,\nJiang H, et al. Lithium chloride attenuates root resorption during orthodontic tooth movement in rats. Exp Ther Med. 2014;7:468\u2013472."},{"key":"i1945-7103-95-3-323-b14","series-title":"Arch Oral Biol","first-page":"244","article-title":"RANKL expression in rat periodontal ligament subjected to a continuous orthodontic force","volume":"52","author":"Kim","year":"2007","unstructured":"Kim T,\nHanda A,\nIida J,\nYoshida S. RANKL expression in rat periodontal ligament subjected to a continuous orthodontic force. Arch Oral Biol. 2007;52:244\u2013250."},{"key":"i1945-7103-95-3-323-b15","series-title":"Orthod Craniofac Res","first-page":"113","article-title":"RANK\/RANKL\/OPG during orthodontic tooth movement","volume":"12","author":"Yamaguchi","year":"2009","unstructured":"Yamaguchi M. RANK\/RANKL\/OPG during orthodontic tooth movement. Orthod Craniofac Res. 2009;12:113\u2013119."},{"key":"i1945-7103-95-3-323-b16","series-title":"Biochem Biophys Res Commun","first-page":"394","article-title":"Low dose lithium supplementation activates Wnt\/\u03b2-catenin signalling and increases bone OPG\/RANKL ratio in mice","volume":"511","author":"Kurgan","year":"2019","unstructured":"Kurgan N,\nBott KN,\nHelmeczi WE, et al. Low dose lithium supplementation activates Wnt\/\u03b2-catenin signalling and increases bone OPG\/RANKL ratio in mice. Biochem Biophys Res Commun. 2019;511:394\u2013397."},{"key":"i1945-7103-95-3-323-b17","series-title":"Biomater Sci","first-page":"1101","article-title":"Effect of the Wnt signal-RANKL\/OPG axis on the enhanced osteogenic integration of a lithium incorporated surface","volume":"7","author":"Huang","year":"2019","unstructured":"Huang TB,\nLi YZ,\nYu K, et al. Effect of the Wnt signal-RANKL\/OPG axis on the enhanced osteogenic integration of a lithium incorporated surface. Biomater Sci. 2019;7:1101\u20131116."},{"key":"i1945-7103-95-3-323-b18","series-title":"Clin Oral Implants Res","first-page":"921","article-title":"GSK3b-inhibitor lithium chloride enhances activation of Wnt canonical signaling and osteoblast differentiation on hydrophilic titanium surfaces","volume":"24","author":"Galli","year":"2013","unstructured":"Galli C,\nPiemontese M,\nLumetti S,\nManfredi E,\nMacaluso GM,\nPasseri G. GSK3b-inhibitor lithium chloride enhances activation of Wnt canonical signaling and osteoblast differentiation on hydrophilic titanium surfaces. Clin Oral Implants Res. 2013;24:921\u2013927."},{"key":"i1945-7103-95-3-323-b01","series-title":"Am J Orthod Dentofacial Orthop","first-page":"462","article-title":"Root resorption associated with orthodontic tooth movement: a systematic review","volume":"137","author":"Weltman","year":"2010","unstructured":"Weltman B,\nVig KWL,\nFields HW,\nShanker S,\nKaizar EE. Root resorption associated with orthodontic tooth movement: a systematic review. Am J Orthod Dentofacial Orthop. 2010;137:462\u2013476."},{"key":"i1945-7103-95-3-323-b02","series-title":"Eur J Orthod","first-page":"350","article-title":"Association between root resorption incident to orthodontic treatment and treatment factors","volume":"34","author":"Motokawa","year":"2012","unstructured":"Motokawa M,\nSasamoto T,\nKaku M, et al. Association between root resorption incident to orthodontic treatment and treatment factors. Eur J Orthod. 2012;34:350\u2013356."},{"key":"i1945-7103-95-3-323-b03","series-title":"Angle Orthod","first-page":"502","article-title":"Force magnitude and duration effects on amount of tooth movement and root resorption in the rat molar","volume":"78","author":"Gonzales","year":"2008","unstructured":"Gonzales C,\nHotokezaka H,\nYoshimatsu M,\nYozgatian JH,\nDarendeliler MA,\nYoshida N. Force magnitude and duration effects on amount of tooth movement and root resorption in the rat molar. Angle Orthod. 2008;78:502\u2013509."},{"key":"i1945-7103-95-3-323-b04","series-title":"Am J Orthod Dentofacial Orthop","first-page":"610","article-title":"Association of orthodontic force system and root resorption: a systematic review","volume":"147","author":"Roscoe","year":"2015","unstructured":"Roscoe MG,\nMeira JB,\nCattaneo PM. Association of orthodontic force system and root resorption: a systematic review. Am J Orthod Dentofacial Orthop. 2015;147:610\u2013626."},{"key":"i1945-7103-95-3-323-b05","series-title":"Angle Orthod","first-page":"235","article-title":"Root resorption in bicuspid intrusion. A scanning electron microscope study","volume":"52","author":"Harry","year":"1982","unstructured":"Harry MR,\nSims MR. Root resorption in bicuspid intrusion. A scanning electron microscope study. Angle Orthod. 1982;52:235\u2013258."},{"key":"i1945-7103-95-3-323-b06","series-title":"Eur J Orthod","first-page":"346","article-title":"Effects of systemic medication on root resorption associated with orthodontic tooth movement: a systematic review of animal studies","volume":"41","author":"Makrygiannakis","year":"2019","unstructured":"Makrygiannakis MA,\nKaklamanos EG,\nAthanasiou AE. Effects of systemic medication on root resorption associated with orthodontic tooth movement: a systematic review of animal studies. Eur J Orthod. 2019;41:346\u2013359."},{"key":"i1945-7103-95-3-323-b07","series-title":"Nordisk Tandl\u00e4kare Tidskrift","first-page":"236","article-title":"Einige Beitrage zur Theorie der Zahnregulierung","volume":"5","author":"Sandstedt","year":"1904","unstructured":"Sandstedt C. Einige Beitrage zur Theorie der Zahnregulierung. Nordisk Tandl\u00e4kare Tidskrift. 1904;5:236\u2013256."},{"key":"i1945-7103-95-3-323-b08","series-title":"Eur J Orthod","first-page":"249","article-title":"The initial phase of orthodontic root resorption incident to local compression of the periodontal ligament","volume":"15","author":"Brudvik","year":"1993","unstructured":"Brudvik P,\nRygh P. The initial phase of orthodontic root resorption incident to local compression of the periodontal ligament. Eur J Orthod. 1993;15:249\u2013263."},{"key":"i1945-7103-95-3-323-b09","series-title":"Eur J Orthod","first-page":"249","article-title":"Root resorption beneath the main hyalinized zone","volume":"16","author":"Brudvik","year":"1994","unstructured":"Brudvik P,\nRygh P. Root resorption beneath the main hyalinized zone. Eur J Orthod. 1994;16:249\u2013263."},{"key":"i1945-7103-95-3-323-b10","series-title":"Angle Orthod","first-page":"547","article-title":"Lithium reduces orthodontically induced root resorption by suppressing cell death, hyalinization, and odontoclast formation in rats","volume":"92","author":"Ueda-Ichinose","year":"2022","unstructured":"Ueda-Ichinose Y,\nHotokezaka H,\nMiyazaki T, et al. Lithium reduces orthodontically induced root resorption by suppressing cell death, hyalinization, and odontoclast formation in rats. Angle Orthod. 2022;92:547\u2013554."},{"key":"i1945-7103-95-3-323-b11","series-title":"Angle Orthod","first-page":"240","article-title":"Early-stage periodontal ligament compression predicts orthodontically induced root resorption in rats","volume":"94","author":"Nakamura","year":"2024","unstructured":"Nakamura T,\nHotokezaka Y,\nKaradeniz C, et al. Early-stage periodontal ligament compression predicts orthodontically induced root resorption in rats. Angle Orthod. 2024;94:240\u2013246."},{"key":"i1945-7103-95-3-323-b12","series-title":"Angle Orthod","first-page":"474","article-title":"Lithium chloride reduces orthodontically induced root resorption and affects tooth root movement in rats","volume":"88","author":"Ino-Kondo","year":"2018","unstructured":"Ino-Kondo A,\nHotokezaka H,\nKondo T, et al. Lithium chloride reduces orthodontically induced root resorption and affects tooth root movement in rats. Angle Orthod. 2018;88:474\u2013482."},{"key":"i1945-7103-95-3-323-b13","series-title":"Exp Ther Med","first-page":"468","article-title":"Lithium chloride attenuates root resorption during orthodontic tooth movement in rats","volume":"7","author":"Wang","year":"2014","unstructured":"Wang Y,\nGao S,\nJiang H, et al. Lithium chloride attenuates root resorption during orthodontic tooth movement in rats. Exp Ther Med. 2014;7:468\u2013472."},{"key":"i1945-7103-95-3-323-b14","series-title":"Arch Oral Biol","first-page":"244","article-title":"RANKL expression in rat periodontal ligament subjected to a continuous orthodontic force","volume":"52","author":"Kim","year":"2007","unstructured":"Kim T,\nHanda A,\nIida J,\nYoshida S. RANKL expression in rat periodontal ligament subjected to a continuous orthodontic force. Arch Oral Biol. 2007;52:244\u2013250."},{"key":"i1945-7103-95-3-323-b15","series-title":"Orthod Craniofac Res","first-page":"113","article-title":"RANK\/RANKL\/OPG during orthodontic tooth movement","volume":"12","author":"Yamaguchi","year":"2009","unstructured":"Yamaguchi M. RANK\/RANKL\/OPG during orthodontic tooth movement. Orthod Craniofac Res. 2009;12:113\u2013119."},{"key":"i1945-7103-95-3-323-b16","series-title":"Biochem Biophys Res Commun","first-page":"394","article-title":"Low dose lithium supplementation activates Wnt\/\u03b2-catenin signalling and increases bone OPG\/RANKL ratio in mice","volume":"511","author":"Kurgan","year":"2019","unstructured":"Kurgan N,\nBott KN,\nHelmeczi WE, et al. Low dose lithium supplementation activates Wnt\/\u03b2-catenin signalling and increases bone OPG\/RANKL ratio in mice. Biochem Biophys Res Commun. 2019;511:394\u2013397."},{"key":"i1945-7103-95-3-323-b17","series-title":"Biomater Sci","first-page":"1101","article-title":"Effect of the Wnt signal-RANKL\/OPG axis on the enhanced osteogenic integration of a lithium incorporated surface","volume":"7","author":"Huang","year":"2019","unstructured":"Huang TB,\nLi YZ,\nYu K, et al. Effect of the Wnt signal-RANKL\/OPG axis on the enhanced osteogenic integration of a lithium incorporated surface. Biomater Sci. 2019;7:1101\u20131116."},{"key":"i1945-7103-95-3-323-b18","series-title":"Clin Oral Implants Res","first-page":"921","article-title":"GSK3b-inhibitor lithium chloride enhances activation of Wnt canonical signaling and osteoblast differentiation on hydrophilic titanium surfaces","volume":"24","author":"Galli","year":"2013","unstructured":"Galli C,\nPiemontese M,\nLumetti S,\nManfredi E,\nMacaluso GM,\nPasseri G. GSK3b-inhibitor lithium chloride enhances activation of Wnt canonical signaling and osteoblast differentiation on hydrophilic titanium surfaces. 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