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The effects of low-intensity pulsed ultrasound on the rate of orthodontic tooth movement
The effects of low-intensity pulsed ultrasound on the rate of orthodontic tooth movement Hui Xue1, Jun Zheng1, Michelle Yuching Chou1, Hong Zhou, and Yinzhong Duan Accelerating alveolar bone remodeling and thus accelerating the velocity of orthodontic tooth movement is highly desirable by orthodontists and patients. Low-intensity pulsed ultrasound (LIPUS) stimulation has been reported to promote fracture healing to treat bone nonunion, and to accelerate bone maturation and remodeling during the consolidation stage of distraction osteogenesis. Low-intensity pulsed ultrasound (LIPUS) is a safe, non-invasive approach, which has demonstrated the potential to increase the rate of tooth movement. The purpose of this review article is to help readers understand the science behind this technology and to discuss the different potential applications of LIPUS in orthodontics. (Semin Orthod 2015; 21:219–223.) & 2015 Elsevier Inc. All rights reserved.
Introduction
O
rthodontic treatment is a process to achieve appropriate esthetics and masticatory function through movement of teeth by applying an external physical force. In this regard, stimulating proper physiological reactions in the surrounding tissue is the main focus of orthodontic treatment.1,2 Optimizing proper biological responses may not only accelerate tooth movement, but also decrease side effects. In order to improve the velocity of orthodontic treatment, previous studies have utilized different biochemical agents, such as osteocalcin and parathyroid prostaglandin E2 (PGE2),3 Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi’an, 710031 PR China; Department of Dentistry, Hegang People’s Hospital, Hegang, 310006 PR China; Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Xi’an Jiaotong University, Xi’an, 710004 PR China; Department of Developmental Biology, Harvard School of Dental Medicine, Boston, 02138 MA; Department of Orthodontics, Stomatological Hospital of Xi’an Jiaotong University, Xi’an, 710004 PR China. Corresponding authors. E-mail: [email protected]; [email protected] 1 These authors contributed equally to this work. Funding: This study was supported by grants from The Scientific and Technological Project of Shaanxi Province of China, PR China (2008K14-03 to Dr. Duan), who had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. & 2015 Elsevier Inc. All rights reserved. 1073-8746/12/1801-$30.00/0 http://dx.doi.org/10.1053/j.sodo.2015.06.009
hormone,4 and dihydroxyvitamin D3 [1,25(OH)2D3].5 However, due to systemic effects, their application in orthodontics has not been justified.1 Therefore, recent studies have focused on exploring the potential use of non-invasive physical methods to achieve faster orthodontic tooth movement.2,6,7 One of the potential physical approaches suggested in these studies is low-intensity pulsed ultrasound (LIPUS). To validate the use of LIPUS in orthodontics, a search of the current literature was conducted using ISI Web of Knowledge, Science Direct, and PubMed search engines.
Biological effects of LIPUS LIPUS (30–100 mW/cm2) is a form of mechanical energy that is transmitted through living tissues as acoustic pressure waves, resulting in biochemical changes at the cellular and molecular levels.8 These biochemical changes may have several therapeutic benefits, one of which includes an increase in rate of soft and hard tissue healing.9,10 Therefore, LIPUS is widely used in the field of physical therapy, and has been approved by the U.S. Food and Drug Administration (FDA) as a modality of treatment. Since LIPUS can improve the rate of bone healing after trauma, a number of studies have tried to understand its biostimulatory effects, especially in regard to the osteoblastic and osteoclastic responses. It has been reported that
Seminars in Orthodontics, Vol 21, No 3 (September), 2015: pp 219–223
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in response to LIPUS, there is up-regulation of osteogenic markers, such as IL-8, bFGF, VEGF, TGF-β, alkaline phosphatase, and noncollagenous bone proteins, as well as concomitant down-regulation of the osteoclastic markers.4,11–14 It has also been reported that the biostimulatory effects of LIPUS are derived from the induction of micro-stream signals and mechanical stresses. These signals directly stimulate cell membranes, cytoskeletal structures, and focal adhesion molecules, which result in signal transduction and subsequent gene transcription.15 Previous studies16,17 have shown that the periodontal ligament contains precursor cells of cementoblasts and osteoblasts in the perivascular area. Cyclic mechanical stimulation of the PDL, via the regulation of EGF/EGFR system, would induce the differentiation of these precursor cells toward either the osteoblastic or cementoblastic pathway.16,18 This biological effect of LIPUS may help with repair of root resorption.19,20 Similarly, LIPUS has been reported to upregulate fibroblast growth factors (from a macrophage-like cell line) and angiogenic factor (CD31).21,22 It also has been demonstrated that applying LIPUS on human gingival fibroblasts (5 min per day for 3 weeks) upregulates ALP and OPN expressions in these cells, which indicates the possibility of osteogenic differentiation.23 LIPUS is distinguished by being non-invasive and easy to use, and the signal is considered neither thermal nor destructive.24 Compared with other types of ultrasound, LIPUS has a better biological effect in promoting tissue healing.25–27 Therefore, LIPUS has been used to promote the healing of various types of hard and soft tissues, such as fractured bone, intervertebral disc, and cartilage.28 It has also been used to enhance mandibular growth in children with hemifacial microsomia.29 In addition, LIPUS induces a significant increase in the amount of predentin, cementum, and the number of cells in the PDL and the sub-odontoblast layer29–33; which indicates that LIPUS is a potential method to prevent root resorption during orthodontic tooth movement.30 LIPUS is generally utilized in 1.5 MHz frequency pulses with a pulse width of 200 ms, repeated at 1 kHz at an intensity of 30 mW/cm2 for 20 min per day as recommended by the FDA.34–36
While the clinical applications of LIPUS in the medical field are well-studied, there are very few studies on LIPUS stimulation for orthodontic tooth movement.34,37
LIPUS treatment and orthodontic tooth movement There is a narrowing of the PDL in the pressure side of the tooth immediately upon orthodontic forces on the periodontium. Shortly after, osteoclasts differentiate along the wall of alveolar bone, initiating bone resorption, which is considered the initial stage of the tooth movement. Regions of bone resorption are seen as an increase in the width of the PDL. In the later stage of tooth movement, there is an increase in the proliferation and differentiation of local cells into fibroblasts and osteoclasts, followed by the deposition of osteoid tissue on the tension side of the tooth. The original periodontal fibers are gradually embedded in the new layers of osteoid until the PDL has returned to its original width.38 There is no difference observed between the tissue reactions in orthodontic tooth movement with or without LIPUS stimulation.37,39 However, the changes observed in tissue upon LIPUS stimulation are more extensive, resulting in the rapid movement of teeth during the orthodontic treatment.37,40 A list of previous studies on the application of LIPUS during orthodontic treatment is shown in the Table. These studies illustrated that LIPUS can be used in orthodontics to reduce the risk of root resorption, increase the rate of tooth movement, or modify mandibular growth. In addition, LIPUS promotes the proliferation of cells in PDL and alveolar bone, which improves the quality of the periodontium and reduces the possiblity of relapse after orthodontic treatment.41,42
Discussion The ultimate aim of orthodontic tooth movement is to move teeth in the most effective way with minimal side effects such as root resorption. Recent studies have provided evidence of the beneficial effects of LIPUS on the rate of orthodontic tooth movement37; however, the
Use of LIPUS in orthodontics
221
Table. Summary of studies assessing effects of LIPUS on orthodontic tooth movement Study
LIPUS Parameter
Duration
Study Type Results
el-Bialy et al.32
200 ms (1.5 MHz) 1 kHz 30 mW/cm2
20 min/day 4 weeks
In vivo
El-Bialy et al.30 El-Bialy et al.29 Dalla-Bona et al.33 2 ms (1 MHz) 100 Hz 30 (150) mW/cm2 31 200 ms (1.5 MHz) 1 kHz El-Bialy et al. 30 mW/cm2 37 200 ms (1.5 MHz) 1 kHz Xue et al. 30 mW/cm2 51 200 ms (1.5 MHz) 1 kHz Hu et al. 90 mW/cm2
15 min/day
In vivo In vivo In vitro
5 (10) min/day
Ex vivo
20 min/day
In vivo
20 min/day
In Vitro
mechanisms of these biochemical effects still remain unclear. In El-Bialy et al.’s31 study of mandibular organ culture, they suggested that LIPUS might promote tooth movement by enhancing alveolar bone remodeling. Using a rat orthodontic model, Xue et al.37 showed that LIPUS may promote alveolar bone remodeling via increasing the gene expression of the HGF/Runx2/BMP-2 signaling pathway; as a result, the velocity of orthodontic tooth movement was increased. Furthermore, in the in vitro study of human PDL cells (hPDL), it was confirmed that in response to LIPUS stimulation, the expression of BMP-2 mRNA and protein was enhanced via Runx2 expression.37 These findings are in agreement with previous studies and confirm that BMP expression is significantly increased upon mechanical stimulation, such as compressive and shear stress.43,44 The BMP-2 activation induced by orthodontic forces plays a significant role in increasing the rate of bone remodeling by enhancing osteoblast proliferation and indirectly supporting osteoclast differentiation,45,46 which in turn increases the rate of tooth movement. Another benefit of LIPUS application in orthodontics comes from the preventive effect of LIPUS on root resorption. As root resorption may present as a complication during or after orthodontic tooth movement, some therapeutic approaches have been proposed to either inhibit root resorption or to induce periodontal regeneration after root resorption has occured.47–50 However, the effectiveness of these approaches still remains controversial. el-Bialy et al.31 suggested that LIPUS might minimize orthodontically-induced root resorption by enhancing cementum and dentine deposition,
Enhanced the mandibular incisors eruption and incisor apical ends growth Decreased orthodontic root resorption Modified the growth pattern of mandible LIPUS protected against root resorption Enhanced cementum and predentin formation Accelerated orthodontic tooth movement Facilitated osteogenic differentiation of hPDLCs
which provides a preventive layer against root resorption. Considering the benefits of LIPUS, which include its safety, non-invasive nature, and the ability to be reapplied over the course of the orthodontic treatment, it can serve as a great option to accelerate orthodontic tooth movement. However, further studies are required to fully validate the biological effects of LIPUS.
Conclusion In orthodontics, seeking non-invasive techniques to accelerate the rate of tooth movement has been a continuous effort. To our knowledge, LIPUS is a potentially useful tool in clinical orthodontics. While many studies have explored the effects of LIPUS on the periodontal tissue, very few studies have assessed its effects on tooth movement. Therefore, further studies are needed to fully understand the use of LIPUS in orthodontics.
Reference 1. Vig KW. Taking stock: a century of orthodontics—has excellence been redefined as expediency?Orthod Craniofac Res 2004;7:138–142. 2. Kim YD, Kim SS, Kim SJ, Kwon DW, Jeon ES, Son WS. Low-level laser irradiation facilitates fibronectin and collagen type I turnover during tooth movement in rats. Lasers Med Sci. 2010;25:25–31. 3. Yamasaki K, Shibata Y, Fukuhara T. The effect of prostaglandins on experimental tooth movement in monkeys (Macaca fuscata). J Dent Res. 1982;61:1444–1446. 4. Soma S, Iwamoto M, Higuchi Y, Kurisu K. Effects of continuous infusion of PTH on experimental tooth movement in rats. J Bone Miner Res. 1999;14:546–554. 5. Kawakami M, Takano-Yamamoto T. Local injection of 1,25-dihydroxyvitamin D3 enhanced bone formation for
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tooth stabilization after experimental tooth movement in rats. J Bone Miner Metab. 2004;22:541–546. Dominguez A, Velasquez SA. Tooth movement in orthodontic treatment with low-level laser therapy: systematic review imprecisions. Photomed Laser Surg. 2014;32:476–477. Fujita S, Yamaguchi M, Utsunomiya T, Yamamoto H, Kasai K. Low-energy laser stimulates tooth movement velocity via expression of RANK and RANKL. Orthod Craniofac Res. 2008;11:143–155. Buckley MJ, Banes AJ, Levin LG, et al. Osteoblasts increase their rate of division and align in response to cyclic, mechanical tension in vitro. Bone Miner. 1988;4:225–236. Claes L, Willie B. The enhancement of bone regeneration by ultrasound. Prog Biophys Mol Biol. 2007;93:384–398. Romano CL, Romano D, Logoluso N. Low-intensity pulsed ultrasound for the treatment of bone delayed union or nonunion: a review. Ultrasound Med Biol. 2009;35:529–536. Sun JS, Hong RC, Chang WH, Chen LT, Lin FH, Liu HC. In vitro effects of low-intensity ultrasound stimulation on the bone cells. J Biomed Mater Res. 2001;57:449–456. Li JK, Chang WH, Lin JC, Ruaan RC, Liu HC, Sun JS. Cytokine release from osteoblasts in response to ultrasound stimulation. Biomaterials. 2003;24:2379–2385. Sena K, Leven RM, Mazhar K, Sumner DR, Virdi AS. Early gene response to low-intensity pulsed ultrasound in rat osteoblastic cells. Ultrasound Med Biol. 2005;31:703–708. Sant’Anna EF, Leven RM, Virdi AS, Sumner DR. Effect of low intensity pulsed ultrasound and BMP-2 on rat bone marrow stromal cell gene expression. J Orthop Res. 2005;23:646–652. Khan Y, Laurencin CT. Fracture repair with ultrasound: clinical and cell-based evaluation. J Bone Joint Surg Am. 2008;90(suppl. 1):138–144. Matsuda N, Yokoyama K, Takeshita S, Watanabe M. Role of epidermal growth factor and its receptor in mechanical stress-induced differentiation of human periodontal ligament cells in vitro. Arch Oral Biol. 1998;43:987–997. Morsczeck C, Götz W, Schierholz J, et al. Isolation of precursor cells (PCs) from human dental follicle of wisdom teeth. Matrix Biol. 2005;24:155–165. Bosshardt DD, Degen T, Lang NP. Sequence of protein expression of bone sialoprotein and osteopontin at the developing interface between repair cementum and dentin in human deciduous teeth. Cell Tissue Res. 2005;320:399–407. Inubushi T, Tanaka E, Rego EB, et al. Effects of ultrasound on the proliferation and differentiation of cementoblast lineage cells. J Periodontol. 2008;79: 1984–1990. Rego EB, Takata T, Tanne K, Tanaka E. Current status of low intensity pulsed ultrasound for dental purposes. Open Dent J. 2012;6:220–225. Young SR, Dyson M. The effect of therapeutic ultrasound on angiogenesis. Ultrasound Med Biol. 1990;16:261–269. Abtahi NS, Eimani H, Vosough A, et al. Effect of therapeutic ultrasound on folliculogenesis, angiogenesis and apoptosis after heterotopic mouse ovarian transplantation. Ultrasound Med Biol. 2014;40:1535–1544.
23. Mostafa NZ, Uludag H, Dederich DN, Doschak MR, El-Bialy TH. Anabolic effects of low-intensity pulsed ultrasound on human gingival fibroblasts. Arch Oral Biol. 2009;54:743–748. 24. Suzuki A, Takayama T, Suzuki N, Sato M, Fukuda T, Ito K. Daily low-intensity pulsed ultrasound-mediated osteogenic differentiation in rat osteoblasts. Acta Biochim Biophys Sin (Shanghai). 2009;41:108–115. 25. Tanzer M, Harvey E, Kay A, Morton P, Bobyn JD. Effect of noninvasive low intensity ultrasound on bone growth into porous-coated implants. J Orthop Res. 1996;14:901–906. 26. Cook SD, Salkeld SL, Popich-Patron LS, Ryaby JP, Jones DG, Barrack RL. Improved cartilage repair after treatment with low-intensity pulsed ultrasound. Clin Orthop Rel Res. 2001;391:S231–S243. 27. Leung KS, Lee WS, Tsui HF, Liu PP, Cheung WH. Complex tibial fracture outcomes following treatment with low-intensity pulsed ultrasound. Ultrasound Med Biol. 2004;30:389–395. 28. Khanna A, Nelmes RT, Gougoulias N, Maffulli N, Gray J. The effects of LIPUS on soft-tissue healing: a review of literature. Br Med Bull. 2009;89:169–182. 29. El-Bialy T, Hassan A, Albaghdadi T, Fouad HA, Maimani AR. Growth modification of the mandible with ultrasound in baboons: a preliminary report. Am J Orthod Dentofacial Orthop. 2006;130:435e437-e414. 30. El-Bialy T, El-Shamy I, Graber TM. Repair of orthodontically induced root resorption by ultrasound in humans. Am J Orthod Dentofacial Orthop. 2004;126:186–193. 31. El-Bialy T, Lam B, Aldaghreer S, Sloan AJ. The effect of low intensity pulsed ultrasound in a 3D ex vivo orthodontic model. J Dent. 2011;39:693–699. 32. el-Bialy TH, el-Moneim Zaki A, Evans CA. Effect of ultrasound on rabbit mandibular incisor formation and eruption after mandibular osteodistraction. Am J Orthod Dentofacial Orthop. 2003;124:427–434. 33. Dalla-Bona DA, Tanaka E, Inubushi T, et al. Cementoblast response to low- and high-intensity ultrasound. Arch Oral Biol. 2008;53:318–323. 34. Angle SR, Sena K, Sumner DR, Virdi AS. Osteogenic differentiation of rat bone marrow stromal cells by various intensities of low-intensity pulsed ultrasound. Ultrasonics. 2011;51:281–288. 35. Pounder NM, Harrison AJ. Low intensity pulsed ultrasound for fracture healing: a review of the clinical evidence and the associated biological mechanism of action. Ultrasonics. 2008;48:330–338. 36. Mundi R, Petis S, Kaloty R, Shetty V, Bhandari M. Lowintensity pulsed ultrasound: fracture healing. Indian J Orthop. 2009;43:132–140. 37. Xue H, Zheng J, Cui Z, et al. Low-intensity pulsed ultrasound accelerates tooth movement via activation of the BMP-2 signaling pathway. PloS One. 2013;8:e68926. 38. Krishnan V, Davidovitch Z. On a path to unfolding the biological mechanisms of orthodontic tooth movement. J Dent Res. 2009;88:597–608. 39. Liu Z, Xu J, EL, Wang D. Ultrasound enhances the healing of orthodontically induced root resorption in rats. Angle Orthod. 2012;82:48–55. 40. Bandow K, Nishikawa Y, Ohnishi T, et al. Low-intensity pulsed ultrasound (LIPUS) induces RANKL, MCP-1, and
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MIP-1beta expression in osteoblasts through the angiotensin II type 1 receptor. J Cell Physiol. 2007;211:392–398. Singh G, Batra P. The orthodontic periodontal interface: a narrative review. J Internat Clin Dent Res Organ. 2014;6:77. Deepa D, Mehta DS, Puri VK, Shetty S. Combined periodontic-orthodonticendodontic interdisciplinary approach in the treatment of periodontally compromised tooth. J Indian Soc Periodontol. 2010;14:139–143. Mitsui N, Suzuki N, Maeno M, et al. Optimal compressive force induces bone formation via increasing bone morphogenetic proteins production and decreasing their antagonists production by Saos-2 cells. Life Sci. 2006;78:2697–2706. Hsieh PC, Kenagy RD, Mulvihill ER, et al. Bone morphogenetic protein 4: potential regulator of shear stress-induced graft neointimal atrophy. J Vasc Surg. 2006; 43:150–158. Kohno T, Matsumoto Y, Kanno Z, Warita H, Soma K. Experimental tooth movement under light orthodontic forces: rates of tooth movement and changes of the periodontium. J Orthod. 2002;29:129–135.
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46. Long MW, Robinson JA, Ashcraft EA, Mann KG. Regulation of human bone marrow-derived osteoprogenitor cells by osteogenic growth factors. J Clin Invest. 1995;95:881–887. 47. Loberg EL, Engstrom C. Thyroid administration to reduce root resorption. Angle Orthod. 1994;64:395–399 [discussion 399–400]. 48. Igarashi K, Adachi H, Mitani H, Shinoda H. Inhibitory effect of the topical administration of a bisphosphonate (risedronate) on root resorption incident to orthodontic tooth movement in rats. J Dent Res. 1996;75:1644–1649. 49. Talic NF, Evans C, Zaki AM. Inhibition of orthodontically induced root resorption with echistatin, an RGDcontaining peptide. Am J Orthod Dentofacial Orthop. 2006;129:252–260. 50. Fujishiro N, Anan H, Hamachi T, Maeda K. The role of macrophages in the periodontal regeneration using Emdogain gel. J Periodontal Res. 2008;43:143–155. 51. Hu B, Zhang Y, Zhou J, et al. Low-intensity pulsed ultrasound stimulation facilitates osteogenic differentiation of human periodontal ligament cells. PloS One. 2014;9:e95168.
Introduction
O
rthodontic treatment is a process to achieve appropriate esthetics and masticatory function through movement of teeth by applying an external physical force. In this regard, stimulating proper physiological reactions in the surrounding tissue is the main focus of orthodontic treatment.1,2 Optimizing proper biological responses may not only accelerate tooth movement, but also decrease side effects. In order to improve the velocity of orthodontic treatment, previous studies have utilized different biochemical agents, such as osteocalcin and parathyroid prostaglandin E2 (PGE2),3 Department of Orthodontics, School of Stomatology, Fourth Military Medical University, Xi’an, 710031 PR China; Department of Dentistry, Hegang People’s Hospital, Hegang, 310006 PR China; Department of Oral and Maxillofacial Surgery, Stomatological Hospital of Xi’an Jiaotong University, Xi’an, 710004 PR China; Department of Developmental Biology, Harvard School of Dental Medicine, Boston, 02138 MA; Department of Orthodontics, Stomatological Hospital of Xi’an Jiaotong University, Xi’an, 710004 PR China. Corresponding authors. E-mail: [email protected]; [email protected] 1 These authors contributed equally to this work. Funding: This study was supported by grants from The Scientific and Technological Project of Shaanxi Province of China, PR China (2008K14-03 to Dr. Duan), who had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. & 2015 Elsevier Inc. All rights reserved. 1073-8746/12/1801-$30.00/0 http://dx.doi.org/10.1053/j.sodo.2015.06.009
hormone,4 and dihydroxyvitamin D3 [1,25(OH)2D3].5 However, due to systemic effects, their application in orthodontics has not been justified.1 Therefore, recent studies have focused on exploring the potential use of non-invasive physical methods to achieve faster orthodontic tooth movement.2,6,7 One of the potential physical approaches suggested in these studies is low-intensity pulsed ultrasound (LIPUS). To validate the use of LIPUS in orthodontics, a search of the current literature was conducted using ISI Web of Knowledge, Science Direct, and PubMed search engines.
Biological effects of LIPUS LIPUS (30–100 mW/cm2) is a form of mechanical energy that is transmitted through living tissues as acoustic pressure waves, resulting in biochemical changes at the cellular and molecular levels.8 These biochemical changes may have several therapeutic benefits, one of which includes an increase in rate of soft and hard tissue healing.9,10 Therefore, LIPUS is widely used in the field of physical therapy, and has been approved by the U.S. Food and Drug Administration (FDA) as a modality of treatment. Since LIPUS can improve the rate of bone healing after trauma, a number of studies have tried to understand its biostimulatory effects, especially in regard to the osteoblastic and osteoclastic responses. It has been reported that
Seminars in Orthodontics, Vol 21, No 3 (September), 2015: pp 219–223
219
220
Xue et al
in response to LIPUS, there is up-regulation of osteogenic markers, such as IL-8, bFGF, VEGF, TGF-β, alkaline phosphatase, and noncollagenous bone proteins, as well as concomitant down-regulation of the osteoclastic markers.4,11–14 It has also been reported that the biostimulatory effects of LIPUS are derived from the induction of micro-stream signals and mechanical stresses. These signals directly stimulate cell membranes, cytoskeletal structures, and focal adhesion molecules, which result in signal transduction and subsequent gene transcription.15 Previous studies16,17 have shown that the periodontal ligament contains precursor cells of cementoblasts and osteoblasts in the perivascular area. Cyclic mechanical stimulation of the PDL, via the regulation of EGF/EGFR system, would induce the differentiation of these precursor cells toward either the osteoblastic or cementoblastic pathway.16,18 This biological effect of LIPUS may help with repair of root resorption.19,20 Similarly, LIPUS has been reported to upregulate fibroblast growth factors (from a macrophage-like cell line) and angiogenic factor (CD31).21,22 It also has been demonstrated that applying LIPUS on human gingival fibroblasts (5 min per day for 3 weeks) upregulates ALP and OPN expressions in these cells, which indicates the possibility of osteogenic differentiation.23 LIPUS is distinguished by being non-invasive and easy to use, and the signal is considered neither thermal nor destructive.24 Compared with other types of ultrasound, LIPUS has a better biological effect in promoting tissue healing.25–27 Therefore, LIPUS has been used to promote the healing of various types of hard and soft tissues, such as fractured bone, intervertebral disc, and cartilage.28 It has also been used to enhance mandibular growth in children with hemifacial microsomia.29 In addition, LIPUS induces a significant increase in the amount of predentin, cementum, and the number of cells in the PDL and the sub-odontoblast layer29–33; which indicates that LIPUS is a potential method to prevent root resorption during orthodontic tooth movement.30 LIPUS is generally utilized in 1.5 MHz frequency pulses with a pulse width of 200 ms, repeated at 1 kHz at an intensity of 30 mW/cm2 for 20 min per day as recommended by the FDA.34–36
While the clinical applications of LIPUS in the medical field are well-studied, there are very few studies on LIPUS stimulation for orthodontic tooth movement.34,37
LIPUS treatment and orthodontic tooth movement There is a narrowing of the PDL in the pressure side of the tooth immediately upon orthodontic forces on the periodontium. Shortly after, osteoclasts differentiate along the wall of alveolar bone, initiating bone resorption, which is considered the initial stage of the tooth movement. Regions of bone resorption are seen as an increase in the width of the PDL. In the later stage of tooth movement, there is an increase in the proliferation and differentiation of local cells into fibroblasts and osteoclasts, followed by the deposition of osteoid tissue on the tension side of the tooth. The original periodontal fibers are gradually embedded in the new layers of osteoid until the PDL has returned to its original width.38 There is no difference observed between the tissue reactions in orthodontic tooth movement with or without LIPUS stimulation.37,39 However, the changes observed in tissue upon LIPUS stimulation are more extensive, resulting in the rapid movement of teeth during the orthodontic treatment.37,40 A list of previous studies on the application of LIPUS during orthodontic treatment is shown in the Table. These studies illustrated that LIPUS can be used in orthodontics to reduce the risk of root resorption, increase the rate of tooth movement, or modify mandibular growth. In addition, LIPUS promotes the proliferation of cells in PDL and alveolar bone, which improves the quality of the periodontium and reduces the possiblity of relapse after orthodontic treatment.41,42
Discussion The ultimate aim of orthodontic tooth movement is to move teeth in the most effective way with minimal side effects such as root resorption. Recent studies have provided evidence of the beneficial effects of LIPUS on the rate of orthodontic tooth movement37; however, the
Use of LIPUS in orthodontics
221
Table. Summary of studies assessing effects of LIPUS on orthodontic tooth movement Study
LIPUS Parameter
Duration
Study Type Results
el-Bialy et al.32
200 ms (1.5 MHz) 1 kHz 30 mW/cm2
20 min/day 4 weeks
In vivo
El-Bialy et al.30 El-Bialy et al.29 Dalla-Bona et al.33 2 ms (1 MHz) 100 Hz 30 (150) mW/cm2 31 200 ms (1.5 MHz) 1 kHz El-Bialy et al. 30 mW/cm2 37 200 ms (1.5 MHz) 1 kHz Xue et al. 30 mW/cm2 51 200 ms (1.5 MHz) 1 kHz Hu et al. 90 mW/cm2
15 min/day
In vivo In vivo In vitro
5 (10) min/day
Ex vivo
20 min/day
In vivo
20 min/day
In Vitro
mechanisms of these biochemical effects still remain unclear. In El-Bialy et al.’s31 study of mandibular organ culture, they suggested that LIPUS might promote tooth movement by enhancing alveolar bone remodeling. Using a rat orthodontic model, Xue et al.37 showed that LIPUS may promote alveolar bone remodeling via increasing the gene expression of the HGF/Runx2/BMP-2 signaling pathway; as a result, the velocity of orthodontic tooth movement was increased. Furthermore, in the in vitro study of human PDL cells (hPDL), it was confirmed that in response to LIPUS stimulation, the expression of BMP-2 mRNA and protein was enhanced via Runx2 expression.37 These findings are in agreement with previous studies and confirm that BMP expression is significantly increased upon mechanical stimulation, such as compressive and shear stress.43,44 The BMP-2 activation induced by orthodontic forces plays a significant role in increasing the rate of bone remodeling by enhancing osteoblast proliferation and indirectly supporting osteoclast differentiation,45,46 which in turn increases the rate of tooth movement. Another benefit of LIPUS application in orthodontics comes from the preventive effect of LIPUS on root resorption. As root resorption may present as a complication during or after orthodontic tooth movement, some therapeutic approaches have been proposed to either inhibit root resorption or to induce periodontal regeneration after root resorption has occured.47–50 However, the effectiveness of these approaches still remains controversial. el-Bialy et al.31 suggested that LIPUS might minimize orthodontically-induced root resorption by enhancing cementum and dentine deposition,
Enhanced the mandibular incisors eruption and incisor apical ends growth Decreased orthodontic root resorption Modified the growth pattern of mandible LIPUS protected against root resorption Enhanced cementum and predentin formation Accelerated orthodontic tooth movement Facilitated osteogenic differentiation of hPDLCs
which provides a preventive layer against root resorption. Considering the benefits of LIPUS, which include its safety, non-invasive nature, and the ability to be reapplied over the course of the orthodontic treatment, it can serve as a great option to accelerate orthodontic tooth movement. However, further studies are required to fully validate the biological effects of LIPUS.
Conclusion In orthodontics, seeking non-invasive techniques to accelerate the rate of tooth movement has been a continuous effort. To our knowledge, LIPUS is a potentially useful tool in clinical orthodontics. While many studies have explored the effects of LIPUS on the periodontal tissue, very few studies have assessed its effects on tooth movement. Therefore, further studies are needed to fully understand the use of LIPUS in orthodontics.
Reference 1. Vig KW. Taking stock: a century of orthodontics—has excellence been redefined as expediency?Orthod Craniofac Res 2004;7:138–142. 2. Kim YD, Kim SS, Kim SJ, Kwon DW, Jeon ES, Son WS. Low-level laser irradiation facilitates fibronectin and collagen type I turnover during tooth movement in rats. Lasers Med Sci. 2010;25:25–31. 3. Yamasaki K, Shibata Y, Fukuhara T. The effect of prostaglandins on experimental tooth movement in monkeys (Macaca fuscata). J Dent Res. 1982;61:1444–1446. 4. Soma S, Iwamoto M, Higuchi Y, Kurisu K. Effects of continuous infusion of PTH on experimental tooth movement in rats. J Bone Miner Res. 1999;14:546–554. 5. Kawakami M, Takano-Yamamoto T. Local injection of 1,25-dihydroxyvitamin D3 enhanced bone formation for
222
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