Biphasic theory: breakthrough understanding of tooth movement

Published:August 24, 2018DOI:


      • A critical look at the literature tooth movement biology
      • Propose a new theory - The Biphasic Theory of Orthodontic Tooth Movement
      • The theory divides tooth movement two phases
      • Initial Catabolic Phase, during which osteoclasts resorb bone at both compression
      • Later Anabolic Phase, which occurs subsequently to restore alveolar bone to its pre-treatment levels



      Research on the biology of orthodontic tooth movement has led to the prevailing compression-tension theory, which divides the response to orthodontic force into two opposing reactions spatially separated: on the compression side, osteoclasts resorb bone to create space for tooth movement, whereas on the tension side, osteoblasts form bone to restore the alveolar bone structure.


      Here we take a critical look at the literature on how force-induced inflammation, the periodontal ligament, osteoclasts, and osteoblasts contribute to the biological reaction to orthodontic force. We introduce new evidence that supports a novel theory to explain the biology of tooth movement—the Biphasic Theory.


      The Biphasic Theory of Orthodontic Tooth Movement divides tooth movement into the initial Catabolic Phase, during which osteoclasts resorb bone at both compression and tension sites, and the Anabolic Phase, which occurs subsequently to restore alveolar bone to its pretreatment levels.


      The Biphasic Theory of Tooth Movement successfully addresses shortfalls in the Compression-Tension Theory of Tooth Movement, provides clinicians with a better understanding of how orthodontic forces move teeth, and offers new targets for therapies aimed at accelerating tooth movement.


      To read this article in full you will need to make a payment


        • Shen Z.
        • Crotti T.N.
        • Flannery M.R.
        • Matsuzaki K.
        • Goldring S.R.
        • McHugh K.P.
        A novel promoter regulates calcitonin receptor gene expression in human osteoclasts.
        Biochim Biophys Acta. 2007; 1769: 659-667
        • Park J.K.
        • Rosen A.
        • Saffitz J.E.
        • et al.
        Expression of cathepsin K and tartrate-resistant acid phosphatase is not confined to osteoclasts but is a general feature of multinucleated giant cells: systematic analysis.
        Rheumatology (Oxford). 2013; 52: 1529-1533
        • Guha M.
        • Srinivasan S.
        • Koenigstein A.
        • Zaidi M.
        • Avadhani N.G.
        Enhanced osteoclastogenesis by mitochondrial retrograde signaling through transcriptional activation of the cathepsin K gene.
        Ann N Y Acad Sci. 2016; 1364: 52-61
        • Dolci G.S.
        • Ballarini A.
        • Gameiro G.H.
        • Onofre de Souza D.
        • de Melo F.
        • Fossati A.C.M.
        Atorvastatin inhibits osteoclastogenesis and arrests tooth movement.
        Am J Orthod Dentofacial Orthop. 2018; 153: 872-882
        • Teixeira C.C.
        • Khoo E.
        • Tran J.
        • et al.
        Cytokine expression and accelerated tooth movement.
        J Dent Res. 2010; 89: 1135-1141
        • Tompkins K.A.
        The osteoimmunology of alveolar bone loss.
        Connect Tissue Res. 2016; 57: 69-90
        • Liu J.
        • Chen B.
        • Yan F.
        • Yang W.
        The influence of inflammatory cytokines on the proliferation and osteoblastic differentiation of MSCs.
        Curr Stem Cell Res Ther. 2017; 12: 401-408
        • Uda Y.
        • Azab E.
        • Sun N.
        • Shi C.
        • Pajevic P.D.
        Osteocyte mechanobiology.
        Curr Osteoporos Rep. 2017; 15: 318-325
        • Matsumoto T.
        • Iimura T.
        • Ogura K.
        • Moriyama K.
        • Yamaguchi A.
        The role of osteocytes in bone resorption during orthodontic tooth movement.
        J Dent Res. 2013; 92: 340-345
        • Joeng K.S.
        • Lee Y.C.
        • Lim J.
        • et al.
        Osteocyte-specific WNT1 regulates osteoblast function during bone homeostasis.
        J Clin Invest. 2017; 127: 2678-2688
      1. Odagaki N, Ishihara Y, Wang Z, et al. Role of osteocyte-PDL crosstalk in tooth movement via SOST/sclerostin [published online ahead of print June 1, 2018]. J Dent Res doi: 10.1177/0022034518771331.

        • Teixeira C.C.
        • Alansari S.
        • Sangsuwon C.
        • Nervina J.
        • Alikhani M.
        Biphasic theory and the biology of tooth movement.
        in: Alikhani M. Clinical guide to accelerated orthodontics. Springer, Heidelberg, Germany, 2017: 1-18
        • Rubin C.T.
        • Lanyon L.E.
        Regulation of bone formation by applied dynamic loads.
        J Bone Joint Surg Am. 1984; 66: 397-402
        • Alikhani M.
        • Khoo E.
        • Alyami B.
        • et al.
        Osteogenic effect of high-frequency acceleration on alveolar bone.
        J Dent Res. 2012; 91: 413-419
        • Verna C.
        • Dalstra M.
        • Lee T.C.
        • Melsen B.
        Microdamage in porcine alveolar bone due to functional and orthodontic loading.
        Eur J Morphol. 2005; 42: 3-11
        • Alikhani M.
        • Alyami B.
        • Lee I.S.
        • et al.
        Saturation of the biological response to orthodontic forces and its effect on the rate of tooth movement.
        Orthod Craniofac Res. 2015; 18: 8-17
        • Taddei S.R.
        • Andrade Jr., I.
        • Queiroz-Junior C.M.
        • et al.
        Role of CCR2 in orthodontic tooth movement.
        Am J Orthod Dentofacial Orthop. 2012; 141: 153-160
        • Grant M.
        • Wilson J.
        • Rock P.
        • Chapple I.
        Induction of cytokines, MMP9, TIMPs, RANKL and OPG during orthodontic tooth movement.
        Eur J Orthod. 2013; 35: 644-651
        • Fuller K.
        • Kirstein B.
        • Chambers T.J.
        Murine osteoclast formation and function: differential regulation by humoral agents.
        Endocrinology. 2006; 147: 1979-1985
        • Jimi E.
        • Ikebe T.
        • Takahashi N.
        • Hirata M.
        • Suda T.
        • Koga T.
        Interleukin-1 alpha activates an NF-kappaB-like factor in osteoclast-like cells.
        J Biol Chem. 1996; 271: 4605-4608
        • O'Brien C.A.
        • Gubrij I.
        • Lin S.C.
        • Saylors R.L.
        • Manolagas S.C.
        STAT3 activation in stromal/osteoblastic cells is required for induction of the receptor activator of NF-kappaB ligand and stimulation of osteoclastogenesis by gp130-utilizing cytokines or interleukin-1 but not 1,25-dihydroxyvitamin D3 or parathyroid hormone.
        J Biol Chem. 1999; 274: 19301-19308
        • Suzawa T.
        • Miyaura C.
        • Inada M.
        • et al.
        The role of prostaglandin E receptor subtypes (EP1, EP2, EP3, and EP4) in bone resorption: an analysis using specific agonists for the respective EPs.
        Endocrinology. 2000; 141: 1554-1559
        • Yasuda H.
        • Shima N.
        • Nakagawa N.
        • et al.
        Osteoclast differentiation factor is a ligand for osteoprotegerin/osteoclastogenesis-inhibitory factor and is identical to TRANCE/RANKL.
        Proc Natl Acad Sci U S A. 1998; 95: 3597-3602
        • Andrade Jr., I.
        • Silva T.A.
        • Silva G.A.
        • Teixeira A.L.
        • Teixeira M.M.
        The role of tumor necrosis factor receptor type 1 in orthodontic tooth movement.
        J Dent Res. 2007; 86: 1089-1094
        • Iwasaki L.R.
        • Haack J.E.
        • Nickel J.C.
        • Reinhardt R.A.
        • Petro T.M.
        Human interleukin-1 beta and interleukin-1 receptor antagonist secretion and velocity of tooth movement.
        Arch Oral Biol. 2001; 46: 185-189
        • Jager A.
        • Zhang D.
        • Kawarizadeh A.
        • et al.
        Soluble cytokine receptor treatment in experimental orthodontic tooth movement in the rat.
        Eur J Orthod. 2005; 27: 1-11
        • Kesavalu L.
        • Chandrasekar B.
        • Ebersole J.L.
        In vivo induction of proinflammatory cytokines in mouse tissue by Porphyromonas gingivalis and Actinobacillus actinomycetemcomitans.
        Oral Microbiol Immunol. 2002; 17: 177-180
        • Yoshimatsu M.
        • Shibata Y.
        • Kitaura H.
        • et al.
        Experimental model of tooth movement by orthodontic force in mice and its application to tumor necrosis factor receptor-deficient mice.
        J Bone Miner Metab. 2006; 24: 20-27
        • DeLaurier A.
        • Allen S.
        • deFlandre C.
        • Horton M.A.
        • Price J.S.
        Cytokine expression in feline osteoclastic resorptive lesions.
        J Comp Pathol. 2002; 127: 169-177
        • Knop L.A.
        • Shintcovsk R.L.
        • Retamoso L.B.
        • Ribeiro J.S.
        • Tanaka O.M.
        Non-steroidal and steroidal anti-inflammatory use in the context of orthodontic movement.
        Eur J Orthod. 2012; 34: 531-535
        • Chumbley A.B.
        • Tuncay O.C.
        The effect of indomethacin (an aspirin-like drug) on the rate of orthodontic tooth movement.
        Am J Orthod. 1986; 89: 312-314
        • Mohammed A.H.
        • Tatakis D.N.
        • Dziak R.
        Leukotrienes in orthodontic tooth movement.
        Am J Orthod Dentofacial Orthop. 1989; 95: 231-237
        • Quinn R.S.
        • Yoshikawa D.K.
        A reassessment of force magnitude in orthodontics.
        Am J Orthod. 1985; 88: 252-260
        • Ren Y.
        • Maltha J.C.
        • Kuijpers-Jagtman A.M.
        The rat as a model for orthodontic tooth movement—a critical review and a proposed solution.
        Eur J Orthod. 2004; 26: 483-490
        • Yee J.A.
        • Turk T.
        • Elekdag-Turk S.
        • Cheng L.L.
        • Darendeliler M.A.
        Rate of tooth movement under heavy and light continuous orthodontic forces.
        Am J Orthod Dentofacial Orthop. 2009; 136 (discussion 150-1): 150.e1-150.e9
        • Alikhani M.
        • Alyami B.
        • Lee I.S.
        • et al.
        Biological saturation point during orthodontic tooth movement.
        Orthod Craniofac Res. 2015; 18: 8-17
        • Ikegame M.
        • Ishibashi O.
        • Yoshizawa T.
        • et al.
        Tensile stress induces bone morphogenetic protein 4 in preosteoblastic and fibroblastic cells, which later differentiate into osteoblasts leading to osteogenesis in the mouse calvariae in organ culture.
        J Bone Miner Res. 2001; 16: 24-32
        • Rubin C.T.
        • Sommerfeldt D.W.
        • Judex S.
        • Qin Y.
        Inhibition of osteopenia by low magnitude, high-frequency mechanical stimuli.
        Drug Discov Today. 2001; 6: 848-858
        • Garman R.
        • Rubin C.
        • Judex S.
        Small oscillatory accelerations, independent of matrix deformations, increase osteoblast activity and enhance bone morphology.
        PLoS One. 2007; 2: e653
        • Bassett C.A.
        Biologic significance of piezoelectricity.
        Calcif Tissue Res. 1968; 1: 252-272
        • Hert J.
        • Liskova M.
        • Landrgot B.
        Influence of the long-term, continuous bending on the bone. An experimental study on the tibia of the rabbit.
        Folia Morphol (Praha). 1969; 17: 389-399
        • Alikhani M.
        • Alanari S.
        • Sangsuwon C.
        • Teo M.C.
        • Hiranpradit P.
        • Teixeira C.C.
        Anabolic effects of MOPs: cortical drifting.
        in: Alikhani M. Clinical guide to accelerated orthodontics. Springer, Heidelberg, Germany, 2017: 79-98
        • Matsuo K.
        • Irie N.
        Osteoclast-osteoblast communication.
        Arch Biochem Biophys. 2008; 473: 201-209