biological mechanism of tooth movement

Summary

For millennia we were unable to understand why teeth can be moved by finger pressure, as advocated by Celsusaround the dawn of the common era, but it was working.Indeed, our ancestors were keenly aware of malocclusionsand the ability to push teeth around by mechanical force.The modern era in dentistry began in earnest in 1728 withthe publication of the first comprehensive book on den-tistry by Fauchard. In it Fauchard described a procedureof “instant orthodontics,” whereby he aligned ectopicallyerupted incisors by bending the alveolar bone. A centuryand a half later, in 1888, Farrar tried to explain why teethmight be moved when subjected to mechanical loads. Hisexplanation was that teeth move either because theorthodontic forces bend the alveolar bone, or because theyresorb it. The bone resorption idea of Farrar was provenby Sandstedt in 1901 and 1904, with the publication ofthe first report on the histology of orthodontic toothmovement. Histology remained the main orthodonticresearch tool until and beyond the middle of the twentiethcentury. Basic medical research then began evolving at anincreasing pace, and newly developed research methodswere being adapted by investigators in the various fields ofdentistry, including orthodontics. At that time Farrar’sassumption that orthodontic forces bend the alveolarbone was proven to be correct, and the race was on tounravel the mystery of the biology of tooth movement.During the second half of the twentieth century, tissuesand cells were challenged and studied in vitro and in vivofollowing exposure to mechanical loads. Among theinvestigative tools were high quality light and electronmicroscopes, and a large array of instruments used inphysiological and biochemical research. The main fields ofresearch that have been plowed by these investigationsinclude histochemistry, immunohistochemistry, immuno-logy, cellular biology, molecular biology, and moleculargenetics. A logical conclusion from this broad researcheffort is that teeth can be moved because cells around theirroots are enticed by the mechanical force to remodel the tissues around them. This conclusion has opened thedoor for quests aimed at discovering means to recruit the

involved paradental cells to function in a manner thatwould result in increased dental velocity. The means usedin these investigations have been pharmaceutical, phys-ical, and surgical. In all these categories, experimental out-comes proved that the common denominator, the cell, isindeed very sensitive to most stimuli, physical and chem-ical. Hence, the way ahead for orthodontic biologicalresearchers is well illuminated. It is a two-lane highway,consisting of a continuous stream of basic experimentsaimed at uncovering additional secrets of tissue and cellu-lar biology, alongside a lane of trials exploring means toimprove the quality of orthodontic care. Gazing towardthe horizon, these two lanes seem to merge.

Keywords: Orthodontic tooth movement; Tissue, cellular,and molecular biology; Enhancement of tooth velocity;Effects of age on tooth movement

Introduction

Our ancestors, as far back as the dawn of history, in allcivilizations, cultures, and nations, were interested inimages of bodies and faces, covered or exposed. Theirartists painted these images on cave walls, on cathedralceilings, and on canvas pieces that were hung in privatehomes. They also created a huge array of sculptures asmonuments, religious fixtures, or outdoor decorations.These works of art reflected images of faces that werecurved and crafted along guidelines unique for each tribal,ethnic, and cultural group. Figure 1.1 presents a profileview of a marble statue of a man’s head, found in anarcheological dig in Greece. Typically, the facial profile isdivided into three equal parts (upper, middle, and lower),and the outline of the nose is continuous with the fore-head. Figure 1.2 shows a contemporary sculpture of ashrine guardian in Korea. The features are exaggerated,but the facial proportions are similar to those of theancient Greek statue. Some artists, for example Picasso,attracted attention by intentionally distorting well estab-lished facial features. Frequently, facial features in old aswell as in contemporary paintings and sculptures express

1The Adaptation and Development of BiologicalConcepts in OrthodonticsZe’ev Davidovitch and Neal C. Murphy

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Fig. 1.1 Ancient Greek marble statue of a man’s head.National Museum of Greece, Athens.

Fig. 1.2 Contemporary bust sculpture of a shrine guardian,Seoul, Korea.

a variety of emotions, ranging from love to fear, and awide array of shapes, from the ideal to the grotesque. Theimportant role of teeth in determining the shape of theface goes back to Biblical times, where straight, shinyteeth were compared to “a flock of white sheep afteremerging from a wash” (Song of Songs). Every artisticwork that displays human faces displays only the facialsurface, not any of the tissues located under the skin,including skeletal, muscular, and dental elements. How-ever, we are keenly aware that these tissues are essentialparticipants in the determination of facial form, as well as the shape of the dental arches. Naturally, therefore,orthodontic research has followed closely the scientificfootsteps imprinted by biologists and physicians. At first,the investigations focused on the microscopic appearanceof the tissues, followed by a close examination of theinvolved cells, and most recently the emphasis has shiftedtoward the fields of molecular biology and genetics, andtissue engineering.

The enlightening findings about the intimate details ofthe organism’s response to mechanical loads have pavedthe way to searches for means to improve the efficiency of orthodontic treatment. For this purpose, investigatorsutilized pharmaceuticals, physical stimuli, and surgicalprocedures. Their results have demonstrated that, in mostcases, the application of mechanical force to teeth, in the presence of another factor(s) known to affect themetabolism and function of various cell types in the

2 Biological Mechanisms of Tooth Movement

involved areas in and around the teeth, may, predictably,increase or inhibit the velocity of tooth movement. Theseexperiments are spearheading ongoing efforts to improvethe quality of orthodontic care for all patients.

Orthodontic treatment in the ancient world,the Middle Ages, and through the Renaissanceperiod: shear mechanics, but few biologicalconsiderations

Archeological evidence from all continents and many coun-tries, including written documents, reveals that our fore-fathers were aware of the presence of teeth in the mouth,and of various associated health problems. Early civiliza-tions confronted diseases such as caries and periodontitiswith a variety of medications, ranging from prayers toextractions and fabrication of dentifrice pastes. Goldinlays and incisor decorations were discovered in SouthAmerica, while gold crowns and bridges, still attached tothe teeth, were discovered in pre-Roman era Etruscangraves (Weinberger, 1926). All these findings bear witnessto our ancestors’ awareness of oral health issues.

Recognition of malocclusions and individual variabil-ity in facial morphology and function were first noted in Ancient Greece. Hippocrates of Cos (460–377 BCE),founder of Greek medicine, instituted for the first time acareful, systematic, and thorough examination of the

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Fig. 1.3 Carl Sandstedt, 1860–1904.

Biological Concepts in Orthodontics 3

patient. In his writings is found the first known literaturepertaining to the teeth. He discussed the timing of shed-ding of primary teeth, and stated that “teeth that comeforth after this, grow old with the person, unless diseasedestroys them.” He also commented that the teeth areimportant in processing nutrition and in the production ofsound. Hippocrates, like other well educated people of histime, was keenly aware of the variability in the shapes ofthe human craniofacial complex. He stated that “amongthose individuals whose heads are long-shaped, some havethick necks, strong limbs and bones; others have highlyarched palates, their teeth are disposed irregularly, crowd-ing one on the other, and they are afflicted by headachesand otorrhea” (Weinberger, 1926). This statement isapparently the first written description of a human maloc-clusion. Interestingly, Hippocrates saw here a direct con-nection between the malocclusion and other craniofacialpathologies.

A prominent Roman physician, Celsus (25 BCE–50CE), was apparently the first to recommend the use ofmechanical force to evoke tooth movement. He wrote: “If a permanent tooth happens to grow in children beforethe deciduous one has fallen out, that which ought to beshed, is to be extracted and the new one daily pushedtowards its place by means of the finger until it arrives at its proper position.” Celsus was also the first to recommend the use of a file in the mouth, mainly for thetreatment of carious teeth (Weinberger, 1926). AnotherRoman dentist, Plinius Secundus (23–79), expressed op-position to the extraction of teeth for the correction ofmalocclusions, and advocated filing elongated teeth “tobring them into proper alignment.” Plinius was evidentlythe first to recommend using files to address the verticaldimension of malocclusion, and this method was widelyused until the nineteenth century (Weinberger, 1926).

There were few, if any, known advances in the fields of medicine, dentistry, and orthodontics from the first tothe eighteenth centuries, with the exception of Galen(131–201), who established experimental medicine anddefined anatomy as the basis of medicine. He devotedchapters to teeth, and, like Celsus a century earlier, advoc-ated the use of finger pressure to align malposed teeth.Another exception was Vesalius (1514–1564), whose dis-sections produced the first illustrated and precise book onhuman anatomy.

Orthodontic treatment during the IndustrialRevolution: emergence of identification ofbiological factors

Fauchard (1678–1761) was the first to advocate broadereducation for dentists, and gave dentistry its first scient-ific work. In the book he published in 1728, Faucharddescribed an orthodontic appliance that used silk or silver

ligatures to move malposed teeth to new positions, and“pelican” pliers that were used for instant alignment ofincisors, facilitated by bending of the alveolar bone.Hunter (1728–1793), in 1778, explained that teeth mightbe moved by applied force, because “bone moves out ofthe way of pressure.” In 1815, Delabarre reported thatorthodontic forces cause pain and swelling of paradentaltissues. Pain and swelling are two cardinal signs of inflam-mation. In 1888, Farrar hypothesized that orthodonticforces move teeth by bending of the alveolar bone, and/orby causing resorption of this bone. He therefore recom-mended the application of heavy forces to teeth in order tomove them rapidly.

Orthodontic tooth movement in the twentiethand twenty-first centuries: from lightmicroscopy to tissue engineering

Histological studies of paradental tissues duringtooth movement

The results of the first histological examination of tissuessurrounding orthodontically treated teeth were reportedby Sandstedt (1904–1905) (Figure 1.3). He subjectedteeth in a dog to orthodontic forces for increasing periodsof time, and observed stretching of the periodontal liga-ment (PDL) in tension sites, and narrowing of this tissue inpressure sites. New alveolar bone formation was seen inthe former locations, while necrosis (hyalinization) andbone resorption, direct and undermining, were noticed in the latter sites. Figure 1.4 is a photograph of a cross section of a premolar root, showing areas of necrosis in thePDL, as well as multiple osteoclasts in Howship’s lacunae

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Fig. 1.4 A figure from Carl Sandstedt’s historic article in 1904,presenting a histological picture of a dog premolar in crosssection and showing the site of PDL compression, including anosteoclastic front and necrotic (hyalinized) areas.

Fig. 1.5 Kaare Reitan, 1903–2000.

Fig. 1.6 A 6 mm sagittal section of a frozen, unfixed, non-demineralized cat maxillary canine, stained with hematoxylinand eosin. This canine was not treated orthodontically (con-trol). The PDL is situated between the canine root (left) and the alveolar bone (right). Most cells appear to have an ovoidshape. ×320.

at the PDL–alveolar bone interface. These cells were, inSandstedt’s opinion, the main cells responsible for force-induced tooth movement. In 1911–1912, Oppenheimreported that tooth movement in one pre-adolescentbaboon resulted in complete transformation (remodeling)of the entire alveolar process, indicating that orthodonticforce effects spread beyond the limits of the PDL. Theeffects of orthodontic force magnitude on dog paradentaltissue responses were examined with light microscopy bySchwarz (1932). He concluded that an optimal force issmaller in magnitude than that capable of occluding PDLcapillaries. Occlusion of these blood vessels, he reasoned,would lead to necrosis of surrounding tissues, whichwould be harmful, and would slow down the velocity oftooth movement. This opinion was supported by Reitan(1957, 1958, 1961) and Reitan and Kvam (1971) (Figure1.5), who conducted thorough histological examinationsof paradental tissues incidental to tooth movement.Reitan’s studies (Reitan, 1957, 1958, 1961; Reitan andKvam, 1971) were conducted on a variety of species, in-cluding rodents, canines, and primates including humans,and their results were published during the 1950s to the1970s. Figure 1.6 displays the appearance of an unstressedPDL of a cat maxillary canine. The cells are equally dis-tributed along the ligament, surrounding small blood ves-sels. Both the alveolar bone and the canine appear intact.In contrast, the compressed PDL of a cat maxillary caninethat had been tipped distally for 28 days with an 80 gforce (Figure 1.7) appear very stormy. The PDL near theroot is necrotic, but the alveolar bone and PDL at the edgeof the hyalinized zone are being invaded by cells thatappear to remove the necrotic tissue, as evidenced by alarge area where undermining resorption had taken place.Figure 1.8 shows the mesial side of the same root, wheretension prevails in the PDL. Here the cells appear busyproducing new trabeculae arising from the alveolar bonesurface, in an effort to keep pace with the moving root. Toachieve this type of tissue and cellular response to


orthodontic loads, Reitan and Kvam (1971) favored theuse of light intermittent forces, because they cause min-imal amounts of tissue damage and cell death. They notedthat the nature of tissue response differs from species tospecies, reducing the value of extrapolations. They alsocalled attention to the role of factors such as gender, age,and type of the alveolar bone, in determining the nature ofthe clinical response to orthodontic forces.

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Fig. 1.7 A 6 mm sagittal section of a cat maxillary canine, after28 days of application of 80 g force. The maxilla was fixed anddemineralized. The canine root (right) appears to be intact,but the adjacent alveolar bone is undergoing extensive resorp-tion, and the compressed, hyalinized PDL is being invaded bycells from neighboring viable tissues (fibroblasts and immunecells). H & E staining. ×180.

Fig. 1.8 The mesial (PDL tension) side of the tooth shown inFigure 1.7. Here, new trabeculae protrude from the alveolarbone surface, apparently growing towards the distal-movingroot. H & E staining. ×180.


Experimenting in rodents, Storey (1973) used lightmicroscopy to determine that these forces can be classifiedas bioelastic, bioplastic, and biodisruptive. The bioelasticforce is a light force that mainly distorts the tissues,depending upon their degree of elasticity. The bioplasticforce is greater, resulting in remodeling without tissuedamage. The biodisruptive force, on the other hand, islarge enough to cause extensive damage to teeth and theirsurrounding soft and hard tissues. Storey stated that a cer-tain amount of damage may result even when bioelasticforces are employed, primarily because the alveolar bonysocket is not entirely smooth. A common denominator forall these force categories was found to be inflammation.Storey observed migration of leukocytes out of PDL capil-

laries 20 min after orthodontic force application to in-cisors in rabbits. He concluded that inflammation is anintegral part of the tissue response in orthodontics, amechanism providing cells essential for both the resorptiveand depository functions that facilitate tooth movement.The participation of blood-borne cells in the remodeling of the mechanically stressed PDL was confirmed by Ryghand Selvig (1973) and Rygh (1974, 1976), who used trans-mission electron microscopy in studies on rodents. Theydetected macrophages at the edge of the hyalinized zoneduring the early phases of treatment, invading the necroticPDL and phagocytizing its cellular debris and strainedmatrix.

Histochemical evaluation of the tissue response toapplied mechanical loads

Identification of cellular and matrix changes in paradentaltissues following the application of orthodontic forces ledto histochemical studies aimed at elucidating enzymes thatmight participate in this remodeling process. In 1983,Lilja et al. reported on the detection of various enzymes in mechanically strained paradental tissues of rodents,including acid and alkaline phosphatases, β-galactosidase,aryl transferase, and prostaglandin synthetase. Meikle et al. (1989) stretched rabbit coronal sutures in vitro,and recorded increases in the tissue concentrations of met-alloproteinases, such as collagenase and elastase, and aconcomitant decrease in the levels of tissue inhibitors of this class of enzymes. Davidovitch et al. (1976, 1978,1980a–c, 1992, 1996) used immunohistochemistry toidentify a variety of first and second messengers in cats’mechanically stressed paradental tissues. These moleculesincluded cyclic nucleotides, prostaglandins, neurotrans-mitters, cytokines, and growth factors. Computer-aidedmeasurements of cellular staining intensities revealed thatparadental cells are very sensitive to the application oforthodontic forces, that this cellular response begins assoon as the tissues develop strain, and that these reactionsencompass cells of the dental pulp, PDL, and alveolarbone marrow cavities. Figure 1.9 shows a cat maxillarycanine section, stained immunohistochemically for pro-staglandin E2 (PGE2), a 20-carbon essential fatty acid pro-duced by many cells that acts as a paracrine and autocrineregulator. This tooth1 was not treated orthodontically(control). The PDL and alveolar bone surface cells stainlightly for PGE2. In contrast, 24 h after the application offorce to the other maxillary canine, the stretched cells(Figure 1.10) stain intensely for PGE2. The staining intens-ity is indicative of the cellular concentration of the antigenin question. In the case of PGE2, it is evident that ortho-dontic force stimulates the target cells to produce higherlevels than usual of PGE2. Likewise, these forces increasesignificantly the cellular concentrations of cyclic AMP, an intracellular second messenger (Figures 1.11–1.13),

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Control

Fig. 1.9 A 6 mm sagittal section of a cat maxilla, unfixed andnon-demineralized, stained immunohistochemically for PGE2.This section shows the PDL–alveolar bone interface near onecanine that remained untreated by orthodontic forces (con-trol). PDL and alveolar bone surface cells are stained lightly forPGE2. ×840.

Tension, 24 hours

Fig. 1.10 A 6 mm sagittal section of the same maxilla shown inFigure 1.9, but derived from the other canine, that had beentipped distally for 24 h by a coil spring generating 80 g offorce. The PDL and alveolar bone surface cells in the site ofPDL tension are stained intensely for PGE2. ×840.

Control

Fig. 1.11 Immunohistochemical staining for cyclic AMP in a 6 mm sagittal section of a cat maxillary canine untreated byorthodontic forces (control). The PDL and alveolar bone sur-face cells stain mildly for this cyclic nucleotide. ×840.

Tension, 24 hours

Fig. 1.12 Staining for cyclic AMP in a 6 mm sagittal section of acat maxillary canine subjected for 24 h to a distalizing force of80 g. This section, which shows the PDL tension zone, wasobtained from the antimere of the control tooth shown inFigure 1.11. The PDL and bone surface cells are stainedintensely for cyclic AMP, particularly the nucleoli. ×840.

and of the cytokine interleukin-1β (IL-1β), an inflammat-ory mediator, and a potent stimulator of bone resorption(Figures 1.14 and 1.15).

Cellular and molecular biology: majordeterminants of the outcome of orthodontictreatment

A review of bone cell biology as related to orthodontictooth movement identified the osteoblasts as the cells thatcontrol both the resorptive and formative phases of theremodeling cycle (Sandy et al., 1993). Receptor studieshave proven that these cells are targets for resorptive


agents in bone, as well as for mechanical loads. Theirresponse is reflected in fluctuations of prostaglandins,cyclic nucleotides, and inositol phosphates. It was there-fore postulated that mechanically induced changes in cellshape produce a range of effects, mediated by adhesionmolecules (integrins) and the cytoskeleton. In this fashion,mechanical forces can reach the cell nucleus directly, cir-cumventing the dependence on enzymatic cascades in thecell membrane and the cytoplasm.

Efforts to identify specific molecules involved in tissue remodeling during tooth movement have unveilednumerous components of the cell nucleus, cytoplasm, andplasma membrane that seem to impact the stimulus–cell

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Control, IL-1b

Fig. 1.14 Immunohistochemical staining for IL-1b in PDL andalveolar bone cells near a cat maxillary canine untreated byorthodontic forces (control). The PDL and alveolar bone sur-face cells are stained lightly for IL-1b. ×180.

1 hour, compression, IL-1b

Fig. 1.15 Staining for IL-1b in PDL and alveolar bone surfacecells after 1 h of compression resulting from the application ofan 80 g distalizing force to the antimere of the tooth shown inFigure 1.14. The cells stain intensely for IL-1b in the PDL com-pression zone, and some have a round shape, perhaps signify-ing detachment from the extracellular matrix. ×840.

Tension, 7 days


interactions. These interactions, as well as those betweenadjacent cells, seem to determine the nature and the extentof the cellular response to mechanical loads. The receptoractivator of nuclear factor kappa B ligand (RANKL) andits decoy receptor and osteoprotegerin (OPG) were foundto play important roles in the regulation of bone meta-bolism. Essentially, RANKL promotes osteoclastogenesiswhereas OPG inhibits this effect. The expression ofRANKL and OPG in human PDL cells was measured byZhang et al. (2004). The cells were cultured for 6 days inthe presence or absence of vitamin D3, a hormone thatevokes bone resorption. The expression of mRNA forboth molecules was assessed by RT–PCR, while the levelof secreted OPG in the culture medium was measured by

ELISA. It was found that both molecules were expressedin PDL cells, and that vitamin D3 down-regulated theexpression of OPG and up-regulated the expression ofRANKL. These results suggest that these molecules playkey roles in regulating bone metabolism. The effect ofcompressive force on RANKL expression in human PDLcells in vitro was reported by Nakao et al. (2007). Thecells were subjected to compressive forces for either 8 or24 h/day for 2–4 days. The cells exposed intermittentlyexpressed higher levels of RANKL than cells treated con-tinuously, and these increases were inhibited by adding anIL-1 receptor antagonist to the culture medium. Anotherrelated study, by Yamaguchi et al. (2006), was conductedon human PDL cells removed from teeth that had experi-enced severe root resorption during orthodontic treatment,or from teeth that were not damaged by such treatment.The increase in RANKL and the decrease of OPG weregreater in the severe root resorption group than in thenon-resorptive group.

In contrast, Kanzaki et al. (2004) tested the effect ofcyclical tensile forces on human PDL cells in vitro. Thetensile forces up-regulated mRNA expression for RANKLand OPG, as well as TGF-β in these cells. The conditionedmedia in which these cells were cultivated up-regulatedOPG mRNA and inhibited osteoclastogenesis. Admin-istration of neutralizing antibodies to TGF-β abolishedthe OPG up-regulation and the inhibitory effect of theconditioned media.

The presence of RANKL in vivo in compressed PDLwas demonstrated by immunohistochemistry (Kim et al.,2007). In 55-day-old rats, maxillary molars were movedlaterally for 1–7 days. This movement was accompaniedby a finding of positive staining for RANKL in PDL cellsin compression sites after 1 day of treatment, suggesting

Fig. 1.13 Staining for cyclic AMP in the tension zone of thePDL after 7 days of treatment. The active osteoblasts are pre-dominantly round, while the adjacent PDL cells are elongated.All cells are intensely stained for cyclic AMP. ×840.

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a role for RANKL in bone resorption during tooth move-ment. Zuo et al. (2007) examined the PDL from ratsundergoing orthodontic tooth movement, and detectedsharp increases in the activation of nuclear factor kB(NFkB) by phosphorylation of the p65 component atamino acid 536 after 3 and 12 h of treatment. This reac-tion is apparently crucial in promoting osteoclast differen-tiation by RANKL. In cell culture the concentrations ofp65 did not change in osteoclasts in response to RANKL,but rapid increases occurred after mechanical scraping.These results suggest that NFkB p65 may be important inbone remodeling during orthodontic treatment.

The discovery that RANKL expression is increased incompressed PDL cells, being an important regulator ofosteoclast differentiation, has led to an attempt to inhibitthis reaction (Kanzaki et al., 2004) in order to preventteeth from moving. Such an accomplishment could be veryhelpful in preventing movement of anchor teeth duringorthodontic treatment, and relapse during the post-treat-ment period. To achieve this goal, Kanzaki and coworkers(2004) constructed a mouse OPG expression plasmid forthis purpose. An envelope of an inactivated virus (HVJ)containing the OPG plasmid was injected into the palatalPDL of the maxillary first molar of rats undergoingorthodontic tooth movement. This local gene transferinduced OPG production, inhibited osteoclastogenesis,and significantly reduced tooth movement. This findingdemonstrates the potential value of employing a biolog-ical agent as an adjunct of orthodontic treatment. It isbased on laboratory research, and can be applied judi-cially by the orthodontist whenever needed.

The above-mentioned studies illuminate informationon the biological aspects of orthodontic tooth movement.As this picture continues to unfold, it is evident that theevolving image consists of many details that eventuallyinterlock. But many gaps still exist. Tooth movement isprimarily a process dependent upon the reaction of cells to applied mechanical loads. It is by no means a simpleresponse, but rather a complex reaction. Components ofthis reaction have been identified in experiments on isol-ated cells in vitro. However, in this environment theexplanted cells are detached from the rest of the organism,and are not exposed to signals prevailing in intact animals.In contrast, in orthodontic patients the same cell types areexposed to a plethora of signal molecules derived fromendocrine glands, migratory immune cells, and ingestedfood and drugs. These entities may differ significantlyfrom patient to patient, and such differences may haveprofound effects on treatment outcome. This fact impliesthat an orthodontic diagnosis should include informationabout the overall biological status of each patient, notmerely a description of the malocclusion and the adjacentcraniofacial hard and soft tissues. Moreover, periodicassessments of specific biological signal molecules in bodyfluids, especially in the gingival crevicular fluid, may be


useful for the prediction of the duration and outcome oforthodontic treatment.

Efforts to increase the velocity of orthodontic tooth movement

Effects of pharmacological agents on tooth velocityThe existence of compelling evidence about the importantrole of biology in orthodontics has provided clinicianswith an opportunity to repeat an old question: Is it pos-sible to enhance the rate of orthodontic tooth movementand shorten its duration? The speed of tooth movementwas found to be related to the force magnitude, the level ofcytokines in the GCF, and the IL-1 gene predisposition(Iwasaki et al., 2006). The actual velocity of tooth move-ment may depend on the rate of bone turnover. The lat-ter was modified pharmacologically, in rats undergoingmaxillary molar mesial movement, by inducing eitherhypothyroidism or hyperthyroidism (Verna et al., 2000).In rats with high bone turnover, the rate of tooth move-ment was increased, while it was reduced in animals witha low turnover. Although all teeth had been moved in thesame manner (controlled tipping), the location of the cen-ter of rotation differed, depending on the metabolic stateof the bone. Examination of histological sections from thejaws of these rats (Verna et al., 2003) showed that rootresorption had occurred in both groups, as well as in thecontrol group, but that it was more pronounced in the lowbone turnover group. However, bone metabolism norm-ally demonstrates measurable diurnal fluctuations thatmay affect the rate of tooth movement.

The use of chemical agents in attempts to increase thepace of tissue remodeling and tooth movement has beentested in various laboratories and clinics. Yamasaki et al.(1980, 1984) injected prostaglandin E1 into the gingiva ofmoving teeth in rats and in human subjects, resulting inrapid movement. Systemic application of misoprostol, aPGE1 analog, to rats undergoing tooth movement for 2 weeks increased significantly the velocity of movementwithout enhancing root resorption (Sekhavat et al., 2002).Similar results were reported following intraperitonealinjections of PGE2 in rats (Seifi et al., 2003). Chumbleyand Tuncay (1986) systemically administered the prosta-glandin synthetase inhibitor indomethacin; Collins andSinclair (1988) used local applications of vitamin D, whileEngstrom et al. (1988) moved teeth in hypocalcemic, vitamin D-deficient lactating rats. The bone matrix com-ponent osteocalcin was injected in rats into the palatalbifurcation of a tipping molar, causing rapid tooth move-ment due to the attraction of numerous osteoclasts to thissite (Hashimoto et al., 2001).

The search for biological agents that would increasetooth velocity has led to the experimental application ofthe hormone relaxin to rats undergoing tooth move-ment (Madan et al., 2007). Relaxin is capable of reducing

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the organizational level of connective tissues, facilitatingrapid separation between adjoining bones, i.e. the pubicsymphysis during pregnancy. Maxillary molars weremoved for 2–9 days, with or without relaxin application.Tooth velocity was found to be similar in both groups.However, relaxin reduced the level of PDL organizationand mechanical strength, leading to increased toothmobility.

Acceleration of tooth velocity with physical stimuliThe realization that tissue remodeling in orthodontics ismediated by a variety of cells, including fibroblasts, rootand bone surface lining cells, endothelial, epithelial, andnerve cells, as well as by different leukocytes, promptedclinical investigators to apply physical and chemicalagents concomitant with orthodontic forces, in order toaugment the effect of the mechanical forces. Tweedle(1965) used local application of heat to paradental tissuessurrounding orthodontically treated teeth in dogs. Inanother experiment, rats were exposed to light for 24 or12 h per day for 21 days while subjected to orthodonticforce during the light periods. The teeth in the 24 h lightgroup presented doubling of the rates of tooth movementand bone remodeling, as compared with animals thatreceived the force during the 12 h of daily darkness(Miyoshi et al., 2001).

Minute electric currents were applied locally near mov-ing teeth by Beeson et al. (1975), and by Davidovitch et al.(1980c, 1984). Blechman (1998), on the other hand,advocated the use of static magnetic fields for the purposeof generating optimal forces and for accelerating toothmovement. Beeson et al. reported that their electric device,which had been fabricated for use in cats, with electrodesplaced at a noticeable distance from the tooth, failed toaccelerate its movement. In contrast, Davidovitch et al.placed the electrodes much closer to the cat’s canine,resulting in a significant enhancement of movement.Blechman hypothesized that magnets generate mechanicalforces, as well as magnetic fields, and that this combina-tion acts synergistically causing the teeth to move faster.However, an experiment in rats (Tengku et al., 2000)revealed that magnets do not speed up the mesial move-ment of maxillary molars, and actually increase rootresorption in the early phases of treatment. Application ofstatic magnetic fields to rat calvarial osteoblasts in vitrofor 20 days by Yamamoto et al. (2003) enhanced signific-antly the number and size of bone nodules, and their con-tent of calcium, alkaline phosphatase, and osteocalcin.

When mechanical loads are applied to intact tissues invivo or in vitro, the tissues usually become distorted(strained). In the case of the skeleton, loads such as gravityprompt cells to arrange the architecture of the bony struc-tural features in a way that would resist redundant loads.This phenomenon is known as “Wolff’s Law,” outlinedby Julius Wolff in 1892. However, when bone cells are

subjected to non-redundant loads such as orthodonticforces, the cells are activated and remodeling of the alveo-lar process ensues, which facilitates tooth movement. Invivo applications of compressive loads to ulnae in turkeysand roosters by Lanyon and Rubin (1984), Rubin andLanyon (1984, 1985, 1987) and Skerry et al. (1988, 1990)revealed that extensive osteogenesis can be evoked byshort-term dynamic (intermittent) forces. In those experi-ments, the optimal load magnitude was 2000–4000microstrain, and its daily duration was 10–20 min. Thesefindings suggest that orthodontic forces would be mosteffective when applied for brief periods rather than con-tinuously. This assumption was found to be correct in anexperiment in rats by Gibson et al. (1992). In that experi-ment, maxillary molars were subjected to mesial-movingforces for 1 h, 1 day, or 14 days. Teeth exposed to only 1 h of force application continued to move mesially for 14 days and achieved 75% of the distance reached by theteeth that had been subjected to orthodontic forces con-tinuously for 14 days.

Acceleration of tooth movement by surgical meansSurgery offers another powerful means to significantlyincrease the velocity of orthodontic tooth movement.Specifically, various alveolar corticotomies and selectivealveolar decortication (SAD) are most effective in thisregard. An experiment in young adult beagle dogs by Renet al. (2007) revealed that surgical reduction of theosteonal resistance of tooth extraction socket walls en-hances the rapidity of orthodontic movement of adjac-ent teeth into the sockets. In another experiment in adult beagles, by Iino et al. (2007), premolars were moved for 2 weeks after alveolar corticotomy. This movement wassignificantly greater than that recorded for teeth that werenot treated by alveolar surgery. These authors also reportmore osteoclasts and less PDL hyalinization near teeththat had been operated than near non-surgically treatedteeth. It is likely that these findings result, at least in part,from inflammation and wound healing processes that areevoked by the surgical trauma to the alveolar bone.Alveolar bone surgery may also stimulate a variety of celltypes inside marrow cavities, including mesenchymal stemcells (MSC). These cells can function synergistically withneighboring PDL and alveolar bone cells that have beenactivated by the orthodontic forces, and model* andremodel the bone faster.

* Some authorities, e.g. W.E. Roberts of Indiana University,make a point of distinguishing the term “modeling” (bone reac-tion to exogenous stimulus) from “remodeling” the process ofsteady state equilibrium. This fine semantic point is often over-looked or ignored but it is probably important to use the word“modeling” when discussing changes in bone that derive fromsurgical perturbation or the application of orthodontic force.

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Fig. 1.17 Even where the bucco-lingual dimension of the alveo-lus is great, the decortication depth should not exceed thethickness of the cortex by more than 1–2 mm. Yet the degreeof therapeutically induced reversible osteopenia is commen-surate with the degree of surgical manipulation, given individualpatient biodiversity in response. The pattern of punctate orlinear decortication does not seem to be as critical to the thera-peutic effect as the degree of surgical manipulation per se.

Fig. 1.16 (a) A schematic of selective alveolar decortication(SAD) under a reflected full thickness flap. Note arrows: (1)indicates the decortication does not impinge on root–PDL–cribriform plate complex; (2) indicates SAD does not extend tothe alveolus crest; (3) indicates SAD does not continue furtherinto the spongiosa than 1–2 mm. (© KihapDesigns.com &DentalArt2000.com. Image used with permission.) (b) Actualpatient with linear decortication but without graft placement.(c) Bone graft in place where a thin bucco-lingual dimension ofthe alveolus prohibits labial movement and the orthodontistwishes to lend greater thickness and treatment stability byaltering regional alveolar phenotype.

Understanding the role of osteoprogenitor cells isimportant because, as a tooth is moved through a surgicalwound, healing recapitulates regional tissue ontogeny(Murphy, 2006) and, with the addition of a bone graft,can actually increase the total bone mass of the novel alveo-lus phenotype while enhancing long-term stability. Thebest technique consists of punctate and linear decortica-tion in areas of the alveolus where accelerated and stabletooth movement is desired. Bone is added ad hoc whereaugmentation is needed (Figure 1.16). As teeth are movedthrough a healing wound, with or without a bone graft,the bone is stressed. The normal metabolic rate of inflam-mation and wound healing processes, investigated indepth and coined the “regional acceleratory phenomenon(RAP)” by the collaboration of Frost (1983, 1996, 2000)and Jee (1989), is accelerated. However, because themovement of teeth produces tensional stress in the bone,the maturation and eventual recalcification of the repairedtissue is delayed as long as the bone “senses” tooth move-ment. The reaction is similar to a bone fracture thatrequires immobilization to achieve full development of thehealing callus but will be delayed in final calcification ifsubjected to tensional stress. The clinical orthodontist canexploit this natural phenomenon in dentoalveolar physio-logy to ensure faster tooth movement by engineering the


(a)

(b)

(c)

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regional healing metabolism to a more stable clinical out-come (Kelson et al., 2005; Sebaoun et al., 2006).

With simple orthodontic tooth movement there is noincrease in bone volume, even 2–3 years later, as assessedby computerized tomography 3-D replicates (Fuhrmann,2002). However, when the teeth are moved through acombination of decorticated alveolar bone and certainkinds of bone graft, new phenotypes may be engineeredand a net increase of bone volume is evident. The degree ofbone decalcification is commensurate with the amount oftherapeutic trauma but penetration is rarely deeper than1–2 mm beyond the labial alveolar cortex (Figure 1.17).Where minimal tooth movement is needed, simple seg-mental surgery can be performed on as few as three teethor on either side of an extraction site and the pattern ofdecortication seems less important than the total surfacearea that is decorticated (Figure 1.18).

The usual rate of orthodontic tooth movement (OTM)by conventional biomechanical protocols is relativelyslow (about 1 mm/month) compared with the 1 mm/weekthat is possible with surgical intervention, and movement

Fig. 1.18 (a–d) Punctate decortication is produced to a limit 1 mm apical to alveolar osseous crest. No allograft was employed inthis case because adequate alveolar bone was present. (a) This 20-year-old Caucasian male presented with mild lower anteriorcrowding before orthodontic therapy with selective alveolar decortication (SAD). (b) Full thickness flap reflected past apices ofincisors). (c) Punctate and linear SAD below alveolus crest. (d) Patient 10 days after orthodontic therapy with SAD.

(a) (b)

(c) (d)

approaching 1 mm/day has been reported in some cases(Iseri et al., 2005). This latter rate is significant because itapproaches the optimal speed used by medical orthoped-ists as a guideline for surgical distraction osteogenesis oflong bones (Paley, 2002).

Moreover, the entire “bone morphing” (Figure 1.19)possibilities promise to take dentofacial orthopedics to anentirely new level of science that has witnessed a volcaniceruption of scientific data over the last few decades underthe rubric of “tissue engineering”. While most of thedevelopments in this nascent science have been achievedmerely in “bench-top science”, anecdotal evidence of in vivo achievements by forward-thinking orthodontistshas given the specialty new visions of the role of theorthodontic clinician and educator for the twenty-firstcentury. Clinical results can quite dramatically alter facialform without the risk and morbidity of hospital surgery(Figure 1.20).

The history of surgically facilitated OTM actually pre-dates the twentieth century but little was done in theUnited States until the late 1950s. This may have occurred

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Fig. 1.20 When the PAOO procedure is extended beyond the alveolus and coordinated with a specific protocol oforthodontic/orthopedic mechanotherapy, dramatic results can be achieved by a kind of “face morphing” that mimics the intraoralalveolar phenotype alteration. This patient presented with a skeletal class II malocclusion (left) but declined all options for orthog-nathic surgery. The right image demonstrates the final clinical outcome achieved without hospitalization or the risks and morbidityof orthognathic surgery.

Fig. 1.19 The stability of the surgically facilitated orthodontic treatment derives from the alteration of bony phenotype as the bonemorphogenetic protein (BMP) of human allograft guides regional wound healing to an engineered phenotype more compatiblewith the orthodontic treatment goal. Part (a) demonstrates inadequate bone for a non-extraction OTM, yet with a periodontallyaccelerated osteogenic orthodontic protocol (PAOO) the post-orthodontic treatment is engineered to a manifestly superior treat-ment outcome. The total treatment time in this case was 6 months. The stability of this kind of augmented alveolar form in (b) is inits third year post-retention without signs of regression to the original, inadequate phenotype. Images courtesy of Professor M.Thomas Wilcko, Case Western Reserve University School of Dental Medicine, Cleveland, Ohio, USA.


(a) (b)

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because of the crude nature of rudimentary nineteenth-century surgical techniques and the dubious observationthat “. . . a tooth in its normal position without vitality ismore valuable than a vital tooth in an abnormal relation-ship”. Ironically this original presentation was made inChicago in 1893 but would not be presented again inAmerica for over half a century.

Its American revival appeared in a seminal work byKole (1959), wherein he summarizes a decortication of thedentoalveolar process with some notable refinements.This is the basic technique that is employed today by thosewho promote the integration of orthodontic therapy andperiodontal surgery. The Kole surgery was limited to thecortex of the dental alveolus but subapical decorticationwas embellished by extending buccal and lingual corticalplate incisions until they communicated through the sub-apical spongiosa.

The naiveté of the early surgeons is noted in early admo-nitions about the risk of periodontal pocket formation oralveolar necrosis with facilitative periorthodontic surgery.While the former is doubtful to those who understand thepathogenesis of periodontitis, the latter is perhaps a wiseadmonition indeed where overly aggressive osteotomiesare combined with alveolar decortication, major flapreflection and especially any luxation (“mobilization”) ofthe dentoalveolar complex. Various investigators havegiven professional opinions on the merits and disadvant-ages of the procedure throughout the twentieth century(Bell and Levy, 1972; Düker, 1975; Merrill and Pedersen,1976; Generson et al., 1978; Mostafa et al., 1985;Goldson and Reck, 1987), and slight variations of the pro-cedure have also been studied (Nakanishi, 1982; Sasakuraet al., 1987; Yoshikawa, 1987; Matsuda, 1989).

These contributions were essential to the ultimate development of modern selective alveolar decortication(SAD), but the foundation of Kole’s work lay generallyundeveloped until Suya (1991) revived academic interestin “corticotomy-facilitated orthodontics” by reporting hisexperiences with hundreds of patients. Suya made asignificant change in that he did not connect the buccaland labial incisions through the alveolus, simply relyingon the effects of linear interproximal decortication. Thisrefinement has essentially set the standard for decortica-tion procedures that followed, because it suggested thatthe concept of “bony block” movement of bone–toothmight not be the most appropriate theory of efficacy.

Like Kole, Suya noted accelerated rates of tooth movement. Later, others also reported cases treated withthe combined orthodontic–periodontal treatment, prais-ing the procedure and stimulating contributions byKawakami et al. (1996), and Liou and Huang (1998).Anholm et al. (1986) noted no significant attachment lossthat might contraindicate the procedure. This was fol-lowed up with studies by Gantes et al. (1990), who con-firmed accelerated tooth movement, noting a mild root

resorption (probably a function of their biomechanics)but no loss of root vitality.

Wilcko et al. (2000, 2001) studied the sophisticatedsynthesis of periodontal regenerative techniques and therefinements of selective decortication of the alveolus. Theynot only confirmed the veracity of previous anecdotaldata, but also discovered that adding periodontal regener-ative surgery to the orthodontic protocol increased thequality of care in terms of clinical outcome and long-term stability (Nazarov et al., 2004). The effects on boneare apparent regardless of the biomechanical systemsemployed because Owen (2001) treated himself with aremovable acrylic appliance without significant pain orother negative sequelae. His first-person account confirmedprevious data of researchers and patients.

Academic studies in the twenty-first century have delivered a plethora of investigations that are confirming100 years of testimonial data and explain, with hard dataand creative theories, an exciting new area of surgicaldentofacial orthopedics. This development in the ortho-dontic specialty has essentially marked a parallel path of Ilizarov’s work in medical distraction osteogenesis(Paley, 2002) and the basic sciences that define moderntissue engineering taught by Alberts et al. (2002) andLanza et al. (2007).

The enthusiasm displayed by former patients hasmatched that in postdoctoral students who have con-firmed that both decortication (SAD) and periodontallyaccelerated osteogenic orthodontics (PAOO) can predict-ably produce: increased labio-lingual width (Twaddle,2001; Hajji, 2002), faster tooth movement (Fulk et al.,2002), less root resorption (Machado et al., 2002;Skountrianos et al., 2004), and equal or higher qual-ity outcome than conventional orthodontic protocols(Skountrianos et al., 2004; Ahlawat et al., 2006; Dosanjhet al., 2006; Ferguson et al., 2006; Oliveira, 2006; Walkeret al., 2006). Only time will reveal the full potential of surgical dentoalveolar applications. For now, as an evidence-based complement to conventional biomechan-ical protocols, these surgically accelerated modalities haveachieved a standard of care and a pantheon of clinicalalternatives that can be offered to patients to enable theirfully informed consent to treatment.

Shortening the duration of orthodontic treatment byusing biomechanics properly, and avoiding unnecessaryroot movementsThe reports cited above suggest that the extent of tissueremodeling and the velocity of tooth movement can besignificantly influenced by numerous factors capable ofinteracting with paradental cells. However, if our goal isto complete orthodontic treatment successfully and in the shortest possible time, then we should avoid movingdental roots into areas from which the roots would haveto be retrieved later. As discussed in Chapter 9 of this

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book, following this fundamental principle usually leadsto treatment completion within 18–24 m, with virtuallyno signs of tissue damage. It may be concluded that theduration of orthodontic treatment can be reduced sub-stantially in a number of ways: (a) by moving dental rootsdirectly to their final positions, avoiding unnecessarymovements that require corrections, and (b) by combiningthe mechanical load with another physical and/or chem-ical agent, and/or surgical procedure capable of evokingsynergistic reactions by alveolar bone and PDL cells.

The age factor in tooth movement

Another question that may be asked on the basis of theunderstanding that in orthodontics, mechanics and bio-logy are two parts of the same process is: what is the effectof age on the tissue response to orthodontic force? Thisquestion has occupied the minds of orthodontists sinceHunter, in the eighteenth century and probably earlier.Hunter observed that orthodontic treatment takes longerin adults than in children. Studying histological sections ofhuman teeth and their surrounding tissues, Reitan (1957,1961) concluded that the PDL is less cellular in adults thanin children. He therefore recommended that, when treat-ing adults, their teeth should initially be subjected to lightforces in order to stimulate cellular proliferation, and thenthe force magnitude should be increased in order to stimu-late these cells to remodel the paradental tissues. Thisobservation implies that, in essence, the nature of the bio-logical response to orthodontic forces is similar in youngand adult subjects.

This hypothesis was confirmed by Shimpo et al. (2003),who moved molars lingually in young (13 weeks old) andold (60 weeks old) rats, then studied their compensatoryalveolar bone apposition under the lingual periosteum.They reported that in both age groups there had been vig-orous compensatory alveolar bone growth. Thus, alveolarbone is successfully maintained, even in aged rats. Similarfindings were reported by Ren et al. (2005), who movedmaxillary molars in young (1.5 months old) and old (9–12months old) rats with a force of 10 cN, for 1–12 weeks. Ahistological examination of the roots and their surround-ing tissues revealed that, at PDL compression sites, osteo-clast numbers increased in both age groups. In the youngrats, a maximum number was reached after 2 weeks oftreatment whereas in the adult animals this level wasreached after 4 weeks. In the following weeks, the numberof osteoclasts in the adult rats was twice as high as in theyoung rats, but the velocity of tooth movement was thesame in both groups. It was concluded that osteoclasts inyoung animals are more efficient than in members of theolder age group. It is also possible that bone matrix inyoung rats can be resorbed more readily than in old rats,due to structural and chemical differences such as the


presence of high concentrations of inhibitors of metallo-proteinases in bone of old animals.

Age can also refer to the duration of healing of a post-operative regenerate following distraction osteogenesis(Nakamoto et al., 2002). In an experiment on 15-month-old beagles, mandibular premolars were moved into a 2-weeks or a 12-weeks regenerate. The former consisted ofimmature, fibrous, and poorly mineralized bone, whereasthe latter was composed of mature, well organized andmineralized bone. Tooth movement was significantly fasterin the “young”, immature regenerate, but this movementwas accompanied by extensive resorption that extendedfrom the cemento-enamel junction to the root apex.

Conclusions and the road ahead

Orthodontics started with the use of a finger or a piece ofwood to apply pressure to crowns of malposed teeth. Thesuccess of those manipulations proved convincingly thatmechanical force is an effective means to correct maloc-clusions. Until the early years of the twentieth century,understanding the reasons why teeth move when sub-jected to mechanical forces was only a guess, based on reason and empirical clinical observations. Farrar hypo-thesized in 1888 that teeth are moved orthodontically dueto resorption of the dental alveolar socket and/or bend-ing of the alveolar bone. His assumption was correct, buthad no scientific foundation and could not be proven.Sandstedt’s histological study, which was first publishedin an obscure Scandinavian dental journal in 1901 andlater (1904–1905) in an international periodical, hadopened the gates widely to scientific exploration oforthodontic biology. Sandstedt revealed that the mainfigures in the drama of tooth movement are cells, mainlythose of the PDL and alveolar bone. This landmark dis-covery raised an immediate question about the mechanismwhereby mechanical stress activates various types of den-tal and paradental cells, and what is the best way to obtainan optimal response by these cells. Histology was the firsttool in this quest, followed by histochemistry, electronmicroscopy, immunohistochemistry, molecular biology,and molecular genetics. Much information on the behaviorof cells involved in tooth movement has emerged fromthose investigations. Despite this progress, the final answerto the above question remains elusive. Many parts of thepuzzle have been found, but the picture is still incomplete.

The increasing understanding of the nature of the bio-logical effects of mechanical loading on tissues and cellshas led to experiments aimed at finding means of enhanc-ing velocity of tooth movement. These experiments werebased on the finding that cells are capable of responding to a vast array of chemical and physical stimuli. Accord-ingly, various pharmaceutical agents were applied locallyor systemically during the course of orthodontic treatment.

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Physical entities, such as heat, magnetic fields, and electri-cal currents were utilized, and surgical procedures encom-passing decortication of the alveolar bone were tried.Most of these experiments have yielded evidence support-ing the hypothesis that combining mechanical force withanother cell-stimulating agent(s) is capable of increasingthe pace of tissue remodeling and tooth movement.

Adaptation of new biological investigative tools toorthodontic research is ongoing, and will continue toexpose blank parts of the puzzle. At present, molecularbiology and molecular genetics remain at the cutting edgeof the advancing front of orthodontic research. Multiplegenes that may be involved in the cellular response tomechanical loads have been identified (Reyna et al., 2006),as well as genes associated with orthodontically inducedroot resorption (Abass and Hartsfield, 2006). The roleplayed by specific genes in tooth movement was revealedby Kanzaki et al. (2004). They reported that a transfer ofan OPG gene into the PDL in rats inhibits orthodontictooth movement by inhibiting RANKL-mediated osteo-clastogenesis. According to Franceschi (2005), futureefforts in dental research will include genetic engineering,focusing on bone regeneration. This evolving field mayhave a profound effect on orthodontics and dentofacialorthopedics, by facilitating regenerative processes of hardand soft orofacial tissues. It may be concluded that theway ahead will be paved with new investigations that willcontinue to unveil additional information on the biolog-ical mechanisms of tooth movement.

The body of knowledge that has evolved from multi-level orthodontic research supports the notion that thepatient’s biology is an integral part of orthodontic diag-nosis, treatment planning, and treatment. Therefore, ortho-dontic appliances and procedures should be designed to address the patient’s malocclusion in light of his/herbiological profile, in much the same fashion as is done bymedical specialists in other fields of medicine.

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