beyond the ligament a whole-bone

BPaIM

Wfmtnfs

4

ASO

Dn

2

eyond the Ligament: A Whole-Boneeriodontal View of Dentofacial Orthopedicsnd Falsification of Universal Alveolarmmutabilityichael O. Williams and Neal C. Murphy

When a theoretical basis for manifestly successful clinical outcomes cannot be

fortified by traditional orthodontic tooth movement (OTM) biology that focuses

solely on the periodontal ligament as the operant organ, a new hypothesis

should be built on the old concepts by synthesizing new biological data with it.

This article presents a modest synthesis of contemporary theories in cell biol-

ogy to explain ostensible osteogenic activity and alveolar phenotype alter-

ations by ultra-low orthopedic force from an alveolar development appliance

(ADA). Histological appearance of biopsy specimens demonstrate a “reactive”

woven bone pattern, dramatically illustrated under polarized light, where the

alveolar development appliance puts labial forces on the palatal alveolus via

acrylic panels and 300 g of force induced by coiled nickel titanium springs.

“Internal control” biopsy specimens taken from nontreated alveoli show nor-

mal lamellar pattern in histological sections. The behavior of the bone cannot

be explained totally with a periodontal pressure-tension model. Molecular

biological concepts and the Utah Paradigm of Bone Physiology are recruited to

explain how ultra-light forces applied to the palatal alveolus might stimulate

“compensatory periosteal apposition” on the labial alveolus, thus developing a

new alveolar phenotype through bony developmental “drift.” (Semin Orthod

2008;14:246-259.) © 2008 Published by Elsevier Inc.

ca

�amoesis

ombatp

hen a theoretical basis for manifestlysuccessful clinical outcomes cannot be

ortified by traditional orthodontic toothovement (OTM) biology (that focuses solely on

he periodontal ligament as the operant organ) aew hypothesis should be built on the old. It is

orces acting beyond the ligament that may beignificant determinants of the alveolus and the

Private Practice in Orthodontics and Dentofacial Orthopedics,24 Courthouse Road, Security Square, Gulfport, MS 39507.

Associate Clinical Professor, Department of Periodontology &ffiliated Skeletal Research Center, Case Western Reserve University,chool of Dental Medicine, Cleveland, OH; Lecturer, Sections ofrthodontics UCLA School of Dentistry, Los Angeles, CA.

Address correspondence to Dr. Neal C. Murphy, 28920 Bardellr., Agoura Hills, CA 91301. Phone: (818) 889-6704; E-mail:[email protected]

© 2008 Published by Elsevier Inc.1073-8746/08/1404-0$30.00/0

adoi:10.1053/j.sodo.2008.07.003

46 Seminars in Orthodontics, Vol 14, No

onsequent dentofacial form, which lives, thrives,nd dies by the grace of dental root positions.1

Specifically, an osteogenic threshold of1500 to 3000 microstrain according to Frost2

nd Jee and Li3 may stimulate appositional boneodeling, reflecting the morphogenetic thresh-

ld range of therapeutic “optimal” force thatlicits what should be called an “optimal re-ponse.” It is this concept that Burch4 paraphras-ng Reitan alluded to with their term “compen-atory periosteal apposition.”

Therefore, at the risk of overstating the theoryf “alveolus development,” this article presents aodest synthesis of contemporary theories in cell

iology to explain ostensible osteogenic activitynd alveolar phenotype alterations by ultra-low or-hopedic force from an alveolar development ap-liance (ADA).

Dentofacial orthopedic physiology of the
lveolus does not deny the relevance of peri-
4 (December), 2008: pp 246-259

mailto:[email protected]

obrbbitwticbfa

rodcwaewifF

saiid“tTtstantoae

T

Afrfn

Mbtt

mttngSots

fttosopts

C

Csantsu

C

AmgtpdDwaa0pbp

247Beyond the Ligament

dontal ligament phenomena but merely goeseyond the ligament to analyze the alveolaresponse to orthopedic force from a “wholeone” perspective. This whole bone—or “all-one” according to Melsen5—paradigm is an

mportant complement to the classic pressure-ension model because it lends a consistencyith medical orthopedic and contemporary os-

eology literature. As Baumrind6 has proposedn the past, the periodontal ligament is bestharacterized, not as a pressure-tension sling,ut rather as a contained viscoelastic gel whereorces are distributed equally in all directions,nd this has some merit for bone as well.

A clear contrast is made, however, amongapid palatal expansion (RPE) of the maxilla,rthodontic dental arch expansion and orthope-ic development of the bony alveolus with directontinuous modulated force application. Ifound healing recapitulates regional ontogeny,molecular level event, then tissue may be

ngineered in a similar manner whether theound is surgical or simply microfracture “heal-

ng” of the alveolar osteon (Haversian system)rom excessive force (eg, �3000 �E according torost).

Thus, the alveolus is proposed herein as aeparate ontogenic entity or “organ,” capable of

singularly active biological response to load-ng, irrespective of the subjacent skeleton (max-lla and mandibular corpus) or the subsumedental matrix. In prior publications the termmaxillary expansion” has often been used in allhree contexts without clear differentiation.7

his is unfortunate yet ubiquitous in the litera-ure, and it would be most fortunate indeed fortudents and other neophytes in craniofacial or-hopedics if more nuanced distinctions could berticulated. The concepts herein discussed areot totally new. Melsen spoke eloquently of

hem in her discussion of alveolar bone physiol-gy, citing literature as old as 20 to 40 yearsgo,8,9 which has been echoed in modern tissuengineering dialogues as late as 2006.10

he Mechanobiology of the Alveolus

novel “bottom-up” approach has evolvedrom biomedical engineering and it is wise toeview the perspectives of sister sciences be-ore we pronounce certitude on any field of
atural scholarship. In this regard, van der a
eulen and Huskies’ definition of “mechano-iology” is interesting.11 In a defining articlehey propose a different approach for studyinghe effects of force on tissue and human cells.

Applied to the dentofacial orthopedic realm,echanobiology proffers the integration of

hese sciences into a kind of “new biology” forhe orthodontic specialty. As old as it is new, thisew biology is articulated well within the intelli-ent and compelling perspectives posited byingh’s spatial matrix hypothesis,12 which pointut, through the use of finite element analysis,hat the tissue constantly regresses to homeosta-is.

Specifically, mechanobiology studies mostundamentally how bone is regulated by signalso cells generated by variable degrees and direc-ions of loading. The questions that mechanobi-logy investigates are most compatible with con-tructs defined by Frost and Jee in the activityf bone’s basic multicellular unit (BMU). In ahrase, mechanobiology picks up, in a tradi-ional reductionist progression, where Frost’s tis-ue-level nephron equivalent left off.

ase Examples

ase examples and histological data demon-trated are not intended to prove universality of“whole bone” thesis, but rather the contrary,

amely building on a rich theoretical heri-age,13,14 and medical concepts of osteogene-is,15,16 it seeks to falsify presumptive concepts ofniversal alveolar immutability.17

linical Example #1: Patient E.R.

noncompliant 18-year-old Hispanic-Americanale presented with hemorrhagic hyperplastic

ingivitis and incipient periodontitis after a pro-racted period of inadequate oral hygiene. Ap-roximately 15 months earlier a fixed “alveolarevelopment appliance” (ADA; Max 2000ynaFlex Orthodontic Laboratory, St. Louis, MO)as placed to treat a posterior cross bite as thenterior arch length deficiency was addressed byn 0.018-inch nickel titanium round wire in labial.022-inch slot brackets. This archwire was re-laced with a 0.018-inch stainless steel archwire,ut no activation was made in the anterior orosterior sextants. The ADA was not periodically
ctivated after insertion because it is self-activating

asramTNj

p

wrifruswom

H

Thspfi

FaaUMfi

Frliol(

FhtNilcfi

248 Williams and Murphy

nd self-limiting. Two transverse nickel titaniumprings, each embedded in and connecting sepa-ate acrylic panels, deliver 150 g apiece for a totalppliance force of 300 g (Fig 1). The bands on firstolars and first bicuspids are for retention only.he active force solely lies on the palatal alveolus.o archwire adjustment or palatal appliance ad-

ustments were made for 1 year.Fifteen months after the appliances were

laced they were all removed and the patient

igure 1. Max 2000, an alveolar development appli-nce (ADA) applied ultra-light pressure to the palatallveolus. (Orthodontist: Neal C. Murphy, CWRU,CLA; Max 2000® is a registered trademark of Dr.ichael O. Williams, Gulfport, MS.) (Color version of

gure is available online.)

igure 2. (A and B) Case #1 E.R. Periodontal surgeryeveals buccal bone where, conjecturally, palatal alveo-us forces were transferred to buccal cortical plate, flex-ng the bone to stimulate osteogenesis in areas of peri-steal compression. Note marked dehiscence where

abial archwire “pulled” teeth beyond phenotypic range.
TColor version of figure is available online.)
as treated with periodontal flap surgery toegain periodontal and gingival health. Dur-ng the surgery a biopsy specimen was takenrom the labial alveolar crest of the maxillaryight first bicuspid (Figs 2, 3) and sent to aniversity oral pathologist for blinded micro-copic examination. An image of the specimenas then subjected to fractal analysis, a bi-mathematical parameter diagnostic of boneodeling.18

istological Analysis: Patient E.R.

he specimen demonstrates young bone withematoxylin and eosin (H&E) stain in Fig 4. Theame histological specimen, examined underolarized light, demonstrates both a woven con-rmation and fractal patterns (Figs 5 and 6).

igure 3. (A; top) Routine hematoxylin and eosinistological section at buccal aspect of tooth #5, labial

o Max 2000 palatal alveolus development appliance.ote absence of a “lamellar” pattern that is character-

stic of mature bone. Panel B (bottom) is a polarizedight section of specimen. Note “woven bone” patternharacteristic of immature bone. (Color version ofgure is available online.)

hese patterns are important because they sug-

gtd

ct

mtcpa

FpBk“dato


est immature bone modeling in response toherapy; preexisting bone presumably wouldemonstrate a mature “lamellar” pattern.

Mechanical loading is thought to be an in-reased fractal dimension at a bone interface

igure 4. Fractal analysis demonstrating bone remodrint” of remodeling and provide biomathematicaliology is characterized by a reductionist analysis of sind of microscopic anatomy). How the stuff functgeometric footprint” of cell proliferation creates aissipative systems. Analogously, a point moving in timnd a plane moving through time on a perpendicularo James Borke, PhD, Medical College of Georgia, forf figure is available online.)

hat reflects mechanisms of cell-mediated re- o

odeling presumably within regional deforma-ions of 1500 to 3000 microstrain.19,20 Thesehanges in fractal dimension appear to be pro-ortional to loading and are thought to providenew parameter for force determination in

. Fractal geometric patterns are characteristic “foot-he reductionist histological morphological pattern.er and smaller “stuff” (gross anatomy to histology, athrough time is a mathematical function and thern referred to as a “fractal,” a pattern common toone coordinate defines a line, a line defines a plane,rdinate defines a cube or rectangular solid. (Thanksconsultation and the fractal analysis.) (Color version

elingof tmallionspattee oncoohis

rthodontic tooth movement.

C

AptwdcmAepe

H

Aatfwflflasts

mTstthiftbrtl

pfnrsttsii


linical Example #2: Patient K.L.

marginally compliant 13-year-old white femaleresented with a posterior cross bite. The pa-

ient was hypersensitive to discomfort associatedith strong mechanical manipulation of herentition so rapid palatal expansion was de-lined in favor of slow palatal alveolar develop-ent. Approximately 2 months before biopsy anDA identical in design to that used with clinicalxample #1 (patient E.R.) was placed to treat aosterior cross bite. No labial archwires weremployed (Fig 7A and B).

istological Analysis: Patient K.L.

fter securing full informed consent, 2 monthsfter insertion of the maxillary appliance, sec-ions of the interdental bony septa were takenor microscopic examination. The specimensere obtained with a hand instrument on re-ecting a labial full thickness (mucoperiosteal)ap and examined “blind” by a university oralnd maxillofacial pathologist. With a healthy re-pect for scientific skepticism, an additional “in-ernal control” specimen was taken from inter-
eptal bone between the patient’s ipsilateral p
andibular first bicuspid and canine (Fig 5A-C).he specimens displayed in Fig 6A-C demon-

trate standard H&E-stained histological sec-ions (with and without polarized light respec-ively) of interseptal alveolar bone. Theistologic pattern of woven (immature model-

ng) bone is almost identical to that securedrom patient E.R. In this case #2 (L.K.), however,he sample was taken from the interseptal boneetween teeth numbers 5 and 6, the patient’sight maxillary first bicuspid and canine, an areahat was influenced directly by the palatal alveo-us’ acrylic panels.

Figure 7A and B demonstrate a contrastingattern in the internal control specimens takenrom the mandibular alveolus between teethumbers 22 and 23 (the patient’s mandibularight canine and first bicuspid), which were notubjected to orthodontic or orthopedic stimula-ion. This internal control is typical of the pat-ern in patients’ alveolar bone presenting inteady-state equilibrium suggesting that the max-llary alveolus woven bone pattern was not due tonflammation or normal function but rather by

ure 5. (A) Pt. K.L.: This figure shows the clinicalpearance of a 13-year-old marginally compliant fe-le who elected the slow alveolar development. (B)

nel shows the area of biopsy for Fig 6A and B, whichmonstrated woven “reactive” bone. (C) Panel shows

biopsy site of the “internal control” biopsy. (Colorsion of figure is available online.)

FigapmaPadethever

utative alveolar “bending” to the labial alveolus

ab

ttvblOcptPfa

mr

D

Ss(oadcamEcatrtohrEpapw

ebprvptdqibotbarlqtibd

Finwets(ltttwEto


s the bone is physiologically yet therapeuticallyent (strained).

While these interesting specimens suggesthe possibility of labial osteogenesis with pala-al alveolus stimulation, we do not claim uni-ersality. We modestly propose a hypothesis toe refined by meaningful professional dia-

ogue in the tradition of the Western dialectic.nly time will reveal how prescient our nas-

ent theories will ultimately prove to be as weresent these findings in an attempt to falsifyhe notion of universal alveolar immutability;opper’s falsification principle is a more pro-ound epistemological criterion for truth and

igure 6. (A) Pt. K.L.: This figure shows the histolog-cal pattern of the biopsy specimen in Fig 5A. There iso evidence of an organized pattern normally seenith mature bone. This standard hematoxylin andosin-stained specimen suggests the woven, or “reac-ive,” pattern of physiologic bone remodeling in re-ponse as described by Frost’s minimal effective strain.B) Panels shows woven bone image, with polarizedight, of interseptal alveolar bone biopsy betweeneeth #5 and 6. This appearance demonstrates a pat-ern typical of that where ultra-low stress delivered tohe palatal alveolus (compare palate per se). Theoven bone pattern is similar to that seen in Fig 3 (Pt..R.) and that secured in most patients treated with

his appliance. (Color version of figure is availablenline.)

rigorous test of veracity greater than the r

ore standard method of independent cor-oboration.17

iscussion

ince no active adjustments are necessary with apring-loaded alveolus development applianceADA), it worked in cases E.R. and K.L. as a kindf “osteogenic machine,” altering the palatalnd labial alveolus form biologically without pro-ucing any expected bony or soft tissue dehis-ence. Indeed the only area of bony dehiscenceppeared where the labial archwire may haveechanically “pulled” the roots labially in case.R. (Fig 3). This clinical picture suggests thatontinuous ultra-light loads directly on the pal-tal alveolus may have modeled labial bone as aooth-alveolus complex “moves” labially throughemodeling “drift.” Some theorists speculatehat the alveolus is immutable and “expansion”f the dental arch inevitably produces bony de-iscences or fenestrations and gingival marginalecession (“stripping,” “runners”). The case of.R. ostensibly suggests that bone may model toreclude these complications if two conditionsre met: (1) the movement occurs without activeeriodontitis, and (2) the internal strain fallsithin a threshold modeling range.

The creation of woven bone in Fig 3 is inter-sting because woven bone is characteristic ofone modeling following an injury. For exam-le, after a fracture (and callus formation) boneesponds first by depositing “woven bone.” Wo-en bone is a disorganized structure with a highroportion of osteocytes. Weaker than fully ma-ure bone, it exhibits a small quantity of ran-omly oriented collagen fibers, but formsuickly at the site of injury. Later in the matur-

ng process woven bone develops to lamellarone, which exhibits a highly organized patternf concentric sheets and a relatively low propor-ion of osteocytes (see Fig 7, Pt. K.L.). Lamellarone is stronger than woven bone and is char-cterized by a greater number of collagen fibersunning in opposite directions in alternatingayers, much like plywood. This contributes auality to the bone that is relatively more resis-ant to torsional and tensional stresses. What isnteresting in these examples is easily repeatedy the reader by taking biopsies of the alveolusuring and after the ADA appliances have been
emoved and the alveolus reverts to a steady-

skpb

pmTcnlcfrtoovbbosbtt

C

Cktmeuceamatfiambe

dgwlpowi

FsttibtdtmdietbbBpcls


tate equilibrium of “remodeling.” To ournowledge this is the first time a woven boneattern suggesting therapeutic modeling has

igure 7. (A; top) Pt. K.L.: The panel shows a controlpecimen taken from the mandibular alveolus be-ween teeth numbers 22 and 23, which were subjectedo no orthodontic or orthopedic stimulation. Thisnternal control demonstrating steady-state lamellarone serves as contrast to the typical histological pat-ern of “reactive, woven” bone modeling pattern asramatized in Fig 6A and B. (B; below) Internal con-

rol specimen shows, with polarized light, a normalature lamellar bone pattern. “Reactive” woven bone

oes not appear in this polarized section because it isn a “steady state” of osteoclastic-osteoblastic dynamicquilibrium with a highly organized Haversion sys-ems (osteones) characteristic of relatively unstressedone. This contrasts with the “reactive and wovenone” appearance in the same patient in Fig 6A and, where the Max 2000 appliances applied force to thealatal alveolus, through the spongiosa to the labialortex, which appears in patients subjected to ultra-ight force-induced alveolus development. (Color ver-ion of figure is available online.)

een demonstrated with this kind of appliance. i

The ADA case examples also illustrate aaradoxical but important event where boneodeling occurred even in a field of infection.he reasons that infection has not compli-ated the remodeling are that the force mag-itude was low and unidirectional, not oscil-

ating (“jiggling”), as is generally evident inases of occlusal trauma. In case E.R. the in-ection qualitatively defined gingivitis, not pe-iodontitis; the distinction between these enti-ies is critical for the uninitiated clinician butften problematic to diagnose.21 Thus, insteadf mechanically moving teeth through the al-eolus, it appears that palatal acrylic panelsiologically “moved” the whole alveolus boney resorption/osteogenesis “drift.” This typef modeling of the labial portion contrastsharply with mechanically movements of rootseyond the alveolar envelope, a procedurehat traditionally has been associated with pu-ative bony dehiscence and gingival recession.

onventional “Wisdom” and Innovation

onventional wisdom based on works by Engel-ing and Zachrisson22 and others23 intimate thathe labial alveolus is immutable and labial move-

ent “causes” bony dehiscence (the implicitpistemological ambiguity of causality is typicallynclarified). However, contrasting data andomments by Lindskog-Stokland and cowork-rs,24 Melsen,25 and others26-30 suggest that thelveolar “envelope” or limits of alveolar housingay be more malleable than previously believed

nd can be virtually defined by the position ofhe roots. Thus, the concept of dental roots as aunctional matrix for bone is often validatedmplicitly in the works of many independentuthorities. Indeed the explanation of biologicalechanisms of alveolus bone modeling has

een cited as one mechanism to explain theffects of some functional appliances.

Specifically, referring to a subset of functionalentofacial orthopedic appliances, Norton sug-ests that some “create a space or vacuum intohich teeth moved and the alveolar process fol-

owed . . . .”31 The phenomenon of “phenotypiclasticity,” when applied to the genetic expressionf a single generation organism, explains thisell.30 This plasticity is a well-accepted concept

n the field of developmental biology31,32 and
s manifest only by various environmental or

enebi

smaotimijchapa

hrtjledcTbaMioa

sp


pigenetic perturbations33-37 and may be engi-eered. Whether surgical or nonsurgical, thesexamples argue for the malleability of even adultone in general and against alveolar immutabil-

ty in particular.This control is evident in the effect of the

pring-loaded ADA, presented here grossly andicroscopically. Yet the domain of nonsurgical

lveolar bone engineering is not the monopolyf dentofacial orthopedists. The histological ac-ions of the ADA mimics the principles appliedn the innovative philosophy of Ponseti’s treat-

ent of talipes equinovarus (club foot) in thatt attempts to redirect a pathologic growth tra-ectory toward a physiologic course.38 Since fa-ial morphotype evolves even throughout adult-ood, the ADA appliance may be a more benignlternative to surgically assisted rapid palatal ex-ansion (SARPE) and, certainly, considering rel-
tive morbidity, orthognathic surgery. n
The presumed immutability of the alveolusas been historically problematic in that it caneduce treatment options to extraction or or-hognathic surgery, conventional protocols thatuxtapose “parts” instead of engineering physio-ogic “dynamics.” In this regard any concept thatmphasizes, or worse on occasion dogmaticallyefends, mechanical solutions as “inviolable art”an eclipse emerging biological imperatives.his is a needless and unfortunate limitationecause many patients disdain major surgicallternatives categorically and even preemptively.oreover, the studies of Little and coworkers39

ndicate that routine extraction therapy to cam-uflage dysmorphic skeletal elements is neitherpanacea nor guarantor of stability.A further understanding of the molecular ba-

is for alveolus physiology may take us closer toredictable modification of form by surgical,

ure 8. (A-E) Transmission cantilever (dotted line inshows strain-induced mechanotransduction withinosteoblast transferred to adjacent cells. (A) The cell

contacted. (B) The cell (asterisk) reacts to mechan-l stimulation after lifting the cantilever with an in-ased calcium concentration. (C) The calcium signal

reads to the whole cell, and (D) signals pass on to fiveighboring cells (indicated by crosses). Bar � 20 �m.) localization of green calcium markers withinained osteoblastic cells and at cell-cell contact pointsrows) after a 72-hour culture period. F-actin is

own in red. Bar � 10 �m. (After Charras GT andworkers 2002.) (Color version of figure is availableline.)

FigA)theisicacrespne(Estr(arshcoon

onsurgical, or pharmaceutical means. For now,

tosmfmaimtee

Mo“atpotgwtmtsngltfttmws

soatmwff

T

Tib

p“fstla“wp

etrntgfrtfm

tftadit

omwvcat

ssatipedwhes


hese cases prove the principle that immutabilityf alveolar bone is not universal and alveolarurgery or continuous ultra-low force magnitudeay indeed be an appropriate starting point

rom which orthognathic surgery or extractionay be deferred as a reasonable second choice,“fallback” or “fail-safe” tactic that ensures that

nevitable error will fall on the side of tissueaintenance. This is justified because since the

ime of Wolff and Roux bone has been consid-red a dynamic tissue adapting its form to itsnvironment (form follows function).

For the modern dentofacial orthodontist,oss elaborates through his perennial missives

n the functional matrix hypothesis (FMH) thatdental roots are the functional matrix of thelveolar bone” (Moss ML, personal communica-ion, 2005). While some have dismissed the im-ortance of this FMH perspective as merely anntological sine qua non for the large bones ofhe craniofacial complex,40 it certainly makesood sense to apply it to the human alveolus asell. A fully integrated, comprehensive, and in-

ellectual context of facial growth and develop-ent is incomplete without it. For, after all, if

heory is merely a convenient intellectual con-truct to predict or explain an observed phe-omenon, its modest application here certainlyoes beyond simplistic explanations based onigament histology and supplements other on-ogeny theories. Even the few critiques that theunctional matrix theory has evoked admithat, despite its metaphysical vagaries, as aheory it is not necessarily antithetical to other

orphogenetic mechanisms, and can serveell as a modest but logically essential Weltan-

chauung among others.39

More recently, some molecular biologists areuggesting that, on cellular and biochemical levels,steogenic morphogenesis should be considereds a transcriptional event. Altered extracellular ma-rices, cellular form, and internal cytoskeletal ele-

ents when bone is clinically stressed can manifestithin an optimal range. Thus, gross anatomical

orm follows function and intracellular functionollows form.

he Utah Paradigm in Dentofacial Orthopedics

he Utah paradigm of bone physiology is also annstrumental element in explaining a “whole
one” approach to alveolar bone modeling. It t
roposes that a tissue-level entity (termed themechanostat”) is a definitive but neglectedunctional determinant of bone physiology inteady-state homeostasis or remodeling. Struc-urally a basic multicellular unit (BMU) is a col-ection of regional osteons that act as the bonenalog of the nephron. What Frost called thenephron equivalent” is completely compatibleith the principles of Wolff, Moss, and contem-orary cellular biology.

In this regard, the natural eruption, guidedruption, and even the “forced eruption” of frac-ured teeth can be easily seen as “growth sites”esponding positively to drift and guidance, yetegatively with premature loss and serial extrac-

ion. As prudent clinicians we may never cate-orically rule out the need for tooth extractionor gaining arch length. However, we are wise toecall Pascal’s wager if injudicious bicuspid ex-raction ablates not only the tooth but all theuture bone development and lip support that

ight have developed.The problem for the injudicious clinician is

hat this pernicious sequella may not be evidentor decades, a prevalence that only longitudinalwin studies over decades can explicate clearly. Iflveolar development can call on a strong foun-ation in basic osteology, then the orthodontist

s liberated from strictures of traditional thoughthat accepts pernicious side effects by default.

New ways of thinking (“NewThink”), of course,ften cause some consternation and even funda-ental existential angst among those comfortableith the status quo.41 But change is integral to theery fabric of science, and the reconciliation oflinical expediency with new-science conjecture isn intellectual imperative that may be too rare inhe art of orthodontic treatment.

Often the developed alveolus is somewhathocking to a clinician who is used to seeingmall smiles in small children. Indeed, wherelveolus development can help define eruptionrajectories in the treated adolescent, one mayndeed notice a smile that is seemingly dispro-ortionately large for the immature face. How-ver, Fig 9A and B demonstrate how a smile thatefines the face of youth also fits esthetically wellith the more mature adult face. Regardless ofistorical guidelines we believe that themerging esthetic standard for a so-called fullmile must be recognized and justified scien-
ifically. It seems that the histological docu-

mjdas

cnsfdim

T

Ilfipt“nfoco

cg“m

mttbgasw

G

Ionfpfiidi

Fs r ve


entation of supporting bone modeling mayustify the admonition of that facial orthope-ists should “create an adult smile which thedolescent can grow into, not an adolescentmile the adult grows out of.”

This philosophy suggests that if the alveolusan be orthopedically engineered to an alter-ate phenotype by biological engineering, in-tead of mechanical manipulation, it is pre-erred to extracting teeth where a remainingentition is mechanically fit into a manifestly

nadequate alveolus, deformed by the originalalocclusion.

reatment Timing

t is important to understand that the scientificiterature contains compelling and ample justi-cation for redirecting growth trajectories inrepubescent humans. Therefore, the best time

o treat the growing child with this self-limitingmachine” is measured in dental age not chro-ology. Generally, optimal effects are elicited

rom these kinds of ADA during the transitionalr mixed dentition. At this time phenotypehanges dramatically. Periodontally accelerated

igure 9. (A) Panel shows the esthetically pleasing tremile, esthetically appropriate in the adult face. (Colo

steogenic orthodontics (PAOO) surgery, in n

ontrast, presents no age constraints since sur-ery per se reverts healing tissue to a kind ofneonatal” state of morphogenetic develop-ent.Arch development from the palatal aspect

ay be employed simultaneously with conven-ional labial therapy. However, singular use ofhe ADA sans labial archwires reduces the risk ofracket breakage, pernicious increases in patho-enic bacterial biofilm (dental plaque) load,nd addresses orthopedic problems directly in-tead of camouflaging dysmorphic alveolar formith altered tooth positions.

enetic Expression and Phenotypic Plasticity

t is important to note that phenotype is not ane-to-one manifestation of genotype. While ge-otype has often been defined as a “blueprint”

or tissue form, this allusion is simplistic to theoint of gross misrepresentation and leads torankly erroneous thinking. In fact the genotypes more akin to an “instruction manual” direct-ng tissue development to a myriad of formsepending on the degree of phenotypic plastic-

ty inherent in the biological system and epige-

adolescent “growing” face. (B) Panel shows the samersion of figure is available online.)

ated

etic influences, be they pathologic, therapeu-

ttbdvppdcsoscttd

t“qaitppaem

C

WcTfwoeslee

twptparss

mnpeTs

vspw(mTptmsieacrwf

esntvsMwsowaftstaamdgtdlp


ic, or neutral. In this sense, the case examples ofhe orthodontist’s gentle root manipulation ofone resemble the rationale medical orthope-ist, Dr. Ignacio Ponseti, in his attempts to ob-iate surgery for talipes equinovarus (Ponseti I,ersonal communication, 2007). In the thera-eutic realm, the “biological message” sent by theentofacial orthopedist can be seen as a moreomplex alteration of the alveolus, similar to thateen with the periodontist’s attempts to alter alve-lus form by equilibration when traumatic occlu-ions causes a pathognomonic alveolar “hourglass”ribriform plate profile. Pigliucci defines pheno-ypic plasticity as the “property of a given genotypeo produce different phenotypes in response toistinct environmental conditions.”

In the case of example #1, E.R., the “pull” ofhe labial arch wire is purely orthodontic. Thisenvironmental condition” (perturbation) isuantitatively and qualitatively distinct from thelveolar orthopedic “push” of the acrylic panelsn the ADA. Thus, it is quite logical and consis-ent with epigenetic principles that differenterturbations would necessarily elicit differenthenotypic clinical outcomes because pathosesnd clinical therapy both qualify as determinatenvironmental perturbations; the latter is justore predictable.

onclusions

hen the patient says, “I prefer nonextractionare,” he or she is making a statistical forecast.hat is to say, the patient is saying in effect, “I

orecast in a field of future uncertainty, that Iill experience greater “utility” (subjective sensef worth, value, or satisfaction) if teeth are notxtracted.” In the absence of logical or empiricalcientific certitude that extractions are abso-utely contraindicated (a rare event), the prefer-nce should be in the decision process thatvolves with each patient visit.

Moreover, the authors suggest that the pa-ient is implicitly employing a variant of Pascal’sager by “hedging the bet” and the authorsropose that such a choice, when given to pa-

ients, empowers them with a commitment toarticipation in the decision making and man-gement, including a reasonable assumption ofisk that is rightfully shared. After all, the role ofcience is to solve problems for individuals, not
tatistical cohorts, samples, corporations, arith- p
etic means, or professional organizations. Cli-icians are for the benefit of patients, and notatients for clinicians. It is imperative to viewach patient as an individual and not as a mean.he art and science that the authors propose are

imply methods for the benefit of the patient.The relationship between alternatives is a

ariant of Pascal’s wager wherein the patient,electing a nonextraction alternative, for exam-le, falsifies the notion that extraction therapyill deliver a superior future utility “payoff”maximum esthetic form and function) andinimizes the chances of irreversible “damage.”his “criterion of preference” by an enlightenedatient in the 21st century is just as important tohe informed consent of the patient as cephalo-

etric tracings of statistical norms. It is alsoatisfying on a practical level because, by includ-ng the patient in the “committee” of stakehold-rs, it technically employs patient preference asso-called Bayesian prior, a well-known and ac-

eptable component of health care quality de-ived from the mathematics of decision theory,here progressive data accumulations make

orecasting more robust.The histological data, easily replicated by ev-

ry private practitioner, suggest that ultra-light,elf-limiting force of an embedded nickel-tita-ium spring appliance can ostensibly activate

he bone as a “mechanostat” mechanism—as de-eloped by the Frost-Jee collaboration and de-cribed for dentofacial orthopedics so well byelsen. Perhaps soon the exact biochemistryill disclose that it activates architectural tran-

cription factors, as explained by molecular bi-logists in variable contexts. The appearance ofoven bone in clinical demonstration cases E.R.nd K.L. histological sections and analysis of theractal pattern therein suggest that modeling ofhe alveolar bone can indeed occur where theample was taken. This serendipitous but consis-ent observation gives serious pause to claimsbout the behavior of bone around teeth thatre moved orthodontically. Specifically the im-utability of the dental alveolus and the ten-

ency of dental arch “expansion” to cause gin-ival recession must be reconsidered in light ofhe scientific rationale provided and clinicalemonstration. Further, engineering the alveo-

us by ultra-light force directed to the alveolus,eriodontal surgically facilitated OTM, or in situ
harmacologic management42 is a clinical real-

iapiafcto

tsgolcoovtssa

iidpRmaloadcftfsWatg

bbnwajt

cdetpcctct

mphcfsrpeca

wbenfntTcpawaoiptlcss

ptfoft


ty that suggests routine bicuspid extraction tovoid putative but often illusory “periodontalroblems,” or to lend stability to long-term clin-

cal outcomes, may be questioned. Moreover, theuthors suggest that traditional biologic rationalesor bicuspid extraction (beyond “increased effi-iency”) where they exist should be subjected tohe same caliber of scientific scrutiny that is leveledn new or novel variations of traditional themes.

“Arch expansion” is a dangerously vagueerm, subsuming flattening of the curve of Wil-on, separating the maxillary palatal and ptery-omaxillary sutures, flaring incisors labially toriginal positions, tipping or bodily moving mo-

ars buccally. Whether one is physiologically “re-apturing” original phenotype with an appliancer creating a novel phenotype, the ambiguitiesf “expansion” always haunt us. Whether that beexatious to the reader or enigmatic to the prac-icing clinician, this seems axiomatic: “expan-ion” may “cause” bony or bony dehiscenceometimes, but not foreseeably in the individualnd clearly not always.43

The practical asset the spring appliance has ists “orthopedic machine” mechanism, self-limit-ng and mildly self-adjusting, to elicit “alveolusevelopment” and obviate bony dehiscence anderiodic adjustment pain associated with otherPE appliances. The problems with grosslyechanistic appliances derive from their reli-

nce on mechanical ratcheting instead of bio-ogical engineering. In that respect, the philos-phies implicit in both PAOO surgery and ADAppliance protocols and design of the orthope-ic appliances, if we may condescend to popularontemporary parlance, are clearly “not yourather’s orthodontics.” Thus, the rationale forheir clinical efficacy should at least dispel anyear or loathing that theory in the orthodonticpecialty is moribund or dead. The ADA, like the

ilcko-Ferguson collaboration, may well emerges the singularly most progressive synthesis inhis first decade of the “Century of the Biolo-ist.”

For the sake of intellectual integrity it shoulde stated that this discussion neither condemnsicuspid extraction as an acceptable modalityor contradicts the claim that some patients mayish the expedient care it facilitates. In addition,lthough one may claim that side effects of in-udicious bicuspid extraction are unpredictable,
oo small to be perceived, or, even in the worst s
ase, reversible later in life, it is the very unpre-ictability itself that argues for a prudent non-xtraction preference. However, in respect tohe rigorous scientific criterion of truth as pro-osed by Popper,17 one or two examples thatontradict a scientific theory’s claim (so-calledounterfactual) can weaken or even disprove theheory as legitimate universal law. The authorsonsider that their examples appear to be coun-erfactual to the claim of universal immutability.

To the thoughtful facial orthopedist andodern, even dogmatically strict clinical em-

iricist steeped in modern biologic theory,owever, what is demonstrably obvious in thease presented, and arguably valid deductivelyrom the emerging science, is that any univer-al claim of alveolar immutability must be se-iously rethought, in terms of contemporaryeriodontal regenerative science and tissuengineering, namely the demonstrated clini-al phenomena falsify the idea of universallveolus immutability.

The philosophy implicitly expressed by theseords does not contradict bicuspid extractionut complements it with a scientific basis andpistemological argument supporting a cogentonextraction alternative acknowledging that

or some patients a fixed alveolus deformity cano more define normal than a short leg can be

he standard to pathologize the other longer leg.he argument that remediable hearing loss inhildren should be maintained as a legitimatehysiologic variant also echoes the immutablelveolus contention. Yet there are cliniciansho, subscribing to such apostasies, will defendlveolus immutability despite an infinite numberf counterfactuals. In a sadly droll sort of way,

ntransigent doctrinaire clinicians and dogmaticrotocols are their own worst enemies. Yet forhe thinking clinician one need only quote Wil-iams James, “if you wish to upset the law that allrows are black . . . it is enough if you prove oneingle crow to be white.” This article has pre-ented two.

On a practical level bicuspid extraction willrobably be around for some time. However, tohe extent that an individual patient must beully informed of all alternatives, the malleabilityf the alveolus irrespective of its skeletal basesalsifies any claim of that bicuspid extractionherapy may be either universally necessary or
ufficient. With the presentation of these cases

tatftpifittfcmiftsop1g(oda

dolaaap

A

TsDsCwckcpgFDmS

R

1

1

1

1

1

1

1

1


he burden to disprove universality now lies withcademics and intellectual clinicians, who,hrough further research may confirm, refine,alsify, or reject the legitimacy of these conjec-ures. Only time will tell how prescient theseroposals will prove to be. Future research, both

n vitro and in vivo, should concentrate on de-ning the exact amount of microstrain range

hat stimulates compensatory periosteal apposi-ional osteogenesis of the alveolus. We knowrom craniofacial biology that the microstrain ofranial sutures of approximately 500 to 1000icrostrain44 will elicit evidence of bone model-

ng, a much lower range than that usually foundor long bones. There is no reason to believehat the alveolus should behave exactly like auture, yet despite its critical importance in orth-dontics it has been largely uninvestigated usingrinciples of the Utah paradigm as suggested in965 by Epker and Frost. Investigations are on-oing at University of California in Los AngelesUCLA) on exactly this topic. How the dynamicsf the alveolus are ultimately defined will takeecades but some significant biologic data arelready here.45,46

Meanwhile, the fact remains: clinical evi-ence of phenotypic changes and labial alve-lus modeling have been associated with ultra-

ight forces with a novel alveolar developmentppliance, as demonstrated in Figures 3, 4,nd 6, a clinical phenomenon consistent with“whole bone” approach to dentofacial ortho-edics. (Fig 8).

cknowledgment

“As the twig is bent, so inclines the tree” (Virgil, 70-19 BC).

he authors gratefully acknowledge the intellectual leader-hip of Professor Lysle E. Johnston, Jr., the didactic talents ofr. Ze’ev Davidovitch, the professional assistance of Profes-

or Russell E. Christensen, and the insights of Dr. Angeloaputo. Particular homage is paid to Dr. Spiro Chaconas,ho taught us to take orthodontics beyond the mechanicallinical arts it was, to the realm of intellectual science that wenow it should be. Spiro taught us that emotional and psy-hic pains are not necessary accoutrements for effectiveedagogy and the thrill of discovery in the context of colle-ial fellowship provides a peerless learning environment.inally, we acknowledge the perennially inspiring support ofr. Nabil Bissada, Professor and Chairman of the Depart-ent of Periodontics at Case Western Reserve University

chool of Dental Medicine.

eferences1. Moss ML: The functional matrix hypothesis revisited. 4.

The epigenetic antithesis and the resolving synthesis.Am J Orthod Dentofacial Orthop 112:410-7, 1997

2. Frost HM: A 2003 Update of Bone Physiology andWolff’s Law for Clinicians. Angle Orthod 74:3-15, 2004

3. Jee WS, Li XJ: Adaption of cancellous bone to overload-ing in the adult rat: a single photon absorptiometry andhistomorphometry study. Anat Rec 277:418-426, 1990

4. Burch JG: Periodontal Responses and Problems in Orth-odontics. Chapter 21: Orthodontic and Dentofacial Or-thopedic Section, in Hardin J (ed): Clarks Clinical Den-tistry. Vol. 2. St. Louis, Mosby-Yearbook, 1997

5. Melsen B: Biological reaction of alveolar bone to orthodon-tic tooth movement. Angle Orthod 69:151-158, 1999

6. Baumrind S: A reconsideration of the propriety of the“pressure-tension” hypothesis. Am J Orthod 55:12-22, 1969

7. McNamara JA: The role of the transverse dimension inorthodontic diagnosis and treatment planning, inMcNamara JA (ed): Growth Modification: What Works,What Doesn’t, and Why. Craniofacial Growth Series No.35. Ann Arbor, Center for Human Growth and Develop-ment, University of Michigan Press, 1999:153-192

8. Epker BN, Frost HM: Correlation of bone resorptionand formation with the physical behavior of loadedbone. J Dent Res 44;33-41, 1965

9. Burr DB, Schaffler MB, Yang KH, et al: Skeletal changein response to altered strain environments: is wovenbone a response to elevated strain? Bone 10:223-233,1989

0. Murphy NC: In vivo tissue engineering for orthodontists:a modest first step, in Davidovitch Z, Mah J, SuthanarakS (eds): Biological Mechanisms for Tooth Eruption, Re-sorption and Movement. Boston, Harvard Society for theAdvancement of Orthodontics 2006:385-410

1. van der Meulen MCH, Huiskes R: Why mechanobiology?A survey article. J Biomech 35;401-414, 2002

2. Singh GD: On growth and treatment: the spatial matrixhypothesis, in McNamara JA Jr (ed): Growth and Treat-ment. Craniofacial Growth Series No. 41. Ann Arbor,University of Michigan Press 2004:197-239

3. Johnston LE Jr: Fear and loathing in orthodontics: noteson the death of theory. Br J Orthod 17:333-341, 1990

4. Johnston LE Jr: Growing Jaws for fun and profit: amodest proposal, in McNamara JA (ed): Growth Modi-fication: What Works, What Doesn’t, and Why. Cranio-facial Growth Series No. 35. Ann Arbor, Center forHuman Growth and Development, University of Michi-gan Press 1999:63-86

5. Ilizarov GA, Ledyaev VI, Shitin VP: The courses of repar-ative regeneration of cortical bone in distraction osteo-synthesis under various conditions of fragment fixation.Eksperimental’naia khirurgiia i anesteziologiia 6:3-12,1969

6. Ilizarov G: The tension-stress effect on the genesis andgrowth of tissues: Part I. The influence of stability. ClinOrthop Rel Res 238:249-281, 1989

7. Popper K: The Logic of Scientific discovery. London,
Routledge, Taylor & Francis Group 2002

1

1

2

2

2

2

2

2

2

2

2

2

3

3

3

3

3

3

3

3

3

3

4

4

4

4

4

4

4


8. Wagle N, Do NN, Jack YU, et al: Fractal analysis of thePDL-bone interface and implications for orthodontictooth movement. Am J Orthod Dentofacial Orthop 127:655-661, 2005

9. Frost HM: The Utah Paradigm of Skeletal Physiology.Pueblo, CO, International Society of Musculoskeletaland Neuronal interactions (ISMNI) 2002

0. Frost HM: A Update of Bone Physiology and Wolff’s Lawfor Clinicians. Angle Orthod 74:3-15, 2004

1. Longhurst P, Gillett R, Johnson NW: Electron micro-scope quantitation of inflammatory infiltrates in child-hood gingivitis. J Periodont Res 15:255-266, 1980

2. Engelking G, Zachrisson BU: Effects of incisor reposi-tioning on monkey periodontium after expansionthrough the cortical plate. Am J Orthod 82:23-32, 1982

3. Thilander B, Nyman S, Karring T, et al: Bone regener-ation in alveolar bone dehiscences related to orthodon-tic tooth movements. Eur J Orthod 5:105-114, 1983

4. Lindskog-Stokland B, L. Wennström JL, Nyman S, Thi-lander B: Orthodontic tooth movement into edentulousareas with reduced bone height. An experimental studyin the dog. Eur J Orthod 15:89-96, 1993

5. Cacciafesta V: Dr. Birte Melsen on adult orthodontictreatment. J Clin Orthod 12:703-716, 2006

6. Hom BM, Turley PK: The effects of space closure of themandibular first molar area in adults. Am J Orthod85:457-469, 1984

7. Ferguson DJ, Wilcko WM, Wilcko MT: Selective alveolardecortication for rapid surgical-orthodontic (sic) of skel-etal malocclusion treatment, in Bell WH, Guerrero CA(eds): Distraction of the Facial Skeleton. Hamilton, BC,Decker, Inc 2007:199-203

8. Melsen B: Tissue reaction to orthodontic tooth move-ment—a new paradigm. Eur J Orthod 23:671-681, 2001

9. Norton LA, Melsen B: Functional appliances, in MelsenB (ed): Current Controversies in Orthodontics. Chicago,Quintessence 1991:116

0. Pigliucci M: Phenotypic Plasticity: Beyond Nature andNurture: Syntheses in Ecology and Evolution. Baltimore,The Johns Hopkins University Press 2001

1. Behrents RG: Growth in the Aging Craniofacial SkeletonCraniofacial Growth Series, Vol. 17. Ann Arbor, Need-ham Press 1986

2. Hartsfield JK: Genetics and Orthodontics, In: Orthodon-tics: Current Principles and Techniques, 4th ed, GraberTM, Vanarsdall RL Jr., Vig KWL (Eds), St. Louis, Elsevier
Mosby, 2005, pp. 106-109
3. Waddington CH: The Strategy of the Genes: A Discus-sion of Some Aspects of Theoretical Biology. New York,McMillan 1957

4. Siegal ML, Bergman A: Waddington’s canalization revis-ited: developmental stability and evolution. Proc NatlAcad Sci USA 99:10528-10532, 2002

5. Stearns SC: Progress on canalization. Proc Natl Acad SciUSA 10229-10230, 2002

6. Slack JM, Waddington CH: The last renaissance biolo-gist. Nat Rev Genet 3:889-895, 2002

7. Alperts B, Johnson A, Lewis J, et al (Eds): MolecularBiology of the Cell. 4th ed. New York, The Taylor andFrancis Group Publishers 2002, p. 433

8. Ponseti IV: Common errors in the treatment of congen-ital clubfoot. Int Orthop 21:137-141, 1997

9. Little RM: Stability and relapse of dental arch alignment.Br J Orthod 17:235-241, 1990

0. Johnston LE Jr: The functional matrix hypothesis: reflec-tions in a jaundiced eye, in McNamara JA (ed): FactorsAffecting the Growth of the Midface. CraniofacialGrowth Series No. 6. Ann Arbor, Center for HumanGrowth and Development, University of Michigan Press1976:131-168

1. Kuhn T: The Structure of Scientific Revolutions. 2nd reved. International Encyclopedia of Unified Science:Foundations of the Unity of Science. Vol. 2, No. 2.Chicago, University of Chicago Press 1970

2. Shirazi M, Nilforoushan D, Alghasi H, et al: The role ofnitric oxide in orthodontic tooth movement in rats.Angle Orthod 72:211-215, 2002

3. Djeu G, Hayes C, Zawaideh S: Correlation between man-dibular central incisor proclination and gingival reces-sion during fixed appliance therapy. Angle Orthod 72:238-245, 2002

4. Jeremy J, Mao JJ, Wang X, Mooney MP, Kopher RA,Nudera JA: Strain induced osteogenesis of the craniofa-cial suture upon controlled delivery of low frequencycyclic forces. Front Biosci 8:10-17, 2003

5. Charras GT, Lehenkari PP, Horton MA: Atomic forcemicroscopy can be used to mechanically stimulate osteo-blasts and evaluate cellular strain distributions. Ultrami-croscopy 86:85-95, 2001

6. Charras GT, Mike A, Horton MA: Single cell mechano-transduction and its modulation analyzed by atomicforce microscope indentation. Biophys J 82:2970-2981,
2002

beyond the ligament a whole-bone

Documents