Topics in 0nthodontics Audio $eries

E n d o r s ebdy
A m e r i c a nA s s o c i a t i oonf
Orthodontists
Topics
in 0nthodontics
Audio$eries
Volume1, lssue9:
Casko'sCorner
Gengrrc
Cor'nponrrurs By John S. Casko,DDS, MS, PhD
T O M I S S I N GT E E T H
FEBRUARY
15, 2007
RELEASE
DATE:FEBRUARY
2007
EXPTRATToN
DATE:
2009
JANUARY
Eorons-m-Gnrr:
Drvro McKsHoREr
SAnven,
DMD,MS
ADJUNcT
PRoFEssoR
oF ORTHoDoNTtcs
L J N r v F R s r roYF N o R T HC e n o l t r , t p
ScHooLoF DENTTsTRY
P R T V A TPER A c T T c E
B r R M r N G r . l AAML ,
Mmr R. YANoSK!DMD,MS
PRTvATE PRACTTcE
B I R M I N G H A M ,A L
Sprcru
GoNrnmuron:
lonr.rS. Clsro, DDS,M5, PUD
P R o r E s s o RA N D B . F . A N D H E r E N[ .
D E W E LE N D o w E DC H A T R
tN
C L T N I c AOLR T H o D o N T T c S
DEPARTMEN
T ORTHoDoNncs
oF
T H E U N T V E R S toTFY l o w A
C o T L E G oEF D E N T T S T R Y
lowA Crrt IA
lruTnslssur:
THE RorE or CRAr{rorActAr GEilETtcs til
CLrilrcAL PRAcflcE
PAGE'].
B Y R o B Y NS r r a E R S r E r ND,D S , P H D
AssrsraNT CLrNrcArPRoFEssoR
absolutelyenjoyedDr. Siiberstein's
pre
sentation.-Ihive known Robynfor a
n u m b e ro I y r . a r sa s [ e l l o r vm e n r b e rosI
the MidwestComponentof the EdwardH. Angle
Society,and I am continuallyimpressedr,vithher
nrany'talents.Sheis one oI thoserarepeople
who excelsas botl.ran orthodonticclinician and
a basicscienceresearcher.
As orthodontistswe arevery privilegedto be
able io work in a specialtythat allowsus to signi l i r ' a n
t l y i m p r o v r . 'paa t i e n t 'as p p , ' a r a n caen d '
s e l fe s l c c mI.i i s a g r e a lf c el i n gi o l i n o wt h a ti n
somesmall way you haveimprovedsomeone's
life. I alsofelt veiy gratifieda^numberof years
ago when I revielvedan articlelbr Practirill
Reviewsin Orthodonticsthat documentedhclw
the svmrrtomsof Lvme'sdiseasemimickedTMD.
After this reviewwas pubfished,I receiveda
number of callsfrom oril.rodontists
who were
u n s u c c e s s f usl llyr u g g l i nlgo l r e a lp a t i en t sw h o
l h e yt h o u g l rht a df M O i y m p l o m i ,b u l f r r u r r d
otrt
thai in fac"tthey had Lvme's'disease.
It was very
'
satisfyingto know thai becauseof my review
someoft-hodontists
wereableto pronidebetter
carefor their patients.
number of lives.Hopefully,havingbeenmade
pre
arvareof this relationshipby Dr. Silberstein's
sentation,we will all be ln a betterpositionto
h c l po u r p a l i e n l sw h o p r e s e nrlv i l h ' o l i g o d o n t i a .
At the University of Iorva,I have had the privil e q eo f w o r k i n gw i t l rO r .A n d r e wL i d r a la, f e l l o w
i a c u l t ym e m h e ri n t h eO r l h o d o n l i D
c cparlmenl.
L i k eD r .S i l b e r s t e ihne, b o t hp r a c l i c eosr i h o d o n l i c sa n d d o e sb a s i cr e s e a r cl n
h e e n e l i c sR. e c e n-t l v ,
h e a n d t h eo t h e r sw o r l < i nign h i s l a h o r a t o rdyi s
t o v e r e da g c n cr e l a t e d
l o c l c f tl i p a n dp a l a t cl o r .
mation.What a greatfeelingil id to kn'owthat
becauseofthe contributionioftalentedand ded,
icatedorthodontistslil<eDrs. Silbersteinand
Lidral,we havethe potentialto reducethe inci
denceof colorectalcancerand to betteridentify
and reducethe incidenceof the cleft lip and
palatt'.
presentationif I
As a resultoi Dr. Siiberstein's
s e ci r p a t i e nwt i t ho l i g o d o n t i a 'l ihne [ u t u r el .w i l l
n f l h e s t r o n sr c l a a d v i s el h a tp a t i e n t 'psh y s i c i a o
t i o n s h i pb e l w e e n
o l i g o d o n t iaan d c o l o r e c t a l
cancer,and sendhim or her a copv ofthe article
a b o u l h e A X I N 2c e n et h a tD r .S i l b " e r s t emi ne n tioned.Assuminglhatyou might alsolike to
T h e s ca c h i e v e m e n w
l sh, i l ev e r ys a l i s f y i n gp.a l e
do this, for yourionvehience,'ihaveincluded
i n c o m n a r i s otno t h ec o n l r i b u l i o nt sh a ts i i e n t i s t s a copv of the referencethat Dr. Silberstein
like lr. Silbersteinmake to our nrofession.Bv
meniioned.
m a k i n gl h e p h y s i c i a nosl h e rp a t i e n l sw h o h a v e
o l i g o d o n l iaaw h r eo f l h e v e r ys t r o n gl i k e l i h o o d
o f ReJermce:
LantmiLet aL.Mutations
in AXIN2cause
anlncreasedincidenceof colorectalcancer.she
tootb
agrnesis
and predispose
to colorectal
cancufamilial
may rvell alreadybe responsiblefor savinga
Am J FIum Gen74:1043-1050,
2004.
u N t v E R s r ToYF l L L t N o l s
CoLLEGE
oF DENT|sTRY
H I G H T A NP
DA R K ,I L
The Role of Craniofacial Geneticsin Clinical Practice
By Robyn Silberstein,DDS. PhD
find craniofacial
biolocvan incrcdiblv
i n l i m i d a t i n rgu, ,bj e c l .I t ' [ 6 e l a
s r i l r , r ,rri.t '
l e a r n l n qi r n ( lo r s L o V e n nn{e \ \g' c n e s .
growthfaclorsand transcriptionfacktrsat an
erxponential
ratc.Understandingtheseadvances
r v i l l rc n v i r o n m e r r lgr l, r , nren d g i n e g e n t 'i n t e r a c
tionsis absolutely
overivhclming.
The National
lnstituteclfDcntal and CraniofacialResearcl.r
has
placedgreatemphasison translational
research,
lvhichis research
rvithclinicalanulications.
The
bestexamplethat I ciurthink of I'orthe orthoclontist is the mutationin the AXIN2qcnc.In 2004.
IheAmeritan
lournalol HumanGmiticrpuhlisht,d
"Mutationsin AXIN2
CauseFarnilialTooth
Agcnesis
and Irredisposition
to Coloreclal
Canccr."
Severallamily mcmberslvith oligodon
l i . i .r v h i c hi . b l s i c ; r l l 1m i : : i n gs i x o r m o r ep e r m r r
nentteeth,prcscntcdrvithcolorectal
canceror
precancerous
lesions.Furthertestingin other
i n d i ri d u r l sr , r ' i l A
h X I N Zm r r t r r t i odnF m o n s l r a l u d
lhi: relalionshA
i pX. I N 2r e g u l a l eWs N Ts i g n a l i n g .
r v h i c hi s c r i t i c allo r h o t hl u u l hd e v e l o n m e na tn d
l i s s u eh o r n r , o s l r sIi tsf.o l l , r r va: n a u t o s o n r a
d lo m i
nant and highly penctranttransmissionpattern.
meaningif one hasa mutationin the AXIN2
qene,thereis an increased
likclihoodof colorec
fal cancer.As orthodontists.
we are oftenthe lirst
to idcntily oligodontia.It is arnazingto mc that
missingmLrltiple
teethrnayindicatea predisposi
tion to colorectalcancer.Thereare scveralgenes
lbr missinsteeth,but if thcrcis n-rutation
in thc
AXIN2gene,it will allowone to look lor early
coloncancerscreenings.
Althougholigodclntia
is
relativclyrarc,lessthan l0/0,
I am probablycur
rently treatingsix or so lan"rilies
rvith oligodontia,
onc of u,homl knorv lost a grandlhthcrtb ccllon
cancer.Therefore, when I treat a patient with oligodontia, I
vrlll generally fax a copy of this article to the pa[ent's pediamcran or pnyslcnn.
WNT signaling is basically a protein that regulatesseveral
things. One significant thing fhat it regulatel is tooth developmen-t.It also rEgulatedtissui homeostisis,which is responsil
ble for keepingcells noncarcinogenicand keeping thein from
changingtheiifunaions. Both of thesefunctiohs seemto
play a role in gene mutation. When there is a mutation, it is
the AXN2 gene that is affected.
It is a complex matter since agenesisor tooth agenesisis
associatedwith severalthings. Generallvif vou"includethird
molars, it is over 200/o
of the-population.Hoi,vever,as practicing orthodontistswe really chre about missing lateralsand
missine premolars.Probablvthe most comm6n missine tooth
is the p-remolar,3 to 5olo
of the population, and the lateiil
incisois are iust lessthan that,-abbut2to 4o/0.
Oligodontia,
which is miising six or more permanentteeth,is'tairlv rare,
lessthan l0l0.Co*mpleteoligodbntia,the completeabsenceof
teeth,is very rare.There is=someindication t}at it depends
on the population
studied.African American popula[ions
-prievalence
have a
of missingpermanentteeth df 7 to 8o/o.ln
Agenesiscan be associated
Japanesepopulations,it is 9ol0.
with singlegene mutations,chromosomalmutations,syndromesindenvironmental disturbances.We know thal there
are probably severalgenesresponsiblefor singleqene mutation-s.trrtsxt-isgeneralv involved with missini prEmohrs
and third molals, and oligodontia is associatedi"i* tfre
AXN2 Aene and the PAXggene. That is what we know todav
about single gene mutation"s.Chromosomal mutations, tootli
agenesis,are associatedwith trisomy 13,18and 21.With syn'
diomes, the most corrunonone is ectodermaldysplasia.
There are probably over 47 syndromes associated-with
tooth agenesis.
ln terms of supernumeraryteeth,the incidence is as high as
3ol0,
malesbeing affectedtiariceas frequentlv as femalesllt
mainly occrus In the maxilla, most cdmmo"nlv with the mesodens 6r extra molars. It can be in nonsyrdroriral patients or
part of a slmdrome with cleidocranial dysplasia, Apert
^Gardiner
dvndrome and so on.
Internet Resources
An unbelievable source for information on human genetic
disorders is Online Mendelian Inheritance in Man. Ol,tm.
and I often go to it. It is a current and comprehensive webbasedrefere"nce
for qeneticdiseases.OMIM nrovides clinical
featuresand genetic"lociassociatedwith disrjasesand gene
mutations. Itis an incredible resource for anytime you"have a
question about a human genetic diseaseor disordei".I constantly go to OMIM and type in whateveris interestingto
me. lileads to an incredi6lb amount of information, cfinical
featuresand associatedgeneticdisorders.Look up whatever
comesacrossvour desk-in vour office: Gardiner 3vndrome.
Apert syndrome, and anytliing that you are not cl6ar aboui
oi wanf to find out more aborit.
There are probablv severalgenesfor missine teeth.
Nonsyndromal familial tooih agenesisis kin? of excitins
becadsemost of thesedefectsaie autosomaldominant.Thev
are passedon from parent to child, and there is'a 500/o
chance
that-it is the fust gerie.Singlegene mutation was discovered
by orthodontists,treeinnin! r,,fr'ttrttre MSX gene that is Iinked
with missing premolarsan"dtnira molars.Sincethen, we
have di_qcov"ered
AXIN2 gene and PAXggene for oligodontia.
Generally,tooth agenesilis an autosomll dominanitrait with
incomplete peneulnce and variable expressiviry,which
means it mdy look different in a family. I had oiie family
where the parent was missing teeth and passedthe geneto
their child, and there is a 500/o
chance of transmitting the
gene, whether female or male. The oldest sister was"missing
an upper right secondpremolar,the next son was missing
" a
maxi'llary rilht lateral ina rne third son was missing a
mandibrilar-right secondpremolar.That variable einressivitv
means that tw6 affectedindividuals or three affectedttt*t;- r/
uals.in the same family may have a different clinical profile
or phenotype.
Generally, there are four classic modes to Mendelian inheritance: adtosomal dominance, autosomal recessive,X-linked
dominant and X-linked recessive.Somediseasesfollow a pattern that is classicMendelian, such as tooth agenesis.Cleft Iip
and palate,however,do not necessarilyfolloil such a simple
Mendelian inheritance becausethere a:remultiple genes ahd
environmental issuesthat may cloud such a pdttern.
Autosomal dominance is not sex-linked, and it is a trait that
is expressedwith one copy of the author gene.However,with
autosomalrecessive,tr,voiopies of the aulhor gene need to be
presentfor that trait to be eipressed.The most"common
lamlia tooth agenesisis autbsomaldominant. Sometimesa
trait is not "ittfu expressedeven if one carries the gene. For
example,a parent mhy say,"Oh, my uncle or mv siiter has
that pioblerir." Basicaliy,that pareni has the muiated gene.
Penetrancegives an idea of how often vou would seethat
uait. For exinple, most casesthat havd an AXN2 mutation
and missing teeth will likely have colorectal cancer or precancerouslesions.
One of the most exciting parts of craniofacial qenetics is
growing teeth. When I vlas a student, that seeried so far
away. They have made incredible progress.There are a lot of
labs-workihgon growing teeth.Paril Sharp'slab in london
\
has actuallv-pros;essedTafulv
far. Thev hive srown embrvon-. )
ic mousetrioth p"rimordiauiing stemte[s, m?senchyrnaf
stem cells from a lot of differen'tplacesand embrvonic
epithelium. They have grown a p^rimordium, a torith primordium and tr'ansplaritedthatbxplant into the diastlemaof
adr.rltmice. Transplantation has tobccur in an adult. Thev
have shown crown formation, enamel, dental and pulp frirmation. It has actuallv formed a connective tissue lttathment
to the maxilla, even iir the correct orientation, which I think
is amazing.There are still someproblems in terms of root
formation"in that the root has not actuallv been formed vet
and eruption is still a problem. Nevertheless,I think it ii
tremendous,and the whole field of tissueengineeringis sort
of exploding.
In addition to actually growing teeth or primordia, Dr.
McDougal'slab at thti tiniueriitv of Ala6ama has identified
families. She has done a lot witli cell lines, and I think we all
remember that in dental school, cleidocranial dysplasia is
almost pathognomonicfor supemumerarvteeth.Shehas created cefl [neland investigatebwhat signils are regulating
the other other cells on in*this mutated"gene,the durxZ oi
CBFAImutation, and how they causete6th to keep forming.
They want to leam what proteins are responsiblelor contiiued-toothdevelopment.Thesepatientsattuallv can continue
tooth developmeirt.Thereis soinethinggoine 6n that is an
exciting piec'eof the puzzle.In terms df lene"ral tissue engineerinf, that is also very excitinA.Thev dan use mesench\rmal ste=m
cells in the prbsenceoTone or more growth factors
to make bone. cartilafie,muscle,and tendon, a"ndthev use
^'
bone marrow generaliv,but there are a lot of sourcesbf mespri-uty
enchyrnal steri cells.
teeth are an easy source,as are l-/
permanentteeth,the pulp of both primarv and permanent
ieeth,periodontal ligarnent and faf ceils aie all incredible
sourcesof mesenchfrnalstem cells.Expandinqthesecell
lines in vitro and into a scaffoldadds volume*andsupport.
They potentiallycan be inserledinto dei'ects
to promote
healingand tissucreplacement.
That is a tnrly excitingpart
ol tissuecngineering.
-
Externalapical.root
resorptionclcarlyis a complexcondition
lrritl'rseveralihingscontributing,botli environmentallvancl
gcneiically.Harri.sshorvedthaiihere is a hieh heritrbilitv
indcx,and recentlyIiobertsin Indianahasdemonstrated
a
e r i i p p r o x i m r r l eIl5yu n
, q c t t e l i c . c r r n l r i b r;rrIci oc rorg n t i nl o
9f Urc
l r l e r n r r .l r p i r . rrl o o lr l r o r n l i o ns c e n c . ' l ' h el oy o l < eactl i n t c r
Itrrkin,vr,hichis part of a larnily of interlelkins.Theseare
r n dp t r i g l a n d r r l .drirs
I r f o t r r j na.s. s oita l e dr v i l hi r r l h r m r n r t i or n
IhgV found thrt in individualshomozygoiisfor inter
9as.e,
leukin,ILt, thereis a polymorphismof both'iilclesivith a llve
and a half timesincreasedrisli of cxternalroot resotptionof
moretthan ht'o rlillimeterscomparedto others.I thinl<that it
is reallyexcitingto know that it'is not ahvavsthe ofihodontists'thult or somr)environmentaliactor,brit thereis a strong
heritabilitvin externalroot rcsorption.
CnnttornclnlGgr'rgncs:
Tre CoruplexAND
Coonolnlrro Pnocrss oF ToorH Dsvttopnntnr
Bv Menr< R. YeNosxy, DMD, MS
As onrHoooruTtsrs,wE HAVEALWAyssuspEcrEDA
G E N E T I C C O M P O N E N T T O T O O T H D E V E L O P M E N TA N D D E N -
T A L A N o M A L I E SW
. H T L EG E N E T I C
M U T A T t o N sA R E T H E
M O S T C O M M O NA G E N T SA S S O C I A T E W
D I I H D E N T A LA N O M A L I E S ,V I E W I N GA G E N E T I C
M U T A T I O NA S A S P E C I F I C
ETIOL O G I CM E C H A N I S MR E S U L T I N G
IN A SPECIFIC
DISEASE
E N T t r y M A y B E M | S L E A D t N GD. e t r n l
DysMoRpHocENESts
15THE PRODUCT
O F U N I Q U EG E N E T I CB A C K G R O U NADN D
T H E E N V I R O N M E NITN W H I C HT H E B A C K G R O U NIDS F O R C E D
I actuallylind it vcry difticrrltto classifyenirmeldefects.We
r r r e . l u o l . i nr eql r o s p ct iir e l ya n d r v i l h u um
i i c r o s c o pai tr r u l y s i s
et the oreanicnr;rJ<eup
ol enamel,and we do not-knowa6out
hypornaturatron,
hypocalcilication
and hypoplasia.
It is
cnd.cnricin ourpopulation.When you lobk at prevalence
studics,rersonableestimates
arc over50%.Theiefbrc,
it is a
serious.
problem.\Neencounter
it regularly,
daily.Bond
:-fherclore,
l r e r r g l hm
s a y b e r l e c r e a s eadn. d p i r i e n t n
s r a l h er . o n t . c r r r c d .
Ithinh it is a very rcallssue.However,
it is trou
bling to actuallyretrospectively
sayr,r'hat
the problemwas.In
l . r c lp
. n r b a h l3
l u 0u r m o r el u * n l s , l l n p o t e n t i i l l ya f l e rI l h c
d e r e l o p i r rluo o l hr d v e r s e l ya.n d t h ed e v c l o p m e n l lrilm r .p e r i
o d i : \ c r y l o n g .A l l d r t ' ' ei e s r r liln a v c r y , i m i l l r p h e n o l y poer
c l t r ) r c ai ltp p e i r r a n co{l 'l h oe n a m c lT. h t , r ec a na l s oh e c n v i r o n
- - m e n l r la n dg c n e t i ac g e n l sI l. i s q u i l ed i i l i c u ltto d i s t i n c t r i s h
b e l r v l c nl h e l r r u .W r :k n o r vc e r l a i n l vl h e r t , a r eI o t so l e l i v i r o n _
mentalagentsthat contrihriteto enantelopacities.Very often
it,isnot so muchprematLrre
bjrth,but rr[]thr,complicalions
ol prcmaturebirths,suchas intubation,metabolii disease,
hypoxia,nutritionaldcficienciesand fever.In frct, underlvine
I ' e r - ti'sr p r o b . r b lay b i gr o n t r i b t r t i r rl igr c t o r( . o n s t . i n l lpya r i n t s r t i l l t c l l m t ' ." T h t ' yt o l d m t ,i t w a st ' h ra, n l i b i o l i t . sI .n"' r e h t i t vi t,
is probablythe lcastobviousfactorin contributincto thes'e
e n r r m edl e l i , t t s .
-
Thereis good evidencefor the tetracyclines,
r,vhichr,veno
longeruservhiledevelopingteethare maturing,but all these
otherenvironmentalagentsarc absohitelycoritributing.Thcre
aremany genesthat atlectthe c'nalnclibirnation,and'ihe
combincdprcvalenceof amelogenesis
irnpcrtectais probablv
aboutonc in 14,000.
So-me
w,ayswe can diitinguishb^etween
6r
identify lhat it is heredity,ami'locenesis
impcil,ecta.
Howevcr,
vcry oftenit is di|lcult to distingLrish.
Ameiogenesis
imperlec
l l i . o [ l t ' na r r l o s o m d
r lo m i n a n lr,n d l l r e r e l t r r ev es e ri t i n
everygenerationgcneralizedin the primary dentitionancl
the purmanentdeniition.Thererealivis noi a time relation
ship to the dcfecis.Thesedistinguishit as amelogenesis
imperfecta,but even.soit is stili.toughtclclassify'since
the
phenoty,pe
is so sintilar.Rclativcto bondingortirodontic
appliances,
When looking at electronmicroicctpyof enamel
op.rcitics,
thel' shorvlittle or no enamcltag.I rtiritinelyivill
.tddbondenh.rncing
solutions
to geta chi.micilla, l".11os
rnechanical
bond.I rvillalsoconsidcra microabrasive
oro
p h y l a x i sI .m a k er rl i t t l cp r r i l yu s i n gh t , d r o c l r l oar ict i.da n d
ponrosoclycerin.
It is realll,(ood for thosevellolvbrowndis_
coloratior-rs
or lvhile spotli:sions.Thc slLrrrrrthat I make is
goodIbr thosc,actualiy,qettinc
out someoithe brownvellorv
lcsions.I useSolorin ii, ir I uie thc lltrliancebond-enh'ancing
product.I rrseit almostroutinelylvhenI seeenamclopacitici.
T o O P E R A T ET. H e n e t s c o N s r A N T t N T E R A c r r o NB E T W E E N
T H E G E N O M EO F A D E V E L O P I N F
GE T U S T
, HE EPIGENETIC
MICROENVIRONMEN
TT
H,E I N T R A U T E R I NEEN V I R O N M E N T ,
A N D T H E E X T E R N AM
L I L I E UO R E N V I R O N M E N T AI N
LSULTS.
G E t t Em u t n t t o N s A R E N o r M E c H A N t s M st N T H E M S E L V E s .
B U T A G E N T ST H A T M A Y I N I T I A T EM E C H A N I S M O
S F MALFORMATION
O F D I S E A S EA T S U B C E L L U L A C
RE
, LLULAR
OR
T I S S U Et E V E L S .
T H n o u c H o u r D E N T A LT R A t N t N Gw E H A V E H E A R DT E R M S
S U C HA S A N O D O N T I AH, Y P O D O N T I A N D O L I G O D O N T I A .
W H y r s r H t s t M p o R T A N TT o o R T H o D o r u r r s r s ?M r s s n r c
I E E T H A R E C O R R E L A T E DL A R G E L Y W I T H F A M I L I A L H E R E D I -
T A R y p A T T E R N SA. s o n t H o o o N T t s r s w E A R E o F T E N
F O U N DT R E A T I N G
S E V E R A LC H I L D R E N
O R E V E NT H E
P A R E N T SO F A G I V E N F A M I L Y ,
IHE LAST TIME YOU HEARD TERMS LIKE PHENOTYPE,
G E N O T Y P E , A N D E X P R E S S I O NO F A T R A I T M A Y H A V E B E E N
YOUR FIRST YEAR OF DENTAL SCHOOL OR YOUR IAST
YEAR OF COILEGE, AND IT MAY NOT HAVE BEEN WELL
U N D E R S T 0 o DA T T H A T T t M E . L t K E t r o R N o r . C R A N I o F A C I A LG E N E T I C S
P T A Y SA L A R G ER O L EI N O U R C L I N I C A L
p R A c l c E s . W e s r E p A T I E N T Sw t r H
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T u e s r n n e J U S Ts o M E o F T H Et s s u E ST H A Tw E A R E
FACED
WITHTODAY.
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There is a lot of researchin terms of speedingup or slowinq
down tooth movement.More recentlv'it has Seehinvolved'in
osteoporosiswhere they are targeting osteoblastsand osteoclasts.Thesecells are very sensltivelo genome-environment
interactions and communication. Every time we put a force
on a tooth, it affects the microenvironrirent. tt afl6As the
ultracellular matrix, cell membranes, cytoskeleton, nuclear
proteins,and the genomes.We are looking to tweak that and
inake teeth moveTasteror slower,whateve-rthe need be. In
my doctoral thesis,which was twenty-somethingyearc ago,
it ir*,asvery interestingto me becauseI looked aTmast cell
deficient mice. It waia beautifirl design where I had a genetically similar mice, but one had no mlst cells or verv fe-w.t
fouid that the whole remodeling cvcle was slowed down in
the mast cell deficient mice. Wlich is interestinq becauseit is
not classically
- a bone remodeling cell, but involves that
whole cycle.
The mast cell is not a bone cell, per se,but relatesto the
other cells: immune cells and blood cells that are in the area
and recruit osteoclastsand osteoblasts.Lr my research,I
looked at mice that have deficient mast cells'and the same
genotypethat had mast cells.Thosemast cell-deficientmice
Ihowed a slower cvcle of the whole mast cell turn around.
When I extracted dn upper molar and induced a very simple
bone remodeling cycle, the lower molars aggressedand
extruded.It starteda whole bone remodeling cycle, and in
these mast cell-deficient mice they were mu-chilower. In
humans that have mastocytosis,or too many mast cells,and
the mast cells are being eipressedwhere there is a lot of
heparin being extrudeil,thbsepatientshave more osteolytic
and osteoscleroticlesions.The whole bone remodeling cycle
is spedup.
I think today what is so interesting is Wilckodontics, even
though it is hot really mainstream. they are taking advantage
of the fact that the rate of remodeling in a defect elceeds no-rmal bone remodeling.For thosepeople that do not really
know about wilckodontics,they do a firll thicknessperiodontal flap and partial decorticatioh, where they actuaily make
holes in the cortical bone. and add bone grafting.They see
tooth movement occurring very rapidly. B-asicallv,this is
something that was descriled 6v F-rostvears ago, regional
acceleratolrvDhenomenon.R.qp.thev dlso harTeevidencethat
it occurs sv:t'emicallv. When you do ihis svstemicallv, vou get
an increas-edamouni of bone. tVhile I said this is noi ri:alli
main stream,I think there is a lot to learn about the mechanisms or the sig4aling occurring. Ultimately it will go from a
shotgun.approach like this to a very tightly targeting drug
protem therapy to attect a tooth movement.
Aeaeilitation stntament:Tlns Wgram is jnntly sponsoredby the,\merican Assuiationof Orthodontistsand
Oabstorr PublLsbing.
fhe lmnicai associationof
Orthodontistsis an ,\DA CEPPPP
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t'm nntinuingdmnl
efurcauonm Mimresotn.To recelueWopu oedit Jm
k:'20fl7,it is very exciting becausethey are using recombinant
virus, for example, withirascular endothelial gr6wth factor.
They are literally iniecting in rats in the condyle to enhance
conilvlar gowtli wi[h theie recombinant virui eene therapv.
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Therti are"alot of proteins that are known to aflect bone
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remodeling, Iike Iielaxin, in which casethev found that it
really did ilot affea tooth movement, it jusf affected tooth
mobiliry This targeted,this very tightly focusedgenetherapy
is one of the more exciting things on the horizon.
The whole tissueengineeringfield is iust about to erplode.
There is really not a*lot thatirve can quite point to yei, but
they are also working on condylar scaffolds to make things
Iikti condyles,bony ilefectsanil deal with periodontal disr
ease.It is"almostniind boggling how much there is in the
tissue engineering fi eld.
There has been some researchon nonsteroidal anti-inflammatory drugs,where they looked at aspirin, acetaminophen,
and ibuprofen. We know that those drugs inhibit
prostaglandins.Both the aspirin and ibrlprofen showeda
decreaiednumber of osteoi;lasts.
The acbtaminophen,the
Tylenol type drugs, did not. I do not know exactly how this
tr-anslatesto humlans and tooth movement. I do know that I
often hand out Advil. However, it is something to think about
and there is someinterestingresearch.
There is a very real concem with the bisphosphonates,
becausethe principai action of bisphosphonatesis to inhibit
bone resorption.While there is a lot of evidence,and not a
lot of papers on the subject of orthodontic treatrnent and bisphosphonates,there are some casereportswhich sav cancer
batiehts,for example,that are using bisphosphonic'acidheatinent to contol brine metastasishai'e srjrt of stalledtheir
cuspid retraction. It makes sensethat the bone resorption is
being stopped.That is the point. ln terms of qeneralbisphos- .
phoriate and osteoporosis,the word is not cliar that it is a
tenible thing. There are some concems about having dental
surgery while taking bisphosphonates.
To the whole dental field, the issue of tissue engineering is
tremendousfor periodontist,for periodontal diiease,foifUJ
implants, for bohe repair, anomalies, and for trauma. The
field of tissueengineeringholds huge promise. Genetherapy
is just so exciting. We are just at the beginning stage.There is
so much to leam and understandabout genesand we are
Ieaming so much. We used to think thatlt was one gene,one
manifestation. The AXN2 shows us thev are regulating genes
which control much more and we are liarninglfhat aip"ect
alone is so exciting.
homesudy cowses,yut mwt flibmit a Mhmf5'otnuntinuing dmtal eilrcation card along with your posttestto
O a}a6ne Me/iical Publisbins.
Intendeit auitienn: ortltoldontists
and otbqsintsesud
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Edw;tioml objeaiua: This actitity is dtsignet to
and,othersinttrestedm ortbodDnwwide orthodontists
ia witb aregtlm aatiats of tbe mostcunmt, clinicalIv usefulinformartonauilabie from tbelmdins acrerts
A *i pU. tt s designldn ac{and upon.reinfmce'and
$te additiml prsprctiue to tbe participdnt'sunn
reviau of currmt topia in orthodontis.
After completingearb ksue'saairity, fueparticipantis
acryud, to hauea wmhng faniliarity wth the mast
dmically imporlnrt mfonnationglnarcdfrom thespeaalty'sforanost autbortties.
Drs. Casko,Saruer,and Sihosteinrepmud rc conflictsof
intfrestrcIatndto thb aafuity.
Complazdconnnuingdrrcation bows belpmeetthe CDE
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