UNIVERSITATEA DE MEDICIN I FARMACIE IULIU HAIEGANUCLUJ-NAPOCA

REZUMATUL TEZEI DE DOCTORAT

Cercetri privind factorii

etiologici implicai n
disfuncia temporomandibular

Doctorand Andrea Maria Kurtinecz (Chisnoiu)

Conductor de doctorat Prof.dr. Sever Popa

CLUJ-NAPOCA 2015

Andrea Maria Chisnoiu (Kurtinecz)

CUPRINS



INTRODUCERE

STADIUL ACTUAL AL CUNOATERII
1. Definiie, terminologie
2. Anatomia articulaiei temporomandibulare
2.1. Unicitatea articulaiei temporomandibulare

3. Epidemiologia disfunciei temporomandibulare

4. Simptomatologia disfunciei temporomandibulare
4.1. Durerea muscular
4.2. Durerea articular
4.3. Limitarea micrilor mandibulare
4.4 Zgomotele articulare

5. Etiologia disfunciei temporomandibulare

5.1. Factorii ocluzali
5.2. Factorii psihologici
5.3. Factorii hormonali
5.4. Macrotrauma
5.5. Parafunciile
5.6. Hiperlaxitatea ligamentar i hipermobilitatea ligamentar
5.7. Factorii ereditari
5.8. Tratamentul ortodontic

6. Stresul oxidativ i disfuncia temporomandibular

CONTRIBUIA PERSONAL
1. Ipoteza de lucru/obiective
2. Studiul 1 Evaluarea histologic i cuantificarea modificrilor
articulare temporomandibulare sub aciunea unor factori
etiologici ai disfunciei temporomandibulare
2.1. Introducere
2.2. Ipoteza de lucru/obiective
2.3. Material i metod

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Cercetri privind factorii etiologici implicai n disfuncia temporomandibular

2.4. Rezultate
2.5. Discuii
2.6. Concluzii

3. Studiul 2 Implicaiile stresului oxidativ n mecanismul de

apariie al disfunciei temporomandibulare
3.1. Introducere
3.2. Ipoteza de lucru/obiective
3.3. Material i metod
3.4. Rezultate
3.5. Discuii
3.6. Concluzii

4. Studiul 4 Studiu epidemiologic prospectiv privind frecvena

semnelor i simptomelor disfunciei temporomandibulare la un
grup populaional
4.1. Introducere
4.2. Ipoteza de lucru/obiective
4.3. Material i metod
4.4. Rezultate
4.5. Discuii
4.6. Concluzii

5. Studiul 5 Evaluarea statusului psihoemoional la pacienii cu

disfuncie temporomandibular
5.1. Introducere
5.2. Ipoteza de lucru/obiective
5.3. Material i metod
5.4. Rezultate
5.5. Discuii
5.6. Concluzii

6. Concluzii generale
7. Originalitatea i contribuiile inovative ale tezei

REFERINE

CUVINTE CHEIE: disfuncie temporomandibular, stres biomecanic, stres

emoional, hormoni estrogeni, radicali liberi, analiza ocluzal, anxietate.

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Andrea Maria Chisnoiu (Kurtinecz)

INTRODUCERE
Teza de fa trateaz o tem de actualitate din domeniul medicinii dentare,
oferind o trecere n revist a factorilor etiologici implicai n apariia disfunciei
temporomandibulare i o prezentare a rezultatelor obinute n urma studiilor de
cercetare desfurate n acest domeniu.
Teza este structurat n dou mari pri. Prima parte evideniaz stadiul actual
al cunoaterii temei propuse spre dezbatere. n cea dea doua parte a tezei se prezint
studiile experimentale derulate, n virtutea informaiilor teoretice dobndite.
Partea de cercetare teoretic a tezei stadiul actual al cunoaterii, conine 6
capitole care trateaz teme referitoare la: definiia i terminologia utilizat n domeniul
disfunciei temporomandibulare, precum i detalii legate de anatomia i unicitatea
articulaiei temporomandibulare, aspecte privind epidemiologia i simptomatologia
acestei patologii. Sunt prezentate n detaliu date actuale privind factorii etiologici
implicai n declanarea, perpetuarea i/sau agravarea patologiei disfuncionale
temporomandibulare, respective mecanismele stresului oxidativ i implicarea lor n
fiziopatologia acestei afeciuni.
Pe parcursul studiului doctoral sa urmrit analiza n detaliu i evaluarea
influenei a trei factori etiologici (stresul biomecanic, hormonii estrogeni i stresul
emoional) asupra funcionalitii ATM i a structurilor nvecinate, respectiv
mecanismul de aciune i contribuia lor la apariia simptomatologiei disfunciei
temporomandibulare.

CONTRIBUIA PERSONAL
Ipoteza de lucru. Obiectivele acestei teze constau n: (1) evaluarea
modificrilor articulare la animale de laborator sub aciunea diferiilor factori
etiologici ai disfunciei temporomandibulare, (2) analiza implicrii mecanismelor
stresului oxidativ n patogeneza disfunciei temporomandibulare la animale de
laborator, (3) studiul relaiei dintre anumite caracteristici ocluzale, musculare,
articulare i semnele i simptomele disfunciei temporomandibulare la un grup
populaional, (4) evaluarea nivelului de anxietate la pacienii cu disfunciei temporo
mandibulare.

Cercetri privind factorii etiologici implicai n disfuncia temporomandibular

Studiul 1. Evaluarea histologic i cuantificarea modificrilor articulare

temporomandibulare sub aciunea unor factori etiologici ai disfunciei
temporomandibulare
Scop. Acest studiu pe model animal ia propus analiza histologic a
modificrilor articulare aprute dup aplicarea unor factori etiologici ai
DTM,cuantificareaacestora i identificarea gradului de implicare a fiecrui factor n
apariia i evoluia acestei afeciuni.
Material i metod. Am conceput un studiu experimental pe model animal
realizat n cadrul Biobazei Disciplinei de Fiziologie din cadrul Universitii de Medicin
i Farmacie Iuliu Haieganu ClujNapoca. Am inclus n studiu 60 de femele de
obolan, rasa Wistar alb, repartizate randomizat n ase grupuri (n=10). Primul grup a
fost cel de control n cadrul cruia nu sa aplicat nici un factor etiologic Trei grupuri au
fost expuse individual la un factor etiologic la DTM dup cum urmeaz: grupul doi la
stres biomecanic (SB), grupul trei la supradoz de hormoni estrogeni (HE), iar grupul
patru la stres emoional (SE). Dou grupuri au fost expuse la asocieri de cte doi factori
astfel: grupul cinci la stres biomecanic i supradoz de hormoni estrogeni (SBHE), iar
grupul ase la stres biomecanic i stres emoional (SBSE). Experimentul sa desfurat
pe o perioad de 60 de zile. Dup sacrificarea animalelor, articulaiile temporo
mandibulare au fost ndeprtate n bloc, iar dup prelucrarea lor sau obinut
preparate histopatologice cu coloraia hematoxilineozin. Preparatele
histopatologice (cte 10 seciuni din fiecare ATM luat n studiu) au fost examinate i
fotografiate utiliznd un sistem calibrat de prelucrare i preluare a imaginilor
Olympus. Seciuni reprezentative din fiecare zon de analizat au fost identificate i
fotografiate cu obiectivele de 4x, 10x, 20x i 40x. Examenul histopatologic a urmrit
modificrile aprute la nivelul condilului mandibular, discului articular, osului
temporal i a esutului sinovial.
Rezultate. Din analiza comparativ a rezultatelor obinute n urma
msurtorilor la nivelul cartilajului condilar mandibular se observ c la toate cele
cinci loturi la care sa aplicat un factor, indiferent de natura acestuia, valorile medii
obinute au fost mai mici fa de cele obinute n cazul lotului control (134,24 m). Este
interesant de observat faptul c grosimea cartilajului condilar mandibular sa redus
destul de uniform, la valori destul de apropiate ca medie (ntre 119,56 i 126,75 m) n
ceea ce privete loturile 2 (SB) 3 (HE), 4 (ES) i 5 (SBHE). Modificrile cele mai
importante au fost nregistrate n cazul lotului 6 (SBSE) n cadrul cruia valoarea
medie a grosimii cartilajului (92,39 m) a fost cea mai sczut. n ceea ce privete
analiza histopatologic a modificrilor observate la nivelul ATM la obolanii din cele
ase loturi experimentale, la obolanii din lotul SB,la sfritul perioadei experimentale
la nivelul condilului, mai ales n zonele anterioar i central (zone care corespund
suprafeei portante ale articulaiei) au fost observat o pierdere multifocal de
condrocite n toate straturile cartilajului cu formarea de cuiburi condrocitare. n cazul
lotului 3 (HE) discul articular a fost subiat, cu un aspect hipocelular, iar la nivelul

Andrea Maria Chisnoiu (Kurtinecz)

sinoviului sa observat o proliferare sub form de viloziti. La lotul 4 (SE) sa observat

un aspect hipocelular condrocitar cu un aspect palid al acestora i cu pierdere
multifocal de condrocite, respectiv formare de cuiburi condrocitare. n lotul 5(SBSE),
modificrile histopatologice ntlnite la nivelul ATM au fost ceva mai discrete fa de
cele de la lotul 4. La nivelul ATM provenind de la obolanii din lotul 6 (SBSE), similar cu
aspectele histomorfometrice, leziunile histologice au fost cele mai severe.
Concluzii. Studiul histomorfometric de la nivelul articulaiilor temporo
mandibulare de obolan, a demonstrat c modelul experimental de inducere a
leziunilor ATM a funcionat la toate cele cinci loturi experimentale. Este destul de
interesant faptul c modificrile cele mai grave au fost nregistrate la lotul supus la
stres emoional i biomecanic, fapt care ar putea confirma ipoteza implicrii etiologice
a acestor factori n durerile temporomandibulare de la om.
Studiul 2. Implicaiile stresului oxidativ n mecanismul de apariie al
disfunciei temporomandibulare
Scop. evaluarea implicrii mecanismelor stresului oxidativ n apariia i
evoluia DTM, respectiv validarea asocierii unui anumit factor etiologic al DTM i valori
modificate ale biomarkerilor plasmatici ai stresului oxidativ (SO). Sa pornit de la
ipoteza c nu exist nici o corelaie ntre biomarkerii SO i un anumit factor etiologic al
DTM. Sa realizat un studiu de tip caz martor n cadrul cruia sau comparat valorile
biomarkerilor plasmatici ai SO (MDA i GSH) de la obolani Wistar crora li sau aplicat
cei trei factori etiologici individual sau n combinaii de cte doi, cu cele ale grupului
mator unde nu sa aplicat nici un factor.
Material i metod. Sau utilizat aizeci de femele obolan, rasa Wistar alb
(greutate aproximativ 150g), care au fost mprite randomizat n ase grupuri de
studiu (n=10). Primul grup a fost cel martor cruia nu i sa aplicat nici un factor
etiologic. Urmtoarele trei grupuri au fost expuse separat unui anumit factor etiologic
astfel: grupul doi la stress biomecanic (SB), cel deal treilea grup unei supradoze de
hormoni estrogeni (HE) iar cel deal patrulea grup stresului emoional (SE). Ultimele
dou grupuri au fost expuse unei combinaii de doi factori dup cum urmeaz: grupul
cinci stress biomecanic i supradoz de hormoni estrogeni (SBHE) iar grupul ase stres
biomecanic i emoional (SBSE). Experimentul sa desfurat pe o perioad de 60 de
zile. Sau prelevat probe de snge de la animalele incluse n experiment la intervale de
30 i 60 de zile i au fost evaluate valorile plasmatice ale markerilor de stres oxidativ
glutation (GSH) i malondialdehid (MDA). Analiza statistic a datelor a fost realizat
cu ajutorul Med Calc Software versiunea 15.2.1 (MedCalc Software bvba, Ostend,
Belgium), utiliznd testul ANOVA.
Rezultate. Nivelurile plasmatice ale MDA la 30 zile pentru grupul SB (media
7.216848 .6616420) au fost semnificativ mai mari dect la lotul martor (p
0,001).Valorile au continuat s creasc pn la finalul experimentului (60 zile media:
7, 663564.9070764, p0,005). Pentru grupul HE valorile MDA au nregistrat valori

Cercetri privind factorii etiologici implicai n disfuncia temporomandibular

semnificativ mai mari att la 30 ct i la 60 de zile comparativ cu grupul martor. Valori

crescute ale MDA au fost identificate i la grupul SE la sfritul perioadei
experimentale (media 7, 931940 1, 5827200, p0,001).Cel deal cincilea grup n
cadrul cruia sau aplicat doi factori etiologici ai DTM n asociere (SBHE), MDA a avut
valori semnificativ mai mari att la 30 (p<0.001), ct i la 60 de zile (p<0.001). Cele mai
importante modificri au fost observate la ultimul grup (SBSE) unde sau nregistrat
valori crescute semnificativ att la 30 ct i la sfritul experimentului (p=0.003). n
ceea ce privete dozarea GSH, nu sau nregistrat diferene semnificative statistic ntre
grupul control i cele de studiu pentru valorile nregistrate la 30 de zile. De la pragul de
30 de zile pn la finalul perioadei experimentale valorile dozrilor GSH au avut un
traseu ascendent pentru grupurile BSEH (p<0,001) i BSES (P=0.018). La 60 de zile
evaluarea plasmatic a GSH a evideniat valori crescute pentru toate grupurile de
studiu. Diferenele au fost semnificative statistic pentru grupurile BSEH (p<0,001) i
BSEH (p=0,017).
Concluzii. Datele obinute de noi utiliznd acest model experimental de
obolan, ne indic implicarea cu certitudine a stresului biomecanic, a hormonilor
estrogeni i a stresului emoional n apariia fenomenelor de stres oxidativ, cu
consecine asupra funcionalitii ATM. De asemenea aciunea asociat a acestor
factori cresc mai mult nivelul radicalilor liberi comparativ cu factorii aplicai
individual.
Studiul 3. Studiu epidemiologic prospectiv privind frecvena semnelor i
simptomelor disfunciei temporomandibulare la un grup populaional
Scop. n cadrul acestui studiu sa urmrit evaluarea caracteristicilor ocluzale la
un grup populaional, respective analiza interrelaiei dintre acestea i semnele i
simptomele de disfuncie temporomandibular. n cadrul analizei multivariate
realizate sa urmrit evaluarea parametrilor ocluziei statice i a ctorva micri
excentrice, aceasta reprezentnd abordarea tradiional de examinare a relaiilor
ocluzale.
Material i metod. Diagnosticul DTM sa bazat pe Criteriile de Diagnostic n
cercetare pentru Disfuncia TemporoMandibular (RDC/TMD). Examinatorii, instruii
conform specificaiilor RDC/DTM au colectat date clinice utiliznd msurtori i
chestionare structurate n vederea determinrii statusului ocluzal, muscular i al ATM
la pacienii luai n studiu. Protocolul de examinare a urmrit structura RDC/DTM dar a
inclus si proceduri suplimentare. Au fost analizate micrile mandibulare, articulaia
temporomandibular, muchii masticatori, relaiile de ocluzie statice i dinamice.
Analiza statistic a datelor a fost realizat cu ajutorul Med Calc Software versiunea
15.2.1 (MedCalc Software bvba, Ostend, Belgium). Datele nominale au fost
caracterizate prin frecven i procentual. Datele cantitative au fost exprimate prin
medie i deviaia standard. Au fost utilizate urmtoarele teste statistice: chisquare
test, Student ttest. Pentru analiza multivariat a fost utilizat regresia binar logistic.

Andrea Maria Chisnoiu (Kurtinecz)

Rezultate. Au fost examinai 213 pacieni cu vrsta medie de 234.24 ani, 124
(58.2%) de sex feminin i 89 (41.8%) de sex masculin. Vrsta medie a pacienilor cu
dureri musculare n sfera ADM este de 23 ani (p=0.01). Vrsta medie a pacienilor cu
cracmente a fost de 23.1 ani (p=0.02) iar pentru saltul articular 22.9 ani (p=0.006),
semnificativ statistic. Durerile la nivelul muchilor din sfera ADM predomin la
pacienii de sex feminin (40 pacieni (32%)), comparativ cu 16 pacieni (18%) de sex
masculin care au acuzat aceast simptomatologie (p=0.03). Sa evideniat o legtur
semnificativ ntre sexul feminin i prezena cracmentelor articulare (p=0.02).
Bruxismul a fost diagnosticat la 39 pacieni, mai frecvent la femei (22 (56.4%) dect la
brbai (17 (43.6%)). Durerea articular se coreleaz puternic cu prezenta
cracmentelor la nivelul ATM de aceeai parte (p<0.001), respectiv a crepitaiilor
(p=0.03). Durerea ATM este nsoit de contractura muchiului trapez de aceeai parte
avnd o intensitate ntre 3 i 5 (pe o scara de intensitate 010, p=0.01), muchiul
pterigoidian medial de aceeai parte (p=0.001), cu contractura muchiului
sternocleidomastoidian ipsilateral (SCM, p=0.003), corelaiile fiind semnificative
statistic. Durerea articular apare mai frecvent la pacienii cu interferene pe traseul
dintre relaie centric i intercuspidare maxim (p=0.45, OR 3.771, CI 95% (1.031
13.793). Palparea muscular a evideniat n 56 (26.3%) cazuri durere la nivelul cel
puin al unui muchi din sfera ADM. La aceti pacieni sa pus n eviden i contractura
asociat a muchilor trapez, maseter, pterigoidian medial sau lateral, milohioidian i
SCM (p<0.001). Musculatura masticatorie este influenat de caracteristicile curbei
Wilson. Astfel modificri ale arhitecturii ocluzale normale monomaxilare n zona
lateral n plan frontal (curba Wilson accentuat, invers sau plat) pot determina
contracturi semnificative la nivelul muchilor pterigoidieni mediali, pterigoidieni
laterali, sternocleidomastoidieni, milohioidieni. Rezultatele analizei multivariate au
artat c exist o probabilitate mai mare pentru pacienii care prezint o curb Wison
accentuat s dezvolte i cracmente articulare (p=0.014, OR 17.285, CI 95% (1.774
168.454)), dect cei cu alte caracteristici ocluzale. Tipul raportului ntre RC i IM
(pointcentric sau longcentric) nu influeneaz prezena contracturilor musculare.
Pacienii cu longcentric prezint mai frecvent cracmente articulare dect cei cu point
centric (p=0.05). Prezena interferenelor pe traseul dintre poziia de relaie centric
i intercuspidare maxim se indentific mai frecvent la pacienii diagnosticai cu
durere muscular n regiunea facial (p=0.038, OR 3.089, CI 95% (1.066 8.954)).
Concluzii. Relaiile ocluzale nefuncionale reprezint factori declanatori sau
perpetuani ai disfunciei temporomandibulare. Prezena interferenelor sau a
contactelor premature poate determina contracie i durere la nivelul muchilor
masticatori, dar i la nivelul articulaiei temporomandibulare. Anomaliile n anatomia
curbei Wilson i interferenele pe traseul dintre relaia centric i poziia de
intercuspidare maxim sunt factori de risc n apariia semnelor i simptomelor de
disfuncie temporomandibular.

Cercetri privind factorii etiologici implicai n disfuncia temporomandibular

Studiul 4. Evaluarea statusului psihoemoional la pacienii cu disfuncie

temporomandibular
Scop. Obiectivul prezentului studiu l reprezint evaluarea nivelului stresului
emoional la pacienii DTM comparativ cu cei din grupul martor i stabilirea unei
corelaii posibile ntre nivelul de stres i declanarea patologiei din cadrul DTM.
Material i metod. A fost efectuat un studiu prospectiv, observaional, n care
au fost inclui 79 pacieni (grupul DTM n= 37, grupul martor n=42) care sau prezentat
n serviciul Clinicii de Protetic Dentar UMF Iuliu Haieganu ClujNapoca.
Diagnosticul disfunciei temporomandibulare sa bazat pe Criteriile de Diagnostic n
cercetare pentru Disfuncia TemporoMandibular. n vederea analizei nivelului de
stres emoional sau utilizat chestionare de evaluare conform Beck Anxiety Index
(BAI). Acestea au constat n 21 de ntrebri (pentru fiecare atribuinduse cte un scor
de la 0 la 4) referitoare la statusul emoional al pacientului exprimat prin simptomele
comune ale anxietii (furnicturi, moleeal, transpiraii nedatorate temperaturii
ambientale, frica de ru iminent). Scorul total a permis ncadrarea pacienilor n 4
niveluri de anxietate: nivel minim (07), nivel sczut (815), nivel moderat (1625),
nivel sever (2663). Analiza statistic a fost efectuat cu ajutorul MedCalc Statistical
Software versiunea 15.4 (MedCalc Software bvba, Ostend, Belgium;
https://www.medcalc.org; 2015). Pentru analiza datelor sau utilizat teste statistice de
tipul MannWhitney test i chisquare test. Pentru evaluarea consistenei interne a
chestionarului sa calculat valoarea coeficientului Crobachs Alpha.
Rezultate. Vrsta se coreleaz cu prezena disfunciei temporomandibulare
(p=0.028). Persoanele mai tinere au mai frecvent semne i simptome DTM dect cele
mai n vrst. Mediana vrstei la pacienii cu DTM a fost de 36 ani (28; 52), spre
deosebire de pacienii din grupul martor unde mediana vrstei a fost mai mic [32,
(22.5; 43.5)]. Am identificat o corelaie nalt semnificativ statistic ntre nivelul
anxietii i prezena semnelor i simptomelor disfunciei temporomandibulare
(p<0.001). Valorile BAI nregistrate la pacienii cu DTM au fost semnificativ mai mari
[mediana20 (11;30)], comparativ cu valorile obinute la pacienii din grupul martor
[mediana 10, (6;18)]. Sexul feminin a fost preponderent n cadrul pacienilor cu semne
i simptome DTM (n=22, 59.5%), corelaia nefiind ns validat statistic (p=1). Dintre
pacienii examinai 15 (19%) au provenit din mediul rural iar 64 (81%) din mediul
urban. ase pacieni (16.2%) din mediul rural au prezentat cu simptomatologie DTM.
Mediul de provenien nu influeneaz apariia semnelor i simptomelor DTM. Pentru
pacienii cu domiciliul n mediul rural sa observat o distribuie uniform a nivelelor de
anxietate, spre deosebire de cei din mediul urban unde preponderent sau nregistrat
niveluri sczute i moderate ale anxietii. Nu sa evideniat o legtur semnificativ
statistic ntre mediul de provenien (urban sau rural) i nivelul de anxietate
(p=0.515).

Andrea Maria Chisnoiu (Kurtinecz)

10

Concluzii. Stresul psihologic este factor etiologic al disfunciei temporo

mandibulare. n cele mai multe cazuri factorii psihologici se asociaz cu cei
fiziologici/funcionali, de aceea este important identificarea gradului de implicare a
fiecruia, care va permite elaborarea schemei terapeutice optime n ameliorarea i
eliminarea simptomelor invalidante ale disfunciei temporomandibulare.
Concluzii generale

Evaluarea corect a factorilor etiologici implicai n apariia disfunciei temporo

mandibulare este un element important de luat n considerare n plani icarea
terapeutica . Trei cauze majore au fost propuse ca i factori etiologici ai disfunciei
temporomandibulare: stresul biomecanic, hormonii feminini i factorii psihologici.
Rezultatele studiului experimental au artat reduceri uniforme i similare ale grosimii
discului articular pentru loturile unde sau aplicat factori etiologici individuali (stres
biomecanic, hormoni estrogeni, stres emoional), modificrie fiind mult mai severe
atunci cnd sau aplicat factori n asociere.
Fenomenele de stres oxidativ sunt implicate n patologia ATM, cu consecine
asupra funcionalitii articulare. Evaluarea plasmatic a markerilor stresului oxidativ
a relevat o cretere a nivelului malondialdehidei (MDA) pentru toate grupurile
experimentale. Concentraia glutationului (GSH) a nregistrat iniial valori similare
pentru grupul martor i grupurile experimentale, sugernd eecul mecanismului de
aprare n prevenirea formrii unui exces de radicali liberi. Totui dup 30 zile pn la
finalul experimentului sau observat o cretere a valorilor GSH pentru toate grupurile
experimentale comparativ cu grupul martor, acest aspect semnificnd efortul
organismului pentru ndeprtarea speciilor de radicali liberi cum ar fi peroxidul de
hidrogen, radicalii superoxid, precum i pentru conservarea proteinelor de membran.
Studiul epidemiologic realizat a confirmat implicarea relaiilor ocluzale
nefuncionale n etiologia disfunciei temporomandibulare ca i factori declanatori
sau perpetuani. Prezena interferenelor sau a contactelor premature poate
determina contracie i durere muscular i/sau la nivelul articulaiei temporo
mandibulare. Anomaliile n anatomia curbei Wilson i interferenele pe traseul dintre
relaia centric i poziia de intercuspidare maxim pot fi considerai factori de risc n
apariia semnelor i simptomelor de disfuncie temporomandibular.
n cadrul ultimului studiu sa stabilit o corelaie semnificativ ntre prezena
simptomatologiei de disfuncie temporomandibular i nivelul anxietii. Patologia
disfuncional temporomandibular a fost mai frecvent la pacienii de sex feminin.
Nivelul anxietii crete o dat cu vrsta. Domiciliul urban sau rural nu a influenat
nivelul anxietii sau prezena semnelor i simptomelor disfunciei temporo
mandibulare.

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Originalitatea i contribuiile inovative ale tezei

Studiile efectuate n cadrul acestei teze de doctorat aduc o contribuie tiini ica
importanta , noutatea iind susinuta de mai multe aspecte. Teza ofera n premiera
prezentarea i nelegerea unei patologii a ca rei adresabilitate este n continua cretere
la noi n ara . Evaluarea modificrilor articulare pe model animal sub aciunea mai
multor factori etiologici (individual sau n asociere) reprezint o premier naional,
acesta fiind primul studiu raportat pn la momentul actual. Originalitatea tezei este
susinut i de cercetarea realizat n cardul celui deal doilea studiu n cadrul cruia s
a urmrit evoluia valorilor plasmatice ale markerilor stresului oxidativ sub aciunea
unor factori etiologici ai disfunciei temporomandibulare (individual sau n asociere).
Totodat n cardul tezei sa realizat un studiu epidemiologic care ofer o imagine de
ansamblu asupra caracteristicilor ocluzale i corelaia acestora cu apariia semnelor i
simptomelor disfunciei temporomandibulare. Dimensiunea semnificativ a
eantionului utilizat a permis formularea unor concluzii importante privind implicarea
interferenelor sau a contactelor premature n apariia contraciei i durerii musculare
i/sau la nivelul articulaiei temporomandibulare. Ultimul studiu realizat a urmrit
gradul de implicare al stresului emoional n etiologia disfunciei temporo
mandibulare. Chestionarul folosit pentru determinarea nivelului de anxietate (utilizat
pentru prima dat n cadrul unui studiu naional asupra DTM) a fost validat prin
determinarea coeficientului de consisten intern care a confirmat nivelul crescut de
ncredere al chestionarului.

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Andrea Maria Chisnoiu (Kurtinecz)

UNIVERSITATEA DE MEDICIN I FARMACIE IULIU HAIEGANUCLUJ-NAPOCA

PhD THESIS SUMMARY

Research on etiologic factors

involved in temporomandibular joint disorder

PhD Student Andrea Maria Kurtinecz (Chisnoiu)

PhD Advisor Prof. dr. Sever Popa

CLUJ-NAPOCA 2015


Cercetri privind factorii etiologici implicai n disfuncia temporomandibular

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CONTENTS

INTRODUCTION

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THE CURRENT STATE OF KNOWLEDGE

1. Definition, terminology
2. Anatomy of temporomandibular joint

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2.1. Temporomandibular joint uniqueness

3. Epidemiology of temporo mandibular joint disorder

4. Signs and symptoms of temporo mandibular joint disorder
4.1. Muscular pain
4.2. Articular pain
4.3. Limitation of mandibular movements
4.4 Articular sounds

5. Etiology of temporo mandibular joint disorder

5.1. Occlusal factors
5.2. Psychological factors
5.3. Hormonal factors
5.4. Macrotrauma
5.5. Parafunctions
5.6. Ligament hyperlaxity and hypermobility
5.7. Hereditary factors
5.8. Orthodontic treatment

6. Oxidative stress and temporomandibular joint disorder

PERSONAL CONTRIBUTION
1. Working hypothesis/Objectives
2. 1st study Histological evaluation and quantification of
temporomandibular articular changes under the action of three
etiologic factors of temporomandibular joint disorder
2.1. Introduction
2.2. Working hypothesis
2.3. Material and methods
2.4. Results
2.5. Discussions
2.6. Conclusions

3. 2nd study Oxidative stress implication in temporomandibular

joint disorder development
3.1. Introduction
3.2. Working hypothesis
3.3. Material and methods

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3.4. Results
3.5. Discussions
3.6. Conclusions

4. 3rd study Prospective epidemiologic study regarding the

frequency of temporomandibular joint disorder signs and
symptoms in an population group
4.1. Introduction
4.2. Working hypothesis
4.3. Material and methods
4.4. Results
4.5. Discussions
4.6. Conclusions

5. 4th study Psychoemotional status evaluation in

temporomandibular joint disorder patients
5.1. Introduction
5.2. Working hypothesis
5.3. Material and methods
5.4. Results
5.5. Discussions
5.6. Conclusions

6. General conclusions
7. Originality and innovative contributions of the thesis

REFERENCES

KEYWORDS: temporomandibular joint disorder, biomechanical stress, emotional
stress, estrogen hormones, free radicals, occlusal analysis, anxiety.

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INTRODUCTION
The thesis deals with a current issue in the field of dentistry, offering a review of
the etiologic factors involved in the occurrence of temporomandibular dysfunction and
presenting the results from the research studies conducted in this area.
The thesis is divided into two main parts. The first part highlights the current
state of knowledge of the proposed topic for debate. In the second part of the thesis
presents experimental studies conducted by virtue of the acquired theoretical
information.
The theoretical research of the thesis current state of knowledge, contains 6
chapters dealing with issues related to: definition and terminology used in temporo
mandibular joint disorder and details of anatomy and uniqueness of temporo
mandibular joint, aspects of epidemiology and clinical signs in this pathology. Current
data are presented in detail on the etiological factors involved in the onset, persistent
and/or worsening temporomandibular dysfunctional pathology, the mechanisms and
oxidative stress implication in the pathophysiology of this disorder.
The doctoral research aimed at analyzing in detail and assessing the influence of
three etiological factors (biomechanical stress, estrogen hormones and emotional
stress) on the functionality of temporomandibular joint and neighboring structures,
mechanism of action and their contribution to the emergence of symptoms of temporo
mandibular joint disorder.

PERSONAL CONTRIBUTION
Working hypothesis. The objectives of this thesis consist in: (1) articular
changes evaluation in laboratory animals under the action of three different etiologic
factors of temporomandibular joint disorder, (2) analysis of oxidative stress
mechanism implication in temporomandibular joint disorder pathogenesis in
laboratory animals, (3) study of the relation of occlusal, muscular articular
characteristics and presence of temporomandibular joint disorder signs and
symptoms, (4) anxiety level evaluation in temporomandibular joint disorder patients.

1st study. Histological evaluation and quantification of temporo

mandibular articular changes by the action of three etiologic factors of
temporomandibular joint disorder

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Andrea Maria Chisnoiu (Kurtinecz)

Objective. This animal model study aims at histological of joint damage analysis
arising after applying TMD etiological factors, quantification and identification of the
involvement of each factor in the emergence and development of this condition.
Material and method. We designed an experimental animal model study
conducted within Biobase of Department of Physiology of the "Iuliu Haieganu"
University of Medicine and Pharmacy in ClujNapoca. We included in the study 60
white Wistar female rats, randomly divided into six groups (n = 10). The first group
was the control where no etiologic factor was applied. Three groups were exposed to
an individual etiologic factor of TMD as follows: group two to biomechanical stress
(SB) group three to overdose of estrogen hormones (HE) and group four to emotional
stress (SE). Two groups were exposed to a combination of two such factors: group five
to biomechanical stress and overdose of estrogen (SBHE) and group six to
biomechanical and emotional stress (SBSE). The experiment was conducted over a
period of 60 days. After sacrifice of the animals, TMJ was removed en bloc and after
their processing histological samples with hematoxylin eosin staining were obtained.
Histopathological samples (10 sections by each TMJ) were examined and
photographed using a calibrated processing system. Representative sections from each
analyzed area were identified and photographed with objectives 4x, 10x, 20x and 40x.
Histopathological examination followed the changes in the mandibular condyle,
articular disc, temporal bone and synovial tissue.
Results. A comparative analysis of the results of the measurements obtained
from mandibular condylar cartilage showed that in all five groups where a factors has
been applied, regardless of its nature, the average values were lower than those
obtained with the control group (134.24 m). Interestingly mandibular condylar
cartilage thickness has decreased fairly evenly, fairly close to the average values
(between 119.56 and 126.75 m) for the groups 2 (SB) 3 (HE), 4 ( HE), and 5 (SBHE).
The most significant changes were reported for group 6 (SBSE) in which the mean
cartilage thickness (92.39 m) was the lowest. Regarding the histopathological
analysis of the changes observed in the rat TMJ for the six experimental groups in
group SB at the end of the experimental period in the condyle, especially in anterios
and central areas (corresponding to the loading surface of the joint). Multifocal loss of
chondrocytes was observed and condrocyte nests formation all layers of cartilage was
noticed. At the TMJ level, for the animals in the EH group, in the central and anterior
areas of the condyle a hypocellular aspect was recorded with a pale aspect and zonal
loss of chondrocyte. In the same areas of the cartilage, multifocal development of
chondrocyte nests was observed. All modifications in the BSEH group were observed
in the mandibular condyle area. As in the other groups, the most important lesions
appeared in the anterior and central zones: pale hypocellular aspect, multifocal
chondrocyte nests. In the ES group the chondrocyte loss was more important in the
central zone of condyle cartilage, villous proliferations in synovium and reduced
inflammatory cells were observed. The most severe modifications were observed in

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the BSES group. The same types of changes with similar distribution were recorded,
but their intensity was significantly higher: pale hypocellular aspect, chondrocyte
nests development, multifocal cell loss. The articular disc had a hypocellular aspect
and reduced central thickness.
Conclusions. All presumptive etiologic factors included in our study
determinate articular modifications (confirmed by histomophometric results). The
association of etiologic factors significantly increased the severity of articular lesions.
Emotional associated with biomechanical stress have the most destructive potential
for inducing TMD.

2nd study. Temporomandibular joint disorder and plasmatic

oxidative stress markers in rats
Objectives. This investigation sought to determine whether the appliance of
etiologic factors for TMD was associated with modified values of OS as measured by
biomarkers in plasma. The null hypothesis is that there is no relationship between the
presence of certain etiologic factor and plasmatic biomarkers of OS. Thus, a case
control study design was used to compare OS biomarkers (Malondialdehide MDA and
Glutathione GSH) in plasma from Wistar rats with different etiologic factors compared
to nontemporomandibular joint controls.
Material and methods. We designed an experimental animal model study
conducted within Biobase of Department of Physiology of the "Iuliu Haieganu"
University of Medicine and Pharmacy in ClujNapoca. We included in the study 60
white Wistar female rats, randomly divided into six groups (n = 10). The first group
was the control where no etiologic factor was applied. Three groups were exposed to
an individual etiologic factor of TMD as follows: group two to biomechanical stress
(SB) group three to overdose of estrogen hormones (HE) and group four to emotional
stress (SE). Two groups were exposed to a combinations of two such factors: group
five to biomechanical stress and overdose of estrogen (SBHE) and group six to
biomechanical and emotional stress (SBSE). The experiment was conducted over a
period of 60 days. Blood samples were taken after 30 days and 60 days of experiment.
Malondialdehide (MDA) and glutathione (GSH) levels in plasma were evaluated.
Statistical analysis was performed using the MedCalc Statistical Software version
15.2.1 (MedCalc Software bvba, Ostend, Belgium). The quantitative variables were
tested for normality of the distribution using the KolmogorovSmirnov test, and were
characterized by mean and standard deviation. The differences between the groups
and measurements, regarding the quantitative variables were tested using the
repeated measures ANOVA test.
Results. Plasmatic MDA levels at 30 days for BS group (7.210.66 pg./ml) were
significantly higher than the control group (3.400.32 pg./ml; p0.001). The values
continued to increase until the end of the experiment (60 days; 7.660.90 pg./ml;

18

Andrea Maria Chisnoiu (Kurtinecz)

p0.001). In the EH group MDA showed statistical significantly higher levels both at 30
and 60 days comparing to the control group. Increased values of MDA were also
recorded for the ES group at the end of experimental period (7.931.58 pg./ml;
p0.001). In the BSEH group MDA was significantly higher than the control group both
at 30 days (p0.001) and 60 days (p0.001). The most important modi ications in MDA
levels were recorded for the fifth group (BSES) where values increased significantly
from 30 days to 60 days plasma analysis (p=0.003). Although there are no statistical
differences between the groups at 30 days or at 60 days, the MDA values increased
significantly more for BSES group comparing to the BS group (p=0.020). No statistical
differences were recorded in GSH plasmatic levels between control and experimental
groups at 30 days analysis. At 60 days GSH plasmatic evaluation recorded higher
values than control for all experimental groups. The differences were statistically
significant for BSEH group (p0.001) and BSES group (p=0.017).
Conclusions. Our findings in this rat experimental model clearly indicate that
biomechanical stress, estrogen hormones and emotional stress have an impact on
oxidative stress development and consequently on the functionality of the
temporomandibular joint in rats. Moreover combined actions of these factors augment
the OS phenomena on temporomandibular joint in rats.

3rd study. Epidemiologic prospective study on the frequency of

signs and symptoms of temporomandibular joint disorder in a
population group.
Objective. This study aimed at assessing occlusal characteristics within a
population group and to analyze their correlation with muscular and articular signs
and symptoms in the orofacial region corresponding to temporomandibular joint
disorder. The multivariate analysis in this study evaluated parameters of static
occlusion and few eccentric movements, representing the traditional approach of
examining the occlusal relationships.
Material and methods. The examiners, trained according to the specification of
Research Diagnostic Criteria for TemporoMandibular Joint Disorder, collected the
clinical data using measurements and clinical examination charts structured in order
to determine occlusal, muscular, and TMJ status of subjects included in the study. The
following elements were analyzed: mandibular movements, temporomandibular joint,
masticatory muscles, static and dynamic occlusal relations. Statistical analysis was
performed using the MedCalc Statistical Software version 15.2.1 (MedCalc Software
bvba, Ostend, Belgium). Nominal data was characterized by frequency and percent.
Quantitative data was expressed as mean and standard deviation. The following tests
were used when appropriate: chisquare test, Student ttest. Binary logistic regression
was used for multivariate analysis.

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Results. Two hundred thirteen fourth year dental medicine students were
included in the study, mean age of 23 4.24 years, 124 female (58.2%) and 89 male
(41.8%). Mean age of the subjects with muscular pain in orofacial area was 23 years
(p=0.01) and for joint clicks was 22.9 years, (p=0.006). Pain in the orofacial muscles
was more frequent in females (n=40 (32%)), comparing with 16 males that presented
these symptoms (p=0.03). Bruxism was diagnosed in 39 patients, more common in
women (n=22 (56.4%) than men (n=17 (43.6%)). The joint pain was strongly
correlated with the presence of TMJ clicks on the same side (p<0.001).). TMJ pain was
accompanied by the trapezius muscle contracture on the same side, having an intensity
between 3 and 5 (on a 010 scale, p=0.01), medial pterygoid muscle on the same side
(p=0.001), with the contraction of SCM ipsilateral (p=0.003), correlations being
statistically significant. The patients with long centric present more often joint clicks
than those with pointcentric (p=0.45, OR 3.771, CI 95% (1.03113.793). Masticatory
muscles are influenced by the characteristics of the Wilson curve. Thus changes in the
monomaxillary normal occlusal architecture, in the side, in frontal plane (Wilson curve
accentuated, reversed or horizontal) can cause significant contractions in medial
pterygoid muscles, lateral pretygoid muscles, SCM and milohyoid muscles (p=0.014,
OR 17.285, CI 95% (1.774168.454)).The interferences on the path between Centric
Relation and Maximum Intercuspal position have as a consequence, contractions of the
masticatory muscles, and patients with long centric present a higher risk for temporo
mandibular joint disorder development(p=0.038, OR 3.089, CI 95% (1.066 8.954)).
Concluzii. Abnormal occlusal relations represent etiologic factors for temporo
mandibular joint disorder being involved in the onset, perpetuation and/or
aggravation of this condition. Interferences on the path between centric relation and
maximum may determine contraction and pain in masticatory muscles, but also in
temporomandibular joint. Nonfunctional Wilson curve also represent a risk factor in
the appearance of temporomandibular joint disorder signs and symptoms.

4th study. Psychoemotional status evaluation in temporo

mandibular joint disorder patients
Objectives. The objective of this study was to assess the level of emotional
stress in patients with temporomandibular joint disorder compared with those in the
control group and establish a possible correlation between stress levels and the onset
of pathology in the temporomandibular joint disorder.
Material and methods. A prospective, observational study was realized.
Seventynine patients (DTM group n = 37, control group n = 42) addressing the
Prosthodontics Department of our University were included in the study.
Temporomandibular joint disorder diagnosis was based on research diagnostic criteria
for temporomandibular dysfunction (RDC/TMD). In order to analyze the level of
emotional stress, evaluation questionnaires containing Beck Anxiety Index (BAI) were
used. The questionnaire consists of 21 (each having a 04 score) items regarding the

Andrea Maria Chisnoiu (Kurtinecz)

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patient's emotional status expressed through common anxiety symptoms (tingling,

weakness, sweating ambient temperature undue fear of imminent harm). Total score
allowed the classification of patients into 4 levels of anxiety: minimum (07), low (8
15), moderate (1625) and severe (2663). Statistical analysis was performed using the
MedCalc Statistical Software version 15.2.1 (MedCalc Software bvba, Ostend, Belgium).
For data analysis MannWhitney test and chisquare test were used. For the evaluation
of the questionnaire internal consistency, Crobachs Alpha coefficient was used.
Results. A significant correlation was identified between age and presence of
temporomandibular joint disorder (p=0.028). In younger subjects signs and symptoms
of temporomandibular joint disorder were more frequent than in older patients. The
presence and level of anxiety is linked to the signs and symptoms of anxiety and
temporomandibular joint disorder (p<0.001). BAI values obtained in patients with
temporomandibular joint disorder were significantly higher [median 20 (11; 30)]
compared with values obtained from patients in the control group [median 10 (6; 18)].
The area of origin (rural or urban) does not influence the occurrence of
temporomandibular joint disorder signs and symptoms (p=0.763). The analysis of
interrelation between anxiety and age showed no statistical significance (p=0.171). Of
all the patients included in the study, most had a low level of anxiety (n=18, 38.3%),
moderate (n=10, 21.3%) or severe (n=10, 21.3%) and to a lesser degree, the minimum
anxiety level (n=9, 19.1%). For patients living in rural areas an even distribution of
levels of anxiety was noticed, unlike those in urban areas where mostly low or
moderate levels of anxiety were encountered. In order to assess the usefulness of the
questionnaire applied (Beck Anxiety Index), internal consistency coefficient was
determined. Crobach's Alpha value was 0.915, thus confirming the high level of
confidence of the questionnaire.
Conclusions. Psychological stress can be considered an etiologic factor of
temporomandibular joint disorder. In most cases the psychological factors are
associated with physiological/functional factors, so it is important to identify the
degree of involvement of each, which will enable optimal treatment scheme for the
improvement and elimination of temporomandibular joint disorder debilitating
symptoms.

General conclusions
The correct evaluation of etiologic factors involved in the occurrence of
temporomandibular disorder is an important element to consider in therapy planning.
Three major factors were suggested as etiologic for temporomandibular disorder:
biomechanical stress, female hormones and psychological factors. The results our
experimental studyshowed similar and uniform reductions of articular disc thickness
when individual etiological factors (biomechanical stress, estrogen, emotional stress)
were applied. The modification are more important when associated factors were
applied.

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The oxidative stress phenomena is involved in the pathology of TMJ, with

consequences on his functionality. Plasmatic oxidative stress markers evaluation
revealed an increase level for malondialdehyde (MDA) in all experimental groups. The
concentration of glutathione (GSH) originally recorded similar values for the control
and experimental groups, suggesting the failure of the defense mechanism to prevent
the formation of excess free radicals. However, from 30 days until the end of the
experiment, an increase of GSH levels for all experimental groups compared to the
control group was observed, meaning the body effort for free radicals species
removing such as hydrogen peroxide, superoxide radicals, as well as preservation of
membrane proteins.
The epidemiological studiy confirmed the involvement of nonfunctional
occlusal relationships in the onset and perpetaution of temporomandibular
dysfunction. Interferences can cause muscular contraction and/or articular pain.
Wilson curve anatomic anomalies and interference on the path from centric relation to
maximum intercuspatione can be considered risk factors for the appearance of
temporomandibular dysfunction signs and symptoms.
In the latest study has been established a significant correlation between the
presence of symptoms of temporomandibular dysfunction and anxiety level.
Dysfunctional temporomandibular pathology was more common in female patients.
The level of anxiety increases with age. Urban or rural residence did not affect the
presence of signs and symptoms of anxiety or temporomandibular disorder.

Originality and innovative contributions of the thesis

The research in this thesis has an important scientific contribution, the novelty
being supported by several aspects. First, the thesis offers a presentation and
understanding of a disease whose target audience is growing in our country. The
evaluation of joint modifications in an animal model under the action of several
etiologic factors (individually or in combination) represents a national premiere, being
the first trial reported to date. Originality of the thesis is also supported by the
research conducted in the second study in which the evolution of plasma levels of
oxidative stress markers under the action of etiological factors temporomandibular
dysfunction (individually or in combination) was analyzed. The third study presented
in the thesis is an epidemiologic one, giving an overview of occlusal characteristics and
their correlation with signs and symptoms temporomandibular disorder. Important
dimension of sample size allowed drawing significant conclusions regarding the
involvement of interferences in contraction and pain of masticatory muscles and / or
temporomandibular joint. The last research chapter evaluated the involvement of
emotional stress in the etiology of temporomandibular dysfunction. Validation of
anxiety questionnaire (used for the first time in a national study on TMD) was
performed by determining internal consistency coefficient. It confirmed increased
confidence of the questionnaire.