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Age effect on orthodontic tooth movement rate and the composition of gingival crevicular fluidEinfluss des Alters auf die Geschwindigkeit der kieferorthopädischen Zahnbewegung und die Zusammensetzung des gingivalen Sulkusfluids: A literature reviewEin Literaturreview

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Purpose To evaluate and form a comprehensive understanding of the effect of patient age on bone remodeling and consequently on the rate of orthodontic tooth movement (OTM). Methods A systematic search in PubMed and Embase from 1990 to December 2017 was performed and completed by a hand search. Prospective clinical trials which investigated the rate of OTM and/or studies assessing age-related changes in the composition of gingival crevicular fluid (GCF) in older compared to younger study groups were included. Study selection, data extraction and risk of bias were assessed by two authors. Results Eight studies fulfilled the inclusion criteria. Among them, four evaluated the rate of OTM and six investigated mediators in the GCF (prostaglandin E2, interleukin [IL]-1β, IL‑6, IL‑1 receptor antagonist, receptor activator of nuclear factor kappa‑Β ligand, osteoprotegerin, granulocyte–macrophage colony-stimulating factor, pentraxin 3). Patient age ranged between 16 and 43 years for older and <16 years for younger groups. In most of the studies, the younger patients showed faster OTM in the first phase of treatment and more pronounced cytokine levels. Older patients had a delayed reaction to orthodontic forces. Conclusion The small number of included studies and large heterogeneity in study design give limited clinical evidence that the older patients are less responsive to orthodontic force in comparison to younger patients. The initial cellular response to orthodontic force is expected to be delayed in older patients. Control intervals during orthodontic treatment should be adjusted to the individual’s treatment response.
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1 23
Journal of Orofacial Orthopedics /
Fortschritte der Kieferorthopädie
Official Journal of the German
Orthodontic Society / Offizielle
Zeitschrift der Deutschen Gesellschaft
für Kieferorthopädie
ISSN 1434-5293
J Orofac Orthop
DOI 10.1007/s00056-019-00206-5
Age effect on orthodontic tooth movement
rate and the composition of gingival
crevicular fluid
Anne Schubert, Fabian Jäger, Jaap
C.Maltha & Theodosia N.Bartzela
1 23
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SYSTEMATIC REVIEWS AND META-ANALYSES
https://doi.org/10.1007/s00056-019-00206-5
JOrofacOrthop
Age effect on orthodontic tooth movement rate and the composition
of gingival crevicular fluid
A literature review
Anne Schubert1· Fabian Jäger1· Jaap C. Maltha2· Theodosia N. Bartzela3
Received: 2 November 2018 / Accepted: 20 October 2019
© Springer Medizin Verlag GmbH, ein Teil von Springer Nature 2019
Abstract
Purpose To evaluate and form a comprehensive understanding of the effect of patient age on bone remodeling and
consequently on the rate of orthodontic tooth movement (OTM).
Methods A systematic search in PubMed and Embase from 1990 to December 2017 was performed and completed by
a hand search. Prospective clinical trials which investigated the rate of OTM and/or studies assessing age-related changes
in the composition of gingival crevicular fluid (GCF) in older compared to younger study groups were included. Study
selection, data extraction and risk of bias were assessed by two authors.
Results Eight studies fulfilled the inclusion criteria. Among them, four evaluated the rate of OTM and six investigated
mediators in the GCF (prostaglandin E2, interleukin [IL]-1β, IL-6, IL-1 receptor antagonist, receptor activator of nuclear
factor kappa-Βligand, osteoprotegerin, granulocyte–macrophage colony-stimulating factor, pentraxin 3). Patient age ranged
between 16 and 43 years for older and <16 years for younger groups. In most of the studies, the younger patients showed
faster OTM in the first phase of treatment and more pronounced cytokine levels. Older patients had a delayed reaction to
orthodontic forces.
Conclusion The small number of included studies and large heterogeneity in study design give limited clinical evidence
that the older patients are less responsive to orthodontic force in comparison to younger patients. The initial cellular
response to orthodontic force is expected to be delayed in older patients. Control intervals during orthodontic treatment
should be adjusted to the individual’s treatment response.
Keywords Adults · Humans · Orthodontic force · Periodontal ligament · Interleukin · Cytokines
Einuss des Alters auf die Geschwindigkeit der kieferorthopädischen Zahnbewegung und die
Zusammensetzung des gingivalen Sulkusuids
Ein Literaturreview
Zusammenfassung
Ziel Das Ziel dieses Reviews war die Einschätzung und Entwicklung eines umfassenden Verständnisses des Einflusses
des Patientenalters auf den Knochenumbau und folglich auf die Geschwindigkeit der kieferorthopädischen Zahnbewegung
(OTM).
Dr. med. dent. Theodosia N. Bartzela, MSc, PhD
theodosia.bartzela@charite.de
1Private practice, Berlin, Germany
2Department of Orthodontics and Craniofacial Biology,
Radboud University Medical Center Nijmegen,
6500 HB Nijmegen, The Netherlands
3Department of Orthodontics, Dentofacial Orthopedics
and Pedodontics, Charité Centrum 3, Charité –
Universitätsmedizin Berlin, Aßmannshauser
Str. 4–6, 14197 Berlin, Germany
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Methoden Es wurde eine systematische Suche in PubMed und Embase im Zeitraum von 1990 bis Dezember 2017
durchgeführt, ergänzt durch eine Handsuche. Prospektive klinische Studien zum Vergleich der Geschwindigkeit der OTM
und/oder Studien zu altersabhängigen Veränderungen in der Zusammensetzung des gingivalen Sulkusfluids (GCF) bei
älteren und jüngeren Probandengruppen wurden inkludiert. Die Studienauswahl, Datenextraktion und Bewertung des
Risikos für Bias erfolgte durch 2 der Studienautoren.
Ergebnisse Acht Studien erfüllten die Einschlusskriterien. Vier von ihnen ermittelten die Geschwindigkeit der kiefer-
orthopädischen Zahnbewegung und 6 untersuchten Mediatoren im GCF (Prostaglandin E2, Interleukin [IL]-1β,IL-6,
IL-1-Rezeptorantagonist, „receptor activator of nuclear factor κ-Βligand“, Osteoprotegerin, „granulocyte-macrophage co-
lony-stimulating factor“, Pentraxin 3). Die ältere Probandengruppe war 1643 Jahre alt, die jüngeren Patienten wiesen ein
Alter von <16 Jahren auf. Bei den jüngeren Patienten wurden in der Mehrzahl der Studien eine initial schnellere Zahnbe-
wegung und höhere Zytokinspiegel festgestellt. Die älteren Probanden zeigten eine verzögerte Reaktion auf orthodontische
Kräfte.
Schlussfolgerung Aufgrund der geringen Studienzahl und der Heterogenität der Studiendesigns ist die klinische Evidenz
für eine verminderte Reaktion auf kieferorthopädische Kräfte bei älteren im Vergleich zu jüngeren Patienten eingeschränkt.
Die initialen zellulären Reaktionen scheinen bei älteren Patienten verzögert abzulaufen. Kontrollintervalle während der
kieferorthopädischen Behandlung sollten an das individuelle Reaktionsverhalten angepasst werden.
Schlüsselwörter Erwachsene · Menschen · Kieferorthopädische Kraft · Periodontalligament · Interleukin · Zytokine
Introduction
Increased esthetic awareness [1] and barely visible treat-
ment options are contributing to the increasing number of
adult patients seeking orthodontic treatment during the last
few decades [2]. Patients seek optimal esthetic outcome in
the shortest treatment period possible.
Adult patients showed decreased bone turnover rates,
which was related to limited numbers of progenitor cells [3,
4], reduced blood vessel forming capacity [5,6], and fibrob-
last density [7]. The alveolar walls are mainly covered by
inactive osteoblasts, the so-called lining cells, whereas the
number of active osteoblasts and osteoclasts are markedly
reduced [4,8] and structural changes of osteoblasts have
been described [4]. The bone is becoming gradually denser
[9], while the cortical bone is diminished [10]andtheHow-
ship’s lacunae are increased [4].
In the periodontal ligament (PDL), a comparable decline
in cellular and metabolic activity with increasing age has
been described [7,8,1118]. Sharpey’s fibers are decreased
with irregular insertion into bone [17], while other principal
fibers might become thicker with increasing age [19].
All abovementioned findings suggest a decreased respon-
siveness of the aged dentoalveolar complex, compromis-
ing bone formation and resorption during orthodontic tooth
movement (OTM) [4,20].
Since orthodontically induced bone remodeling is related
to the expression of various inflammatory mediators, extra-
cellular matrix components and tissue-degrading enzymes,
their presence in gingival crevicular fluid (GCF) is supposed
to be related to the rate of OTM [21,22]. Some proinflam-
matory cytokines show a higher expression in aged PDL
subsequent to mechanical stress [2325]. The knowledge
we have with respect to the effect of age on the rate of OTM
is based mainly on animal studies [9,2632]. However, it
is still unclear which molecules can specifically predict the
rate of OTM [3].
To the best of our knowledge, up to now, no attempt has
been made to systematically evaluate the existing prospec-
tive clinical trials (PCT) on the effect of age on the rate of
OTM. Hence, the objective of this literature review was to
form a comprehensive understanding of (1) The effect of
age on the rate of OTM, and (2) the age-dependent changes
in the composition of GCF going along with alveolar bone
remodeling.
Methods
Protocol and registration
This systematic review was performed according to the Pre-
ferred Reporting Items for Systematic Reviews and Meta-
Analysis (PRISMA) statement [33]. The investigation was
registered with the number CRD42016037469in the PROS-
PERO database (http://www.crd.york.ac.uk/PROSPERO).
Eligibility criteria
The Population Intervention Comparison Outcome (PI-
COS) framework was used to define the inclusion criteria
and the search strategy:
Population: Healthy children or adolescents, adults and
elderly, who underwent orthodontic treatment. Included
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Age effect on orthodontic tooth movement rate and the composition of gingival crevicular fluid
Tab le 1 Embase Clas-
sic + Embase search strategy
Tab. 1 Suchstrategie für Em-
base Classic + Embase
Database searched: Embase Classic + Embase
Data Coverage: 1990–December 2017
1 Orthodontics/ or (orthodontic*).tw
2 (age* or aging or matur* or adult* or juvenil* or adolescen* or child* or
grow* or young* or elder*).tw
3 Orthodontic tooth movement/ or (movement* or move or moving or
velocity or orthodontic force*).ti
4 (cytokin* or receptor* or matrix metallop* or crevicular fluid*).ti
5 #1 and #2 and (#3 or #4)
6 Limit #5 to (human and yr=001990 -201700 )
studies compared the two different age groups of interest
and not reporting on young or old individuals only.
Intervention: OTM induced by fixed appliances.
Comparison: Split-mouth design or baseline characteris-
tics versus posttreatment characteristics.
Outcome:
The rate of tooth movement, measured by caliper or
digital superimposition and/or
Changes in the composition of the GCF, especially in
the level of cytokines.
Study types: Prospective randomized or nonrandomized
clinical trials.
Studies that concomitantly investigated the effect of any
medication on the rate of OTM were excluded. Use of anti-
inflammatory drugs or antibiotic therapy within the last
6 months of study initiation, systemic or congenital dis-
eases, smoking habit, and any form of gingival inflamma-
tion and/or periodontal disease were the exclusion criteria.
Databases and search strategy
A systematic search from 1990 to December 2017 was per-
formed in two main databases: PubMed, Embase Classic
and Embase with the assistance of a senior librarian. No
language restrictions criteria were considered. The search
strategy covers terms focusing on:
Tab le 2 PubMed search strat-
egy
Tab. 2 Suchstrategie für
PubMed
Database searched: PubMed
Data Coverage: 1990–December 2017
1 Orthodontic*[tiab]
2 ((age[tiab] OR aging[tiab] OR matur*[tiab] OR adult*[tiab] OR juvenil*[tiab] OR
adolescen*[tiab] OR child[tiab] OR children[tiab] OR grow*[tiab] OR young*[tiab]
OR elder*[tiab])
3 (movement*[ti] OR move[ti] OR moving[ti] OR velocity[ti] OR orthodontic
force*[ti])
4 (cytokin*[ti] OR receptor*[ti] OR matrix metallop*[ti] OR crevicular fluid*[ti])
5 #1 AND #2 AND (#3 OR #4)
6 #5 AND (001990/01/0100[PDAT] : 002016/12/3100 [PDAT]) AND 00 humans00 [MeSH
Ter ms] )
The population of interest, meaning younger and older
individuals. Included studies compared the two different
age groups of interest and did not report on young or old
individuals only
OTM induced by fixed appliances, force application and
rate of OTM
Biochemical mediators of the GCF and
Humans and clinical trials.
The literature search strategies are presented in Table 1
forEmbaseClassicandEmbase data search and in Table 2
for PubMed. References of the retrieved articles were pe-
rused in order to identify additional relevant publications.
Selection process
First, two authors (AS, TB) searched the databases inde-
pendently and reviewed titles and available abstracts after
duplicates removal and hand search. Full text reading ver-
ified the eligibility of the included articles. In case of dis-
agreement, consensus was reached through discussion. All
included articles were based on findings in younger and
older groups of humans and were separated into studies
that evaluated the rate of OTM and studies that evaluated
the composition of GCF.
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Fig. 1 Flow diagram illustrating
the systematic selection process
according to the Preferred Re-
porting Items for Systematic
Reviews and Meta-Analysis
(PRISMA) statement [33]
Abb. 1 Flussdiagramm zum
Prozess der systematischen Lite-
raturauswahl entsprechend den
PRISMA(Preferred Reporting
Items for Systematic Reviews
and Meta-Analysis)-Vorgaben
[33]
Records identified through database
searching
Embase Classic + Embase=468,
PubMed=313(n = 781)
ScreeningIncluded Eligibility Identification
Additional records identified
through hand search
(n = 2)
Records after duplicates removed
(n = 568+2)
Records screened
(n = 570)
Records excluded (n = 555)
Reason: Did not evaluate the
effect of age on OTM
Full-text articles assessed
for eligibility
(n = 15)
Full-text articles excluded (n = 7)
Reasons:
1. Did not evaluate the rate of
OTM (n = 6);
2. The same study group was used
twice (n = 1)
Studies included in
qualitative synthesis
(n = 8)
Studies included in
quantitative synthesis
(meta-analysis)
(n = 0)
Data collection process and data items
Two authors (AS, TB) extracted the data independently fol-
lowing a piloted form. The variables of data sought were
the following:
Participant characteristics: Number of patients in the
younger and older study groups, sex distribution, age of
included patients (mean age± standard deviation or age
range), patient’s inclusion criteria and health status, oral
hygiene regime, periodontal screening, tooth selection
for the OTM evaluation, type of control.
Study characteristics: Mode of investigation, mechanics
and nature of force application, force level, force reac-
tivation, type of tooth movement, observation intervals,
and total duration of force application, side of GCF col-
lection and process, rate of tooth movement and evalua-
tion of level of studied mediators.
Assessment of risk of bias
The selected studies were screened for bias according to
the Cochrane Collaboration’s tool for assessing risk of bias
[34]. Two authors (AS, TB) independently rated the quality
of the selected studies. Differences in decisions of the two
examiners were discussed until consensus was reached.
Results
Study selection
The database search (Tables 1and 2) provided 781 citations.
After duplicates removal and hand search (n= 2), titles and
abstracts of 555 articles were reviewed. A flow chart illus-
trating the selection process according to PRISMA state-
ment [33] is presented in Fig. 1. Fifteen studies were scru-
tinized for eligibility. Eight studies fulfilled the inclusion
criteria. The studies excluded and the reason for exclusion
are presented in Fig. 1andinTable3. The interexaminer
reliability of the two authors AS and TB for eligibility as-
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Age effect on orthodontic tooth movement rate and the composition of gingival crevicular fluid
Tab le 3 Articles excluded from this review and reason for exclusion
Tab. 3 In das Literaturreview nicht aufgenommene Artikel und Begründung für den Ausschluss
Study Reason for exclusion
Dyer et al. (1991) [3] Force application: Class II elastics
Outcome: increased mandibular molar eruption, increased maxillary molar intrusion, increased maxillary
incisor eruption
Giannopoulou et al. (2016) [56] The same study group was used in the study by Dudic et al. [39]
Grzibovskis et al. (2011) [57] The signaling molecules were evaluated in the interradicular septum in 3 age groups. Pilot study
Grzibovskis et al. (2011) [58] The signaling molecules were evaluated in the interradicular septum in 3 age groups. Preliminary study
Krieger et al. (2013) [59] The buccal segment of the periodontal ligament of the mesiobuccal root of the first maxillary molar was
evaluated for fibroblast density. No orthodontic force was applied
Tanne et al. (1998) [60] Outcome: Tooth mobility and differences in the biomechanical response of periodontium and tooth after
orthodontic tooth application in adolescence and adults
Zhang and Ren (2001) [61]Outcome:PGE
2, IL-6 and GM-CSF in GCF of upper lateral incisor before activation and 24 h after labial
orthodontic force application in both child group and adult group
PGE2prostaglandin E2,IL-6 interleukin-6, GM-CSF granulocyte–macrophage colony-stimulating factor, CSF colony-stimulating factor
sessment of the included publications was measured (Co-
hen’s kappa coefficient0.8543), indicating a high degree
of agreement [35]. Studies investigating the effect of age
on the rate of OTM and those that are focusing on age-
dependent changes of the level of mediators in GCF only
(GCF group) are listed in Tables 4and 5respectively, and
were analyzed separately (authors are listed in alphabetical
order).
Study characteristics
All studies included were identified as clinical controlled
trials. Data on these studies are provided in Tables 4and 5.
Within the eight included studies, two studies evaluated the
rate of OTM and changes in the level of mediators in GCF
[36,37]. Two studies reported on the rate of OTM only
[38,39] and four of them investigated mediators just on the
GCF during OTM [21,4042].
Within the eight included studies (Tables 4and 5), the
sample size of the age groups varied markedly between 4
[36] and 43 subjects [21]. Two studies showed distinct dif-
ferences in the number of participants among their two age
groups [38,39]. The age was presented as a range or as
a mean with standard deviation (Tables 4and 5). In two
studies [36,38], the comparison groups were selected based
on patients’ serial body height and cephalometric measure-
ments. Within the included studies the younger study group
comprised adolescents with an age ranging from 105 [39]
to 16 years [39]. The older study group considered a larger
age interval ranging from 151 [36] to 43 years [39]. In one
of the studies the cutoff age between the groups was justi-
fied by the group distribution [39]. Based on growth obser-
vations from data on body height and cephalometric mea-
surements previously mentioned, the study by Nickel et al.
divided the observation groups into growers (10.1–17 years)
and nongrowers (14.2–30.9 years) and consequently a bi-
ological age overlap was observed [38]. From the selected
studies, some used nontreated contralateral(s) [21,36,37]
or/and opposing teeth [37,41,42] and some other studies
used baseline data as control [37,39,40,42]. Blinding of
participants and personnel was not feasible in any of the
included studies. Selection bias and performance bias were
not assessed due to inconsistencies in the study methods.
Randomization and allocation concealment were not feasi-
ble or influenced by the clinician’s judgment.
Mechanics and force application
Three studies of the OTM group (Table 4) considered max-
illary canine retraction either by vertical loops, which were
activated by NiTi coil-springs [36,38]orbyanelastomeric
chain applied on a 0.018 inch stainless steel wire after level-
ing [37]. In one study, sectional TMA wires were used for
buccal movement of maxillary and mandibular premolars
[39]. Among the studies that reported on changes in GCF,
two of them investigated the mediators in GCF (Table 5)
after tipping labially the maxillary lateral incisors with off-
set bends on a 0.012 inch NiTi archwire [21,40]. One other
retracted canines with a laceback on a 0.012 inch NiTi arch-
wire [42] and one more aligned the maxillary incisors with
a sequence of ascending NiTi archwires [41].
A great diversity of force magnitude was applied, rang-
ing from 18 [36,38] to 360 cN [38]. Two studies [41,42]
did not mention the force magnitude at all. In two studies,
continuous forces were applied by NiTi coil-springs [36,
38] whereas all other studies applied descending [21,37,
40,42] or interrupted forces [39,41]. Two studies reported
reactivation of the appliance after 4 [39] and 6 weeks [41].
The duration of force application exhibited large variations
from as low as 7 days [37] to 8 weeks [39]intheOTM
group and 24 h [21]to20weeks[41] in the GCF group
(Table 2). The frequency of GCF collection ranged from 2
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Tab le 4 Overview of studies evaluating the rate of tooth movement
Tab. 4 Studienübersicht zur Geschwindigkeit kieferorthopädischer Zahnbewegung
Study Design Younger group
Size
[age range]
(year(s))
(M/F)
Older group
Size
[age range]
(year(s))
(M/F)
Inclusion criteria
and health status
Oral hygiene
regimes
OH and perio
screening
Type of force
application
Force
level
Observation
period
Rate OTM Additional
considera-
tions on study
design
Dudic
et al.
[39]
CT 19
(11/19)a
(36 teeth)
[<16]
11
(11/19)a
(21 teeth)
[16–43 y]
Good general
health
Good dental and
perio health
Buccal move-
ment of max-
illary and
mandibular pre-
molars with sec-
tional archwire
(0.019 × 0.025
TMA)
100 cN 8 w OTM Y > O
No sig. differ-
ences in sex and
location
Sig. less
OTM with
obstacle: in-
ter-arch < int ra-arch
Intra- and
interarch in-
terferences,
sex and loca-
tion (maxilla
or mandible)
Iwasaki
et al.
[36]
CT 6
(3/7)a
[10.5–14.3]
4
(3/7)a
[15.1–30.11]
NA Mouth rinse day
–28 (anchorage
in situ)
Chlorhexidine
mouth
rinse
2 × daily + routine
oral hygiene
Each visit (day 0
on)
oral prophylaxis
Maxillary canine
retraction by
vertical loop and
coil spring
60 cN
(one
side),
18, 120
or 240 cN
(other
side)
–28, –14, 0 d
(baseline)
1, 3, 14, 28,
42, 56, 70,
84 d
3, 14, 28 d
(lag phase)
Velocity Y > O,
varied between
subjects
Correlation
of OTM with
force level up to
120 cN
Lag phase asso-
ciated with force
of 240 cN
Sex, side,
stress
Force appli-
cation
was deter-
mined
by tooth size
and
target stress
Kawasaki
et al.
[37]
CT 15
(7/8)
[15.1 ± 2.8]
15
(6/9)
[31 ± 3.6]
Good health
No antibiotics
the last 6 months
No anti-inflam-
matory 1 month
before the study
Healthy perio
tissues
Bone loss
Ä3mm
Canine retrac-
tionon0.018SS
by elastomeric
chain
250 cN 0, 1, 24,
168 h
Y > O after 168 h NA
Nickel
et al.
[38]
CT 32
(15/17)
(64 teeth)
[13.4 ± 1.7]
9
(2/7)
(18 teeth)
[19.6 ± 5.4]
NA Chlorhexidine
gluconate mouth
rinse 2 x daily
Day of registra-
tion: supragingi-
val oral prophy-
laxis
Maxillary canine
retraction by
closing loop and
coil spring
18, 60,
120,
240 and
360 cN
1, 3, 14, 28,
42, 56, 70,
84 d
Velocity 1.6
times higher
in Y than O
Velocity higher
in force levels of
60, 120, 240 cN;
increased loga-
rithmically with
force level
OTM in re-
lation to ap-
plied load
Individualized
OTM re-
sponse
M/F male, female distribution, OH oral hygiene, OTM orthodontic tooth movement, CT prospective clinical trial, TMA titanium molybdenum alloy, cN centinewton(s), wweek(s), Yyounger study
group, Oolder study group, NA not applicable, dday(s), SS stainless steel, hhour(s), sig significant, perio periodontal
aM/F distribution was only provided for the total sample and not for each group separately
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Tab le 5 Studies reporting on age-related composition changes in gingival crevicular fluid in humans
Tab. 5 Studien zu altersabhängigen Veränderungen der Zusammensetzung des gingivalen Sulkusfluids (GCF)
Study Design Younger
group
Size [age
range]
(y)
Older group
Size [age
range]
(y)
Inclusion crite-
ria and health
status
Oral hy-
giene
regimes
and OH
Side of GCF collec-
tion and process
Control Type of
force ap-
plication
Force level Observation
period
Data on GCF analy-
sis
(M/F) (M/F) Evaluation
Chibebe
et al.
[40]
CT 25
(10/15)
[13.6 ± 2.1 y]
23
(7/16)
[24.1 ± 2.1 y]
Good health
No antibiotics
the last 6m
No anti-inflam-
matory the last
2m
Good perio
health
OH instruc-
tion during
the study
Mesiobuccally
Area was isolated
with cotton rolls,
gently dried
Paper strip inserted
and kept for 30 s
Baseline
level
Labial
movement
of one
maxillary
right
lateral
incisors
by 0.012
NiTi
0.7 N 2, 21
and 28 d
PGE2level at base-
line and end: O > Y
Increase of PGE2
level to day 21,
then decrease to
baseline in O + Y
Sig. changes in PGE2
levels only in Y
(baseline compared
to day 21)
Iwasaki
et al.
[36]
CT 6
(3/7)a
[10.5–14.3 y]
4
(3/7)a
[15.1–30.11 y]
NA Chlorhexidine
mouth rinse
2xdaily
Strict OH
In each
appointment
modified GI
+OP
Distally
Washed with water,
isolated with cotton
and dried
Sterile strips in GC
for 30 s and a 2nd
strip1minlater,
then strips sealed
in polypropylene
containers
Opposing
teeth
Maxillary
canine
retraction
by verti-
cal loop
and coil
spring
60 cN (one
side), 18,
120 or
240 cN
(opposing)
Lag phase
associated
with force
of 240 cN
1, 3, 14,
28, 42,
56,
70, 84 d
Correlation of veloc-
ity and level of IL-1β
in GCF
Correlation of
changes in cytokine
levels in SWB and
velocity/IL-1 activity
index
Kawasaki
et al.
[37]
CT 15
(7/8)
[15.1 ± 2.8 y]
15
(6/9)
[31 ± 3.6 y]
Good health
No antibiotics
the last 6m
No anti-inflam-
matory 1 m
preceding the
study
Color of
gingiva was
recorded
Plaque as-
sessment
Silness and
Loe index
Distally
Plaque was re-
moved with perio
probe
Teeth were washed
with water and
isolated with cotton
Strip was remained
in GC for 1 min
and then a 2nd strip
was used
Contra-
lateral
and
opposing
teeth
Canine
retrac-
tion on
0.018 SS
by elas-
tomeric
chain
250 cN 0, 1, 24,
168 h
Mean volume of
GCF Y > O
Level of RANKL
raised at 24 h, Y > O
Level of OPG de-
creased at 24 h, Y > O
RANKL-OPG ratio
at 24 h, Y > O
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A. Schubert et al.
Tab le 5 (Continued)
Tab. 5 (Fortsetzung)
Study Design Younger
group
Size [age
range]
(y)
Older group
Size [age
range]
(y)
Inclusion crite-
ria and health
status
Oral hy-
giene
regimes
and OH
Side of GCF collec-
tion and process
Control Type of
force ap-
plication
Force level Observation
period
Data on GCF analy-
sis
(M/F) (M/F) Evaluation
Ren
et al.
[21]
CT 43
(all males)
[11 ± 0.7 y]
41
(all males)
[24 ± 1.6 y]
Good health
No antibiotics
the last 6 m
No anti-inflam-
matory 1 m
preceding the
study
OH
instructions
before study
Distobuccally
Plaque was re-
moved
Area was isolated
with cotton Sterile
strip on GC for 30 s
Contra-
lateral
tooth
Labially
tipped
maxillary
lateral
incisors
by 0.012
NiTi
70 cN 24 h GCF volume Y > O
Baseline cytokine
level O > Y
Sign. increase
of PGE2,IL-6,
GM-CSF in Y
Sign. increase of
PGE2in O
Rody
et al.
[41]
CT 10
(3/7)
[14.4 ± 1.4 y]
10
(4/6)
[28.5 ± 7.8 y]
Good health
Nonsmokers and
drug users
2 weeks be-
fore fixed
appliance
professional
tooth-clean-
ing and
assessment
for perio
health
Labially
Dried and isolated
with cotton
Strip inserted for
60 s
Opposing
teeth
Alignment
of max-
illary
incisors
with NiTi
wires
NA 3, 6, 18,
20 w
No differences in
IL-1 level in control
vs. experimental side
Sig. increase in
IL-1RA in O after
3w
RANKL-OPG ratio
increased
at w 3 in Y + O; high-
estatw20inY
No sig. changes in
MMP-9
Surlin
et al.
[42]
CT 16
(9/7)
[13.81 ± 0.98 y]
13
(5/8)
[28.23 ± 3. 4 y]
Good health sta-
tus, nonsmoking
No antibiotic the
last 3 m
No anti-inflam-
matory
the last 30d
OH instruc-
tions and
motivated
during the
study
PI was mea-
sured
Distally
Supragingival
plaque removal
with curette
Air syringe and
saliva ejector for
isolation
Paper strips in GC
for 30 s
GCF measure in
precalibrated device
andstoredin
polypropylene tubes
Baseline
level,
con-
tralateral
tooth
Maxillary
canine
retrac-
tion by
laceback
NA 4, 8, 24,
72 h,
1and2w
PTX3 baseline level
not influenced by age
Increase in PTX3
earlier in Y than O
Maximum level at
24 h
PTX3 decrease to
baseline level faster
in O than Y
M/F male/female distribution, OH oral hygiene, GCF gingival crevicular fluid, CT prospective controlled trial, yyear(s), mmonth(s), sseconds, NiTi nickel–titanium, NNewton, dday(s),
PGE2prostaglandin E2,Oolder study group, Yyounger study group, sig. significant, NA not applicable, GI gingival index, OP oral prophylaxis, GC gingival crevice, min minute(s),
cN centinewton(s), IL-1ß Interleukin-1ß, SWB stimulated whole blood, SS stainless steel, hhour(s), RANKL receptor activator of NF-κB ligand, OPG osteoprotegerin, IL-6 interleukin-6,
GM-CSF granulocyte–macrophage colony-stimulating factor, wweek(s), IL-1RA interleukin-1 receptor antagonist, MMP-9 matrix metalloproteinase 9, PI plaque index, PTX3 pentraxin 3,
perio periodontal
aM/F distribution was only provided for the total sample and not for the two groups separately
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Age effect on orthodontic tooth movement rate and the composition of gingival crevicular fluid
Tab le 6 The mediators in gin-
gival crevicular fluid (GCF)
composition that were exam-
ined during orthodontic tooth
movement
Tab. 6 Mediatoren des während
der kieferorthopädischen Zahn-
bewegung untersuchten gingi-
valen Sulkusfluids (GCF)
Parameter categories Individual mediators
Cytokines Interleukin-1 beta (IL-1β)[16]
Interleukin-1 (IL-1) without differentiation [48]
Receptor activator of NF-κB ligand (RANKL) [21,48]
Prostaglandin E2(PGE2)[8,46]
Interleukin 6 (IL-6) [46]
Granulocyte macrophage colony-stimulating factor (GM-CSF) [46]
Receptors and their antago-
nists
Interleukin-1 receptor antagonist (IL1-RA) [16,48]
Osteoprotegerin (OPG) [21,48]
Pentraxin 3 (PTX-3) [50]
Enzymes for matrix degrada-
tion
Matrix metalloproteinase 9 (MMP-9) [48]
[21] to 9 times [36] over the experimental period. Proper
oral hygiene regimen and gingival health assessment was
considered in 6 studies ([21,3638,40,42]; Tables 4and 5).
Assessment strategies for the rate of OTM
The rate of OTM was assessed by measurements on plaster
casts either by a caliper [36,37], a measuring microscope
[38] or by digital superimposition of the digitalized plaster
models [39]. Results associated with the rate of OTM are
listed in Table 4.
GCF collection and level of mediators
Within the included studies (Table 5), the mediators in GCF
that were evaluated during the OTM are presented in Ta-
ble 6. All studies (Table 5) used periodontal paper strips
for the collection of the GCF. The strips were inserted into
the gingival crevice for either 30 [21,36,40,42]or60s
[37,41]. In one study, additional GCF samples were taken
at the tension side [36], but the data were not followed fur-
ther. Repeated measurements were considered in one study
only [37].
Three studies measured changes in GCF volume using
a Periotron [21,37,42]. Quantitative GCF analysis was
performed with radioimmunoassay (RIA) [21] or enzyme-
linked immunosorbent assay (ELISA) [36,37,4042]. Me-
diators were presented either by their weight [21], or by the
concentration of total GCF volume [21,37,41,42]oras
activity index [36].
Two studies observed higher mean baseline volumes of
GCF in the younger than the older group [30,37]. Baseline
concentration of mediators (PGE2, IL-6, GM-CSF) in GCF
was higher in the older than in the younger group [30,40].
PTX-3 [42] and RANKL baseline level [37] did not differ
significantly in GCF between the age groups [42].
Regulation pattern
Prostaglandin E2
One of the studies showed that at baseline, the younger pa-
tients had a lower PGE2concentration in the GCF than the
older group. After 24h, the concentration was increased
in both the younger and the older groups, but no differ-
ences between the two groups were present anymore [21].
The other study showed no differences between the groups,
although after 3 weeks of force application a significant
increase of PGE2concentration was found in the younger
group [40].
Interleukin-1
The concentration of IL-1 in GCF did not differ signifi-
cantly between the experimental and control teeth through-
out the time of force application in any of the age groups
involved [41]. The ratio of IL-1 to IL-1RA, however, de-
creased significantly in the older group after 3 weeks of
force application, indicating an increase in IL-1RA levels.
The average IL-1 activity index was significantly higher
in the younger group, showing a positive correlation with
the velocity of OTM [36]. The mean activity index was
further significantly influenced by the force magnitude and
the presence of a lag phase. In comparison to a force ap-
plication lower than 120 cN, a significantly higher activity
index was observed in the post-lag phase for canines where
the applied force was 240 cN [36].
Receptor activator of NF-κB ligand/osteoprotegerin
In the short term, 24 h after force application, RANKL
showed significantly elevated levels in the GCF in both age
groups, whereas OPG decreased simultaneously [37]. The
level of RANKL and OPG was significantly lower in the
older compared to the younger groups. The ratio of RANKL
to OPG significantly increased after 3 weeks of force ap-
plication in both age groups [41] and reached a peak in the
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A. Schubert et al.
18th observational week in the younger group. This was
related to a decrease in OPG. The level of OPG in the older
group did not differ significantly between the experimental
and control group at any time point.
Matrix metalloproteinase 9
The level of MMP-9 in GCF did differ neither between the
control and experimental teeth nor between the age groups
[41].
Pentraxin 3
The PTX-3 level increased after force application with
a peak at 24 h (2.5-fold in the younger group; 2-fold in
the older group) followed by a decline to baseline after
2 weeks in the younger and after 1 week in the adult group
[42]. Significant differences compared to the baseline level
were detected at 4, 8, 24 and 72h in younger patients and
at 8, 24 and 72 h in older patients, indicating an increased
rate of OTM in the younger group.
Risk of bias within studies
A summary of the risk of bias for the included studies is
presented in Fig. 2. Serious risk of bias was found in 6
of the 8 studies for one domain [41,42] or two domains
[3639]. The most problematic issues were lack of blinding
for the OTM outcome assessor [37,38] and the existence
of other potential bias [3639,41,42]. Two studies did not
report complete outcome data [38,39].
Risk of bias across studies
Significant signs of selection bias, attrition bias and other
bias were seen for the assessment of OTM in all four in-
cluded studies [3638], which indicate weakness of the
study design and the potential of unreliable data for this
outcome. Three of the studies that investigated the GCF
showed similar weaknesses in study design, creating bias
in the analysis of the GCF [37,41,42].
Discussion
Quality of evidence
This systematic review included eight prospective clinical
trials, which investigated the rate of OTM and/or changes
in the GCF of juvenile and adult individuals subsequent to
orthodontic force application. In the literature, most trials
reporting on age-related differences in the rate of OTM are
small observational studies or case series showing slower
Fig. 2 Risk of bias across the included studies. The signs indicate:
low risk of bias (+), high risk of bias () and unclear risk of bias (?).
OTM orthodontic tooth movement, GCF gingival crevicular fluid
Abb. 2 Risiko für das Auftreten eines Bias für die inkludierten Studi-
en. Bedeutung der Symbole: geringes Risiko für Bias (+), hohes Risi-
ko für Bias (), unklares Risiko für Bias (?). OTM kieferorthopädische
Zahnbewegung, GCF gingivales Sulkusfluid
tooth movement in adults in comparison to juvenile sub-
jects. Little evidence exists regarding higher levels of in-
flammatory mediators in aged PDL.
This systematic review revealed a large heterogeneity
in the included clinical trials (study group size and wide
age intervals, mode of force application, level of force and
reactivation, observation period, GCF collection method,
oral hygiene regimen).
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Age effect on orthodontic tooth movement rate and the composition of gingival crevicular fluid
The mediators were evaluated either by their weight [21],
or by their concentration in total GCF [21,37,41,42]oras
activity index [36]. There is no scientific evidence whether
the amount of or the concentration of a mediator is a better
indicator for the evaluation of the rate of OTM. The study by
Ren et al. showed that the concentration of a mediator in the
CGF is more sensitive in the detection of OTM responses
for the comparison between younger and older individuals
[21]. Their threshold is higher in older than younger study
probands [21] indicating more responsive cytokine levels in
juveniles than in adults [21].
The response to force application is site-specific, depend-
ing on the bone deformation and the distortion of the pe-
riodontal ligament (stress/strain). The data of the collected
mediators were provided mainly from the distal side [36,
37,42] or the distobuccal side [21], but also from the labial
[42] or the mesiobuccal side ([40]; Table 5).
The optimal mechanical stimulus for OTM response may
differ between younger and older individuals and among
individuals of the same age [43]. Adults also may have
a later initial response [21] leading to a delay in the overall
orthodontic treatment time. The force application of con-
tinuous or interrupted forces also has an impact on the rate
of OTM, altering the cytokine levels in the GCF [32]. Light
continuous forces induce longer lasting levels of cytokines
during OTM [32] and heavy, decreasing forces create fluc-
tuating cytokine levels and increase the risk for root re-
sorption and hyalinization [44]. In retraction OTM with
laceback [42] or elastomeric chain [37] smaller forces are
applied, while retraction with vertical loops or coil spring
[36] or alignment [41] and labial movement [40] with NiTi
wires, continuous forces are delivered (Table 2). Some cy-
tokines, showing an upregulation subsequent to orthodontic
stresses, should not be overrated, since these studies de-
tected large fluctuations in cytokine level and the size of
the study groups were small [32].
Irrespective of the serious bias found in the included
OTM studies, juveniles appear to present a higher rate of
OTM than adults [3639]. However, accurate prediction of
the rate of OTM is difficult due to the high interindivid-
ual variability [36], the genetic background and complexity
of bone remodeling induced by OTM [45]. Many different
intrinsic factors including sex and possibly the ethnicity
[9], root length, bone level, bone density [9,46] affected
by weight and bone turnover rates [47] have an impact
on the rate of OTM. These factors were not considered
in any of the included studies. A genetic predisposition to
a high bone turnover rate was associated with increased
rate of OTM compared to normal or low turnover rates
when applying the same force in different subjects [47].
Pharmacologic agents for prevention or treatment of dis-
eases, including painkillers and dietary supplements altered
the rate of OTM [48]. General health [21,37,3942]and
the intake of medication (antibiotics and anti-inflammatory
drugs only) were considered for the participants in most of
the studies. The last use of antibiotics was settled to more
than3[42] or 6 months [21] and the last anti-inflammatory
medication intake to more than 1 [21] or 2 months [40].
Estrogen fluctuation (sex hormones/estradiol and estrone)
during menopause or the reproductive female period or vi-
tamin D3 supplementation (for prevention or treatment of
osteoporosis) or even dietary calcium intake (low- vs. high-
calcium diet) [49] play an important role in the RANK/
RANKL/OPG signaling pathway affecting the rate of OTM
[50]. Also osteopenia, a condition in which bone mineral
density is reduced as a sign of normal aging, is often ob-
served before estrogen decline or menopause [51], or eat-
ing disorders, or suppressed estrogen balance seen often in
young female athletes may affect the rate of OTM [52]. The
selection of exclusively male individuals, like in the study
by Ren et al. [21] eliminates sex-related bone turnover bias.
The high heterogeneity in study design and outcome param-
eters of all included studies preclude clear evidence-based
conclusions.
Limitations of the study set-up
None of the included studies reported on any randomization
method. The experimental sides are likely to be selected
and allocated by judgement of the clinician. Opposing or
neighboring teeth may prevent the experimental tooth to
move or decrease the effective force level applied, thus,
leading to bias in the outcome measurement.
The velocity of OTM at crown level is influenced by the
type of OTM [53] and varies among the included studies.
Tipping [37,39] will be accomplished faster than bodily
tooth movement [38]. The amount of tipping is related to the
patient’s bone level. Decreased bone levels result in more
tipping when the same line of force is applied. Since the
bone level will decrease with age due to periodontal prob-
lems, more tipping and apparently faster tooth movement
can be expected in the adult group. Furthermore, if OTM
is defined by space closure without a proper anchorage de-
vice, the results may be biased by the undefined movement
of the adjacent teeth [36].
Proper control of oral hygiene throughout the study is
important, since the outcome is likely to change with the
presence of gingival inflammation. Gingivitis has an influ-
ence on the expression of IL-1β[22] and the level of IL-1
may be increased in patients with poor or moderate oral
hygiene [41].
Most of the studies included in this review present re-
sults of short observational periods. Since the biological
response to orthodontic stimuli varies among and within
the patient and throughout the stages of OTM, short obser-
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A. Schubert et al.
vational periods are not representative and might provide
misleading conclusions [54].
The above-mentioned problems may be avoided in an-
imal studies, for example in rodents. Such studies allow
a design with more homogenous study groups, proper ran-
domization procedures, and the availability of more analyt-
ical tools for the analysis of cellular and molecular events
during OTM. The results of such studies can serve as a basis
for properly designed hypothesis-driven clinical studies.
The increased interest of adult patients for high esthetic
and short-lasting orthodontic treatment outcome has turned
the experimental and clinical orthodontic interest on cus-
tomized appliances, surgical procedures [55]orpharmaco-
logical and dietary agents that may accelerate the OTM
[48]. Whether aging is a factor that influences the rate
of OTM is rather unclear. It is a fact that interindividual
variations seem to play a role in the biological responses
triggered by the orthodontic forces. The three-dimensional
computer-simulated OTM with accurate stress–strain dis-
tribution and biological profiles of each patient may be
valuable for optimizing the treatment time and eliminating
complications on the involved soft and hard tissues.
Conclusions
The small number of studies and large heterogeneity in
study design preclude a meta-analysis. There is limited clin-
ical evidence that older patients are less responsive to or-
thodontic stress than younger ones. Future animal studies
and well-designed prospective clinical studies should focus
on multiple variables involved in the rate of OTM.
Compliance with ethical guidelines
Conflict of interest A. Schubert, F. Jäger, J.C. Maltha and T.N. Bartzela
declare that they have no competing interests.
Ethical standards For this article no studies with human participants
or animals were performed by any of the authors. All studies performed
were in accordance with the ethical standards indicated in each case.
For this type of study informed consent is not required.
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... Prostaglandin E2 (PGE2), which is one of the inflammatory mediators, makes a contribution to stimulating bone resorption, and its level is elevated during orthodontic movements both on the pressure side and on the tension side [21][22][23]. Bone resorption is caused by the activity of the osteoclasts, which are stimulated by a pro-inflammatory cytokine called tumor necrosis factor (TNF α) [24]. The levels of TNF-α increase 1 h and 24 h after the application of orthodontic forces, both in patients with pre-adjusted edgewise appliances (PEA) and in those with self-ligating (SL) systems. ...
Article
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Background: Changes in the positions of teeth occur during orthodontic treatment due to the application of forces that cause restructuring of the periodontal tissue. In the last decade, substantial research has been conducted to detect different biomarkers in the gingival crevicular fluid (GCF) to obtain a better assessment of the periodontal status. Aim: The purpose of this review is to describe how the levels of certain biomarkers from the gingival fluid change during tissue remodeling throughout orthodontic treatment. Materials and methods: To carry out the purpose of this research, electronic databases were searched using specific keywords, leading to 387 articles, out of which 19 were used in writing this narrative review. A sampling period of the last 10 years was used in selecting the articles. Results: The results highlight that the origin of the gingival crevicular fluid is at the gingival blood vessels’ plexus. GCF has a complex composition with differences depending on the periodontal status and the tissue restructuring which takes place in the periodontium. The levels of inflammatory mediators, enzymes, and metabolic products of tissue remodeling in GCF change during orthodontic treatment. Being aware of their specific role, they can provide valuable information about bone remodeling during orthodontic tooth movement. Conclusions: By determining the biomarkers in GCF, as an investigative method, clinicians could easily monitor the orthodontic tooth movement, and, subsequently, the treatment period could be shortened and the adverse effects associated with it could be avoided.
... We attribute the higher FD values in the condyle region to the metabolic bone activity associated with growth and development in this area. This situation is consistent with the fact that metabolic bone activity is higher in children than in adults [58]. The researchers have reported that higher FD values may be associated with increased bone metabolism and bone apposition [20], whereas decreased FD values related to decreased metabolic bone activity [59,60]. ...
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Background/Objectives: Although there has been extensive research on the orofacial morphologic effects of cleft lip and palate (CLP), the effects of CLP on mandibular structures remain largely unknown. The aim of this study was to investigate the trabeculation differences in the mandibular osseous architecture of patients with bilateral CLP (BCLP) and left-sided unilateral CLP (UCLP) using fractal dimension (FD) analysis and to compare these findings with healthy controls without CLP. Methods: A total of 63 patients (27 females, 36 males) with a mean age of 9.69 ± 1.5 years in the pre-peak growth stage were divided into three groups (n = 21 per group): the control group (CG), the BCLP group, and the UCLP group. The FD analysis was conducted on selected regions of interest (ROIs) from the mandibular condyle, angulus, corpus, and coronoid areas in TIFF-formatted panoramic radiographs. Statistical analyses were performed using the paired t-test and ANOVA for parametric data, and the Wilcoxon and Kruskal–Wallis tests for nonparametric data. Statistical significance was set at p < 0.05. Results: The FD values obtained from the ROIs of the right condyle were found to be significantly lower in the BCLP group compared to the CG and UCLP groups (p < 0.05). Conversely, the FD values for the left condyle were significantly higher in the CG group (p < 0.05), while no significant differences were observed between the BCLP and UCLP groups (p > 0.05). The FD value of the left condyle in the UCLP group was found to be significantly lower than that of the right condyle (p < 0.05). In the CG group, the FD values for both the right and left mandibular condyle and corpus were significantly higher than those for the angulus and coronoid regions; in the UCLP group, only the FD values of the right mandibular condyle and corpus were significantly higher than those for the same regions (p < 0.05). Conclusions: The reduced FD values in the mandibular condyle of CLP patients during the pre-peak growth stage suggest a loss of trabeculation and lower metabolic activity, while similarly, reduced FD values in the corpus region contribute to delayed tooth eruption timing, likely due to decreased masticatory forces during the intercuspal position and altered occlusal relationships. Clinical Relevance: In treating CLP patients, particularly with orthopedic face masks, the reduction in metabolic activities in these areas should be considered to achieve the optimal mandibular growth and development, and dental eruptions during the distribution of force from the chin to the corpus and condyle.
... Furthermore, we found younger age to be associated with a lower refinement risk and, therefore, a shorter treatment duration. This is consistent with many studies that have found age-related effects on orthodontic tooth movement (OTM), with younger age showing faster OTM and older age showing a delayed response to orthodontic forces [31,32]. ...
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Background/Objectives: Machine learning (ML) models predicting the risk of refinement (i.e., a subsequent course of treatment being necessary) in clear aligner therapy (CAT) were developed and evaluated. Methods: An anonymized sample of 9942 CAT patients (70.6% females, 29.4% males, age range 18–64 years, median 30.5 years), as provided by DrSmile, a large European CAT provider based in Berlin, Germany, was used. Three different ML methods were employed: (1) logistic regression with L1 regularization, (2) extreme gradient boosting (XGBoost), and (3) support vector classification with a radial basis function kernel. In total, 74 factors were selected as predictors for these methods and are consistent with clinical reasoning. Results: On a held-out test set with a true-positive rate of 0.58, the logistic regression model has an area under the ROC curve (AUC) of 0.67, an average precision (AP) of 0.73, and Brier loss of 0.22; the XGBoost model has an AUC of 0.67, an AP of 0.74, and Brier loss of 0.22; and the support vector model has a recall of 0.61 and a precision of 0.64. The logistic regression and XGBoost models identify predictors influencing refinement risk, including patient compliance, interproximal enamel reduction (IPR) and certain planned tooth movements, for example, lingual translation of maxillary incisors being associated with the lowest risk of refinement and rotation of mandibular incisors with the highest risk. Conclusions: These findings suggest moderate, well-calibrated predictive accuracy with both regularized logistic regression and XGBoost and underscore the influence the identified factors have on the risk of refinement in CAT, emphasizing their importance in the careful planning of orthodontic treatment and the potential for shorter treatment times, less patient discomfort, and fewer clinic visits. Identification of at-risk individuals could support tailored clinical decision-making and enable targeted interventions
... Those authors recorded a lower predictability of movements in intermediate age, the opposite trend to that which we, like both Harris et al. and Dudic et al., found [44,45]. A potential explanation for the latter case could be the joint effect of biological response, which is more favorable in younger patients [46]., and compliance, which is usually greater in adults than in adolescents and pre-adolescents [47]. That being said, Chisari et al. investigated a sample that was four times lesser than that with respect to the current study, and they investigated the Invisalign system [43]. ...
Article
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Background: To investigate the accuracy of an F22 Aligner system, considering the amount of prescribed movement, tooth type, grip points, sex and age. Methods: Digital models of 120 patients (64 females and 56 males; mean age 35.2 years ± 7.4) affected by mild-to-moderate Class I malocclusion and treated via F22 Aligners, retrospectively selected from the University of Ferrara Orthodontics Clinic’s electronic database; post-treatment models were generated, and three angular values per tooth and four linear intra-arch measurements per arch were acquired. For angular measurements, planned (T1) and achieved (T2) values were obtained thorough digital model superimpositions. Linear measurements were acquired from pre-treatment, reference and post-treatment models. Statistical comparisons were performed to assess accuracy among tooth types and prescribed movements, tooth type, grip points, sex and age were investigated via chi-squared automatic interaction detection regression trees. Results: Mean accuracy for inclination and angulation were 86.76% and 88.01%, respectively, whereas rotation was less accurate (61.59%), especially for rounded teeth. All variables investigated influenced accuracy, with the exception of inclination, which was only influenced by age. Regarding linear measurements, good expansive capacity was shown, except for the distance between mandibular second premolars. Conclusions: F22 aligners are a viable solution for the treatment of Class I malocclusion of mild-to-moderate complexity, although clinicians should bear in mind the lower predictability of rotation, as well as the influence of the variables investigated.
... In this sense, and under the above-mentioned conditions, young patients would show a better and faster biological response to OTM compared to older patients [37]. However, the publications presented so far have shown that it is not possible to predict the rate of tooth movement of one patient based solely on the biological response of another patient, so practitioners should understand and apply the averages of inflammatory markers within the same patient to select an optimal force range that enhances the biological responsiveness to OTM [38]. ...
Chapter
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Orthodontic treatment usually lasts from 2 to 3 years and some intractable cases may require even longer, so the duration of treatment not only leaves the patient dissatisfied, but is also the main reason why many patients reject or refuse orthodontic treatment; Therefore, various areas of research, hand in hand with the needs of orthodontists, have been developing methods to accelerate tooth movement and reduce the duration of orthodontic treatment, in such a context, the biology of tooth movement is a fascinating field of study that focuses on understanding the biological and biomechanical processes involved in tooth movement; thus, through research and scientific advances, it has been possible to obtain greater knowledge about this phenomenon and its application in clinical practice through the expression of RANKL/OPG. On the other hand, in addition to bone remodeling, the biology of tooth movement also focuses on other biological factors that influence the process of inflammatory response, cellular response and soft tissue response, these factors would play a crucial role in the adaptation of alveolar and periodontal tissues to the forces applied during orthopedic/orthodontic treatment of the cranio-cervical maxillofacial region.
Article
Orthodontic treatment with fixed appliances is applied nowadays to children, teenagers and adults, the goal being mainly dental aesthetics, with obtaining a beautiful and healthy smile, but also a stable and functional occlusion. Orthodontic therapy can cause biological changes in the oro-dental system, with the appearance of lesions whose characteristics depend on the orthodontic treatment itself (duration, type of appliance, nature of orthodontic forces, orthodontic mechanics), but also of factors related to the patient (age, oral health, the peculiarities of the stomatognathic system, malocclusions, vicious habits, systemic diseases, dental hygiene). This review highlights the clinical features of the normal anatomical variations and the oro-dental pathology reported during the orthodontic consultations performed monthly in patients with fixed appliances. It is it is important for the patient that the orthodontist recognizes the clinical aspects of the oro-dental pathology determined or not by the orthodontic treatment, so that, correctly diagnosed, to be correctly treated.
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Introduction: The transformation of the Metallurgy industry over the years has brought outstanding improvement in Nickel Titanium (NiTi) alloy, resulting into orthodontic NiTi archwires with improved properties, which are routinely employed during the initial phase of orthodontic treatment. Nevertheless, the clinical superiority between the second and third generation of NiTi arch-wires; the Super Elastic NiTi (SE NiTi) and Copper NiTi (Cu NiTi) archwires respectively has not been studied in the Tanzanian population. Hence, this study aimed to compare the clinical efficiency of Super Elastic NiTi (SE NiTi) and Copper NiTi (Cu NiTi) arch-wires during the alignment phase of orthodontic treatment. Material and Methods: A total of 82 patients with an irregularity index of >2 mm on the mandibular anterior site were randomly allocated to one of the two treatment groups, group 1 (0.014-in SE NiTi) and group 2 (0.014-in Cu NiTi). Randomization was accomplished by random number generation via Microsoft Excel, participants were randomly assigned equally into respective groups. The arch-wire types were labeled and placed in sequentially numbered opaque sealed envelopes for participant allocation. Blinding to group assignment was applied to the participant and during outcome assessment. Data were analyzed by SPSS Statistics version 25 with a p-value set at <0.05. Results: A total of 153 potential participants were evaluated for eligibility. 67 of those were excluded. Therefore 86 patients were randomly allocated to either the study control group (group 1, n=43) or intervention (group 2, n=43). The number of participants analyzed were n=42 in group 1 and n=42 in the control group. The Little's irregularity index significantly decreased over time in both groups (p<0.001), however, there was no statistically significant difference between the two arch-wires types in their efficiency on teeth alignment (p = 0.435) and arch width expansion (p>0.05). Conclusion: There was no significant difference between SE NiTi and Cu NiTi in alignment efficiency and arch width changes. There was no statistically significant inter-canine arch width change in the Cu NiTi group.
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A thorough comprehension of age‐related variances in orthodontic tooth movement (OTM) and bone remodeling response to mechanical force holds significant implications for enhancing orthodontic treatment. Mitophagy plays a crucial role in bone metabolism and various age‐related diseases. However, the impact of mitophagy on the bone remodeling process during OTM remains elusive. Using adolescent (6 weeks old) and adult (12 months old) rats, we established OTM models and observed that orthodontic force increased the expression of the mitophagy proteins PTEN‐induced putative kinase 1 (PINK1) and Parkin, as well as the number of tartrate‐resistant acid phosphatase‐positive osteoclasts and osteocalcin‐positive osteoblasts. These biological changes were found to be age‐related. In vitro, compression force loading promoted PINK1/Parkin‐dependent mitophagy in periodontal ligament stem cells (PDLSCs) derived from adolescents (12–16 years old) and adults (25–35 years old). Furthermore, adult PDLSCs exhibited lower levels of mitophagy, impaired mitochondrial function, and a decreased ratio of RANKL/OPG compared to young PDLSCs after compression. Transfection of siRNA confirmed that inhibition of mitophagy in PDLSC resulted in decreased mitochondrial function and reduced RANKL/OPG ratio. Application of mitophagy inducer Urolithin A enhanced bone remodeling and accelerated OTM in rats, while the mitophagy inhibitor Mdivi‐1 had the opposite effect. These findings indicate that force‐stimulated PDLSC mitophagy contributes to alveolar bone remodeling during OTM, and age‐related impairment of mitophagy negatively impacts the PDLSC response to mechanical stimulus. Our findings enhance the understanding of mitochondrial mechanotransduction and offer new targets to tackle current clinical challenges in orthodontic therapy.
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Compared with teenage patients, adult patients generally show a slower rate of tooth movement and more pronounced alveolar bone loss during orthodontic treatment, indicating the maladaptation of alveolar bone homeostasis under orthodontic force. However, this phenomenon is not well-elucidated to date, leading to increased treatment difficulties and unsatisfactory treatment outcomes in adult orthodontics. Aiming to provide a comprehensive knowledge and further inspire insightful understanding towards this issue, this review summarizes the current evidence and underlying mechanisms. The age-related abatements in mechanosensing and mechanotransduction in adult cells and periodontal tissue may contribute to retarded and unbalanced bone metabolism, thus hindering alveolar bone reconstruction during orthodontic treatment. To this end, periodontal surgery, physical and chemical cues are being developed to reactivate or rejuvenate the aging periodontium and restore the dynamic equilibrium of orthodontic-mediated alveolar bone metabolism. We anticipate that this review will present a general overview of the role that aging plays in orthodontic alveolar bone metabolism and shed new light on the prospective ways out of the impasse.
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Objective To compare the anterior crowding correction after sequential use of the first 5 aligners between two aligner exchange protocols (7 and 14 days) in mature adult patients. Materials and Methods Thirty‐six patients over 35 years who received orthodontic treatment with Invisalign® were randomly allocated to two different aligner replacement sequence protocols: Group 1: exchange every 7 days (n = 18); and Group 2: exchange every 14 days (n = 18). All patients were scanned with iTero Element 5D® (Align Technology) in two treatment times: at pre‐treatment (T1) and after using the first five aligners (T2). Little's Irregularity Index (LII) and arch widths were evaluated with OrthoCAD software. Intra and intergroup comparisons were performed with the dependent and independent t ‐tests. The results were considered significant for P < .05. Results Thirty‐five patients completed the study. Both groups' maxillary and mandibular Irregularity Indexesi were significantly lower at T2. There was no significant difference in inter‐canine, inter‐premolar, and intermolar distances. G2 (14 days) presented a greater decrease in mandibular irregularity than G1 (7 days). Conclusion Both exchange protocols (7 and 14 days) effectively correct anterior crowding in the initial phase of orthodontic treatment with aligners in mature adult patients. However, the 14‐day exchange protocol provided a greater correction in mandibular anterior crowding in the evaluated period than the 7‐day exchange protocol.
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Bone loss in women commences before the onset of menopause and oestrogen deficiency. The increase of follicle-stimulating hormone (FSH) precedes oestrogen decline and may be a cause for bone loss before menopause. This review summarizes the current evidence on the relationship between FSH and bone derived from cellular, animal and human studies. Cellular studies found that FSH receptor (FSHR) was present on osteoclasts, osteoclast precursors and mesenchymal stem cells but not osteoblasts. FSH promoted osteoclast differentiation, activity and survival but exerted negligible effects on osteoblasts. Transgenic FSHR or FSH knockout rodents showed heterogenous skeletal phenotypes. Supplementation of FSH enhanced bone deterioration and blocking of FSH action protected bone of rodents. Human epidemiological studies revealed a negative relationship between FSH and bone health in perimenopausal women and elderly men but the association was attenuated in postmenopausal women. In conclusion, FSH may have a direct action on bone health independent of oestrogen by enhancing bone resorption. Its effects may be attenuated in the presence of overt sex hormone deficiency. More longitudinal studies pertaining to the effects of FSH on bone health, especially on fracture risk, should be conducted to validate this speculation.
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Systematic reviews and meta-analyses have become increasingly important in health care. Clinicians read them to keep up to date with their field [1],[2], and they are often used as a starting point for developing clinical practice guidelines. Granting agencies may require a systematic review to ensure there is justification for further research [3], and some health care journals are moving in this direction [4]. As with all research, the value of a systematic review depends on what was done, what was found, and the clarity of reporting. As with other publications, the reporting quality of systematic reviews varies, limiting readers' ability to assess the strengths and weaknesses of those reviews. Several early studies evaluated the quality of review reports. In 1987, Mulrow examined 50 review articles published in four leading medical journals in 1985 and 1986 and found that none met all eight explicit scientific criteria, such as a quality assessment of included studies [5]. In 1987, Sacks and colleagues [6] evaluated the adequacy of reporting of 83 meta-analyses on 23 characteristics in six domains. Reporting was generally poor; between one and 14 characteristics were adequately reported (mean = 7.7; standard deviation = 2.7). A 1996 update of this study found little improvement [7]. In 1996, to address the suboptimal reporting of meta-analyses, an international group developed a guidance called the QUOROM Statement (QUality Of Reporting Of Meta-analyses), which focused on the reporting of meta-analyses of randomized controlled trials [8]. In this article, we summarize a revision of these guidelines, renamed PRISMA (Preferred Reporting Items for Systematic reviews and Meta-Analyses), which have been updated to address several conceptual and practical advances in the science of systematic reviews (Box 1). Box 1: Conceptual Issues in the Evolution from QUOROM to PRISMA Completing a Systematic Review Is an Iterative Process The conduct of a systematic review depends heavily on the scope and quality of included studies: thus systematic reviewers may need to modify their original review protocol during its conduct. Any systematic review reporting guideline should recommend that such changes can be reported and explained without suggesting that they are inappropriate. The PRISMA Statement (Items 5, 11, 16, and 23) acknowledges this iterative process. Aside from Cochrane reviews, all of which should have a protocol, only about 10% of systematic reviewers report working from a protocol [22]. Without a protocol that is publicly accessible, it is difficult to judge between appropriate and inappropriate modifications.
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Introduction: The aim of this study was to investigate the variation in the amount of the orthodontically induced tooth movement in humans and potential associations between the amount of tooth movement with age and location in the mandible or maxilla. Subjects and methods: This study included 11 participants (7 females, 4 males) with an age range of 11.3-28.6 years. In a standardized experimental orthodontic tooth movement protocol, two premolars of each participant were moved buccally during 8 weeks with the use of 1 N force. No functional or localized obstacles were affecting the displacement. Plaster models before and after the experimental tooth movement were constructed, digitized, and superimposed, to evaluate the amount of tooth movement of each tooth. Random effects linear regression analysis was performed to examine associations between tooth displacement, age, and tooth location. Results: The mean displacement of the teeth was 2.7±1.4mm. The range of tooth movement varied substantially between individuals (0.6-5.8mm). The displacement of the teeth within the same individual was highly correlated (R (2) = 0.78, P < 0.001). The tooth displacement decreased with age; however, this finding did not reach statistical significance (β = -0.11, 95% CI: -0.28, 0.05, P = 0.172). The tooth movement was higher in the maxilla than in the mandible (β = 0.47, 95% CI: 0.81, 0.86, P = 0.018). Conclusion: Wide range of tooth displacement revealed slow and fast movers in this sample. Larger displacements were recorded in the maxilla compared to the mandible and in younger individuals.
Article
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Objective: To investigate differences in the amount of tooth movement and root resorption that occurred after tipping and bodily movement of the maxillary first molar in rats. Materials and methods: Ten-week-old female Wistar rats were divided into two groups according to type of tooth movement and subdivided into four subgroups according to the magnitude of applied force. Nickel-titanium closed-coil springs exerting forces of 10, 25, 50, or 100 g were applied to the maxillary left first molars to induce mesial tooth movement. We designed a novel orthodontic appliance for bodily tooth movement. Tooth movement distance and root resorption were measured using microcomputed tomography and scanning electron and scanning laser microscopy. Results: The amount of tooth movement in the bodily tooth movement group was less than half that in the tipping tooth movement group. The greatest amount of tooth movement occurred in the 10-g tipping and 50-g bodily tooth movement subgroups, and the amount of tooth movement decreased with the application of an excessive magnitude of force. Conversely, root resorption increased when the heavier orthodontic force was applied in both groups. Root resorption in the tipping tooth movement group was approximately twice that in the bodily tooth movement group. Conclusions: Root resorption in the tipping tooth movement group was more pronounced than that in the bodily tooth movement group. Although the amount of tooth movement decreased when extremely heavy forces were applied, root resorption increased in both the tipping and bodily tooth movement groups in rats.
Book
This book presents the current knowledge and understanding of the biological processes involved in the orthodontic movement of teeth and discusses recent progress in the field. It links research advances to their immediate clinical applications and offers researchers and clinicians a state of the art reference on topical issues relating to orthodontic tooth movement. Biological events play a central role in the movement of teeth during orthodontic therapy. The basis for understanding the sequence of cellular events that leads to orthodontic movement has been well established in the literature through the use of animal models. In recent years, researchers and clinicians have focused their efforts on developing treatment modalities to increase the speed of orthodontic treatment and provide better anchorage options for noncompliant patients. This book will be an invaluable aid in understanding the biology of tooth movement and the relevance of the latest concepts to clinical practice.
Article
Introduction: Primary stability is essential to the success of orthodontic mini-implants (OMIs) and heavily depends on the mechanical retention between OMIs and their supporting bone. Alveolar cortical bone commonly serves as the supporting bone for OMIs during treatment. The purposes of this study were to characterize alveolar cortical bone thickness and density in the maxilla and to explore patient factors that may significantly affect these bone properties. Methods: Sixty medical computed tomography scans of the maxilla were analyzed from a selected sample of patients seen at the Radiology Department of Boston Children's Hospital. Interradicular alveolar bone thickness and density were measured at 2, 4, 6, and 8 mm from the buccal and palatal alveolar bone crests using the Synapse 3D software (version 4.1; FUJIFILM Medical Systems USA, Stamford, Conn). Analyses were conducted with STATA /1C (version 12.0 for Windows; StataCorp, College Station, Tex) using multivariate mixed-effects regression models and paired t tests. Results: Mean age and body mass index of the study sample were 17.88 years and 22.94 kg/m(2), respectively. Cortical bone density and thickness significantly increased from the coronal (2 mm) to the apical (8 mm) regions of the alveolar bone (P <0.05). At 8 mm from the alveolar crest, interradicular buccal cortical bone was thickest (1 mm) and densest (1395 Hounsfield units) between the first and second molars. On the palatal side, the thickest bone (1.15 mm) was found between the canine and first premolar; it was similarly densest (1406 Hounsfield units) between the first premolar and canine, and between the first premolar and second premolar interradicular bones. On average, palatal cortical bone was thicker and denser compared with buccal; this difference was statistically significant (P <0.01) in the anterior and middle maxilla, with the anterior maxillary region showing the greatest difference. Female subjects have significantly denser bone compared with male subjects; however, sex is not significantly associated with bone thickness. Body mass index and age are positively associated with bone thickness and density. Radiologic absence of bone was more commonly seen in the anterior maxilla. Conclusions: Alveolar bone properties vary in the maxilla in patterns that could guide clinicians in selecting sites best suited for placement of OMIs.
Article
A common problem in clinical dentistry is the significant and rapid bone loss that occurs after tooth extraction. Currently there is no solution for the long-term preservation of alveolar bone. Previously, we showed that high-frequency acceleration (HFA) has an osteogenic effect on healthy alveolar bone. However, it is not known if HFA can preserve alveolar bone after extraction without negatively affecting wound healing. The purpose of this study was to evaluate the effect of HFA on alveolar bone loss and the rate of bone formation after tooth extraction. Eighty-five adult Sprague-Dawley rats were divided into 3 groups: control, static (static load), and HFA. In all groups, the maxillary right third molar was extracted. The HFA group received HFA for 5 min/d, applied through the second molar. The static group received the same magnitude of static load. The control group did not receive any stimulation. Some animals received fluorescent dyes at 26 and 54 d. Samples were collected on days 0, 7, 14, 28, and 56 for fluorescence microscopy, micro-computed tomography, histology, RNA, and protein analyses. We found that HFA increased bone volume in the extraction site and surrounding alveolar bone by 44% when compared with static, while fully preserving alveolar bone height and width long-term. These effects were accompanied by increased expression of osteogenic markers and intramembranous bone formation and by decreased expression of osteoclastic markers and bone resorption activity, as well as decreased expression of many inflammatory markers. HFA is a noninvasive safe treatment that can be used to prevent alveolar bone loss and/or accelerate bone healing after tooth extraction.
Article
The growth in adult orthodontics presents new challenges to both the general dental practitioner and the orthodontist. Although many of the main objectives of orthodontic treatment are similar for adults, young adults and children, adult patients frequently bring significant challenges in several areas not often seen in the younger patient group. In areas such as planning realistic treatment outcomes, it is paramount that the patient's expectations are identified, respected and managed where appropriate. The adult patient's dental health often dictates deviation from the ideal treatment plan and periodontal problems are a common example. Based on current evidence, this paper presents an overview of some of the difficulties in the management of these issues, as well as highlighting developments with regard to pain conditions and their relevance to orthodontic treatment and its effects on temporomandibular joint disorders (TMD) management.