Heliyon 9 (2023) e14621

Contents lists available at ScienceDirect

Heliyon
journal homepage: www.cell.com/heliyon

Research article

The effect of orthodontic tooth movement on the sensitivity of

dental pulp: A systematic review and meta-analysis
A. Golež a, b, *, M. Ovsenik b, c, K. Cankar a
a
University of Ljubljana, Faculty of Medicine, Institute of Physiology, Zaloska Cesta 4, Ljubljana, Slovenia
b
Orthos Institute, Vilharjev podhod 18, Ljubljana, Slovenia
c
University of Ljubljana, Faculty of Medicine, Department of Orthodontics and Dentofacial Orthopaedics, Hrvatski trg 6, Ljubljana, Slovenia

A R T I C L E I N F O A B S T R A C T

Keywords: Objectives: Orthodontic tooth movement (OTM) is a process that’s initiated by orthodontic forces.
Tooth movement techniques As a consequence, the forces could restrict pulpal blood supply, possibly affecting dental pulp.
Orthodontic tooth movement The study aimed to review the available evidence on the short and long-term effects of ortho­
Dental pulp
dontic tooth movement on dental pulp sensitivity and to identify clinically relevant risk factors.
Dental pulp test
Sources: PubMed, Embase, Scopus, and Web of Science were searched for papers from 1990 to the
end of December 2021.
Study selection: The studies that evaluated dental pulp sensitivity of teeth undergoing OTM were
included in the systematic review. Randomized, nonrandomized and case-controlled studies were
included in the analysis. Risk of bias in each study was assessed using the ROBINS-I tool.
Data: The systematic search yielded an initial sample of 1110 studies, 17 were included in
qualitative analysis. Most studies were classified as moderate risk of bias, however only limited
long-term evidence with a higher risk of bias exists. Electric pulp test (EPT) sensitivity threshold
during active OTM was increased by 4.25 SD (P < 0.001) and the relative risk (RR) of pulpal non-
sensitivity was 13.27 (P < 0.001) higher compared to pre-orthodontic baseline status. Significant
differences were between subgroups associated with the type of OTM. A positive relationship
between pulpal non-sensitivity and mean patient age was discovered (P = 0.041). After OTM the
risk of pulpal non-sensitivity remained 5.76 times higher (P < 0.001) in the long term.
Conclusions: Evidence showed that OTM could affect dental pulp sensitivity. The type of OTM and
patients’ age were identified as clinically relevant risk factors.
Clinical significance: Orthodontic tooth movement negatively impacts the sensitivity of dental pulp
during active treatment and to a lesser degree in the long term. Pulpal sensitivity tests during
active OTM should therefore be interpreted with caution. Data indicates younger patients have a
lower risk of negative pulpal sensitivity during orthodontic treatment.

1. Introduction

Orthodontic tooth movement (OTM) is a biological process, which starts with the application of mechanical, orthodontic force on
the tooth and is carried out through the mechanisms of the periodontal ligament and alveolar bone [1]. The cascade of local signaling
mediators elicit resorptive changes on the pressure side and apposition of alveolar bone on the tension side. Unlike processes in the

* Corresponding author. University of Ljubljana, Faculty of Medicine, Institute of Physiology, Zaloska Cesta 4, Ljubljana, Slovenia.
E-mail address: aljaz.golez@mf.uni-lj.si (A. Golež).

https://doi.org/10.1016/j.heliyon.2023.e14621
Received 29 September 2022; Received in revised form 2 March 2023; Accepted 13 March 2023
Available online 24 March 2023
2405-8440/© 2023 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license
(http://creativecommons.org/licenses/by-nc-nd/4.0/).
A. Golež et al. Heliyon 9 (2023) e14621

periodontal ligament and alveolar bone, processes in the dental pulp aren’t as well studied and documented [2–4].
The dental pulp is a specialized, well-vascularized and richly innervated soft connective tissue, which is located in the dental pulp
chamber, its furcations and root canals enclosed by hard dental tissues [5]. The main functions of the dental pulp are structural
(synthesis of dentine), trophic (blood and lymphatic vessel supply), protective (synthesis of reparative dentine), and sensory (inner­
vation) [6–8]. Limitations due to the morphology and physiology of the dental pulp - clinical evaluation of the dental pulp that is
objective, quantifiable and has a biological basis is difficult to obtain [9]. Moreover, no universal measure of dental pulp condition
exists so far.
Because pulpal tissue is encased in hard tooth structures, it is fully dependent on blood vessels passing through the apical foramen.
Any alteration in pulpal blood flow or vascular tissue pressure may affect the dental pulp health condition [10,11]. Occasional reports
of pulpal necrosis during orthodontic treatment have led to assumptions, that OTM may cause a loss of pulpal vitality, while others
associate it with external events, such as trauma or previous caries treatment [7,8,12–14]. Due to a lack of strong comprehensive
evidence, these dilemmas remain controversial and debated [15].
Innervation of the dental pulp is assessed via sensitivity testing of dental pulp, which includes electrical and thermal pulp tests, as
pulpal sensibility is closely related to pulpal innervation. A lower sensibility testing threshold is associated with a higher number of
pulpal nerve fibers [16]. Sensitivity testing is a simple and non-invasive method. It is widely clinically used to indirectly assess the state
of dental pulp by the qualitative sensory output of the dental pulp. It is assumed that changes in dental pulp condition are accompanied
by abnormal responses to sensitivity tests. If nerve fibers’ integrity is disrupted or their physiological status is altered, their response
thresholds may be changed [17,18]. A thermal or electrical test causes a change of membrane potential on the neuron. If large enough,
it causes an action potential in myelinated and unmyelinated nerve fibers of the dental pulp [19]. Electric pulp tests (EPT) and thermal
tests stimulate fast-acting, low threshold, myelinated A-fibers (Aδ are the most prevalent) [20]. Thermal stimulation of C fibers
(slower, high threshold, unmyelinated) does not occur before the thermal stimulus of the Aδ fibers produces an intense response.
During thermal testing, C fibers reach their threshold only when A fibers are unresponsive [18]. Sensitivity testing may not always
reliably reflect cellular or structural changes of the pulp, even though a relationship between a volumetric density of myelinated
neurons and electric pulp test threshold in healthy dental pulp is established (the higher the number of neurons - the lower the
threshold) [16,21]. Electrical pulp testing may be even less reliable in immature teeth, where the Raschkow plexus has not yet fully
developed [22]. OTM by suppressing the blood supply of the dental pulp could cause hypoxia suppressing Aδ fiber response and
altering the integrity of the Aδ fibers. Response thresholds to EPT would therefore possibly either be increased or EPT may not issue
any pulpal sensory response at all [23].
A direct investigation of the dental pulp could be difficult due to the hard tissues that limit its accessibility. Initial data raised a
concern that OTM could potentially affect the dental pulp condition, however, due to a lack of data, no conclusions could be made
[24]. Advances in the development of pulpal measurements have propelled new original research, which contributed to increased
scientific interest in the area. Several recent reviews thoroughly examined the effects of OTM on dental pulp [25–27]. However, so far
no quantification of evidence via meta-analysis was performed, nor were clinically relevant risk factors yet evaluated. To the best of
our knowledge, until now no review focused on long-term effects on dental pulp. Therefore, the present study aimed to systematically
review the available evidence in the short and long term, evaluate the data qualitatively and quantitatively as well as determine
whether some risk factors could affect dental pulp sensitivity during OTM.

2. Methods

The systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines
[28]. The review was previously registered at PROSPERO [29] under registration number CRD 42020198550. Before the PROSPERO
registration, a search of the PROSPERO database was made to identify similar systematic review registrations. There were only minor
deviations from registered protocol arising mostly from the unification of terminology with current literature and a delay from the
original schedule due to the extensiveness of data. The main review question based on the PICO principle was: “Does orthodontic tooth
movement affect the dental pulp condition in healthy patients?”

• Participants: Teeth with uncompromised pulps of healthy human participants undergoing orthodontic treatment
• Intervention: Orthodontic tooth movement. Includes orthodontic tooth movement in all directions caused by an orthodontic force
• Comparator: Control teeth with uncompromised dental pulps. Stable teeth which did not or did not yet undergo orthodontic tooth
movement
• Outcome: Sensitivity of dental pulp

All original randomized, nonrandomized clinical trials and case-controlled studies were included. Case reports, comments, short
comments, reviews and systematic reviews were excluded from the study selection.
Inclusion criteria.

• Human participants
• Treatment intervention, which included any type of orthodontic tooth movement

Exclusion criteria.

2
A. Golež et al. Heliyon 9 (2023) e14621

• Animal studies
• Studies on virtual or cellular models
• Participant’s systemic health conditions or drugs used that would affect either dental pulp condition or tooth movement
• Compromised dental pulp vitality because of local factors or procedures
• Review articles
• Comments, short comments and case reports
• Articles written in a non-English language (and author-approved English version of the manuscript unavailable)

2.1. Systematic search methods

A systematic search was performed in the following medical databases: PubMed, EmBase, Scopus, and Web of Science in the English
language for papers published between 1990 and 2021. A hand search was also performed using referenced or known sources. A search
was conducted using Medical Subject Headings (MeSH) terms: “Tooth Movement Techniques” and its corresponding entry terms, the
term “Dental pulp”, “Orthod* force”, “Pulpal blood flow” and “Dental pulp blood flow” by using Boolean operator AND or OR in
several combinations. The full search strategy is, because of its length, provided in the supplemental material.

2.2. Screening and data extraction

All identified records from online medical databases were retrieved and imported into the bibliographic software EndNote
(Endnote X7.5; Thomson Reuters, NY, USA), which performed machine deduplication. The records were then exported into Excel
spreadsheets (Microsoft Excel 2016, Microsoft corp. Redmond, WA, USA) for screening of titles and abstracts independently by two
reviewers: eligibility for inclusion in the systematic review was examined. Along with the screening the hand deduplication was
performed to identify any duplicates machine deduplication missed. In case of disagreement between the reviewers, the problem was
discussed until a consensus was reached. The full text of every paper that passed the screening stage was obtained and assessed for
eligibility by applying inclusion and exclusion criteria. For inclusion, the same protocol of two reviewers as for screening was
employed. All exclusions and reasons for them were recorded. For every included article the following data for qualitative evaluation
was extracted into spreadsheets: study design, number of participants, use of randomization and its method, control group size, patient
demographic (age), type of orthodontic movement, force source, force magnitude (g or cN), duration of active force or time between
active force initiation and measurement, a measure of outcome and outcome (effect on dental pulp condition). Since different effects of
OTM on the short-term and the long-term dental pulp condition are expected and are supported by a biological basis [30,31], the data
were separated into two main categories: the short-term and the long-term. The short-term (acute) category was selected for studies
that measured pulpal sensitivity 1–30 days from the onset of active orthodontic force application and the long-term category was for
studies that measured pulpal sensitivity at least 8 months after the first active orthodontic force application. Type of OTM was
classified into categories based on the direction of the tooth movement, if teeth moved non-specifically in several directions (such as
first phases of edgewise or straight wire arch appliance), they were classified into leveling and aligning category. In case OTM was
more controlled in a single direction, it was classified into groups based on the direction of the movement: intrusion for the apical
direction of OTM, expansion for buccal movement of upper teeth etc.
Both reviewers verified independently extracted data accuracy.

2.3. Risk of bias assessment

ROBINS-I risk of bias tool was used for risk of bias assessment at the study level [32]. The same two reviewers independently
assessed bias due to confounding (when one or more prognostic variables predict the intervention received at baseline), bias in the
selection of participants into the study (when the exclusion of some eligible participants or outcome events is related to both inter­
vention and outcome), bias in classification of interventions (introduced by either differential or non-differential misclassification of
intervention status), bias due to deviations from intended interventions (when there are systematic differences between experimental
intervention and comparator groups in the care provided), bias due to missing data (when later follow-up is missing for individuals
initially included and followed), bias in the measurement of outcomes (introduced by either differential or non-differential errors in
measurement of outcome data) and bias in the selection of the reported result (selective reporting of results in a way that depends on
the findings). After the biases for the study have been assessed each study received an overall grade based on its methodological quality
ranging from low risk of bias to critical risk of bias (the low risk of bias studies to be comparable to a well-performed randomized trial,
while studies assessed as the critical risk of bias are too problematic to provide any useful evidence). In case the two reviewers’ grades
did not match, the studies in question were discussed until either consensus was reached or the third reviewer was consulted. The risk
of bias for each category was visualized with “traffic light” plots using a Robvis tool [33]. Studies judged to be of critical risk of bias
were not included in the qualitative or quantitative synthesis.
ROBINS-I risk of bias assessment tool was used and was considered most appropriate because most of the studies were not (or could
not be) randomized in a standard fashion [32]. Full randomization in studies of dental pulp may not be always obtainable. Moreover,
blinding when evaluating OTM can rarely be achievable, since both researchers and participants can see and feel the orthodontic force,
which is applied through an oral appliance [34].

3
A. Golež et al. Heliyon 9 (2023) e14621

2.4. Quantitative analysis

Studies that reported quantitative data compatible with the analysis were included in a meta-analysis. Meta-analysis was per­
formed using Review Manager (RevMan) [Computer program] Version 5.4.1, The Cochrane Collaboration, 2020 and using Open Meta
Analyst software [35]. Similar to qualitative analysis, data were separated into short-term (measured pulpal sensitivity 3–30 days after
onset of OTM) and long-term categories (measured at least 8 months after the onset of OTM). If the study reported several mea­
surements during the first month of OTM, the measurement at or closest to 7 days after the onset of OTM was chosen. Data for
meta-analysis, which included the main outcome at baseline and during active OTM, and controlled co-variables such as force
magnitude, mean age of participants, type of OTM and force source for OTM were extracted into RevMan and Open Meta software for
quantitative evaluation. Since types of OTM and force source are co-dependent variables, the only type of OTM was used for subgroup
analysis. In case a study had several groups with differences in one of the before-mentioned controlled co-variables, the study was split
(noted in a systematic table and Forest plot with a letter after the Author and year of the study). For indicators of pulpal innervation,
two different quantitative outcomes were identified: the dichotomous outcome of sensitivity testing (sensitive/non-sensitive dental
pulp), which was calculated as relative risk (RR) of negative sensitivity test and threshold of electric pulp testing (EPT), which was a
continuous variable; the compound effect was calculated as standardized mean difference (SMD). SMD was the most appropriate
measure because the authors reported EPT thresholds using different scales.

Fig. 1. Flow chart of study selection and analysis.

4
 Table 1
Short-term effect of OTM on dental pulp sensitivity.

A. Golež et al.
Study Author-Year Alomari 2011 [30] Briseno 2021 [9] Cave 2002 [42] Cho 2010 [44] Hall 1998 [23] Han 2013 [43]
Study design Controlled clinical trial Prospective Controlled prospective Prospective Prospective Controlled
prospective
Number of 70 39 48 25 7 27
participants
Randomization (Y/ N N N N N Y
N),
randomization
method
Control group 23 0 15 0 2 3
number
Participant 12-17 yo 14-48 yo 10-29 yo 10-16 yo 14-17 yo 14-24 yo
demographic
Orthodontic Leveling Leveling Leveling Expansion Leveling Intrusion
movement type
Force source Archwires NiTi Archwire Archwires Hyrax screw Archwire Elastomeric band
Force magnitude (g) NA NA NA 1360–4600 NA 50 g (a)/300 g (b)
Duration of active 16 m of treatment 9–15 months of 8–9 months of 2–3 weeks 4–8 weeks 12 weeks
force treatment treatment
Measure of outcome Electro-sensitivity test (EPT), EPT EPT, thermal test EPT, cold test EPT, thermal tests EPT, thermal tests
thermal test
Effect Higher No. of negative tests in Not significant Increased EPT More negative EPT during expansion, no change More negative EPT after Increased No. Of
the treatment group. Higher threshold during in CT 4–8 weeks of treatment negative EPT and
EPT threshold. Highest after 60 entire treatment (max higher EPT threshold
days of active force at 2 months)
ROBINS-I risk of bias Low Moderate Moderate Moderate Moderate Moderate
5

Study Author-Year Khoshbin 2019 [39] Leavitt 2003 [40] Modaresi 2015 [46] Naoum 2019 [47] Veberiene 2010 [48] Veberiene 2009 [41]

Study design Controlled prospective Controlled Prospective Prospective Prospective Controlled

prospective prospective

Number of 129 18 39 20 13 21
participants
Randomization (Y/ N N N N N N, split-mouth
N),
randomization
method
Control group 43 9 0 0 0 NA
number
Participant 12-44 yo 13-37 yo 13-22 yo SARME: 16–26 yo; RPE: 9–15 yo 14-22 yo 11-21 yo
demographic
Orthodontic Leveling Leveling Leveling Expansion Intrusion Intrusion
movement type
Force source NiTi Archwire NiTi Archwire NiTi Archwire SARME (a), RPE (b) SS Spring SS Spring
Force magnitude (g) NA NA NA NA mean 82 mean 61
Duration of active 1 month 1 month 4 weeks 10+ days 14 days, 7 days 7 days

Heliyon 9 (2023) e14621

force
Measure of outcome EPT
Effect Increased EPT thresholds right
after active force. Thresholds
decrease after 1 month
ROBINS-I risk of bias Moderate
EPT, VAS scale EPT EPT, thermal test EPT EPT
Highest VAS 1 day Higher EPT threshold Higher No. Of negative EPT after SARME surgery No difference between 7 Higher EPT
after active force. No after OTM, higher No. and at the end of expansion in SARME & RPE. and 14 days of active thresholds. No
significant change in Of negative tests Decrease of negative EPTs after 3 months higher intrusion. Increased EPT correlation with AST.
EPT No. Of negative thermal tests after surgery and threshold after OTM
SARME.
Moderate Moderate Serious Moderate Low
A. Golež et al. Heliyon 9 (2023) e14621

Due to clinical and methodological diversity among included studies, a random-effects model meta-analysis was selected, using the
inverse variance method. The confidence interval (CI) was assigned at 95% and for all test results p-value ≤ 0.05 was considered
statistically significant [36]. Meta-analysis was calculated at the tooth level since the condition of the tooth pulp was central to the
research question. Heterogeneity was explored by chi-square (Chi2) and I-square (I2) statistics [37]. Publication bias was explored
using a Funnel plot. Possible factors influencing the outcome such as the type of orthodontic force used, the magnitude of force used for
OTM and the mean age of participants were explored using subgroup analysis and meta-regression. Subgroup analysis according to the
type of OTM stratified studies into subgroups: leveling and aligning, intrusion, expansion and traction of impacted canine. For
meta-regression, a random-effects meta-regression model was used.

3. Results

The systematic search yielded 407 records from the PubMed database, 377 from Scopus, 162 from Web of Science, 86 from Embase
and 78 were obtained through hand search, which cumulated in 1110 records before deduplication and screening. Titles and abstracts
of 615 records were screened, in case of doubt; a full-text article was obtained. 145 articles were selected for further full-text evaluation
and 75 were excluded: 28 were animal studies, 20 did not meet inclusion criteria, 11 were reviews or systematic reviews, 9 were
comments or case studies, 6 were written in a non-English language and one study was excluded because it was published twice [38]. A
list of excluded studies is provided in the supplementary material. 17 studies reported dental pulp sensitivity after OTM: 12 were
short-term evaluations and 5 were long-term studies. The study selection process is summarized in the flow chart (Fig. 1) (see Fig. 2).

3.1. Dental pulp sensitivity – qualitative analysis

3.1.1. Short-term
Short-term effects of OTM on dental pulp innervation were examined in 12 papers. All studies were of prospective design. Six
studies used control groups or control teeth [9,30,39–42], and only one was randomized [43]. Participants were between 10 and 48
years old, and most of them were adolescents. The authors observed the effects of OTM during leveling and aligning, intrusion and
expansion. Orthodontic forces between 50 and 300 g and orthopedic forces 1360–4600 g were used [44]. Three main measures of
outcome were reported: the number of negative sensitivity tests, EPT thresholds and pain intensity according to the VAS scale.
Characteristics and outcomes of the included studies are reported in Table 1.

3.1.2. Long-term
Five studies reported the long-term effects of OTM on dental pulp innervation indicators [9,30,42,44,45]. All long-term studies
except one were of prospective design [45]. Dental pulp condition was evaluated 8 months to 3 years after initiation of leveling and
aligning, expansion, or impacted canine traction. Participants were 10–48 years old. Studies reported mixed outcomes. Results are
presented in Table 2.

3.2. Risk of bias

The risk of bias for each domain and across domains on individual study level was assessed using the ROBINS-I risk assessment tool

Table 2
Long-term effect of OTM on dental pulp sensitivity.
Study Author-Year Alomari 2011 [30] Briseno 2021 [9] Cave 2002 [42] Cho 2010 [44] Woloshyn 1994 [45]

Study design Controlled prospective Prospective Controlled prospective Prospective Partly Prospective
Number of participants 70 39 48 25 62
Randomization (Y/N), N N N N N, split-mouth
randomization
method
Control group number 23 0 15 0 contralateral (non-
impacted) canines
Participant demographic 12-17 yo 14-48 yo 10-29 yo 10-16 yo 14-46 yo
Orthodontic movement Leveling Leveling Leveling Expansion Impacted canine traction
type
Force source Archwires Archwires Archwires Hyrax screw Various
Force magnitude (g) NA NA NA 1360–4600 NA
The time between the average 2 years 9–15 months of 252 days 9 months average 3 years
active force and treatment
measurement
Measure of outcome Electrosensitivity test EPT EPT, thermal test EPT, cold test EPT
(EPT), thermal test
Effect No differences Not significant: EPT Increased EPT threshold All teeth have A higher share of negative
thresholds compared to the non- positive EPT EPT in impacted canines
increased treated control group after OTM
ROBINS-I risk of bias Low Moderate Moderate Moderate Serious

6
A. Golež et al. Heliyon 9 (2023) e14621

[32]. The risk of bias assessment according to each domain and their summaries are graphically represented in Figs. 2 and 3 (Fig. 2a,
Fig. 2b, Fig. 3a, Fig. 3b). In general, long-term studies had a higher risk of bias (see Fig. 3).
Studies that evaluated pulpal sensitivity due to the effect of active OTM: nine studies were evaluated as the moderate overall risk of

Risk of bias domains

D1 D2 D3 D4 D5 D6 D7 Overall

Alomari 2011 ++ ++ ++ ++ ++ ++ ++ ++
Briseno 2021 −− −− ++ ++ −− −− ++ −−
Cave 2002 −− −− −− −− −− ++ ++ −−
Cho 2014 −− ++ −− ++ −− −− −− −−
Hall 1998 −− −− −− ++ −− ++ −− −−
Han 2013 ++ −− ++ ++ −− ++ −− −−
Study

Khoshbin 2019 −− −− ++ ++ ++ ++ −− −−
Leavitt 2003 −− −− −− ++ −− ++ ++ −−
Modaresi 2015 −− −− −− ++ −− −− −− −−
Naoum 2019 xx xx ++ ++ −− ++ −− xx
Veberiene 2010 −− −− ++ −− ++ ++ ++ −−
Veberiene 2009 ++ ++ ++ ++ ++ ++ ++ ++
Domains: Judgement
D1: Bias due to confounding.
D2: Bias due to selection of participants. x Serious
D3: Bias in classification of interventions. − Moderate
D4: Bias due to deviations from intended interventions.
D5: Bias due to missing data. + Low
D6: Bias in measurement of outcomes.
D7: Bias in selection of the reported result.

Bias due to confounding

Bias due to selection of participants
Bias in classification of interventions
Bias due to deviations from intended interventions
Bias due to missing data
Bias in measurement of outcomes
Bias in selection of the reported result
Overall risk of bias
0% 25% 50% 75% 100%

Low risk Moderate risk Serious risk

Fig. 2. (a) Traffic lights plot of the risk of bias assessment according to ROBINS-I for short-term effects of OTM on dental pulp sensitivity. (b) Risk of
bias summary plot of short-term effects of OTM on dental pulp sensitivity.

7
A. Golež et al. Heliyon 9 (2023) e14621

bias, two were evaluated as low risk and one as serious bias risk according to ROBINS-I. Long-term studies were mostly graded to be a
moderate risk; one was graded low risk and one serious risk of bias.

3.3. Meta-analysis

Thirteen studies that evaluated pulpal sensitivity and reported quantitative data were selected for meta-analysis. Both short and
long-term meta-analyses of negative sensitivity risk and EPT thresholds were calculated. Results are presented in Forest plots
(Figs. 4–7).
Short-term OTM had a significant effect on the risk for negative dental pulp sensitivity (P < 0.00001). The overall risk ratio (RR) for
negative pulpal sensitivity (95% CI) was 13.27 (5.80–30.36) times higher compared to the pre-orthodontic baseline. That translates
into approximately 24% (13–35%) higher risk for the tooth to have negative pulpal sensitivity. Heterogeneity among studies was
moderate I2 = 57% [37]. There were significant differences between groups in RR, based on the type of OTM. Leveling and aligning
were associated with higher RR (P < 0.04) compared to expansion (Fig. 6).
Long-term OTM did have a significant effect on RR of negative pulpal sensitivity test (P < 0.00001). At least 8 months after the
initial OTM patients’ RR was 5.76 times higher (95%CI: 2.8–11.86). At the level of the tooth, the net risk of a negative pulp sensitivity
test was 10% (5–15%) higher compared to the pre-orthodontic baseline. Heterogeneity was low I2 = 14%. Due to a low number of
available studies, differentiation between groups was not possible (P = 0.18) Fig. 7.

Risk of bias domains

D1 D2 D3 D4 D5 D6 D7 Overall

Alomari 2011 ++ ++ ++ ++ ++ ++ ++ ++
Briseno 2021 −− −− ++ ++ −− −− ++ −−
Study

Cave 2002 −− −− −− −− ++ ++ ++ −−
Cho 2014 ++ ++ −− ++ −− −− −− −−
Woloshyn 1994 xx −− xx −− −− ++ ++ xx
Domains: Judgement
D1: Bias due to confounding.
D2: Bias due to selection of participants. x Serious
D3: Bias in classification of interventions. − Moderate
D4: Bias due to deviations from intended interventions.
D5: Bias due to missing data. + Low
D6: Bias in measurement of outcomes.
D7: Bias in selection of the reported result.

Bias due to confounding

Bias due to selection of participants
Bias in classification of interventions
Bias due to deviations from intended interventions
Bias due to missing data
Bias in measurement of outcomes
Bias in selection of the reported result
Overall risk of bias
0% 25% 50% 75% 100%

Low risk Moderate risk Serious risk

Fig. 3. (a) Traffic lights plot of the risk of bias assessment according to ROBINS-I for long-term effects of OTM on dental pulp sensitivity. (b) Risk of
bias summary plot of long-term effects of OTM on dental pulp sensitivity.

8
A. Golež et al. Heliyon 9 (2023) e14621

Fig. 4. Forest plot of OTM effects on short-term risk of negative pulpal sensitivity test.

Fig. 5. Forest plot of OTM effects on long-term risk of negative pulpal sensitivity test.

Short-term OTM did also significantly affect the threshold of electrosensitivity test (EPT) P < 0.00001. Teeth undergoing OTM had
4.25 (95%CI: 2.65–5.85) standard deviations and higher EPT thresholds. Heterogeneity was considerable I2 = 100%. There were
significant differences in EPT between groups based on the type of OTM. Leveling type of movement was associated with a higher EPT
threshold compared to intrusive movements (P < 0.00001). Leveling subgroup had considerable heterogeneity I2 = 100%, intrusion
subgroup had low heterogeneity I2 = 0% (Fig. 8).
Orthodontic tooth movement more than 8 months after initiation no longer had a significant effect on the EPT threshold. EPT
threshold was higher by 0.45 SMD (− 0.34 – 1.23) P = 0.26. Heterogeneity was considerable I2 = 100% (Fig. 9).
Random model meta-regression of log(RR) of negative pulpal sensitivity test was plotted in dependence on the mean age of the
participant. Meta-regression confirmed positive relation between mean age and log(RR). Equation: log(RR) = mean age*coefficient +

9
A. Golež et al. Heliyon 9 (2023) e14621

Fig. 6. Forest plot of OTM effects on short-term EPT threshold.

Fig. 7. Forest plot of OTM effects on long-term EPT threshold.

Fig. 8. Meta-regression of mean age on a log of relative risk (RR) for negative pulpal sensitivity test.

constant. Mean age coefficient (95% CI) was 0.296 (95%CI: 0.012–0.579) P = 0.041 (Fig. 8). Meta-regression of orthodontic force
magnitude on log(RR) did not show statistical significance (P > 0.05).
A funnel plot was created to evaluate publication bias (Fig. 9). Sensitivity analysis revealed that the exclusion of any single study
would not change the results in a major way. The direction and significance of the results were unaffected by the use of a statistical
model (fixed vs. random effects) or measure of outcome (risk ratio, odds ratio, risk difference …)

4. Discussion

Orthodontic treatments are very frequently used; however, there are concerns, that OTM could negatively affect the dental pulp
condition, causing further complications [49]. The results of the present study confirmed assumptions that OTM could cause changes

10
A. Golež et al. Heliyon 9 (2023) e14621

Fig. 9. Funnel plot.

in the state of the dental pulp. Meta-analysis of dental pulp sensitivity revealed that short-term OTM caused a significant increase in
pulpal electro-sensitivity threshold; the increased risk of negative pulpal sensitivity test was significantly higher during active OTM
and remained elevated to a lesser degree in the long term.
Dental pulp sensitivity in several studies consistently reported outcomes as several negative sensitivity tests or changes in EPT
thresholds after the application of orthodontic force. That allowed a quantitative analytic approach; a meta-analysis was therefore
employed. As pulpal condition is tooth centered and not patient-centered meta-analysis was conducted on the tooth level. During the
short term, OTM significantly increased the electro-sensitivity test threshold, which could be considered a large effect [50].
To explore high heterogeneity, a subgroup analysis was performed, as previous studies suggested certain types of OTM to be more
hazardous to the condition of the dental pulp [51,52]. Some authors considered intrusive forces (due to the more pronounced apical
direction of pressure) to be especially damaging to pulpal tissue [53,54].
Subgroup analysis revealed an increased EPT threshold in both intrusion and leveling subgroups (Fig. 6). Response to OTM in
subgroups was significantly different; the increase of EPT threshold in leveling group was significantly higher. Based on the available
data, popular assumptions that intrusive forces are more harmful to dental pulp could be rejected. Statistical heterogeneity (measured
by I2 statistic) was considerable in leveling group and negligible in the intrusion group. High heterogeneity could be contributed both
to the properties of data: the number of test teeth in leveling group was very high, which resulted in narrow confidence intervals.
Furthermore, non-overlapping confidence intervals are calculated into high statistical heterogeneity [37]. There is also likely a clinical
reason for the observed high heterogeneity. Leveling and aligning is the first phase of treatment with fixed appliances and is one of the
least controlled phases in orthodontic treatment. It initiates treatment with a high speed of tooth movement and with forces in all
directions; the magnitude of forces depending on the initial malposition of the teeth [55,56]. Results could therefore be very variable,
depending on the difficulty of malocclusion, initial positions of the teeth and patient selection.
In the short-term, during active OTM, the overall risk of a negative sensitivity test was higher compared to baseline risk (Fig. 4).
Heterogeneity was moderate and could be explained by differences due to the tooth movement type. Compared to expansion forces,
orthodontic forces during leveling and aligning phase resulted in a significantly higher risk of pulpal negative sensitivity test compared
to expansion. That is in agreement with previous EPT threshold results. Data indicates compound OTM such as leveling and aligning
affect dental pulp more negatively when compared to OTM in a single direction (expansion). Considering the forces in expansion are
far heavier, that is an unexpected outcome. Could it be partly explained by the different properties of the alveolar bone? Expansion is
possible only in the upper jaw, unlike leveling and aligning which can be performed in both jaws. Even though it is accepted maxillary
lower bone density does affect the speed of OTM, there is, to the best of our knowledge, no data on whether these different bone
properties could affect pulpal state as well [57]. It is, however, important to note there is no clinical trial directly comparing pulpal
sensitivity during leveling and aligning with palatal expansion, results from trials under the same circumstances could be helpful in
explaining these open dilemmas.
Statistical heterogeneity in subgroups was low [37]. The funnel plot of the studies in the meta-analysis was reasonably symmetric
(Fig. 9), indicating no major publication bias [58]. Pulpal sensitivity testing is one of the most prevalent ways to assess pulpal status; it
provides information on the state of pulpal nerve fibers and indirectly assesses their vitality [16,30]. Generally, a positive response to
EPT is interpreted as vital pulp, while changes in the dental pulp during OTM could affect Aδ pulpal nerves [20]. Some advantages of
pulpal sensitivity testing include that it is safe, non-invasive and can be repeated several times [20]. Its limitations are that it may be
technique sensitive; it requires good conductive contact between electrodes and test teeth. The test teeth need to be isolated to avoid
false positives due to gingival sensing or sensing of adjacent teeth [59,60]. For example in patients with fixed appliances, all the wires
on the test tooth should be removed [59]. Sensitivity testing could be unreliable in immature or traumatized teeth [61,62] and are
dependent on patient cooperation [60]. The EPT does not provide information about the vascular supply to the pulp, which is a better
determinant of pulp condition [20]. Some studies indicated that there is a poor correlation between clinical sensitivity and the his­
topathological status of the pulp [63]. However, newer evidence shows, that there is a correlation between pulpal sensitivity threshold
and myelinated nerve fiber density [16]. The observed higher EPT thresholds and higher RR of negative pulpal EPT during OTM could

11
A. Golež et al. Heliyon 9 (2023) e14621

be due to both the immediate pressure or tension on apical nerve fibers or due to hypoxia of the pulpal tissues because of decreased
blood supply [30,42,64]. Pulpal sensitivity test during active OTM should therefore be interpreted with caution, a non-sensitive pulp
during active OTM should not be considered necrotic.
To further explore some possible risk factors as covariates such as the patient’s age and magnitude of force a meta-regression was
used [65,66]. The only confirmed risk factor until now was previous dental trauma [15]. A random-effects meta-regression showed a
significant positive relationship between the logarithm of RR and the patient’s mean age (Fig. 8). Our quantitative data could therefore
confirm the suggested, but so far unconfirmed assumptions that a patient’s age could be a risk factor for dental pulp during active OTM
[13,15,65,66]. With age, a decrease in the lumen of apical foramen, pulpal volume and reduced responsiveness of the dental pulp could
occur, each increasing effects of circulatory disturbances caused by OTM [54,67–70]. Another common professional assumption is that
greater orthodontic forces will elicit more harmful effects on the state of the dental pulp [66,71,72]. Even though there is a sound
scientific basis supporting it, due to the lack of data available, our analysis was unable to confirm the relationship [11,70,72]. For
future research, consistent reporting of force during OTM will be essential.
Compared to the short-term effect of OTM the number of studies that evaluated the long-term effect (more than 8 months after
initial OTM) was markedly lower. The present study is, to the best of our knowledge, the first review to consider the long-term effects of
OTM on dental pulp. The threshold of EPT was in the long-term no longer significantly higher compared to baseline values; all studies
evaluated the effect after the leveling type of movement (Fig. 7). Heterogeneity was high, probably due to the same reasons as pre­
viously discussed. Unlike the EPT threshold, a meta-analysis of the negative pulpal sensitivity risk was significantly increased also in
the long-term (Fig. 5). At least 8 months after the initial OTM the risk for negative pulpal sensitivity was higher compared to the pre-
orthodontic baseline. Differentiation of risks between types of OTM was not possible due to a low number of available studies. As
previously noted, the data on the long-term effects of OTM on the state of dental pulp is very scarce, further research in the area is
necessary [15,24].
From a clinical point of view, our data support the thesis that pulpal response to Aδ fiber stimulation becomes inconsistent during
orthodontic treatment [23,64]. Results of sensitivity testing should therefore be interpreted cautiously [17,41,73]. It should be noted,
that a negative sensitivity test during OTM should not be interpreted as a necrotic pulp since most of the pulps regained their sensitivity
over time [41,42]. A positive relationship between higher risks of negative pulpal sensitivity indicates that younger patients could be at
lower risk for unwanted pulpal reactions during orthodontic treatment. To support this statement, an analysis of the vascular state of
pulpal tissue during active OTM could provide valuable evidence. In case other indicators of pulpal state confirm the patient’s older
age as a risk factor for OTM - a clinical recommendation of treating orthodontic patients as early as reasonably possible could be made.
The systematic review confirms the conclusions of previous authors, that OTM could affect the dental pulp status, measured by
some of its sensitivity indicators [24–27]. As the first review, which used meta-analytic methodology and considered effects on dental
pulp in the long-term, the results bring a new synthesis of available evidence and offer fundaments for new, focused research of the
OTM effect on the state of the dental pulp. However, the quality of pooled evidence can only be as high as the data provided by its
constituent studies. Some limitations of this systematic review with meta-analysis include the substantial diversity in clinical study
design that also resulted in study heterogeneity and the lack of long-term data. Dental pulp sensitivity as an outcome also has limi­
tations due to its indirectness, since its response is highly dependent on the innervation condition of the dental pulp and patient
cooperation [16]. Additional valuable data on dental pulp could be obtained by its direct assessment by molecular markers or his­
tological analysis, which has the disadvantage of being highly invasive.

5. Conclusion

A systematic review confirmed that orthodontic tooth movement could negatively impact the sensitivity of the dental pulp. Or­
thodontic tooth movement increased the EPT threshold and the risk of a negative pulpal sensitivity test. The meta-analysis indicates
that certain types of OTM and the patient’s age could be considered risk factors, influencing the pulpal outcome. The risk of pulpal non-
sensitivity was to a lesser degree also increased in the long term.

Registration

Prospero No. CRD42020198550.

Author contribution statement

Aljaz Golez and Ksenija Cankar: Conceived and designed the experiments; Performed the experiments; Analyzed and interpreted
the data; Contributed reagents, materials, analysis tools or data; Wrote the paper.
Maja Ovsenik: Analyzed and interpreted the data; Contributed reagents, materials, analysis tools or data; Wrote the paper.

Funding statement

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

12
A. Golež et al. Heliyon 9 (2023) e14621

Data availability statement

Data included in article/supp. material/referenced in article.

Declaration of interest’s statement

The authors declare no competing interests.

References

[1] G. Isola, et al., Mechanobiology of the tooth movement during the orthodontic treatment: a literature review, Minerva Stomatol. 65 (5) (2016) 299–327.
[2] R.M. Abdul Wahab, et al., Molecular markers of dental pulp tissue during orthodontic tooth movement: a pilot study, Sci. World J. 2012 (2012), 236427.
[3] L. Vansant, et al., Expression of biological mediators during orthodontic tooth movement: a systematic review, Arch. Oral Biol. 95 (2018) 170–186.
[4] Y. Li, et al., Orthodontic tooth movement: the biology and clinical implications, Kaohsiung J. Med. Sci. 34 (4) (2018) 207–214.
[5] M. Goldberg, et al., Dentin: structure, composition and mineralization, Front. Biosci. 3 (2011) 711–735.
[6] S. Kim, Neurovascular interactions in the dental pulp in health and inflammation, J. Endod. 16 (2) (1990) 48–53.
[7] C.E. Nixon, et al., Histomorphometric study of dental pulp during orthodontic tooth movement, J. Endod. 19 (1) (1993) 13–16.
[8] G. Perinetti, et al., Alkaline phosphatase activity in dental pulp of orthodontically treated teeth, Am. J. Orthod. Dentofacial Orthop. 128 (4) (2005) 492–496.
[9] B. Briseno-Marroquin, et al., Pulp sensitivity changes during orthodontic treatment at different time periods: a prospective study, Clin. Oral Invest. 25 (5) (2021)
3207–3215.
[10] T. Deguchi, et al., The use of small titanium screws for orthodontic anchorage, J Dent Res 82 (5) (2003) 377–381.
[11] R.S. Hamilton, J.L. Gutmann, Endodontic-orthodontic relationships: a review of integrated treatment planning challenges, Int Endod J 32 (5) (1999) 343–360.
[12] M. Ikawa, et al., The effect of short-term tooth intrusion on human pulpal blood flow measured by laser Doppler flowmetry, Arch. Oral Biol. 46 (9) (2001)
781–787.
[13] G. Perinetti, et al., Aspartate aminotransferase activity in pulp of orthodontically treated teeth, Am. J. Orthod. Dentofacial Orthop. 125 (1) (2004) 88–92.
[14] M. Bjorksved, et al., Open vs closed surgical exposure of palatally displaced canines: a comparison of clinical and patient-reported outcomes-a multicentre,
randomized controlled trial, Eur J Orthod 43 (5) (2021) 487–497.
[15] F. Javed, et al., Influence of orthodontic forces on human dental pulp: a systematic review, Arch. Oral Biol. 60 (2) (2015) 347–356.
[16] A. Tenyi, et al., Comparison of the vitality tests used in the dental clinical practice and histological analysis of the dental pulp, Bosn J Basic Med Sci 22 (3)
(2022) 374–381.
[17] H. Jafarzadeh, P.V. Abbott, Review of pulp sensibility tests. Part I: general information and thermal tests, Int Endod J 43 (9) (2010) 738–762.
[18] M. Narhi, et al., Role of intradental A- and C-type nerve fibres in dental pain mechanisms, Proc Finn Dent Soc 88 (Suppl 1) (1992) 507–516.
[19] E. Chen, P.V. Abbott, Dental pulp testing: a review, Int J Dent 2009 (2009), 365785.
[20] J. Lin, N.P. Chandler, Electric pulp testing: a review, Int Endod J 41 (5) (2008) 365–374.
[21] P.M. Dummer, R. Hicks, D. Huws, Clinical signs and symptoms in pulp disease, Int Endod J 13 (1) (1980) 27–35.
[22] Z. Fuss, et al., Assessment of reliability of electrical and thermal pulp testing agents, J. Endod. 12 (7) (1986) 301–305.
[23] C.J. Hall, T.J. Freer, The effects of early orthodontic force application on pulp test responses, Aust. Dent. J. 43 (5) (1998) 359–361.
[24] M. von Bohl, et al., Pulpal reactions to orthodontic force application in humans: a systematic review, J. Endod. 38 (11) (2012) 1463–1469.
[25] F.C. Vitali, et al., Effect of orthodontic force on dental pulp histomorphology and tissue factor expression, Angle Orthod. 91 (6) (2021) 830–842.
[26] F.C. Vitali, et al., Association between orthodontic force and dental pulp changes: a systematic review of clinical and radiographic outcomes, J. Endod. 48 (3)
(2022) 298–311.
[27] T. Weissheimer, et al., Do orthodontic tooth movements induce pulp necrosis? A systematic review, Int. Endod. J. 29 (2021).
[28] L.A. Stewart, et al., Preferred reporting Items for systematic review and meta-analyses of individual participant data: the PRISMA-IPD statement, JAMA 313 (16)
(2015) 1657–1665.
[29] S. Sideri, S.N. Papageorgiou, T. Eliades, Registration in the international prospective register of systematic reviews (PROSPERO) of systematic review protocols
was associated with increased review quality, J. Clin. Epidemiol. 100 (2018) 103–110.
[30] F.A. Alomari, R. Al-Habahbeh, B.K. Alsakarna, Responses of pulp sensibility tests during orthodontic treatment and retention, Int Endod J 44 (7) (2011)
635–643.
[31] F. Taspinar, et al., The histopathological investigation of pulpal tissue following heavy orthopaedic forces produced by rapid maxillary expansion, J. Int. Med.
Res. 31 (3) (2003) 197–201.
[32] J.A. Sterne, et al., ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions, BMJ 355 (2016) i4919.
[33] L.A. McGuinness, J.P.T. Higgins, Risk-of-bias VISualization (robvis): an R package and Shiny web app for visualizing risk-of-bias assessments, Res. Synth.
Methods 12 (1) (2021) 55–61.
[34] H.E. Flint, J.E. Harrison, How well do reports of clinical trials in the orthodontic literature comply with the CONSORT statement? J. Orthod. 37 (4) (2010)
250–261.
[35] B.C. Wallace, et al., Meta-Analyst: software for meta-analysis of binary, continuous and diagnostic data, BMC Med. Res. Methodol. 9 (2009) 80.
[36] M. Cumpston, et al., Updated guidance for trusted systematic reviews: a new edition of the Cochrane Handbook for Systematic Reviews of Interventions,
Cochrane Database Syst. Rev. 10 (2019) ED000142.
[37] J.P. Higgins, S.G. Thompson, Quantifying heterogeneity in a meta-analysis, Stat. Med. 21 (11) (2002) 1539–1558.
[38] F.A. Sabuncuoglu, S. Ersahan, Comparative evaluation of pulpal blood flow during incisor intrusion, Aust. Orthod. J. 31 (2) (2015) 171–177.
[39] E. Khoshbin, et al., Evaluation of sensibility threshold of dental pulp to electric pulp test (EPT) in the teeth under fixed orthodontic treatment with 0.014 and
0.012 initial NiTi Archwire, J. Clin. Diagn. Res. 13 (1) (2019) ZC16–ZC19.
[40] A.H. Leavitt, et al., A longitudinal evaluation of pulpal pain during orthodontic tooth movement, Orthod. Craniofac. Res. 5 (1) (2002) 29–37.
[41] R. Veberiene, et al., Effects of intrusive force on selected determinants of pulp vitality, Angle Orthod. 79 (6) (2009) 1114–1118.
[42] S.G. Cave, T.J. Freer, H.M. Podlich, Pulp-test responses in orthodontic patients, Aust. Orthod. J. 18 (1) (2002) 27–34.
[43] G. Han, et al., Pulp vitality and histologic changes in human dental pulp after the application of moderate and severe intrusive orthodontic forces, Am. J.
Orthod. Dentofacial Orthop. 144 (4) (2013) 518–522.
[44] J.J. Cho, S. Efstratiadis, G. Hasselgren, Pulp vitality after rapid palatal expansion, Am. J. Orthod. Dentofacial Orthop. 137 (2) (2010) 254–258.
[45] H. Woloshyn, et al., Pulpal and periodontal reactions to orthodontic alignment of palatally impacted canines, Angle Orthod. 64 (4) (1994) 257–264.
[46] J. Modaresi, et al., The effect of orthodontic forces on tooth response to electric pulp test, Iran. Endod. J. 10 (4) (2015) 244–247.
[47] S. Naoum, et al., Changes in pulp blood flow and pulp sensibility resulting from surgically assisted rapid maxillary expansion: a clinical study, Am. J. Orthod.
Dentofacial Orthop. 155 (5) (2019) 632–641.
[48] R. Veberiene, et al., Change in dental pulp parameters in response to different modes of orthodontic force application, Angle Orthod. 80 (6) (2010) 1018–1022.
[49] T.W. Popp, J. Artun, L. Linge, Pulpal response to orthodontic tooth movement in adolescents: a radiographic study, Am. J. Orthod. Dentofacial Orthop. 101 (3)
(1992) 228–233.
[50] J. Cohen, Statistical Power Analysis for the Behavioral Sciences, second ed., L. Erlbaum Associates. xxi, Hillsdale, N.J., 1988, p. 567.

13
A. Golež et al. Heliyon 9 (2023) e14621

[51] B.A. Ramazanzadeh, et al., Histological changes in human dental pulp following application of intrusive and extrusive orthodontic forces, J. Oral Sci. 51 (1)
(2009) 109–115.
[52] Y.A. Mostafa, K.G. Iskander, N.H. El-Mangoury, Iatrogenic pulpal reactions to orthodontic extrusion, Am. J. Orthod. Dentofacial Orthop. 99 (1) (1991) 30–34.
[53] M.J. Guevara, S.G. McClugage Jr., Effects of intrusive forces upon the microvasculature of the dental pulp, Angle Orthod. 50 (2) (1980) 129–134.
[54] A. Stenvik, I.A. Mjor, Pulp and dentine reactions to experimental tooth intrusion. A histologic study of the initial changes, Am. J. Orthod. 57 (4) (1970)
370–385.
[55] R.P. McLaughlin, J.C. Bennett, Bracket placement with the preadjusted appliance, J. Clin. Orthod. 29 (5) (1995) 302–311.
[56] R.P. McLaughlin, J.C. Bennett, Evolution of treatment mechanics and contemporary appliance design in orthodontics: a 40-year perspective, Am. J. Orthod.
Dentofacial Orthop. 147 (6) (2015) 654–662.
[57] T. Chugh, et al., Bone density and its importance in orthodontics, J Oral Biol Craniofac Res 3 (2) (2013) 92–97.
[58] M. Egger, et al., Bias in meta-analysis detected by a simple, graphical test, BMJ 315 (7109) (1997) 629–634.
[59] J.W. Myers, Demonstration of a possible source of error with an electric pulp tester, J. Endod. 24 (3) (1998) 199–200.
[60] R.L. Cooley, J. Stilley, R.M. Lubow, Evaluation of a digital pulp tester, Oral Surg. Oral Med. Oral Pathol. 58 (4) (1984) 437–442.
[61] D.C. Johnsen, Innervation of teeth: qualitative, quantitative, and developmental assessment, J Dent Res 64 Spec (1985) 555–563.
[62] A. Waikakul, J. Kasetsuwan, J. Punwutikorn, Response of autotransplanted teeth to electric pulp testing, Oral Surg. Oral Med. Oral Pathol. Oral Radiol. Endod.
94 (2) (2002) 249–255.
[63] S. Seltzer, I.B. Bender, H. Nazimov, Differential diagnosis of pulp conditions, Oral Surg. Oral Med. Oral Pathol. 19 (1965) 383–391.
[64] R.R. Burnside, F.M. Sorenson, D.L. Buck, Electric vitality testing in orthodontic patients, Angle Orthod. 44 (3) (1974) 213–217.
[65] P.J. Barwick, D.S. Ramsay, Effect of brief intrusive force on human pulpal blood flow, Am. J. Orthod. Dentofacial Orthop. 110 (3) (1996) 273–279.
[66] P.A. Hamersky, A.D. Weimer, J.F. Taintor, The effect of orthodontic force application on the pulpal tissue respiration rate in the human premolar, Am. J. Orthod.
77 (4) (1980) 368–378.
[67] B.B. Marroquin, M.A. El-Sayed, B. Willershausen-Zonnchen, Morphology of the physiological foramen: I. Maxillary and mandibular molars, J. Endod. 30 (5)
(2004) 321–328.
[68] A. Morfis, et al., Study of the apices of human permanent teeth with the use of a scanning electron microscope, Oral Surg. Oral Med. Oral Pathol. 77 (2) (1994)
172–176.
[69] E.H. Ponce, J.A. Vilar Fernandez, The cemento-dentino-canal junction, the apical foramen, and the apical constriction: evaluation by optical microscopy,
J. Endod. 29 (3) (2003) 214–219.
[70] F.A. Sabuncuoglu, S. Ersahan, Changes in maxillary molar pulp blood flow during orthodontic intrusion, Aust. Orthod. J. 30 (2) (2014) 152–160.
[71] R.E. Unsterseher, et al., The response of human pulpal tissue after orthodontic force application, Am. J. Orthod. Dentofacial Orthop. 92 (3) (1987) 220–224.
[72] Y. Ren, J.C. Maltha, A.M. Kuijpers-Jagtman, Optimum force magnitude for orthodontic tooth movement: a systematic literature review, Angle Orthod. 73 (1)
(2003) 86–92.
[73] I.B. Bender, et al., The optimum placement-site of the electrode in electric pulp testing of the 12 anterior teeth, J. Am. Dent. Assoc. 118 (3) (1989) 305–310.

14