Clinical Research
Understanding External Cervical Resorption
in Vital Teeth
Athina M. Mavridou, DDS, MSc,*† Esther Hauben, MD, PhD,‡ Martine Wevers, PhD,§
Evert Schepers, DDS, PhD,* Lars Bergmans, DDS, MSc, PhD,* and Paul Lambrechts, DDS, PhD*
Abstract
Introduction: The aim of this study was to investigate
the 3-dimensional (3D) structure and the cellular and tis-
sue characteristics of external cervical resorption (ECR)
in vital teeth and to understand the phenomenon of
ECR by combining histomorphological and radiographic
findings. Methods: Twenty-seven cases of vital perma-
nent teeth displaying ECR were investigated. ECR
E xternal cervical resorp-
diagnosis was based on clinical and radiographic exam-
ination with cone-beam computed tomographic imag-
ing. The extracted teeth were further analyzed by
using nanofocus computed tomographic imaging, hard
tissue histology, and scanning electron microscopy.
Results: All examined teeth showed some common
characteristics. Based on the clinical and experimental
findings, a 3-stage mechanism of ECR was proposed.
At the first stage (ie, the initiation stage), ECR was initi-
ated at the cementum below the gingival epithelial
attachment. At the second stage (ie, the resorption
stage), the resorption invaded the tooth structure
3-dimensionally toward the pulp space. However, it
did not penetrate the pulp space because of the pres-
ence of a pericanalar resorption-resistant sheet. This
layer was observed to consist of predentin, dentin,
and occasionally reparative mineralized (bonelike) tis-
sue, having a fluctuating thickness averaging 210 mm.
At the last advanced stage (ie, the repair stage), repair
took place by an ingrowth and apposition of bonelike
tissue into the resorption cavity. During the reparative
stage, repair and remodeling phenomena evolve simul-
taneously, whereas both resorption and reparative
stages progress in parallel at different areas of the tooth.
Conclusions: ECR is a dynamic and complex condition
that involves periodontal and endodontic tissues. Using
clinical, histologic, radiographic, and scanning micro-
scopic analysis, a better understanding of the evolution
of ECR is possible. Based on the experimental findings, a
3-stage mechanism for the initiation and growth of ECR
is proposed. (J Endod 2016;-:1–15)
From the *Department of Oral Health Sciences, BIOMAT Research Cluster, KU Leuven and University Hospitals Leuven, Leuven, Belgium; †Private Practice, Endo
Rotterdam, Rotterdam, The Netherlands; ‡Department of Imaging and Pathology, KU Leuven and University Hospitals Leuven, Leuven, Belgium; and §Department
of Materials Engineering (MTM), KU Leuven, Leuven, Belgium.
Address requests for reprints to Dr Athina-Maria Mavridou, Department of Oral Health Sciences, BIOMAT Research Cluster, Kapucijnenvoer 33, 3000 Leuven,
Belgium. E-mail address: athimavridou@gmail.com
0099-2399/$ - see front matter
Copyright ª 2016 American Association of Endodontists.
http://dx.doi.org/10.1016/j.joen.2016.06.007
JOE — Volume -, Number -, - 2016
Key Words
Cone-beam computed tomography, external cervical resorption, hypoxia, nanofocus
computed tomography, reparative mineralized tissue
tion (ECR) has at-
tracted the interest of
Significance
This work helps in exploring the evolving phenom-
ena of ECR in vital teeth. By understanding the 3D
endodontists and dental
nature and repair mechanisms, which are underes-
clinicians because of its
timated because of radiographic limitations and
complex and invasive
lack of know-how, a more adequate treatment
pattern (1, 2). This inte-
decision will be achieved.
rest is confirmed by the
amount of recently pub-
lished articles in this field (3, 4). However, the majority of this research work
focuses only on individual ECR case reports. Indeed, to date, only a few have
attempted to thoroughly analyze the phenomena that occur during ECR (5–13). The
first fundamental work was performed by Heithersay in which an extended report on
ECR was introduced based on the combination of clinical, radiographic,
epidemiological, and histopathological findings (6–10). This researcher observed
that there are various degrees of ECR progression, indicating that this condition
evolves in different stages. It should be mentioned that, in current clinical practice,
the treatment and prognosis of ECR are still based on the classification proposed by
Heithersay (14, 15). However, this classification has 2 main limitations:
1. This approach is only based on the 2-dimensional extent of the resorption. Indeed,
the implementation of more recent in vivo and ex vivo techniques such as cone-
beam computed tomographic scanning and nano–computed tomographic (CT) im-
aging, respectively, has provided new information on the 3-dimensional (3D) nature
of this condition (16–18).
2. Heithersay’s classification does not take into consideration the reparative nature
of ECR. Recent reports revealed that ECR could be both destructive and reparative
(16, 18).
The phenomena that occur during ECR are very complex (1). For example, during
the initiation phase, the nature and structure of the portal(s) of entry (starting point of
the resorption) can influence the progression of ECR (18). Furthermore, the pattern
and types of cells involved during ECR progression and repair are still unclear (1).
In addition, it is believed that the pulp tissue is not involved in ECR (1) and that
resorption does not penetrate the pulp because of the presence of a resistant
External Cervical Resorption in Vital Teeth 1
Clinical Research
mineralized pericanalar layer (18). The importance of this layer,

27
x
x
x
x
which is referred to as the pericanalar resorption-resistant sheet
(PRRS) (18), and its relationship to the pulp tissue and ECR evolution

26
x
x
x

x
should be investigated.
Therefore, this study aimed to provide a thorough overview on the

25
initiation, progression, and especially the repair phase of ECR. In order

x
x
x

x
to get a better understanding on the evolving mechanisms, the recently
established multimodular approach proposed by Mavridou et al (18)

24
x
x
x
x
was applied on 27 individual ECR clinical cases. This methodology
combines clinical and epidemiological findings, in vivo CBCT imaging,

23
x
x
x
x
ex vivo 3D nanofocus CT imaging, scanning electron microscopic
analysis, and histologic analysis.

22
x
x
x
x
x
In this way, a consistent approach is applied in order to bridge
the existing know-how and proposed theories of ECR. Indeed, most

21
x
x
x
x
of the published work only presents individual and autonomous
case studies, which makes it very difficult for clinicians to combine

20
x
x
x
x
this information and draw conclusions on how to interpret and
manage this complex condition (14, 19–21).

19
x
x
x
x
x
Materials and Methods

18
x
x

x
In this study, 27 patients who were referred to the University
Hospital Leuven, Leuven, Belgium, for advice and possible treatment

17
x
x
x
x

x
of teeth with evidence of ECR were included. The diagnosis of ECR
was based on clinical and radiographic (digital periapical and CBCT

16
x
x
x
x
imaging) examination. All ECR cases involved vital teeth as confirmed

ECR cases
by the initial diagnosis. The analysis of ECR case was done in 2 steps:

15
clinical examination and ex vivo analysis.

x
x
x
x

CBCT, cone-beam computed tomographic; ECR, external cervical resorption; nano-CT, nano–computed tomographic; SEM, scanning electron microscopy.
14
Clinical Examination

x
x
x
x
The patients were clinically examined by means of an optical

13
x
x
x
x
x
microscope (Zeiss, Oberkochen, Germany). The aim was to
observe the existence of tooth discoloration and cracks; examine 12
the periodontal health and more specifically the existence of cal- x
x

x
culus and plaque and measure the pockets’ depth; evaluate the
11

probing feasibility of the ECR cavity and bleeding during probing;

x
x

notice if there was any evident resorption of the tooth structure; x

and try to identify if the resorption cavity contained granulation
10
x
x
x
x

tissue.
Apart from the clinical examination, an interview was conducted
9
x
x
x
x

based on our clinical and research experience (17, 18, 2–24) and
8
x
x
x
x

existing literature (1–3, 8, 25–31). The collected information was

linked to the dental and medical history of the patient, which was
7
x
x
x
x

provided by the referring dentists in an attempt to indirectly identify

some potential predisposing factor(s) involved in ECR.
6
x
x
x
x
x
TABLE 1. An Overview of the Techniques Used per Case

5
x
x
x
x
x

Ex Vivo Analysis
After clinical examination, a prescreening of selected case studies
4
x
x
x
x
x

was made with the use of a CBCT scanner (3D Accuitomo 80; J Morita,
Kyoto, Japan) in order to confirm the diagnosis, evaluate the extent of
3
x
x
x
x
x

the resorption, and judge treatability (32–34). The exposure

2
x
x
x

parameter settings were set at 90 kV, 5.0 mA, and 17.5 seconds.
The resolution parameters included a field of view of 6  6, and
1
x
x
x

the images were reconstructed with a slice interval of 0.125 mm

and a slice thickness of 0.500 mm (17, 18). Based on the outcome
Clinical examination
Used techniques

of the CBCT analysis, the long-term prognosis of the examined cases

Nano-CT imaging

was determined as poor, and, thus, extraction was indicated.

CBCT imaging
Digital x-ray

After extraction, the extracted teeth were fixed in a CaCO3-

Histology

buffered formalin solution as described by Duyck et al (35). Based

on the experimental approach (multimodular approach) proposed
SEM

by Mavridou et al (18), nano-CT imaging, hard tissue histology, and

scanning electron microscopic (SEM) microscopic analysis were

2 Mavridou et al. JOE — Volume -, Number -, - 2016

 Clinical Research

Figure 1. ECR of tooth #6. (A) Radiographic view. (B) Macroscopic view after extraction. (C) Enlargement of the portal of entry (initiation point of resorption).
(D) A transaxial histologic image at the portal of entry. (E) Enlargement of the red area in D. (F) Enlargement of the yellow in E showing reparative bonelike tissue
and Heithersay resorption channel on dentin. (G) Enlargement of the black area in F showing osteoid tissue and further mineralized bonelike tissue. (H) Enlarge-
ment of the red area in F showing bacteria and small multinucleated cells (red arrows).

JOE — Volume -, Number -, - 2016 External Cervical Resorption in Vital Teeth 3

Clinical Research

Figure 2. ECR of tooth #6. (A) Radiographic view. (B) Clinical view showing signs of pathological tooth wear and plaque accumulation. (C) Macroscopic view
after extraction. (D) Enlargement at the portal of entry. (E) coronal, sagittal, and transaxial nano-CT images of tooth #6 showing the ingrowth and apposition of
reparative bonelike tissue through the portal of entry, resorption channels, and the PRRS. The interface between resorption and repair is clearly visible as a radio-
pacity shift (white arrows).

applied on the extracted teeth in order to study the extent and growth
mechanisms of ECR. A detailed overview of the performed tests is pre-
sented in Table 1. A description of the instruments is given hereafter.
Nano-CT Imaging
During nano-CT scanning procedures, the teeth were wrapped in
parafilm and kept in formalin solution between the different scans. To
prevent possible drying out of the teeth during 3D tomography, the
scanning time was kept as short as possible.
A Phoenix NanoTom S (GE Measurement and Control Solutions,
Wunstorf, Germany) scanner was used. It was equipped with a
180-kV/15-W high-performance nanofocus X-ray tube and a
2304  2304 pixel Hamamatsu detector (Hamamatsu Photonics K.K,
Hamamatsu, Japan). A tungsten target was used, and the applied voltage
and current were 80 kV and 320 mA, respectively, with an exposure time
of 500 milliseconds. The fast scan mode was used (ie, a frame averaging
of 1 and no image skip, resulting in a scanning time of 20 minutes).
Because the height of the examined teeth was larger than the field of
view, 2 scans were made to capture the full specimen, resulting in a final
scanning time of 40 minutes. A 0.5-mm filter of copper was used to
reduce the beam hardening effect (36). After scanning, the radiographs
were reconstructed using NRecon software (version 1.6.9.8; Bruker
micro-CT, Kontich, Belgium). The resulting images had an isotropic
voxel size of 7 mm3. Structural analysis was performed using CTAn soft-
ware (version 1.14, Bruker micro-CT). By using this software, the
reparative mineralized tissue was segmented from dentin. In addition,
the PRRS tissue was selected as a volume of interest, and the thickness
of this structure was calculated by using the CTAn 3D analysis routines.
Multiple 3D models were made using the same scan to visualize simul-
taneously the different tooth and ECR structures, namely cementum,
enamel, dentin, pulp, pulp stones, resorption cavity, reparative tissue,
PRRS tissue, and resorption channels.
Visualization of the 3D surface and 3D volume models was done
with CTVol (version 2.2.3.0, Bruker micro-CT) and CTVox (version
2.7, Bruker micro-CT), respectively. Different colors and transparen-
cies were applied to each structure to create the optimal visual proper-
ties. Further adjustment and enhancement of the 3D view were made
with the creation of animated movies.
By loading the reconstructed set of slices in DataViewer (version
1.5.0, Bruker micro-CT), the internal structure of the tooth along all

4 Mavridou et al. JOE — Volume -, Number -, - 2016


Figure 3. (A) The histologic image matches the (B) nano-CT image of tooth #31. Observe the calculus deposition at the cervical tooth part and the ingrowth
of reparative bonelike tissue, which leads to local fusion with the adjacent alveolar bone. Observe the different radiographic contrast of the pericanalar dentin
(multiple black arrows).
orientation planes was best revealed, and the optimal cutting axis for the
hard tissue histologic analysis was selected. The teeth were then pre-
pared for histologic analysis.
Histologic Analysis
The teeth were dehydrated in a graded series of ethanol concen-
trations (70%, 80%, 90%, 97%, and 100%) and then embedded in
methylmethacrylate. The histologic sections were prepared in a trans-
axial, sagittal, or coronal direction according to the plane of interest
(as defined previously by nano-CT imaging) using a rotary microtome
and a diamond saw (Leica PSI600; Leica, Wetzlar, Germany). The sec-
tions were reduced to a final thickness of 70 mm by grinding and polish-
ing (Buehler Minimet Polisher, Chicago, IL). The specimens were then
stained with a combination of Stevenel’s blue and Von Gieson’s picro-
fuchsin, visualizing mineralized tissue (red) and nonmineralized tissue
(blue-green). The sections were evaluated using a DM2500 M Leica mi-
croscope with a digital HD camera (Leica DFC295) by means of the Le-
ica Application Suite color image software. Overview and detailed
images were obtained using a magnification up to 63. By using Leica
Application Suite LAS software, multiple histologic images were stitched
together to reconstruct the whole histologic section.
SEM Analysis
The teeth that were broken during extraction were prepared for
SEM evaluation in order to illustrate morphological characteristics of
ECR. After extraction, the organic tissue was dissolved by immersion
of the teeth specimens in sodium hypochlorite (3.5%) for 24 hours.
The teeth samples were then mounted on aluminum stubs, sputter
coated with gold, and examined under a scanning electron microscope
at different magnifications (XL30 FEG SEM; Philips, Eindhoven, The
Netherlands).
Results
All ECR cases of vital teeth shared the following common charac-
teristics:
JOE — Volume -, Number -, - 2016
Clinical Research
1. The portal(s) of entry (initiation point of resorption)
2. The 3D resorption progression
3. The structure of the PRRS tissue and pulp reaction
4. The repair that occurs by substitution of the resorbed tissues by
reparative mineralized (bonelike) tissue when dentin is in contact
with the adjacent bone
5. The active remodeling of this reparative bonelike tissue
Analysis of each of these characteristics is given hereafter.
Portal(s) of Entry
The portal(s) of entry was located in the cementum below the
gingival epithelial attachment. In our study, 2 different patterns were
observed in this area (Figs. 1–4):
1. Resorption and invasion of granulation tissue at the portal border
(Fig. 1). Resorption lacunae were visible on cementum and dentin,
often containing multinucleated cells (Fig. 1). In the resorption cav-
ity, connective tissue was present with a dense inflammatory lympho-
plasmacytic infiltrate. Epithelial tissue is often noted to cover the
granulation tissue (Fig. 1).
2. Repair by ingrowth of reparative bonelike tissue through the portal
of entry and local fusion of the adjacent alveolar bone with dentin
(Figs. 2–4). In this situation, the PDL tissue was absent (Fig. 4),
and there were no signs of PDL regeneration. Macroscopically,
the portal of entry was sometimes difficult to identify because it
was replaced by bonelike tissue (Fig. 2).
In the portal of entry, active resorption is seen at close proximity
with active repair and osteoid (nonmineralized bone matrix) formation
by osteoblastlike cells (Fig. 1). Bacteria (Fig. 1), calculus, and plaque
(Figs. 3 and 4) were also regularly found.
In the apical part of the portal of entry (Fig. 4), a layer of newly
formed cementum and a re-established PDL were observed. Collagen
fibers were found to penetrate into the newly formed cementum and
adjacent to the alveolar bone. Also, histologic analysis did not reveal
External Cervical Resorption in Vital Teeth 5
Clinical Research

Figure 4. (A) A histologic image of tooth #31 with ECR. Local fusion between the adjacent alveolar bone and the dentin is evident. (B) Enlargement of area 1 in A
showing the apical part of the portal of entry. Repair of the root resorption by reparative cementum and regeneration of the PDL are observed. However, more
coronal, there is no PDL evident (area 4). (C) Enlargement of area 2 in A showing calculus and vascularized granulation tissue in the coronal part of the portal of
entry. (D) Enlargement of area 3 in A showing a re-established PDL and reparative cementum.

Figure 5. (A) CBCT, (B) nano-CT, and (C) histologic imaging of tooth #14 with ECR. Observe the portal of entry and the resorption extension between the pulp
horns and on the enamel. The resorption progresses toward the pulp and in an apical direction, and repair takes place by bonelike tissue.

6 Mavridou et al. JOE — Volume -, Number -, - 2016


Figure 6. (A) A histologic image of the PRRS. (B) When ECR progresses
toward the pulp, odontoblasts can become atrophic. (C) In other cases, odon-
toblasts react as ECR attacks by producing predentin. PRRS consists occasion-
ally of reparative bonelike tissue.
any presence of epithelial cell rests of Malassez (37, 38) in close
proximity to the portal of entry.
Resorption Progression
All examined teeth showed a similar resorption progression pattern.
ECR initiated through 1 or more portals of entry (Figs. 2, 4, and 5) and
then progressed toward the pulp space (Figs. 2–5), leaving the PRRS
JOE — Volume -, Number -, - 2016
Clinical Research
intact (Figs. 2–4, 6–9). The tooth structure was invaded in a 3D way,
resulting in cementum, dentin (Fig. 4), and enamel (Fig. 5) resorption
as well. In this way, multiple resorption channels (Figs. 1 and 2) and
interconnections with the PDL (portals of exit) were created. ECR pro-
gressed around the pulp space and, in particular, below the pulp floor
and between the pulp horns (Figs. 3 and 5). (Supplemental Videos
S1–S3 are available online at www.jendodon.com.)
Resorption (clastic) cells were identified as large osteoclastlike
multinucleated cells located within resorption lacunae having a
size at around 20  30 mm (Figs. 9–11). The nuclei polarity
and the dispersed red spots observed in their cytosol, which
resemble lysosomes filled with acid phosphatase, indicate that these
osteoclastlike cells were active (Figs. 10 and 11).
Often, clastic cells were found to be detached (resting) from the
resorption lacunae (Fig. 10). In these cases, resorption lacunae were
populated either with other types of cells, such as mononuclear
phagocytes, or with osteoid tissue and entrapped osteoblastlike cells
(Figs. 9 and 11).
The border between resorption and tooth tissue was visible as a
basophilic line, which ultimately became the repair border between
newly formed reparative bonelike tissue and resorbed dental tissue
(Figs. 2 and 12).
PRRS Tissue and Pulp Reaction
The PRRS tissue consisted of predentin, dentin, and eventually
reparative (bonelike) tissue apposition (Figs. 6 and 7). The
thickness of the PRRS was accurately calculated by using the 3D
nano-CT data set, and it was found to range from 70 up to 490 mm
with an average value of 210  60 (standard deviation) mm. In the cor-
onal part of the root, the PRRS was thinner with occasional disruptions
(Figs. 3, 5, and 8; Supplemental Video S2). Alternatively, in the middle
and apical part the PRRS was thicker, whereas at the most apical part of
the root it was completely absent (Fig. 3; Supplemental Videos S1
and S2). In some areas, partial substitution of the PRRS tissue with
reparative bonelike tissue was revealed (Fig. 7). (Supplemental
Videos S1 and S2 are available online at www.jendodon.com.)
Major histologic findings in the pulp space include diffuse cal-
cifications and the formation of pulp stones (Figs. 3, 8, and 9),
which could be free in the pulp space or attached to dentin and
the PRRS (Fig. 8). In Figure 8, it is clearly visible that there is a
modification of the pulp tissue consistency, with a decrease of the
cellular elements and an increase of the intercellular substance of
the pulp tissue because of calcification. This modification of the
pulp tissue consistency was also visible in areas with small PRRS dis-
ruptions (Fig. 8). Other observations included hyalinosis (thickening
of the walls) of the blood vessels (Fig. 8), increased deposition
of predentin (Fig. 6), and the presence of atrophic odontoblasts
(Figs. 6 and 7).
Reparative Bonelike Tissue
All examined teeth showed repair when the dentin was in contact
with the adjacent bone. This repair took place by an ingrowth and
apposition of hard (bonelike) tissue through the portal(s) of entry
into the tooth (Figs. 2–5). The extent of repair was evaluated based
on the experimental approach of Mavridou et al (18) and is presented
in the form of animated movies (Supplemental Videos S1–S3). In
Figure 2, it is clearly visible that reparative bonelike tissue apposition
took place also in the periphery of the resorption cavity. Reparative
tissue resembles mainly lamellar trabecular bone, which is at some
areas combined with woven bone formed in a rapid bone repair re-
modeling cycle (Figs. 11–13). Osteoblastlike cells (Figs. 7 and 11)
External Cervical Resorption in Vital Teeth 7
Clinical Research
Figure 7. (A) Partial substitution of the PRRS tissue by reparative bonelike tissue. (B) Enlargement of the black area in A. The reparative bonelike tissue is formed
by osteoblastlike cells (Ob), which have a characteristic alignment and produce osteoid tissue.
are located immediately above the osteoid (Figs. 7, 11, and 12), which
represents the newly formed bone matrix. Osteocytelike cells are
found trapped within lacunae (Fig. 12). The interface between re-
sorbed and repaired (bonelike) tissue looks cohesive, and its bound-
aries are distinguished by a radiopacity shift (Figs. 2 and 3) or a fine
basophilic strap (Fig. 12). (Supplemental Videos S1–S3 are available
online at www.jendodon.com.)
Active Remodeling of Reparative Bonelike Tissue
Signs of active and dynamic remodeling of the reparative
bonelike tissue were visible with resorption lacunae, clastic, and blastic
cells (Figs. 10 and 11). Clastic cells can be easily discerned by
their giant morphology, multiple nuclei, and characteristic
cytoplasm (Figs. 10 and 11). The red spots within the cytoplasm
possibly correspond to lysosomes filled with acid phosphatase
(Figs. 10 and 11).
Apart from the clastic cells, other cells associated with bonelike
tissue are also identified. A characteristic alignment of blastic cells asso-
ciated with osteoid matrix formation (Figs. 7 and 11), and stellate cells
trapped into the reparative bone tissue resembling osteocytes (Fig. 12)
were seen. Bonelike reparative tissue is surrounded by connective tis-
sue, having a fibrous matrix (Fig. 12), blood vessels (Fig. 12), and a
variety of different cells, namely fibroblasts, mast cells, leukocytes,
and adipocytes (fat cells) (Fig. 9).
It should be emphasized that active resorption of dentin, active
repair by osteoid formation, and remodeling of the bonelike tissue
were observed to occur simultaneously at different areas of the tooth
8 Mavridou et al.
(Figs. 10 and 11). It is clearly visible that these phenomena are in dy-
namic equilibrium. Furthermore, histologic observation revealed that
the same type of clastic cells were involved during dentin resorption
and remodeling of the reparative bonelike tissue (Figs. 10 and 11).
A detailed overview of the experimental techniques used and phe-
nomena that can be observed with each technique are presented in
Table 2 in order to help the readers understand the experimental
approach and applicability.
Discussion
Histologic and nano-CT findings indicated that similar phenomena
occur in all cases, regardless of the etiology. However, the different
extent of these phenomena shows that ECR possibly consists of various
stages.
It was found that ECR is mainly characterized by 3 major stages,
namely, resorption initiation (first stage), resorption progression (sec-
ond stage), and repair (third stage).
Resorption Initiation
In the first stage of ECR evolution, a local destruction/disruption of
the normal PDL structure and homeostasis takes place (13, 39). Injury
of the PDL will lead to the formation of a blood clot and a subsequent
localized inflammation (40). Macrophages then migrate into the
wounded area and, in addition to wound debridement, help in the for-
mation of granulation tissue. This healing process is evident by the for-
mation of granulation tissue from the adjacent alveolar bone (41). This
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 Clinical Research

Figure 8. (A) Histologic images from tooth #11 with ECR. (A) Small PRRS disruptions are combined with excessive calcification of the pulp space close to the
resorption attack. (B) Enlargement of the red area in A showing hyalinosis (thickening of the walls) of the blood vessels (black arrows) and pulp stone formation.
(C) Pulp stone attached at the PRRS. (D) Pulp tissue consistency modification after the PRRS disruption (black area). (E) Enlargement of the black area in D. Note
the area of inflammation with excessive blood vessel formation.

granulation tissue could reach the dentin through an exposure in the
cementoenamel junction. This ‘‘gap’’ could be caused by a localized
cementum removal, brought about by traumatic damage or a cemental
tear (42), or caused by a natural incomplete closure of enamel over
cementum at this area (43, 44). Thus, the exposed dentin could be
immunologically vulnerable to a resorptive attack from the adjacent
bone or the circulating immune cells. Depending on the tissue that it
is adjacent to the exposed dentin at the portal of entry, 3 different
phenomena may occur (45). In the first case, if the wounded area be-
comes repopulated with bone cells, this will lead to ankylosis (fusion
between bone and exposed dentin) (41, 46, 47). In the second case,
if the wound is repopulated by PDL cells, regeneration of the PDL
and cementum formation will take place (41, 46, 47). In the third
case, if exposed dentin is in contact with gingival connective tissue,
no repair will take place (48).
In the majority of our examined cases, it was clearly visible that, at
the portal of entry(s), no PDL structure was evident and that there was a
local fusion and ingrowth of the alveolar bone inside the resorption cav-
ity (Fig. 4). This suggests that the PDL locally failed to survive and/or
regenerate, and repair by bone formation occurred.
In order for ECR to continue, a stimulating factor is required. It has
been proposed that infection (bacteria), continuous mechanical force
(orthodontic treatment), or a combination of these factors can stimu-
late ECR continuation (39, 49).

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Clinical Research

Figure 9. (A) A transaxial histologic image of tooth #11. (B) Enlargement of the red area in A showing the resorption area on dentin. (C and D) Enlargement of
black areas in B showing osteoclastlike (clastic) cells and resorption lacunae of dentin populated with other types of cells. (E) Fat cells.

Recent evidence suggests that severe impairment of the peri-
odontal vasculature leads to a local hypoxic microenvironment of the
PDL cells (50). However, hypoxia (low oxygen tension) damages the
metabolism and impedes recovery of human PDL fibroblasts (51).
Therefore, it is best to repopulate the damaged PDL area by bone cells.
Furthermore, the synergetic effect of hypoxia and bacteria in the PDL
accelerates inflammation (52).
Hypoxia has also been reported to have a significant influence on
bone resorption. Recent reports in bone research show that the phe-
nomenon of a reduced or disrupted supply of oxygen to tissues is asso-
ciated with osteoclast differentiation from human (53) monocytes and
their activation (54, 55). It is has been proven that hypoxia accelerates
bone resorption (56) by increasing osteoclast activity and viability in a
time- and oxygen-dependent manner (54). It also inhibits bone forma-
tion (57) by inhibiting osteoblast growth, differentiation, and collagen
production (55).
Hypoxia has been associated with the activation of feline osteo-
clasts and feline odontoclastic resorptive lesions (58, 59), with PDL

10 Mavridou et al. JOE — Volume -, Number -, - 2016


Figure 10. Histologic images showing that active resorption, active osteoid formation, and remodeling can occur simultaneously in different areas of the tooth. (A)
Remodeling of reparative bonelike tissue and resorption channels on dentin. (B) Enlargement of the black area in A showing resting osteoclastlike (clastic) cells
within a resorption channel. (C) Osteoclastlike (clastic) cells are found simultaneously attached on dentin and reparative bonelike tissue. (D) Enlargement of the
black area in C showing osteoclastlike (clastic) cells.
compression during orthodontic movement and bone remodeling (50,
60, 61), inflammation (55), mechanical unloading caused by chewing
and grinding (55, 62), and ECR cases (17).
In this work, it is plausible that hypoxia is possibly the driving force
in the resorption initiation stage. Indeed, it was recorded that most of
the patients had either treatments that could result in mechanical
stresses in the PDL (eg, previous orthodontic treatment or traumatic
injury) or had PDL inflammation (eg, plaque, calculus), which can
lead to a local hypoxic environment. However, this hypothesis should
be further investigated.
Resorption Progression
In the second stage, resorption invades the tooth structure by
destroying cementum, dentin, and enamel (Fig. 2). It was observed
that clastic cells are involved in this process (Fig. 10) (63). The resorp-
tion then expands toward the pulp and creates multiple resorption
channels, generating a 3D structure.
However, it does not penetrate the pulp because of the presence of
a resistant layer (PRRS). Using the nano-CT data set, the thickness of the
PRRS is measured at a mean value of 210 mm. It was also observed that
the pericanalar dentin has a different contrast than the rest of the dentin
(Fig. 3B), which can be linked to a different mineral content (64).
As the resorption progresses, the pulp tissue retains its vitality. Pre-
vious researchers suggested that the pulp tissue plays no role during
ECR. However, our data suggest that the pulp tissue reacts at the resorp-
tion attack, mainly through calcification of the extracellular matrix
(Fig. 8).
It is possible that the existence and high resistance of the PRRS tis-
sue is either linked to the pulp vital tissue or the gradient mineralization
JOE — Volume -, Number -, - 2016
Clinical Research
distribution of this layer. In the first case, it is possible that the vital pulp
tissue can regulate the oxygen tension at the interface between the
resorption and the PRRS. In particular, the free nerve endings in
the periphery of the vital pulp tissue participate in the regulation of
the pulp blood flow, which changes the pressure and subsequently
causes an oxygen gradient within the PRRS (65). Because of this oxygen
gradient, hypoxia is observed in the resorption area, whereas in the
PRRS and pulp tissue normoxia occurs. Thus, the osteoclastic activity
is up-regulated by hypoxia, and ECR is directed toward local hypoxic
microenvironments, leaving the PRRS intact. In some cases, ECR is
observed to locally destroy the PRRS layer (Figs. 5 and 8) and progress
up to the pulp space, creating small interconnections between the
resorption cavity and the pulp (Fig. 8). In these areas, it is believed
that localized excessive calcification can lead to oxygen tension changes
in the pulp.
In the second case, as confirmed by nano-CT (Fig. 3 and Supple-
mental Video S2), the pericanalar dentin actually has a gradient struc-
ture, having a higher mineral content at its outer layers and decreasing
toward the pulp (18, 66). It is possible that the resistance of the
PRRS is also related to the difference in the mineral content of this
layer. (Supplemental Video S2 is available online at www.jendodon.
com.)
Reparative Stage
At the last stage, repair takes place by an ingrowth of bonelike tis-
sue into the resorption cavity (Figs. 3 and 4). In particular, the bonelike
tissue grows into the cavity through the portal of entry and substitutes
the resorbed tooth tissues (Figs. 2–4). Furthermore, it is clearly
visible that a localized fusion between the substitution tissue and the
External Cervical Resorption in Vital Teeth 11
Clinical Research

Figure 11. (A) A histologic image of tooth #3 showing simultaneous active resorption, repair, and remodeling of the reparative bonelike tissue. (B) Enlargement of
area 1 in A showing osteoclastlike (clastic) cells resorbing dentin and osteoid formation within the resorption lacunae. (C) Enlargement of area 2 in A showing
osteoblastlike cells. (D) Enlargement of the osteoclastlike cells in B. (E) Enlargement of area 3 in A showing osteoclastlike cells resorbing dentin and reparative
bonelike tissue.

Figure 12. Histologic images showing the repair border and osteoid formation. Note the fine basophilic strep.

12 Mavridou et al. JOE — Volume -, Number -, - 2016

 Clinical Research

Figure 13. SEM images of tooth #31. (A) Reparative bonelike tissue showing the lamellar structure of the tissue. (B) Enlargement of area 1 in A showing the
remodeling units of the reparative bonelike tissue.

adjacent bone takes place (Fig. 4). This observation is in complete
agreement with previous studies mentioning that such a fusion can
occur when the PDL is removed (41, 45, 48). However, it should be
mentioned that in the case of ECR, fusion takes place only in a
localized scale where rupturing of the PDL occurs. The formation
and structural pattern of this reparative bonelike tissue resembles
that of a normal lamellar bone (Fig. 13).
Histologic analysis confirmed that the cells responsible for the
formation of reparative bonelike tissue are osteoblastlike cells, which
possibly originate from the adjacent bone (Figs. 7 and 11). The gener-
ation of osteoblasts from precursors and their bone-forming activity is
based on a coupling mechanism between bone formation and bone
resorption. This process involves the interaction of a wide range of
cell types and control mechanisms (67) as well as the effect of the extra-
cellular pH and oxygen tension (55).
The reparative bone tissue is then gradually formed and fills the
resorption cavity from the exterior toward the pulp. The formation of
bone onto the dentin surface is not necessarily a pathological process
but rather one that can be regarded as a form of healing (39). A 3D
model showing the growth of reparative bone is made via CTVox soft-
ware from the nano-CT images and is presented in Supplemental Video
S3. (Supplemental Video S3 is available online at www.jendodon.com.)
After formation of the bonelike tissue, signs of active remodeling
that occur asynchronously at many sites are visible (Figs. 10 and 11).
This phenomenon is also responsible for the changing CBCT image
during long-term follow-up of ECR lesions.
It is evident from these figures that the reparative tissue and the
tooth structure eventually become part of the normal alveolar bone
physiology. Thus, during the reparative stage, repair and remode-
ling phenomena evolve simultaneously, whereas both resorption

TABLE 2. An Overview of the Experimental Techniques Used and the Phenomena That Can Be Observed with Each Technique
Clinical
examination Digital x-ray CBCT Nano-CT Histology SEM
Observations (27 teeth) (27 teeth) (24 teeth) (22 teeth) (9 teeth) (4teeth)
Bleeding on probing Yes 13/27 NA NA NA NA NA
Tooth discoloration Yes 8/27 NA NA NA NA NA
Portal(s) of entry Yes 15/27 Yes 12/27 Yes 24/24 Yes 22/22 Yes 9/9 No
PRRS NA Yes 19/27 Yes 20/24 Yes 22/22 Yes 9/9 Yes 4/4
Resorption on dentin No Yes 27/27 Yes 24/24 Yes 22/22 Yes 9/9 Yes 4/4
Resorption on enamel Yes 4/27 Yes 2/27 Yes 9/24 Yes 10/22 Yes 3/9 No
Resorption channels NA Yes 11/27 Yes 21/24 Yes 20/22 Yes 9/9 No
PDL interconnections NA No Yes 15/24 Yes 20/22 Yes 8/9 No
Granulation tissue Yes 6/27 No No No Yes 5/9 No
Reparative bonelike tissue NA Yes 14/27 Yes 13/24 Yes 21/22 Yes 9/9 Yes 4/4
Epithelial tissue NA NA NA NA Yes 4/9 NA
Osteoid tissue NA NA NA NA Yes 9/9 NA
Osteoblastlike cells NA NA NA NA Yes 8/9 NA
Osteoclastlike cells NA NA NA NA Yes 6/9 NA
Bacteria NA NA NA NA Yes 3/9 NA
Calculus Yes 12/27 Yes 4/27 Yes 4/24 Yes 6/22 Yes 3/9 No
Reparative cementum NA NA NA Yes 8/22 Yes 7/9 No
Resorption lacunae NA NA NA Yes 22/22 Yes 9/9 Yes 4/4
PRRS disruption NA Yes 7/27 Yes 11/24 Yes 14/22 Yes 4/9 No
Bonelike tissue apposition on PRRS NA NA No Yes 16/22 Yes 9/9 Yes 3/4
Pulp calcification NA Yes 8/27 Yes 10/24 Yes 21/22 Yes 9/9 No
Atrophic odondoblasts NA NA NA NA Yes 5/9 NA
Osteocytelike cells NA NA NA NA Yes 9/9 NA
Remodeling NA NA NA No Yes 8/9 Yes 4/4
Connective tissue NA NA NA NA Yes 9/9 NA
Necrotic pulp at PRRS disruption NA NA NA NA Yes 2/9 NA
NA, not applicable; PRRS, pericanalar resorption-resistant sheet.
No indicates not observed, and yes indicates observed.

JOE — Volume -, Number -, - 2016 External Cervical Resorption in Vital Teeth 13

Clinical Research
and reparative stages progress in parallel at different areas of the
tooth.
It should be noted that in some cases the gingival epithelium
and subgingival plaque migrate to the ECR cavity (Fig. 1) and
grow deeper into the dentin (Fig. 4), preventing bonelike tissue
ingrowth because of the epithelium barrier and the secondary inflam-
mation.
Conclusions
ECR is identified as a very dynamic and continuously evolving pro-
cess, whereas its nature is observed to be both destructive and repara-
tive. Therefore, in this study, an attempt was made to understand the
mechanism of ECR by a multimodular approach combining clinical
data and in vivo CBCT, in vitro nano-CT, hard tissue histologic, and
SEM findings.
The main conclusions are summarized as follows:
1. At the initiation phase, a local destruction/disruption of the normal
PDL architecture and cementum took place. Indeed, at the portal of
entry, no PDL tissue was found, whereas ingrowth of the adjacent
bone tissue and fusion with the tooth structure were observed.
2. In the resorption stage, ECR invaded the tooth structure by destroy-
ing cementum, dentin, and enamel. At the pulp, pulp stone(s) and
diffuse calcification are evident. The PRRS was observed to have a
nonuniform thickness, depending strongly on the examined region.
The average value was approximately 210 mm.
3. At the reparative stage, repair took place by formation of mineralized
tissue, which substituted the resorbed tooth structure. This phenom-
enon was observed to eventually result in a localized fusion area
between the tooth structure and the adjacent alveolar bone.
4. Resorption and repair can progress in parallel at the same time at
different areas of the same tooth.
Acknowledgments
The authors deny any conflicts of interest related to this study.
Supplementary Material
Supplementary material associated with this article can be
found in the online version at www.jendodon.com (http://dx.doi.
org/10.1016/j.joen.2016.06.007).
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