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ORIGINAL ARTICLE
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Risk factors of medication-related osteonecrosis of the jaw:
a retrospective study in a Turkish subpopulation
Onur Şahin
1
, Onur Odabaşı
2
, Toghrul Aliyev
1
, Birkan Tatar
1
1
Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, İzmir Katip Çelebi University, İzmir,
2
Department of Oral and Maxillofacial Surgery, Ankara Yıldırım Beyazıt University, Ankara, Turkey
Abstract (J Korean Assoc Oral Maxillofac Surg 2019;45:108-115)
Objectives: Medication-related osteonecrosis of the jaw (MRONJ) is a well-known side effect of certain drugs that are used to influence bone metab-
olism to treat osteometabolic disease or cancers. The purpose of our study was to investigate how high-concentration and low-concentration bisphos-
phonate (BP) intake affects the disease severity.
Materials and Methods: Data collected from the medical records of 52 patients treated with BPs, antiresorptive, antiangiogenic drugs and diagnosed
with MRONJ were included in this study. Age, sex, type of systemic disease, type of drug, duration of drug treatment, jaw area with MRONJ, drug
administration protocol, and MRONJ clinical and radiological findings were obtained. Patients were divided into two groups: anti-neoplastic (Group I,
n=23) and anti-osteoporotic (Group II, n=29). Statistical evaluations were performed using the IBM SPSS ver. 21.0 program.
Results: In both groups, more females had MRONJ. MRONJ was found in the mandibles of 30 patients (Group I, n=14; Group II, n=16). When we
classified patients according to the American Association of Oral and Maxillofacial Surgeons staging system, significant differences were seen between
groups (χ
2
=12.23, P<0.01). More patients with advanced stage (stage 2-3) MRONJ were found in Group I (60.9%).
Conclusion: According to our results, high-concentration BP intake, age and duration of drug intake increased disease severity.
Key words: Bisphosphonate-associated osteonecrosis of the jaw, Osteonecrosis, Risk factors, Zoledronic acid
[paper submitted 2018. 7. 2 / revised 2018. 7. 30 / accepted 2018. 7. 31]
Copyright © 2019 The Korean Association of Oral and Maxillofacial Surgeons. All
rights reserved.
https://doi.org/10.5125/jkaoms.2019.45.2.108
pISSN 2234-7550·eISSN 2234-5930
I. Introduction
Bisphosphonates (BPs) are the most commonly used anti-
resorptive drugs for the prevention of skeletal complications
in many diseases. The term bisphosphonate-related osteo -
necrosis of the jaw (BRONJ) was first coined by Marx
1
in
2003. An increase in localized osteonecrosis in jaw bones is
related to BPs. The adverse effects of bisphosphonates on
quality of life and increased morbidity, the researchers have
led to the investigation of early diagnosis and effective treat-
ment strategies. In addition to BPs, other antiresorptive (e.g.,
denosumab) and antiangiogenic drugs (e.g., bevacizumab and
sunitinib) can cause osteonecrosis, so the American Associa-
tion of Oral and Maxillofacial Surgeons (AAOMS) proposed
using medication-related osteonecrosis of the jaw (MRONJ)
as the terminology to replace BRONJ
2
. Drugs that cause os-
teonecrosis of the jaw are defined as antiresorptive and anti-
angiogenic drugs. Drugs such as high-concentration and low-
concentration BPs and denosumab are antiresorptive drugs.
Intravenous (IV) BPs are frequently used to treat hypercalce-
mia associated with malignant tumors due to their antitumor-
al effects in the treatment of cancers with bone metastases
including breast, prostate and lung, and to prevent skeletal
complications in multiple myeloma. Oral BPs are frequently
associated with osteoporosis and osteopenia and rarely, with
treatment of Paget’s disease and osteogenesis imperfecta
3
.
Osteonecrosis of the jaw is a rare condition that develops as a
result of impaired blood supply to the mandible and maxilla.
The incidence of osteonecrosis in individuals treated with BP
therapy varies between 1% and 21%
4
. Bisphosphonates and
other antiresorptive drugs increase apoptosis by inhibiting
Onur Şahin
Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, İzmir
Katip Çelebi University, Aydınlıkevler Mahallesi, Cemil Meriç Bulvarı, 6780
Sokak, #48, İzmir 35640, Turkey
TEL: +90-(232)-325-25-35 F AX: +90-5054410192
E-mail: onursahin43@hotmail.com
ORCID: https://orcid.org/0000-0001-7816-1443
Risk factors of medication-related osteonecrosis of the jaw
109
osteoclast differentiation and function, and these events cause
bone resorption and reduced bone remodeling. Although
osteoclast differentiation and function play a crucial part in
the remodeling of all the bones in the skeletal system, osteo-
necrosis is most commonly observed in jaw bones owing to
high bone metabolism in jaw bones
5
.
In 2014, three criteria were defined by the AAOMS for dif-
ferential diagnosis of MRONJ from other diseases that can
cause clinical osteonecrosis. These criteria are: the presence
of antiresorptive and antiangiogenic drug use in the patient’s
medical history, clinical exposure of the bone site for more
than 8 weeks, and no radiotherapy or metastasis in the jaw
bone
2
. In 2006, a staging system and treatment protocol was
developed by Ruggiero et al.
6
. This staging system was up -
dated by the AAOMS in 2007, 2009, and 2014. Our study
was based on the staging system updated in 2014
2
.(Table 1)
The purpose of our study was to investigate how high-
concentration and low-concentration BP intake affected the
severity of MRONJ. Patient records were evaluated retro -
spectively for demographic data, medical information, clini-
cal and radiological examination findings, drug type, usage
information, and related disease.
Table 1. American Association of Oral and Maxillofacial Surgeons staging system
At-risk category Asymptomatic stage without necrotic bone
Stage 0 No exposure bone, but clinical and radiological nonspecific findings and symptoms
Stage 1 In asymptomatic patients with no signs of infection, presence of exposed and necrotic bone
Stage 2 Symptomatic stage, radiological findings, exposed, necrotic bone, fistula and infection are localized in the alveolar bone region
Stage 3 The exposure may range from necrotic bone, fistula and infection, symptomatic stage, necrotic bone from the alveolar bone to
the lower border of the mandible, to the ramus or to the maxillary sinus, to the zygomatic bone. There may be pathological
fractures, extra-oral fistula, oral-antral or oral-nazal relationship and osteolytic area extending to the lower border of the
mandible or sinus base.
Data from the article of Ruggiero et al. (J Oral Maxillofac Surg 2014;72:1938-56)
2
.
Onur Şahin et al: Risk factors of medication-related osteonecrosis of the jaw: a retrospective study in a Turkish subpopulation. J Korean Assoc Oral Maxillofac Surg 2019
A B
C D
Fig. 1. Clinical findings of some med -
ication-related osteonecrosis of the
jaw (MRONJ) patients in this study. A.
MRONJ lesion developed that follow -
ing tooth extraction at right mandibular
premolar area. B. Clinical image of
maxillary exposed, necrotic bone in
a MRONJ patient due to prosthesis
trauma. C. Stage II MRONJ in a female
patient treated with alendronate for os -
teoporosis. D. Extra-oral draining fistula
at the submandibular region of the jaw
in a patient with stage 3 MRONJ.
Onur Şahin et al: Risk factors of medication-related
osteonecrosis of the jaw: a retrospective study in
a Turkish subpopulation. J Korean Assoc Oral
Maxillofac Surg 2019
J Korean Assoc Oral Maxillofac Surg 2019;45:108-115
110
II. Materials and Methods
This retrospective study included 52 patients over a 5-year
period (January 2013 to December 2017) using database re -
cords of the Department of Oral and Maxillofacial Surgery,
Faculty of Dentistry, İzmir Katip Çelebi University (İzmir,
Turkey). Patients who were diagnosed with MRONJ were in-
cluded. The study was approved by the Ethical Committee of
İzmir Katip Çelebi University (approval No. 207), and it was
conducted in accordance with the Declaration of Helsinki.
Data collected from the medical records of patients in -
cluded age, sex, type of systemic disease, type of drug, du -
ration of drug treatment, jaw area seen with MRONJ, drug
administration protocol, MRONJ staging and radiological
findings. According to information collected on patients, we
determined staging and treatment systems as defined by the
AAOMS position paper, on MRONJ for each patient
2
.(Table
1) Patients with head and neck radiotherapy or necrotic bone
areas less than 8 weeks were not included. Several stud -
ies have been published using the AAOMS staging system
updated in 2014. However, as far as we know, few studied
the use of the staging system to classify patients into anti-
neoplastic (Group I, n=23) and anti-osteoporotic (Group II,
n=29) groups. We analyzed sex, age, related disease, type
of drug, location of MRONJ, local etiological factors and
clinical and radiological findings and their relationships to in-
vestigate how high-concentration and low-concentration BP
intake affected disease severity.(Fig. 1, 2, Table 2)
Statistical evaluations were performed with the IBM SPSS
Statistics program (ver. 21.0; IBM Corp., Armonk, NY ,
USA). The Kolmogorov–Smirnov test was applied to all con-
tinuous variables to determine if distributions met the nor -
mality assumption. Parametric tests were used for variables
that met normality assumptions. Comparisons of categorical
variables were made with chi-square or Fisher’s exact tests.
The Student’s t-test was used to compare quantitative vari -
ables between Group I and Group II. All data were evaluated
at a significance level of P<0.05.
III. Results
Of the 52 patients included in the study, 7 were male and
A B
C D
Fig. 2. Radiological findings of some
medication-related osteonecrosis of the
jaw (MRONJ) patients in this study. A.
Panoramic radiograph demonstrating
a pathologic fracture of the left molar
region of the mandible in a patient with
metastatic breast and stage 3 MRONJ.
B. Panoramic radiography demon -
strated osteolytic process at the left
mandible. C. Panoramic radiography
showing persisting alveolar socket in
the mandible. D. Panoramic radiogra -
phy demonstrated diffuse osteolysis of
the jaw with areas of bone sclerosis.
Onur Şahin et al: Risk factors of medication-related
osteonecrosis of the jaw: a retrospective study in
a Turkish subpopulation. J Korean Assoc Oral
Maxillofac Surg 2019
Risk factors of medication-related osteonecrosis of the jaw
111
45 were female. Of these, 29 were given BP or antiresorp -
tive drugs orally (2 males and 27 females) and 23 were given
drugs by IV (5 males and 18 females). The mean age of pa -
tients was 61.91±10.84 years (range, 44-80 years) in Group
I and 62.72±10.55 years (range, 40-76 years) in Group II.
In Group I, osteonecrosis was observed in the mandible in
14 patients, in the maxilla in 8 patients and in both jaws in
one patient. In Group II, 16 patients had mandibular and 12
patients had maxillary MRONJ, and one patient had MRONJ
findings in both jaws. MRONJ was found in the mandibles in
30 patients. No significant difference was seen between the
groups by location (P>0.05).
All patients in Group II were taking medications to prevent
osteoporosis. Patients in Group I were taking high-concen -
tration BPs for oncological reasons. Of the patients, 3 were
treated for lung cancer, 1 for renal cancer, 6 for breast cancer,
3 for multiple myeloma, 1 for nasopharynx cancer, 6 for os-
teoporosis, 1 for ovarian cancer, and 2 for prostate cancer.
All patients in Group II were treated for osteoporosis. In
Group I, 6 patients were taking parenteral medication for
osteoporosis, 3 using ibandronate and 3 zoledronate. Patients
in Group I were treated 2 to 10 years (mean, 29 months)
and patients in Group II were treated 1 to 8 years (mean, 44
months).
Of patients in Group I, 12 were using ibandronate (52.2%),
9 zoledronate (39.1%), and 2 a combination of zoledronate
and denosumab (8.7%). Of the patients in Group II, 5 were
using ibandronate (17.2%), 21 alendronate (72.4%), and 3
residronate (10.3%).
When local etiologic factors causing MRONJ were exam-
ined, 14 patients in Group I showed MRONJ after tooth ex -
traction, 6 after receiving dental prosthesis, 2 spontaneously
and 1 after dental implant treatment. Of patients in Group
II, 15 had MRONJ post tooth extraction, 6 after receiving
prosthetics, and 8 had spontaneous osteonecrosis. In both
groups, the etiologic factor that caused MRONJ was mainly
tooth extraction. The difference between the groups was not
significant.
When clinical and radiological findings were examined for
pain, infection, suppuration, fracture and exposed bone, pain
Table 2. Patient characteristics and outcomes
Group I (n=23) Group II (n=29) t or χ
2
P-value
Age (yr) 61.91±10.84 62.72±10.55 t=–0.272 >0.05
Sex
Male 5 (21.7) 2 (6.9) >0.05
1
Female 18 (78.3) 27 (93.1)
Disease Lung cancer: 3 (13.0) Osteoporosis: 29 (100) χ
2
=31.85 <0.01
Renal cancer: 1 (4.3)
Breast cancer: 6 (26.1)
Multiple myeloma: 3 (13.0)
Nasopharynx cancer: 1 (4.3)
Osteoporosis: 6 (26.1)
Over cancer: 1 (4.3)
Prostate cancer: 2 (8.7)
Drug Ibandronate: 12 (52.2) Ibandronate: 5 (17.2) χ
2
=37.70 <0.01
Zoledronate: 9 (39.1) Alendronate: 21 (72.4)
Zoledronate+denosumab: 2 (8.7) Residronate: 3 (10.3)
Location of MRONJ χ
2
=3.79 >0.05
Mandible 14 (60.9) 16 (55.2)
Upper jaw 8 (34.8) 12 (41.4)
Both 1 (4.3) 1 (3.4)
Local etiologic factor χ
2
=1.64 >0.05
Dental extractions 14 (60.9) 15 (51.7)
Prosthesis 6 (26.1) 6 (20.7)
Spontaneous 2 (8.7) 8 (27.6)
Implant treatment 1 (4.3) 0 (0)
Clinical and radiographic sign
Pain 15 (65.2) 17 (58.6) χ
2
=0.24 >0.05
Infection 4 (17.4) 1 (3.4) χ
2
=2.87 >0.05
Suppuration 8 (34.8) 2 (6.9) <0.05
1
Fracture 2 (8.7) 0 (0) >0.05
1
Exposed bone 18 (78.3) 18 (62.1) χ
2
=1.58 >0.05
(Group I: anti-neoplastic, Group II: anti-osteoporotic, MRONJ: medication-related osteonecrosis of the jaw)
1
Fisher’s exact test.
Values are presented as mean±standard deviation or number (%).
Onur Şahin et al: Risk factors of medication-related osteonecrosis of the jaw: a retrospective study in a Turkish subpopulation. J Korean Assoc Oral Maxillofac Surg 2019
J Korean Assoc Oral Maxillofac Surg 2019;45:108-115
112
and exposed bone were observed in both groups. No signifi-
cant difference was found between the groups except for sup-
puration (P>0.05).(Table 2)
When we classified patients according to the AAOMS
staging system, significant differences were seen between
the groups (χ
2
=12.23, P<0.01). Advanced stage (stage 2-3)
disease was found at higher rates in Group I (60.9%). Early
stage cases were significantly higher in Group II (82.7%).
(Table 3)
A significant difference was found in the relationship
between age and stage. The incidence of stage 2 and 3 dis -
ease increased with age in patients with MRONJ (χ
2
=17.73,
P<0.05).(Table 4) We found that 3 patients smoked a package
of 20 cigarettes per day for more than 10 years: 2 had stage 2
and 1 patient had stage 3 disease.
IV. Discussion
Although the first case of MRONJ was reported in 2003,
MRONJ physiopathology is not fully understood, and poten-
tial mechanisms are still being discussed
1
. The physiopathol-
ogy of MRONJ is explained as modified bone remodeling or
suppression of bone resorption, inflammation or infection,
inhibition of angiogenesis, soft tissue toxicity, congenital or
acquired immunodeficiency, microtrauma, and vitamin D in-
sufficiency
7
.
According to the AAOMS classification, risk factors for
osteonecrosis formation in jaw bones due to use of BPs are
medication-related, local, and demographic/systemic
8
. Risk
factors associated with drug use include type of BP used,
method of drug administration, and duration of treatment. In
particularly, intravenous use of BPs increases risk
9,10
. Local
risk factors include periodontal diseases, inflammatory dental
diseases (such as dental abscesses), torus mandibularis and
palatinus, dental caries, dental alveolar surgery (tooth extrac-
tion, dental implant application, periodontal surgery including
bone tissue, periapical surgery), and traumatic factors such as
bone exostoses, mylohyoid protrusion, or unadapted dental
prostheses
11
.
Demographic and systemic risk factors are defined as dia-
betes mellitus, immunosuppression, anemia and thalassemia,
malnutrition, osteoporosis/osteopenia diagnosed with cancer,
sex, chronic corticosteroid use, radiotherapy, estrogen thera-
py, smoking, cancer diagnosis, coagulation disorders, blood
anomalies, vascular and connective tissue diseases, and hypo-
thyroidism
12
. This study also investigated how these risk fac-
tors affect patient low-concentration and high-concentration
BP intake.
Osteoporosis can occur in individuals over 50 years of age
and antiresorptive agents are often preferred for treatment.
In patients with osteoporosis using low-concentration BPs,
the incidence of MRONJ is between 0.00038% and 0.1%.
For use longer than 4 years, the incidence is reported to be
0.21%
13
.
In patients with osteoporosis using high-concentration
BPs, MRONJ incidence is reported to be 0.017% in a 3-year
follow-up period. This ratio remained unchanged in a 6-year
follow-up
14
. In our study, 23 patients with MRONJ were
using high-concentration and 29 patients were using low-
concentration BPs. In Group I, the duration of use of BPs or
antiresorptive drugs was 29 months. In Group II, duration
of use was 44 months, similar to Zervas et al.
12
(24 months).
Our results are not consistent with those of Berenson et al.
15
(18 months of zoledronate) and Dimopoulos et al.
16
(53.4
months of pamidronate and zoledronate therapy). The high
MRONJ incidence for patients taking low-concentration BPs
could be linked to a longer duration of drug use and greater
influence of local etiological factors. Also, we examined pa-
tients who were diagnosed with MRONJ. When we classified
patients according to the AAOMS staging system, Group I
had a higher rate of advanced disease stage than Group II.
We found 14 patients (60.9%) with advanced-stage (2 or 3)
disease in Group I and 5 patients (17.2%) in Group II.
Table 3. Staging of patients with high-concentration (Group I) and
low-concentration (Group II) bisphosphonate use
Stage Group I (n=23) Group II (n=29) Total (n=52)
0 3 (13.0) 11 (37.9) 14 (26.9)
1 6 (26.1) 13 (44.8) 19 (36.5)
2 10 (43.5) 5 (17.2) 15 (28.8)
3 4 (17.4) 0 (0) 4 (7.7)
χ
2
=12.23, P<0.01.
Onur Şahin et al: Risk factors of medication-related osteonecrosis of the jaw: a
retrospective study in a Turkish subpopulation. J Korean Assoc Oral Maxillofac Surg
2019
Table 4. Relationship between disease stage and age groups
Stage
Age group (yr)
Total
40-50 51-60 61-70 71-80
0 3 9 2 0 14
1 2 3 11 3 19
2 1 5 5 4 15
3 0 1 1 2 4
Total 6 18 19 9 52
χ
2
=17.73, P<0.05.
Onur Şahin et al: Risk factors of medication-related osteonecrosis of the jaw: a
retrospective study in a Turkish subpopulation. J Korean Assoc Oral Maxillofac Surg
2019
Risk factors of medication-related osteonecrosis of the jaw
113
In Group I, rates of use for different drugs that cause
MRONJ were similar. Half of patients were using ibandro -
nate (52.2%) and the other half denosumab (47.8%) together
with zoledronate. In Group II, alendronate (72.4%) was the
most common drug causing MRONJ.
The reason that BPs cause osteonecrosis in the jaw bones
rather than other bones is that BPs accumulate at high levels
in alveolar bones with high regenerative capacity and in soft
tissue adjacent to the bones. The inability to create an aseptic
environment due to the large microflora of the oral cavity, the
constant association with this microflora through the peri -
odontal gap, and a high trauma incidence increase the risk of
osteonecrosis in the jaw bones
17
. Marx et al.
18
reported that
68.1% of MRONJ cases were mandibular and 27.7% were
maxillary in their study. Similar results were reported by
Badros et al.
19
. According to their study on multiple myeloma
patients with BRONJ, 15 patients had mandibular, 2 had only
maxillary and 5 had both mandibular and maxillary lesions.
In our study, 14 cases were mandibular, 8 cases were maxil-
lary and 1 case was in both jaws in Group I. In Group II, 16
cases were mandibular, 12 cases were maxillary and 1 case
of MRONJ was in both jaws. MRONJ was found in the man-
dibles of 30 patients.
In the cohort study conducted by Vahtsevanos et al.
20
,
they calculated the relative risk for osteonecrosis of the jaw
(ONJ) development to be 18 times higher in patients who
experienced dental extractions and patients who use dentures
had an at least two-fold increased risk for ONJ development.
Dental extraction alone is a predisposing factor for 52% to
61% of examples of MRONJ formation
21
. The incidence of
osteonecrosis after tooth extraction in patients using low-
concentration BPs is reported to be 0.5%; it is reported to
be 1.6% to 14.8% in patients receiving high-concentration
BPs
22
. In our study, the factor that caused the formation of
MRONJ was usually tooth extraction, in accordance with
previous study
20-22
. In Group I, 14 of patients had MRONJ af-
ter tooth extraction, 6 after receiving dental prosthetics and 2
had spontaneous MRONJ. In addition, we observed osteone-
crosis of the right mandible after dental implant therapy due
to use of zoledronate and denosumab.( Fig. 3) Of patients in
Group II, 15 had MRONJ post tooth extraction, 6 because of
prosthetics, and 8 had spontaneous MRONJ. In both groups,
the etiologic factor that caused MRONJ was mostly tooth ex-
traction.
Lesions were staged by AAOMS classification. The param-
eters examined were pain, suppuration, presence of exposed
bone, infection, and jaw fractures. Bagan et al.
23
and Fedele
et al.
24
reported the most frequently encountered symptoms as
pain and necrotic bone. Bagan et al.
23
found pain in 77% and
necrotic bone in 69% of patients in their study. These two
signs of MRONJ were the most common clinical symptoms
in our study in accordance with previous studies. However,
70% of patients in our study had bone exposure and 63%
had pain. In our study, exposed bone was more common than
pain in both groups, but no significant difference was found
between groups except for suppuration (P=0.024).
Demographic and systemic factors and other drug use also
affect MRONJ formation. Age and sex are risk factors for
MRONJ
25
. The types of drugs that cause osteonecrosis are
given more frequently to women due to their indicational sta-
tus. In our study, the majority of patients with MRONJ were
female: 78.3% in Group I and 93.1% in Group II. The mean
age of patients in this present study is in accordance with the
age of those in the literature
23,25
. We also observed correla -
tions between patient age and lesion stage. The older the age,
the higher the incidence of stage 2 and 3 disease. A signifi -
cant difference was found in the relationship between age and
stage. The incidence of stage 2 and 3 increased with age in
patients with MRONJ (χ
2
=17.73, P<0.05).
Whether smoking is a risk factor for MRONJ is still be -
A B
Fig. 3. Clinical and radiologic findings after dental implant treat -
ment in medication-related osteonecrosis of the jaw (MRONJ)
patients using zoledronate and denosumab. A. Clinical view after
dental implant treatment in MRONJ patient using denosumab. B.
Panoramic radiography showed sequestrum line around of the
dental implant at the right mandible molar area.
Onur Şahin et al: Risk factors of medication-related osteonecrosis of the jaw: a
retrospective study in a Turkish subpopulation. J Korean Assoc Oral Maxillofac Surg
2019
J Korean Assoc Oral Maxillofac Surg 2019;45:108-115
114
ing discussed in the literature. Some studies find it to have
an effect while others report that it is not a risk factor for
MRONJ
17
. In our study, 3 patients smoked 20 cigarettes per
day for more than 10 years: 2 had stage 1 disease and one had
stage 3 MRONJ lesions.
V. Conclusion
According to results of our study, high-concentration BP
intake, age, and duration of drug intake increased disease se-
verity. According to the AAOMS staging system, updated in
2014, clinical and radiological findings have great importance
for diagnosing MRONJ. In studies to date, the pathogenesis
of MRONJ was explained theoretically but the pathophysiol-
ogy of this disease is not exactly understood, despite the long
time since the first reported case of MRONJ in the litera -
ture. Future studies should aim to explain the pathogenesis
of MRONJ and find effective treatment strategies in larger
groups of patients. Before intake of any BP or antiresorptive
drugs, patients with cancer or osteoporosis should have an
extensive dental examination, especially by an oral and max-
illofacial surgeon who is experienced in the prevention and
treatment of MRONJ. Patients with a challenging dental situ-
ation should participate in dental care before starting these
medications.
ORCID
Onur Şahin, https://orcid.org/0000-0001-7816-1443
Onur Odabaşı, https://orcid.org/0000-0001-7771-048X
Toghrul Aliyev, https://orcid.org/0000-0002-6312-476X
Birkan Tatar, https://orcid.org/0000-0002-8917-575X
Authors’ Contributions
O.Ş., T.A., and B.T. participated in data collection and
wrote the manuscript. O.Ş. and O.O. participated in the study
design and coordination. O.O. and B.T. performed the statisti-
cal analysis. O.O. helped to draft the manuscript. All authors
read and approved the final manuscript.
Ethics Approval and Consent to Participate
The study was approved by the Ethical Committee of İzmir
Katip Çelebi University (approval No. 207).
Consent for Publishing Photographs
Written informed consent was obtained from the patients
for publication of this article and accompanying images.
Conflict of Interest
No potential conflict of interest relevant to this article was
reported.
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