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Comparison of fractal dimension analysis and panoramic-based radiomorphometric indices in the assessment of mandibular bone changes in patients with type 1 and type 2 diabetes mellitus
Accepted Manuscript Title: Comparison of fractal dimension analysis and panoramic-based radiomorphometric indices in the assessment of mandibular bone changes of type 1 and type 2 diabetes mellitus patients Author: Emine Şebnem Kurşun-Çakmak, Seval Bayrak PII: DOI: Reference:
S2212-4403(18)30927-1 https://doi.org/10.1016/j.oooo.2018.04.010 OOOO 2004
To appear in:
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Received date: Revised date: Accepted date:
7-12-2017 16-4-2018 21-4-2018
Please cite this article as: Emine Şebnem Kurşun-Çakmak, Seval Bayrak, Comparison of fractal dimension analysis and panoramic-based radiomorphometric indices in the assessment of mandibular bone changes of type 1 and type 2 diabetes mellitus patients, Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology (2018), https://doi.org/10.1016/j.oooo.2018.04.010. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
COMPARISON OF FRACTAL DIMENSION ANALYSIS AND PANORAMIC-BASED RADIOMORPHOMETRIC INDICES IN THE ASSESSMENT OF MANDIBULAR BONE CHANGES OF TYPE 1 AND TYPE 2 DIABETES MELLITUS PATIENTS
Emine Şebnem KURŞUN-ÇAKMAK1, Seval BAYRAK2
1
Associate Prof. Türkiye Public Hospitals Agency, Ministry of Health
2
Assistant Prof. Abant İzzet Baysal University, Dentistry Faculty, Department of Dentomaxillofacial
Radiology
Manuscript Correspondence: Seval BAYRAK Contact address: Abant İzzet Baysal University Faculty of Dentistry, 14000, Gölköy, Bolu, Turkey e-mail address: [email protected] Telephone number: +90 374 254 8361 Fax number: +90 374 270 0066
Word count for abstract: 200 Word count for manuscript:2900 Number of tables: 5 Number of figures: 4 The authors declare no financial support and conflicts of interest.
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Statement of Clinical Relevance The results of this study showed that there was no significant difference between DM and control groups in terms of mean FD values.Contrary to T2DM patients, T1DM patients had significantly lower MCW and PMI measurements compared to controls. Cortical and trabecular bone architecture of T1DM and T2DM patients were not different.
ABSTRACT Objectives: This study compared the fractal dimension (FD) and radiomorphometric indices in the assessment of mandibular bone of patients with type 1 (T1DM) and type 2 diabetes mellitus (T2DM). Study Design: Panoramic radiographs of 104 patients were evaluated to calculate FD, mandibular cortical width (MCW), panoramic mandibular index (PMI), and mandibular cortical index (MCI) in the mandible. Results: No statistically significant differences were found in FD when T1DM and T2DM groups were compared to controls (p≥0.168). T1DM patients had significantly lower MCW (p<0.001) and PMI (p=0.030) than controls. Patients with T2DM had no significant differences in MCW (p=0.228) or PMI (p=0.137) compared to controls. No significant differences were observed between T1DM and T2DM patients for FD, MCW, and PMI (p>0.05). In T1DM and T2DM groups, there was a significant correlation between MCW and FD (p≤0.011). No correlation was observed between FD and PMI in either the T1DM or T2DM group (p≥0.142). No significant differences in MCI were observed between the DM groups and controls (p=0.740) or between the T1DM and T2DM groups (p = 1.000). Conclusions: The cortical and trabecular bone architecture of patients with T1DM and T2DM was not different. Patients with T1DM had lower cortical measurements than controls. Key words: Diabetes mellitus; fractal analyses; panoramic radiography; radiomorphometric indices
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INTRODUCTION Diabetes mellitus (DM) is a chronic metabolic disorder that affects more than 415 million individuals worldwide, and this number is expected to double by 2040. Microvascular impairments, such as retinopathy and nephropathy, are the well-known major complications of DM. Bone has not been regarded as a target organ for diabetes-related complications until recently. Over the past decade, strong evidence has accumulated in support of a high fracture risk in both types of DM, with the consequences of fractures being more harmful than those in nondiabetics. 1-3 Hip fracture is frequently observed at the age of 40 years and above in patients with type 1 diabetes mellitus (T1DM). Together with hip fractures, the fracture risk at all sites is increased in patients with T1DM compared with nondiabetics at all ages because of a moderate reduction in bone mineral density (BMD).4,
5
Insulin treatment is additionally
associated with an increased risk of fractures, although it is unclear whether this is a direct effect of the medication itself or if insulin use is a proxy for a more advanced disease. 6, 7 Low mineral density and fracture risk due to DM were first indicated by Albright and Reifenstein in 1948. However, subsequent surveys indicated lower
8, 9
, similar
10, 11
, or
higher12, 13 BMD values in patients with type 2 diabetes mellitus (T2DM) than in nondiabetic subjects. In patients with DM, circulating levels of biochemical markers of bone formation and resorption are diminished. Low turnover of bone in diabetes may lead to defective microfracture repairs and, consequently, to their accumulation, promoting reduced bone quality. Contrary to postmenopausal and senile osteoporosis, a deterioration of bone strength
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in diabetes is related to increased cortical porosity that is not accompanied by a loss of trabecular bone mass. 14-16 Measurement of cortical thickness and fractal dimension (FD) has been proved to be effective in examining bone microarchitecture of several skeletal sites.17 Mandibular cortical width (MCW) could be beneficial in estimating osteoporosis and hip fractures because the uniform bone loss was observed in the mandibular cortical bone and hip.18 The evaluation of mandibular bone FD is another popular indicator of bone structure analysis. FD analysis is a mathematical method that can assist in quantifying complex structures and can be used to define the complex structure of the trabecular bone.19,
20
The structure is
characterized by a single number that is calculated using a computer algorithm. FD is commonly used to assess and quantify a cancellous bone structure for detecting bone changes, apical healing, periapical bone, and systemic conditions such as osteoporosis. The analysis of FD uses a box-counting algorithm to quantify the trabecular bone pattern by measuring the bone marrow and trabecular bone interface and also to assess the trabecular and medullary bone boundary. In this technique, when a higher box-counting value is reached, the bone structure is more complex.21 The goal of this retrospective study was to compare the FD and 3 panoramic radiographic indices [MCW, panoramic mandibular index (PMI), and mandibular cortical index (MCI)] in the assessment of cortical and trabecular mandibular bone geometry of patients with T1DM and T2DM. MATERIALS AND METHODS This was a single-center, retrospective matched case-control study of panoramic radiographs collected from patients’ files that were part of the database of the School of Dentistry at the University of Abant İzzet Baysal. The study protocol was carried out according to the
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principles described in the Declaration of Helsinki, including all amendments and revisions. Ethical approval was granted by the Abant Izzet Baysal University Ethical Committee (institutional review board number: 2017/164). The panoramic radiographs were evaluated based on the criteria of clearly visible mandibular molar, premolar, and anterior regions, temporomandibular joint (TMJ), mental foramina, smooth and continuous mandibular inferior cortex, and absence of ghost images that would hinder the analysis of the mandibular bone. The inclusion criteria were as follows: (1) absence of systemic disease, infections, or illness except for well-controlled DM (for diabetic groups only); (2) absence of systemic disease, infections, or illness (for controls only); (3) no current use of drugs that could influence the bone quality; (4) no smoking; (5) no missing teeth; and (6) no signs of TMJ disorder. Out of a total of 133 patients, 29 were excluded and 104 patients were included in the study. Of these, 26 were patients with T1DM (11 males, 15 females; mean age 24.38 ± 3.57 years; range between 19 and 32 years) and 26 were patients with T2DM (12 males, 14 females; mean age 48.65 ± 9.51years; range between 32 and 65 years). The control groups for T1DM and T2DM consisted of 52 systemically healthy patients who were age and sex matched with the study groups (Fig.1). Standardized digital panoramic radiographs were obtained using Soredex (Cranex Novus, Tuusula, Finland) at 70 kVp and 10 mA for 8 s exposure time. Linear measurements were performed using ImageJ version 1.3 software (National Institutes of Health, MD, USA) at a correction for 30% magnification to better simulate the clinical situation. The following measurements were performed. FD analysis of each sample was conducted as suggested by White and Rudolph
22
using the
box-counting method. The images were analyzed using ImageJ version 1.3 software (National
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Institutes of Health, MD, USA). FD measures of the trabecular bone were estimated from four regions of interest (ROI) on the left side of the panoramic radiographs. The four ROIs were molar, premolar, anterior, and condylar regions of the mandibular jaw bone. Figure 2 shows the regions of interest chosen for fractal analysis. The digital panoramic radiographs of the groups were converted into tagged image file formats because of high resolution. ROI was selected with the size of 18 × 19 pixels, cropped, and duplicated. Gaussian blur was used to remove brightness variations due to the overlying soft tissues and varying thickness of bone. The resulting image was then subtracted from the original image. Bone marrow spaces and trabeculae were discriminated from each other with the addition of a gray value of 128 to each pixel location. After performing binary, erode, dilate, invert, and skeletonize processes, FD was calculated (Fig. 3). MCW at the mental foramen region was assessed according to the technique described by Ledgerton et al. 23. The mental foramen was identified and a line was traced perpendicular to the tangent to the lower border of the mandible and through the center of the mental foramen. MCW was measured separately on the right and left mandibular sides, and the mean values were calculated. PMI was calculated according to the method of Benson et al 24 as the ratio of the thickness of the mandibular cortex to the distance from the lower border to the inferior edge of the mental foramen. The mental foramen is considered as the standard region for study in most of the surveys because masticatory muscles are not attached to this region. PMI was calculated separately on each side of the mandible and the mean values were calculated. MCI was evaluated and classified according to Klemetti et al.25 classification based on the morphological changes in the cortical bone at the mandibular base into three groups: C1, the endosteal margin of the cortical bone is even and sharp on both sides; C2, the endosteal
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margin shows semilunar defects (lacunar resorption) or seems to form the endosteal cortical layer (one to three layers) on one or both sides; and C3, the cortical layer forms heavy endosteal cortical residues and is clearly porous. Figure 4 depicts the analysis of the panoramic images performed in calculation of the morphometric indices. All measurements were performed by a single dentomaxillofacial radiologist (SB) with 10 years of experience in the field. Twenty panoramic images were randomly selected and reevaluated 2 weeks after the initial evaluation to permit calculation of the intraclass correlation coefficient (ICC) with a confidence interval of 95%. This was done to measure the intraobserver reliability of ROI selection/fractal analysis of the trabecular structure of the four ROIs and measurement of panoramic-based radiomorphometric indices. The SPSS 10.0 software (SPSS Inc., IBM Company Headquarters, IL, USA) was used for storing and analyzing data. The significance level value was set at 0.05. The independent-samples test was used for comparing FD values with MCW and PMI of the diabetic and control groups. The Pearson chi-square test was used to analyze the significance of difference in MCI between DM groups and controls, and between T1DM and T2DM patients. The one-way analysis of variance test was used for comparing four regions in terms of FD. RESULTS The systemic intraobserver error was evaluated at p<0.05, indicating no statistically insignificant differences in measurements. The ICC calculations indicated good reliability for each measurement including FD of molar region (ICC=0.788), premolar region (ICC=0.822), anterior region (ICC=0.796), condylar region (ICC=0.809), MCW (ICC=0.868) and PMI (ICC=0.877). The mean FD values were found to be lower in the T1DM group (1.25 ± 0.10) compared with the control group (1.29 ± 0.10) (p=0.168) . However, nearly equal results were obtained when
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comparing the T2DM (1.27 ± 0.07) and control groups (1.26 ± 0.09), without statistical significance (p=0.582). When the study and control groups were evaluated according to regions using a one-way analysis of variance test, the findings revealed that the mean FD values were not significantly different between regions (p>0.05). Tables I and II show the mean FD values in the study and control groups according to regions. The T1DM group had significantly lower MCW (2.06 ± 0.57) and lower PMI measurements (0.28 ± 0.07) compared with the control group (2.62±0.76, p<0.001; 0.33±0.06, p= 0.030, respectively) (Table III). No statistically significant differences were observed between the T2DM and control groups in terms of MCW (2.62 ± 0.78 and 2.35 ± 0.77, respectively; p=0.228) or PMI measurements (0.31± 0.09 and 0.28± 0.06, respectively; p=0.137) (Table IV). When the T1DM and T2DM groups were compared according to FD, MCW, and PMI measurements, no statistically significant differences were observed (p>0.05). In the T1DM and T2DM groups, the MCW measures were correlated with the FD values (r=0.462, p=0.011; r=0.57, p<0.001, respectively) whereas PMI measures were not correlated (r=-0.253, p=0.700; r=0.207, p=0.142, respectively). According to MCI classification, group C3 was not observed in either the DM groups or the controls. No significant difference was observed between the DM and control groups (p=0.740) or between the T1DM and T2DM groups (p = 1.000) (Table V).
DISCUSSION The results indicated that FD measurements of the trabecular bone were not statistically different between the DM and control groups. No significant difference was observed between patients with T1DM and T2DM in terms of FD, MCW, or PMI. Among the
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panoramic-based indices, MCW measurements exhibited a correlation with the FD results of patients with DM. In the dental literature, DM has been associated with severe forms of periodontal disease, an increased rate of dry socket after extractions, oral candidiasis, burning mouth, and dry mouth.26 However, few studies have investigated the mandibular bone structure of patients with DM, and these were mainly focused on bone implant problems. Abduljabbar et al.27 evaluated the peri-implant inflammatory parameters in prediabetes, T2DM, and control groups and stated that peri-implant inflammatory parameters were worse among patients with prediabetes and T2DM compared with controls. Yamawaki et al.28 assessed the effects of high glucose levels on hard tissue formation on a nanoscale-modified titanium surface in the bone of rats with T2DM. The authors found that high glucose concentration increased hard tissue formation, but the quality of the mineralized tissue decreased. Nemtoi et al.29 investigated the mandibular bone quality and quantity of 23 patients with DM and 27 controls in cone beam computed tomographic (CBCT) images by measuring BMD, the distance from the mandibular canal to the alveolar ridge, and the distance from the buccal to the lingual cortical wall. The results of the study showed a significant correlation between bone quality and values of glycosylated hemoglobin. In addition, a significant inverse correlation was observed between the values of cortical and trabecular bone density in the posterior region of the mandible and HbA1c (hemoglobin A1c). Studies have also demonstrated a significant correlation between BMD and FD measurements in patients with osteopenia/osteoporosis and postmenopausal women. FD measurements decreased with the decrease in BMD measurements from the normal to the osteoporotic group. 30, 31
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Fractal analysis has gained popularity in identifying potential abnormalities and severity of existing disorders in bone structure. Higher FD represents complex bone architecture with denser and less porous trabeculae.32 The present study confirmed this report with the lower values in the diabetic groups. The technique most commonly used in the literature to calculate FD is box counting, which was also used in the present study to determine the trabecular structure of the mandible. Alman et al.33 showed that FD of the mandibular trabecular bone was a good surrogate for BMD in both men and women but MCW exhibited worse diagnostic performance for identifying men with low BMD than women. Measurement of the cortical width from one side only and differences in the ROI selection (apical to the roots of the first molar and second premolar) may be the possible factors accounting for different results. Also, the aforementioned study was performed on older individuals (aged more than 50 years) compared with the present study. Age has been suggested as an important factor in MCW assessment.18, 34, 35 Starup-Linde et al.36 conducted a study based on the comparison of bone structure and density between patients with T1DM and T2DM. BMD of the hip and tissue stiffness at the tibia were found to be lower in T1DM patients. Cortical porosity parameters were similar between DM types, indicating that the cortical microstructure was not different. The results also demonstrated that the cortical and trabecular bone microarchitecture was not different according to DM types. Another study by Nillson et al.16 evaluated bone microarchitecture, bone material strength, and physical function in ambulant female patients with T2DM aged 7580 years. The results of the study revealed that trabecular and cortical bone microarchitecture, biomechanical properties, and BMD were better, but bone material strength and physical function were
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worse in patients with T2DM compared to healthy controls. Contrary to Nillson et al.16, patients with T2DM in the present study exhibited results similar to those in the control group in terms of cortical and trabecular bone measurements. Selection of only relatively fit ambulant patients with T2DM as a study group and discrepancies in the methods used to obtain bone microarchitecture and anatomical variations between the measured body parts preclude a direct comparison with the results of both studies. Ay et al.37 examined BMD in patients with T2DM using panoramic radiographs. Dual energy X-ray absorptiometry measurements revealed no statistically significant difference in mandibular BMD between the control and T2DM groups. Measurement of the MCW in panoramic radiographs has been suggested as an alternative and simple way to identify patients with low BMD. 38 Kavitha et al.17 investigated 1047 panoramic radiographs in terms of bone radiographic measurements and reported that MCW could estimate a higher capability of variations with age and gender than FD measures for estimating bone quality and osteoporosis. The authors also added that FD measures in the molar and premolar regions demonstrated a slightly greater significance and correlation with age among women than men, but not as strong as MCW. Contrary to Kavitha et al.17 MCW measurements in the present study were significantly correlated with FD results without distinction of molar, premolar, anterior, and condylar regions. The differences between their study and the present investigation might be due to several factors: first, the size of subject population used for evaluating FD and panoramic indices; second, the ROI size being 64× 64 and 18 × 19 pixels in the aforementioned study and present study, respectively; third, differences in selected ROIs of the studies.
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Gulsahi et al.39 showed that osteoporosis in edentulous patients might be detected with sufficient diagnostic efficacy using MCW and MCI, but not using PMI. Contrary to Gulsahi et al.39, no statistically significant correlation was observed in MCI according to research performed by Amorim et al.40 and Dağıstanlı et al.
41
on patients with osteoporosis and
controls. Similar to the findings of Amorim et al.40 and Dağıstanlı et al.
41
, MCW and PMI
were found to be lower in the DM group than in the healthy controls, whereas no significant difference in MCI was found between these groups. Panoramic radiographs have been employed in various studies to indicate bone resorption and osteoporosis using qualitative and quantitative indices. In the present study, this image was also chosen because it is a routinely used method involving considerably less amount of radiation. Also, fully dentate patients were included in the present study because a significant relationship between dental status and the MCW, PMI, and MCI indices has been reported. 42 This novel study clarified cortical and trabecular mandibular bone changes in patients with T1DM and T2DM by examining both FD and radiomorphometric panoramic indices. The major limitation of this study was the small sample size, which might have prevented some associations to reach statistical significance. Therefore, the findings of this investigation provided only preliminary evidence. Further large-sample studies should be conducted using different imaging modalities in patients with DM. In conclusion, this study demonstrated that neither the T1DM or T2DM groups had significantly different FD values compared with the control group, overall or in any specific region of the jaws. The T1DM group had significantly lower MCW and PMI scores compared with the control group, while the T2DM group had no significant differences. The two DM groups did not differ significantly in terms of FD, MCW, or PMI. A positive correlation was
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found between the DM and control groups in terms of fractal analysis and MCW measurement.
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FIGURE LEGENDS Figure 1. Consort flow chart showing patient flow during the study. Figure 2. Digital panoramic radiograph with molar (M), premolar (P), anterior (A), and condylar (c) regions of interest of trabecular bone for fractal analysis. Figure 3. Stages of fractal dimension analysis. (A) Blurred image of the cropped and duplicated ROI. (B) The blurred image was then subtracted from the original image. (C) Addition of a gray value of 128 to each pixel location. (D) Binarization. (E) Erosion. (F) Dilatation. (G) Inversion. (H) Skeletonization. Figure 4. Cropped digital panoramic radiograph with a line parallel to the inferior border of the mandible (a), distance between the inferior border of the mental foramen and the base of the mandible (b), and cortical thickness (c). The radiomorphometric indices were measured through this analysis.
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Table I. Comparison of mean FD values between T1DM and control groups according to measurement regions Region
N
Group
FD (Mean)
Std. Deviation
Std. Error
t
p-value
Anterior
26 26
T1DM Control
1.27 1.29
0.11 0.12
0.02 0.02
0.38
0.705a
Premolar
26 26
T1DM Control
1.26 1.30
0.10 0.12
0.02 0.02
1.22
0.224a
Molar
26 26
T1DM Control
1.25 1.30
0.18 0.15
0.03 0.03
1.12
0.260a
Condylar
26 26
T1DM Control
1.22 1.30
0.14 0.16
0.02 0.03
1.32
0.192a
a: statistically insignificant value (the one-way analysis of variance test) Abbreviations: FD, Fractal Dimension; T1DM, Type 1 Diabetes Mellitus
Table II. Comparison of mean FD values between T2DM and control groups according to measurement regions Region
N
Group
FD (Mean)
Std. Deviation
Std. Error
t
p-value
Anterior
26 26
T2DM Control
1.25 1.28
0.13 0.14
0.02 0.02
-0.65
0.510a
Premolar
26 26
T2DM Control
1.28 1.24
0.09 0.12
0.01 0.02
1.02
0.315a
Molar
26 26
T2DM Control
1.28 1.26
0.10 0.15
0.02 0.03
0.37
0.700a
Condylar
26 26
T2DM Control
1.28 1.25
0.09 0.15
0.01 0.03
0.90
0.362a
a: statistically insignificant value (the one-way analysis of variance test) Abbreviations: FD, Fractal Dimension; T2DM, Type 2 Diabetes Mellitus
Page 20 of 26
Table III. Mean MCW value (mm) and PMI ratio in T1DM and control groups
N
Mean
Std. Deviation
Std. Error
Minimum
Maximum
26
2.06a
0.57
0.11
1.20
3.10
Control
26
2.62
b
0.76
0.15
1.40
4.40
Total
52
2.34
0.73
0.10
1.20
4.40
26
a
0.07
0.01
0.16
0.45
b
0.06
0.01
0.19
0.48
T1DM MCW
T1DM PMI
Control
26
0.28 0.33
Total 52 0.30 0.07 0 0.16 0.48 Different letters indicate statistically significant differences between groups (the independent-samples t test) Abbreviations: T1DM, Type 1 Diabetes Mellitus; MCW, Mandibular Cortical Index; PMI, Panoramic Mandibular Index
Table IV. Mean MCW value (mm) and PMI ratio in T2DM and control groups.
N
Mean
Std. Deviation
Std. Error
Minimum
Maximum
26
2.35a
0.77
0.15
1.05
4.60
Control
26
2.62
a
0.78
0.15
1.27
4.40
Total
52
2.48
0.78
0.10
1.05
4.60
26
0.28
a
0.06
0.01
0.14
0.39
0.31
a
0.09
0.01
0.14
0.50
T2DM MCW
T2DM PMI
Control
26
Total 52 0.30 0.08 0.01 0.14 0.50 a: statistically insignificant value (the independent-samples t test) Abbreviations: T2DM, Type 2 Diabetes Mellitus; MCW, Mandibular Cortical Width; PMI, Panoramic Mandibular Index
Page 21 of 26
Table V. MCI classification in T1DM, T2DM, and control groups
C1 N(%) T1DM
p-value
19 (73.1)
Control
20 (76.9)
Total
39 (75)
T2DM
19 (73.1)
Control
22 (84.6)
C2
*
N(%) 7 (26.9)
0.320
a
C3 p-value
**
6 (23.1) 7 (26.9)
0.147a
4 (15.4)
p-value
0 0.258
a
13 (25) *
N(%)
Total
0
26(100) 1.000
b
0 **
0
26(100) 52(100)
0 0.210a
N(%)
26(100) 1.000b
26(100)
Total 41(78.8) 11(21.2) 0 52(100) *: p = 1.000, **: p = 1.000, different letters indicate statistically significant differences between groups (Pearson chi-square test). Abbreviations: T1DM, Type 1 Diabetes Mellitus; T2DM, Type 2 Diabetes Mellitus; MCI, Mandibular Cortical Index
Page 22 of 26
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S2212-4403(18)30927-1 https://doi.org/10.1016/j.oooo.2018.04.010 OOOO 2004
To appear in:
Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology
Received date: Revised date: Accepted date:
7-12-2017 16-4-2018 21-4-2018
Please cite this article as: Emine Şebnem Kurşun-Çakmak, Seval Bayrak, Comparison of fractal dimension analysis and panoramic-based radiomorphometric indices in the assessment of mandibular bone changes of type 1 and type 2 diabetes mellitus patients, Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology (2018), https://doi.org/10.1016/j.oooo.2018.04.010. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
COMPARISON OF FRACTAL DIMENSION ANALYSIS AND PANORAMIC-BASED RADIOMORPHOMETRIC INDICES IN THE ASSESSMENT OF MANDIBULAR BONE CHANGES OF TYPE 1 AND TYPE 2 DIABETES MELLITUS PATIENTS
Emine Şebnem KURŞUN-ÇAKMAK1, Seval BAYRAK2
1
Associate Prof. Türkiye Public Hospitals Agency, Ministry of Health
2
Assistant Prof. Abant İzzet Baysal University, Dentistry Faculty, Department of Dentomaxillofacial
Radiology
Manuscript Correspondence: Seval BAYRAK Contact address: Abant İzzet Baysal University Faculty of Dentistry, 14000, Gölköy, Bolu, Turkey e-mail address: [email protected] Telephone number: +90 374 254 8361 Fax number: +90 374 270 0066
Word count for abstract: 200 Word count for manuscript:2900 Number of tables: 5 Number of figures: 4 The authors declare no financial support and conflicts of interest.
Page 1 of 26
Statement of Clinical Relevance The results of this study showed that there was no significant difference between DM and control groups in terms of mean FD values.Contrary to T2DM patients, T1DM patients had significantly lower MCW and PMI measurements compared to controls. Cortical and trabecular bone architecture of T1DM and T2DM patients were not different.
ABSTRACT Objectives: This study compared the fractal dimension (FD) and radiomorphometric indices in the assessment of mandibular bone of patients with type 1 (T1DM) and type 2 diabetes mellitus (T2DM). Study Design: Panoramic radiographs of 104 patients were evaluated to calculate FD, mandibular cortical width (MCW), panoramic mandibular index (PMI), and mandibular cortical index (MCI) in the mandible. Results: No statistically significant differences were found in FD when T1DM and T2DM groups were compared to controls (p≥0.168). T1DM patients had significantly lower MCW (p<0.001) and PMI (p=0.030) than controls. Patients with T2DM had no significant differences in MCW (p=0.228) or PMI (p=0.137) compared to controls. No significant differences were observed between T1DM and T2DM patients for FD, MCW, and PMI (p>0.05). In T1DM and T2DM groups, there was a significant correlation between MCW and FD (p≤0.011). No correlation was observed between FD and PMI in either the T1DM or T2DM group (p≥0.142). No significant differences in MCI were observed between the DM groups and controls (p=0.740) or between the T1DM and T2DM groups (p = 1.000). Conclusions: The cortical and trabecular bone architecture of patients with T1DM and T2DM was not different. Patients with T1DM had lower cortical measurements than controls. Key words: Diabetes mellitus; fractal analyses; panoramic radiography; radiomorphometric indices
Page 2 of 26
INTRODUCTION Diabetes mellitus (DM) is a chronic metabolic disorder that affects more than 415 million individuals worldwide, and this number is expected to double by 2040. Microvascular impairments, such as retinopathy and nephropathy, are the well-known major complications of DM. Bone has not been regarded as a target organ for diabetes-related complications until recently. Over the past decade, strong evidence has accumulated in support of a high fracture risk in both types of DM, with the consequences of fractures being more harmful than those in nondiabetics. 1-3 Hip fracture is frequently observed at the age of 40 years and above in patients with type 1 diabetes mellitus (T1DM). Together with hip fractures, the fracture risk at all sites is increased in patients with T1DM compared with nondiabetics at all ages because of a moderate reduction in bone mineral density (BMD).4,
5
Insulin treatment is additionally
associated with an increased risk of fractures, although it is unclear whether this is a direct effect of the medication itself or if insulin use is a proxy for a more advanced disease. 6, 7 Low mineral density and fracture risk due to DM were first indicated by Albright and Reifenstein in 1948. However, subsequent surveys indicated lower
8, 9
, similar
10, 11
, or
higher12, 13 BMD values in patients with type 2 diabetes mellitus (T2DM) than in nondiabetic subjects. In patients with DM, circulating levels of biochemical markers of bone formation and resorption are diminished. Low turnover of bone in diabetes may lead to defective microfracture repairs and, consequently, to their accumulation, promoting reduced bone quality. Contrary to postmenopausal and senile osteoporosis, a deterioration of bone strength
Page 3 of 26
in diabetes is related to increased cortical porosity that is not accompanied by a loss of trabecular bone mass. 14-16 Measurement of cortical thickness and fractal dimension (FD) has been proved to be effective in examining bone microarchitecture of several skeletal sites.17 Mandibular cortical width (MCW) could be beneficial in estimating osteoporosis and hip fractures because the uniform bone loss was observed in the mandibular cortical bone and hip.18 The evaluation of mandibular bone FD is another popular indicator of bone structure analysis. FD analysis is a mathematical method that can assist in quantifying complex structures and can be used to define the complex structure of the trabecular bone.19,
20
The structure is
characterized by a single number that is calculated using a computer algorithm. FD is commonly used to assess and quantify a cancellous bone structure for detecting bone changes, apical healing, periapical bone, and systemic conditions such as osteoporosis. The analysis of FD uses a box-counting algorithm to quantify the trabecular bone pattern by measuring the bone marrow and trabecular bone interface and also to assess the trabecular and medullary bone boundary. In this technique, when a higher box-counting value is reached, the bone structure is more complex.21 The goal of this retrospective study was to compare the FD and 3 panoramic radiographic indices [MCW, panoramic mandibular index (PMI), and mandibular cortical index (MCI)] in the assessment of cortical and trabecular mandibular bone geometry of patients with T1DM and T2DM. MATERIALS AND METHODS This was a single-center, retrospective matched case-control study of panoramic radiographs collected from patients’ files that were part of the database of the School of Dentistry at the University of Abant İzzet Baysal. The study protocol was carried out according to the
Page 4 of 26
principles described in the Declaration of Helsinki, including all amendments and revisions. Ethical approval was granted by the Abant Izzet Baysal University Ethical Committee (institutional review board number: 2017/164). The panoramic radiographs were evaluated based on the criteria of clearly visible mandibular molar, premolar, and anterior regions, temporomandibular joint (TMJ), mental foramina, smooth and continuous mandibular inferior cortex, and absence of ghost images that would hinder the analysis of the mandibular bone. The inclusion criteria were as follows: (1) absence of systemic disease, infections, or illness except for well-controlled DM (for diabetic groups only); (2) absence of systemic disease, infections, or illness (for controls only); (3) no current use of drugs that could influence the bone quality; (4) no smoking; (5) no missing teeth; and (6) no signs of TMJ disorder. Out of a total of 133 patients, 29 were excluded and 104 patients were included in the study. Of these, 26 were patients with T1DM (11 males, 15 females; mean age 24.38 ± 3.57 years; range between 19 and 32 years) and 26 were patients with T2DM (12 males, 14 females; mean age 48.65 ± 9.51years; range between 32 and 65 years). The control groups for T1DM and T2DM consisted of 52 systemically healthy patients who were age and sex matched with the study groups (Fig.1). Standardized digital panoramic radiographs were obtained using Soredex (Cranex Novus, Tuusula, Finland) at 70 kVp and 10 mA for 8 s exposure time. Linear measurements were performed using ImageJ version 1.3 software (National Institutes of Health, MD, USA) at a correction for 30% magnification to better simulate the clinical situation. The following measurements were performed. FD analysis of each sample was conducted as suggested by White and Rudolph
22
using the
box-counting method. The images were analyzed using ImageJ version 1.3 software (National
Page 5 of 26
Institutes of Health, MD, USA). FD measures of the trabecular bone were estimated from four regions of interest (ROI) on the left side of the panoramic radiographs. The four ROIs were molar, premolar, anterior, and condylar regions of the mandibular jaw bone. Figure 2 shows the regions of interest chosen for fractal analysis. The digital panoramic radiographs of the groups were converted into tagged image file formats because of high resolution. ROI was selected with the size of 18 × 19 pixels, cropped, and duplicated. Gaussian blur was used to remove brightness variations due to the overlying soft tissues and varying thickness of bone. The resulting image was then subtracted from the original image. Bone marrow spaces and trabeculae were discriminated from each other with the addition of a gray value of 128 to each pixel location. After performing binary, erode, dilate, invert, and skeletonize processes, FD was calculated (Fig. 3). MCW at the mental foramen region was assessed according to the technique described by Ledgerton et al. 23. The mental foramen was identified and a line was traced perpendicular to the tangent to the lower border of the mandible and through the center of the mental foramen. MCW was measured separately on the right and left mandibular sides, and the mean values were calculated. PMI was calculated according to the method of Benson et al 24 as the ratio of the thickness of the mandibular cortex to the distance from the lower border to the inferior edge of the mental foramen. The mental foramen is considered as the standard region for study in most of the surveys because masticatory muscles are not attached to this region. PMI was calculated separately on each side of the mandible and the mean values were calculated. MCI was evaluated and classified according to Klemetti et al.25 classification based on the morphological changes in the cortical bone at the mandibular base into three groups: C1, the endosteal margin of the cortical bone is even and sharp on both sides; C2, the endosteal
Page 6 of 26
margin shows semilunar defects (lacunar resorption) or seems to form the endosteal cortical layer (one to three layers) on one or both sides; and C3, the cortical layer forms heavy endosteal cortical residues and is clearly porous. Figure 4 depicts the analysis of the panoramic images performed in calculation of the morphometric indices. All measurements were performed by a single dentomaxillofacial radiologist (SB) with 10 years of experience in the field. Twenty panoramic images were randomly selected and reevaluated 2 weeks after the initial evaluation to permit calculation of the intraclass correlation coefficient (ICC) with a confidence interval of 95%. This was done to measure the intraobserver reliability of ROI selection/fractal analysis of the trabecular structure of the four ROIs and measurement of panoramic-based radiomorphometric indices. The SPSS 10.0 software (SPSS Inc., IBM Company Headquarters, IL, USA) was used for storing and analyzing data. The significance level value was set at 0.05. The independent-samples test was used for comparing FD values with MCW and PMI of the diabetic and control groups. The Pearson chi-square test was used to analyze the significance of difference in MCI between DM groups and controls, and between T1DM and T2DM patients. The one-way analysis of variance test was used for comparing four regions in terms of FD. RESULTS The systemic intraobserver error was evaluated at p<0.05, indicating no statistically insignificant differences in measurements. The ICC calculations indicated good reliability for each measurement including FD of molar region (ICC=0.788), premolar region (ICC=0.822), anterior region (ICC=0.796), condylar region (ICC=0.809), MCW (ICC=0.868) and PMI (ICC=0.877). The mean FD values were found to be lower in the T1DM group (1.25 ± 0.10) compared with the control group (1.29 ± 0.10) (p=0.168) . However, nearly equal results were obtained when
Page 7 of 26
comparing the T2DM (1.27 ± 0.07) and control groups (1.26 ± 0.09), without statistical significance (p=0.582). When the study and control groups were evaluated according to regions using a one-way analysis of variance test, the findings revealed that the mean FD values were not significantly different between regions (p>0.05). Tables I and II show the mean FD values in the study and control groups according to regions. The T1DM group had significantly lower MCW (2.06 ± 0.57) and lower PMI measurements (0.28 ± 0.07) compared with the control group (2.62±0.76, p<0.001; 0.33±0.06, p= 0.030, respectively) (Table III). No statistically significant differences were observed between the T2DM and control groups in terms of MCW (2.62 ± 0.78 and 2.35 ± 0.77, respectively; p=0.228) or PMI measurements (0.31± 0.09 and 0.28± 0.06, respectively; p=0.137) (Table IV). When the T1DM and T2DM groups were compared according to FD, MCW, and PMI measurements, no statistically significant differences were observed (p>0.05). In the T1DM and T2DM groups, the MCW measures were correlated with the FD values (r=0.462, p=0.011; r=0.57, p<0.001, respectively) whereas PMI measures were not correlated (r=-0.253, p=0.700; r=0.207, p=0.142, respectively). According to MCI classification, group C3 was not observed in either the DM groups or the controls. No significant difference was observed between the DM and control groups (p=0.740) or between the T1DM and T2DM groups (p = 1.000) (Table V).
DISCUSSION The results indicated that FD measurements of the trabecular bone were not statistically different between the DM and control groups. No significant difference was observed between patients with T1DM and T2DM in terms of FD, MCW, or PMI. Among the
Page 8 of 26
panoramic-based indices, MCW measurements exhibited a correlation with the FD results of patients with DM. In the dental literature, DM has been associated with severe forms of periodontal disease, an increased rate of dry socket after extractions, oral candidiasis, burning mouth, and dry mouth.26 However, few studies have investigated the mandibular bone structure of patients with DM, and these were mainly focused on bone implant problems. Abduljabbar et al.27 evaluated the peri-implant inflammatory parameters in prediabetes, T2DM, and control groups and stated that peri-implant inflammatory parameters were worse among patients with prediabetes and T2DM compared with controls. Yamawaki et al.28 assessed the effects of high glucose levels on hard tissue formation on a nanoscale-modified titanium surface in the bone of rats with T2DM. The authors found that high glucose concentration increased hard tissue formation, but the quality of the mineralized tissue decreased. Nemtoi et al.29 investigated the mandibular bone quality and quantity of 23 patients with DM and 27 controls in cone beam computed tomographic (CBCT) images by measuring BMD, the distance from the mandibular canal to the alveolar ridge, and the distance from the buccal to the lingual cortical wall. The results of the study showed a significant correlation between bone quality and values of glycosylated hemoglobin. In addition, a significant inverse correlation was observed between the values of cortical and trabecular bone density in the posterior region of the mandible and HbA1c (hemoglobin A1c). Studies have also demonstrated a significant correlation between BMD and FD measurements in patients with osteopenia/osteoporosis and postmenopausal women. FD measurements decreased with the decrease in BMD measurements from the normal to the osteoporotic group. 30, 31
Page 9 of 26
Fractal analysis has gained popularity in identifying potential abnormalities and severity of existing disorders in bone structure. Higher FD represents complex bone architecture with denser and less porous trabeculae.32 The present study confirmed this report with the lower values in the diabetic groups. The technique most commonly used in the literature to calculate FD is box counting, which was also used in the present study to determine the trabecular structure of the mandible. Alman et al.33 showed that FD of the mandibular trabecular bone was a good surrogate for BMD in both men and women but MCW exhibited worse diagnostic performance for identifying men with low BMD than women. Measurement of the cortical width from one side only and differences in the ROI selection (apical to the roots of the first molar and second premolar) may be the possible factors accounting for different results. Also, the aforementioned study was performed on older individuals (aged more than 50 years) compared with the present study. Age has been suggested as an important factor in MCW assessment.18, 34, 35 Starup-Linde et al.36 conducted a study based on the comparison of bone structure and density between patients with T1DM and T2DM. BMD of the hip and tissue stiffness at the tibia were found to be lower in T1DM patients. Cortical porosity parameters were similar between DM types, indicating that the cortical microstructure was not different. The results also demonstrated that the cortical and trabecular bone microarchitecture was not different according to DM types. Another study by Nillson et al.16 evaluated bone microarchitecture, bone material strength, and physical function in ambulant female patients with T2DM aged 7580 years. The results of the study revealed that trabecular and cortical bone microarchitecture, biomechanical properties, and BMD were better, but bone material strength and physical function were
Page 10 of 26
worse in patients with T2DM compared to healthy controls. Contrary to Nillson et al.16, patients with T2DM in the present study exhibited results similar to those in the control group in terms of cortical and trabecular bone measurements. Selection of only relatively fit ambulant patients with T2DM as a study group and discrepancies in the methods used to obtain bone microarchitecture and anatomical variations between the measured body parts preclude a direct comparison with the results of both studies. Ay et al.37 examined BMD in patients with T2DM using panoramic radiographs. Dual energy X-ray absorptiometry measurements revealed no statistically significant difference in mandibular BMD between the control and T2DM groups. Measurement of the MCW in panoramic radiographs has been suggested as an alternative and simple way to identify patients with low BMD. 38 Kavitha et al.17 investigated 1047 panoramic radiographs in terms of bone radiographic measurements and reported that MCW could estimate a higher capability of variations with age and gender than FD measures for estimating bone quality and osteoporosis. The authors also added that FD measures in the molar and premolar regions demonstrated a slightly greater significance and correlation with age among women than men, but not as strong as MCW. Contrary to Kavitha et al.17 MCW measurements in the present study were significantly correlated with FD results without distinction of molar, premolar, anterior, and condylar regions. The differences between their study and the present investigation might be due to several factors: first, the size of subject population used for evaluating FD and panoramic indices; second, the ROI size being 64× 64 and 18 × 19 pixels in the aforementioned study and present study, respectively; third, differences in selected ROIs of the studies.
Page 11 of 26
Gulsahi et al.39 showed that osteoporosis in edentulous patients might be detected with sufficient diagnostic efficacy using MCW and MCI, but not using PMI. Contrary to Gulsahi et al.39, no statistically significant correlation was observed in MCI according to research performed by Amorim et al.40 and Dağıstanlı et al.
41
on patients with osteoporosis and
controls. Similar to the findings of Amorim et al.40 and Dağıstanlı et al.
41
, MCW and PMI
were found to be lower in the DM group than in the healthy controls, whereas no significant difference in MCI was found between these groups. Panoramic radiographs have been employed in various studies to indicate bone resorption and osteoporosis using qualitative and quantitative indices. In the present study, this image was also chosen because it is a routinely used method involving considerably less amount of radiation. Also, fully dentate patients were included in the present study because a significant relationship between dental status and the MCW, PMI, and MCI indices has been reported. 42 This novel study clarified cortical and trabecular mandibular bone changes in patients with T1DM and T2DM by examining both FD and radiomorphometric panoramic indices. The major limitation of this study was the small sample size, which might have prevented some associations to reach statistical significance. Therefore, the findings of this investigation provided only preliminary evidence. Further large-sample studies should be conducted using different imaging modalities in patients with DM. In conclusion, this study demonstrated that neither the T1DM or T2DM groups had significantly different FD values compared with the control group, overall or in any specific region of the jaws. The T1DM group had significantly lower MCW and PMI scores compared with the control group, while the T2DM group had no significant differences. The two DM groups did not differ significantly in terms of FD, MCW, or PMI. A positive correlation was
Page 12 of 26
found between the DM and control groups in terms of fractal analysis and MCW measurement.
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FIGURE LEGENDS Figure 1. Consort flow chart showing patient flow during the study. Figure 2. Digital panoramic radiograph with molar (M), premolar (P), anterior (A), and condylar (c) regions of interest of trabecular bone for fractal analysis. Figure 3. Stages of fractal dimension analysis. (A) Blurred image of the cropped and duplicated ROI. (B) The blurred image was then subtracted from the original image. (C) Addition of a gray value of 128 to each pixel location. (D) Binarization. (E) Erosion. (F) Dilatation. (G) Inversion. (H) Skeletonization. Figure 4. Cropped digital panoramic radiograph with a line parallel to the inferior border of the mandible (a), distance between the inferior border of the mental foramen and the base of the mandible (b), and cortical thickness (c). The radiomorphometric indices were measured through this analysis.
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Table I. Comparison of mean FD values between T1DM and control groups according to measurement regions Region
N
Group
FD (Mean)
Std. Deviation
Std. Error
t
p-value
Anterior
26 26
T1DM Control
1.27 1.29
0.11 0.12
0.02 0.02
0.38
0.705a
Premolar
26 26
T1DM Control
1.26 1.30
0.10 0.12
0.02 0.02
1.22
0.224a
Molar
26 26
T1DM Control
1.25 1.30
0.18 0.15
0.03 0.03
1.12
0.260a
Condylar
26 26
T1DM Control
1.22 1.30
0.14 0.16
0.02 0.03
1.32
0.192a
a: statistically insignificant value (the one-way analysis of variance test) Abbreviations: FD, Fractal Dimension; T1DM, Type 1 Diabetes Mellitus
Table II. Comparison of mean FD values between T2DM and control groups according to measurement regions Region
N
Group
FD (Mean)
Std. Deviation
Std. Error
t
p-value
Anterior
26 26
T2DM Control
1.25 1.28
0.13 0.14
0.02 0.02
-0.65
0.510a
Premolar
26 26
T2DM Control
1.28 1.24
0.09 0.12
0.01 0.02
1.02
0.315a
Molar
26 26
T2DM Control
1.28 1.26
0.10 0.15
0.02 0.03
0.37
0.700a
Condylar
26 26
T2DM Control
1.28 1.25
0.09 0.15
0.01 0.03
0.90
0.362a
a: statistically insignificant value (the one-way analysis of variance test) Abbreviations: FD, Fractal Dimension; T2DM, Type 2 Diabetes Mellitus
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Table III. Mean MCW value (mm) and PMI ratio in T1DM and control groups
N
Mean
Std. Deviation
Std. Error
Minimum
Maximum
26
2.06a
0.57
0.11
1.20
3.10
Control
26
2.62
b
0.76
0.15
1.40
4.40
Total
52
2.34
0.73
0.10
1.20
4.40
26
a
0.07
0.01
0.16
0.45
b
0.06
0.01
0.19
0.48
T1DM MCW
T1DM PMI
Control
26
0.28 0.33
Total 52 0.30 0.07 0 0.16 0.48 Different letters indicate statistically significant differences between groups (the independent-samples t test) Abbreviations: T1DM, Type 1 Diabetes Mellitus; MCW, Mandibular Cortical Index; PMI, Panoramic Mandibular Index
Table IV. Mean MCW value (mm) and PMI ratio in T2DM and control groups.
N
Mean
Std. Deviation
Std. Error
Minimum
Maximum
26
2.35a
0.77
0.15
1.05
4.60
Control
26
2.62
a
0.78
0.15
1.27
4.40
Total
52
2.48
0.78
0.10
1.05
4.60
26
0.28
a
0.06
0.01
0.14
0.39
0.31
a
0.09
0.01
0.14
0.50
T2DM MCW
T2DM PMI
Control
26
Total 52 0.30 0.08 0.01 0.14 0.50 a: statistically insignificant value (the independent-samples t test) Abbreviations: T2DM, Type 2 Diabetes Mellitus; MCW, Mandibular Cortical Width; PMI, Panoramic Mandibular Index
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Table V. MCI classification in T1DM, T2DM, and control groups
C1 N(%) T1DM
p-value
19 (73.1)
Control
20 (76.9)
Total
39 (75)
T2DM
19 (73.1)
Control
22 (84.6)
C2
*
N(%) 7 (26.9)
0.320
a
C3 p-value
**
6 (23.1) 7 (26.9)
0.147a
4 (15.4)
p-value
0 0.258
a
13 (25) *
N(%)
Total
0
26(100) 1.000
b
0 **
0
26(100) 52(100)
0 0.210a
N(%)
26(100) 1.000b
26(100)
Total 41(78.8) 11(21.2) 0 52(100) *: p = 1.000, **: p = 1.000, different letters indicate statistically significant differences between groups (Pearson chi-square test). Abbreviations: T1DM, Type 1 Diabetes Mellitus; T2DM, Type 2 Diabetes Mellitus; MCI, Mandibular Cortical Index
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