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Year : 2019  |  Volume : 22  |  Issue : 10  |  Page : 1435-1440

Evaluation of the effects of hemoglobinopathies on the mandible with fractal dimension analysis

Department of Dentomaxillofacial Radiology, Faculty of Dentistry, Hatay Mustafa Kemal University, Hatay, Turkey

Date of Acceptance03-Jun-2019
Date of Web Publication14-Oct-2019

Correspondence Address:
Dr. G Serindere
Department of Dentomaxillofacial Radiology, Faculty of Dentistry, Hatay Mustafa Kemal University, Hatay
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/njcp.njcp_196_19

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Aims: The aim of this study was to evaluate the mandibular bone changes on panoramic radiographs of thalassemia and sickle cell anemia (SCA) patients using fractal dimension (FD) analysis and to compare the findings obtained from healthy individuals. Materials and Methods: A total of 90 panoramic radiographs (from 30 patients with thalassemia, 30 patients with SCA and 30 healthy individuals) were assessed to measure FD, mandibular cortical width (MCW), panoramic mandibular index (PMI) in the mandible. Three region of interests (ROI) of angulus, corpus, and interdental bone were created. FD was calculated using ImageJ program. Results: In thalassemia group, the mean value of FD was 1.11, 1.03, and 1.02 in interdental bone, corpus, and angulus, respectively. In SCA group, the mean value of FD was 1.10, 1.05, and 1 in interdental bone, corpus, and angulus, respectively. In control group, the mean value of FD was 1.09, 1.04, and 1 in interdental bone, corpus, and angulus, respectively. FD value of interdental bone are significantly higher in thalassemia group than control group. FD values of corpus and angulus values did not show a significant difference between the groups. Conclusions: Fractal analysis may be used and recommended for evaluation of the bone changes induced by hemoglobinopathies.

Keywords: Dijital imaging, fractal analysis, panoramic, sickle cell anemia

How to cite this article:
Serindere G, Belgin C A. Evaluation of the effects of hemoglobinopathies on the mandible with fractal dimension analysis. Niger J Clin Pract 2019;22:1435-40

How to cite this URL:
Serindere G, Belgin C A. Evaluation of the effects of hemoglobinopathies on the mandible with fractal dimension analysis. Niger J Clin Pract [serial online] 2019 [cited 2020 May 28];22:1435-40. Available from:

   Introduction Top

Beta-thalassemia and sickle cell anemia (SCA) are the most common hemoglobinopathies in Turkey especially in the region of the Mediterranean and Cukurova regions of Turkey.[1] Beta-thalassemia results in a decrease in the production of b-globin chains and has multiple organ effects. Additionally, it causes significant morbidity and mortality.[2] Thalassemia bone disease involves some situations such as pain and deformity of bone, marrow expansion, reduction of bone density, and fracture formation.[3] The features of thalassemia bone disease are unique than the features of typical idiopathic osteoporosis that is generally observed in the public. The differences are to occur in the younger age of patients (especially in their 20s to 30s), the risk factors for bone loss that is mostly specific to thalassemia disease, the fracture epidemiology, and the response to treatment with bone-preserving drugs.[4]

SCA is the most common observed disease among abnormal hemoglobin in the world and in our country. As a result of the point mutation in the 6th codon of the beta globin gene sequence, in the GAG codon, which normally synthesizes glutamic acid, replaces the timing in place of the adenine, and the GTG is encrypted and the valine is encoded instead of glutamic acid.[5] Both SCA and the beginning of osteomyelitis have various radiological findings such as abnormal skull radiography findings. These findings include enlargement of diplopic space, the outer table thinning, the classical hair-on-end, and granular appearance of the skull. Additionally, changes in bone trabecular structure, hyperplasia, jaw expansion, enlarged bone marrow spaces, and coarse trabecular structure are observed.[6],[7]

Image analysis methods developed by today's digital technology allow measurement of changes in alveolar bone and specific digital methods which can quantitatively evaluate trabecular bone changes have been developed. One of the mathematical image analysis methods used for this purpose is fractal analysis. Fractal analysis method is a mathematical method used in the analysis of complex shapes and structural formations and the numerical value obtained as a result of analysis is defined as “fractal dimension.”[8]

The aim of this study was to evaluate mandibular bone changes in patients with thalassemia and SCA and to compare findings with healthy individuals using fractal analysis.

   Materials and Methods Top

In this study, anamnesis and panoramic radiographs of 90 patients who applied to Department of Dentomaxillofacial Radiology for various reasons were retrospectively evaluated. The study protocol was approved by the Local Research Ethics Committee (dated 10.01.2019/decision number: 13).

Thirty patients with SCA, 30 patients with thalassemia, and 30 healthy individuals (control group) were included in this study. Inclusion criterias were a clear view of the mandible, continuous mandible cortex, and absence of any ghost images that would prevent the image analysis.

Patients with metabolic, endocrine, connective tissue, chronic liver and kidney disease that affect bone metabolism and who used some drugs that caused secondary osteoporosis such as corticosteroids, anticonvulsants, heparin, thyroid hormones, diuretics, and methotrexate were excluded from the study.

Panoramic radiographs were taken with the Planmeca Digital Panoramic device (Planmeca, Helsinki, Finland) with 70 kVp and 10 mA. The image analysis program (Image J, 1.3 v version, National Institutes of Health, Bethesda, MD) was used for fractal analysis of all digital images obtained. All image processing and analysis procedures were performed by two dentomaxillofacial radiologist. The same personal computer was used for all procedures to avoid differences caused by computer monitor features.

Fractal analysis of the images were performed according to White and Rudolph's [9] method. Based on the study of Şener and Baksı,[10] for the analyzes, three different region of interest (ROI) with the maximum possible size allowed by the region, including angulus, corpus, and interdental bone on the panoramic image of the patient was determined [Figure 1]. While the ROI of angulus region includes the trabecular bone, ROI of corpus region includes both cortical and trabecular bone. In the method of White and Rudolph,[9] a copy of the ROI generated on the original radiography was obtained and this copy was blurred using a Gaussian filter with a diameter of 35 pixels. Then, binary, erode, dilate, invert, and skeletonize operations were performed [Figure 2]. FDs were calculated by using the box counting method with the help of the software [Figure 3]. The mean values of the FD calculated for the ROIs (angulus, corpus, and interdental bone) on each image were recorded for statistical analysis.
Figure 1: Three different ROIs on panoramic radiograph for FD measurement

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Figure 2: The processing parts of fractal analysis. (a). ROI was cropped and duplicated (b). Subtracted image (c). Gaussian blur (d). Binarization (e). Erosion (f). Dilatation (g). Inversion (h). Skeletonization

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Figure 3: Calculation of FD

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The measurement of mandibular cortical width (MCW)

The measurement of MCW was performed based on the study of Ledgerton et al.[11] The localization of mental foramen was determined and a line was drawn at the level of the mental foramen that would be tangent to the mandibular cortex. Then, a second line perpendicular to this line was drawn. The distance from the intersection of these two lines to the lower border of the mandible was used for the measurement of MCW (a) [Figure 3] and [Figure 4].
Figure 4: Representation of mandibular index calculations on panoramic radiographs. (a) cortical thickness, (b) the distance between the lower border of the mental foramen and the lower border of the mandibular cortex

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The measurement of panoramic mandibular index (PMI)

Based on the method of Benson et al.,[12] PMI was calculated by dividing cortical thickness in the mental region by the distance from the lower border of the mental foramen to the lower border of the mandible (b) [Figure 3] and [Figure 4]. The values were recorded for the statisticaly analysis.

The data obtained in this study were analyzed by the SPSS 21 package program. ANOVA was used for three-group comparisons, and Mann--Whitney U test was used for two-group comparisons. The correlation between the variables was examined by correlation analysis. Significance level was used as 0.05, P < 0.05 in the case of significant difference, P > 0.05 is stated that there is no significant difference in the case.

   Results Top

The interobserver reliability was estimated by Intraclass Correlations (ICC) for all observations. ICC indicated excellent reliability for interobserver evaluations.

The study groups comprised 90 patients, of whom 44 were male and 46 were female. The mean age of all patients were 34.49 (thalassemia: 30.33, SCA: 34.47, control: 38.67) There was no significant difference in gender between the groups (P > 0.05). There was no significant difference in age between the groups (P > 0.05) [Table 1] and [Table 2]. The groups were homogeneous in terms of age and gender.
Table 1: The patient numbers of three groups

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Table 2: The age information of three groups

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The FD values of interdental bone, corpus, and angulus were not significantly different between groups (P > 0.05). MCW values were significantly higher in the control group compared with the other two groups. B values were significantly higher in the control group compared with the other two groups. PMI values were significantly higher in the control group than thalassemia and SCA group [Table 3]. As the age increased in the SCA group, MCW values decreased.
Table 3: Mean FD, MCW and PMI values of three groups

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There was no significant difference between the genders and values in the thalassemia group (P > 0,05). In SCA group, there was no significant difference between the genders and values (P > 0.05). There was no significant difference between the genders and values in the control group (P > 0.05).

   Discussion Top

In radiology, fractal analysis is performed by detection of FD values and can identify distinct morphological presence in the cancellous structure and so the cellular process effect that led to changes in the structure may be evaluated.[13]

The prevalence of osteoporosis in transfusion-induced thalassemia is well defined, but studies about the longitudinal change in bone mineral density have been small relatively short term.[14],[15] Mahachoklertwattana et al.[16] reported that osteopenia in suboptimally blood-transfused patients with iron overload is principally caused by focal osteomalacia as well as bone formation decrease. Karimi et al.[17] reported that patients younger than 20 years old with thalassemia showed significant lower lumbar bone mineral density and bone mineral content values than control group.

In patients with thalassemia-induced osteoporosis, bone resorption increases. This causes the use of antiresorption drugs such as bisphosphonates in the treatment of osteoporosis. Bisphosphonates are found to be potent inhibitors of osteoclastic bone resorption.[18] In our study, the lower values of FD, MCW, and PMI was also observed in thalassemic patients than the healthy individuals.

Although bone findings of SCA is the most frequently observed, the maxillofacial bone and skull base is rarely affected because they have small amount of marrow.[19] In the head and neck region, Royal et al.[20] reported that the most common site of bone involvement was the orbital wall, mandible and skull base, respectively. White et al.[21] reported significant bone marrow enlargement and simpler trabecular structure in patients with SCA. Faber et al.[22] also found increase in distance between trabeculae in SCA patients. Avsever et al.[19] reported decreased values of FD, bone density, trabecular number, trabecular pattern factor, number of closed pores, and structural model index for the patients with SCA. In the study of Kaya et al.,[23] decreased trabecular bone density and bone marrow expansion were reported in 67% of SCA patients. Demirbas et al.[7] also reported that patients under age 20 years with SCA had lower FD values than the control group. In our study, the lower values of FD, MCW, and PMI was observed in patients with SCA than the healthy individuals.

Sindeaux et al.[24] reported that FD values on mandible cortex were lower and MCW was thinner in women with osteoporosis. Şener and Baksı[10] reported that there was significant difference between FD values of healthy individuals and the patients who used bisphosphonate drug in different locations. The difference in FD values of interdental bone regions and corpus was significant, while there was no difference between other two locations. Contrast to the study of Demirbas et al.,[7] Avsever et al.,[19] and Bayrak et al.[25] reporting that FD values were lower in SCA [7],[19] or thalassemia [25] than the control group, there was no significant differences between FD values of three regions in the present study. Bayrak et al.[25] reported that the mean MCW value was significantly lower in thalassemia groups. There was no significant difference in PMI between thalassemia groups and control groups. Dagistan and Bilge [26] reported that there were statistically significant differences between the male patients with osteoporosis and control group in PMI values. Additionally, MCW was also lower. Similarly, in our study, MCW values were significantly higher in the control group compared with the other two groups. PMI values were significantly higher in the control group than thalassemia and SCA group.

When the studies about osteoporosis-induced alveolar bone changes are evaluated in terms of the results, it cannot be said that they have reached a common point. If the findings of many studies are briefly summarized, some researchers argue that there is a decrease in FD values in alveolar bones in osteoporosis and in others, higher FD values were determined. The differences in the results of these studies are attributed to changes in their radiological methods.[10] Another important point is that in most of the studies, the films used in the fractal analysis method were obtained by conventional methods and digitized by using scanners.[10] A recent study emphasized that the digitization process produced undesirable noise in which negatively affected fractal analysis measurements.[27] Yaşar et al.[28] compared PMI and FD in patients with osteoporosis and performed PMI measurements on conventional panoramic radiographs and images obtained by direct digital systems for FD measurements. Because of these reasons, we also preferred using direct digital panoramic radiography method. However, although there are several studies using the panoramic radiography in the literature, a limitation of our study may be that the three-dimensional imaging system was not used. In order to compare two-dimensional and three-dimensional imaging systems in terms of FD values and mandibular indexes, studies on images taken from the same patient will be useful.

In conclusion, the results of the present study showed that fractal analysis can be used to evaluate bone changes in the patients with hemoglobinopathies. To the best of our knowledge, this study is one of the few studies about the evaluation of mandibular bone changes in hemoglobinopathies with using fractal analysis. When we planned this study, we decided to study about this subject because it is very common in our region. Further studies will be helpful to evaluate mandibular bone changes in hemoglobinopathies.

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Conflicts of interest

There are no conflicts of interest.

   References Top

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Şener E, Baksı BG. Saǧlıklı Ve Osteoporoz Tanılı Hastalarda Fraktal Boyut Ve Mandibular Kortikal İndeks Deǧerlendirilmesi. EÜ Dişhek Fak Derg 2016;37:159-67.  Back to cited text no. 10
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Karimi M, Ghiam AF, Hashemi A, Alinejad S, Soweid M, Kashef S. Bone mineral density in beta-thalassemia major and intermedia. Indian Pediatr 2007;44:29-32.  Back to cited text no. 17
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Bayrak S, Göller Bulut D, Orhan K, Sinanoǧlu EA, Kurşun Çakmak EŞ, Mısırlı M, et al. Evaluation of osseous changes in dental panoramic radiography of thalassemia patients using mandibular indexes and fractal size analysis. Oral Radiol 2019. doi: 10.1007/s11282-019-00372-7.  Back to cited text no. 25
Dagistan S, Bilge OM. Comparison of antegonial index, mental index, panoramic mandibular index and mandibular cortical index values in the panoramic radiographs of normal males and male patients with osteoporosis. Dentomaxillofac Radiol 2010;39:290-4.  Back to cited text no. 26
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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2], [Table 3]


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