Document Type : Original Article
Authors
- Parastoo Namdar 1, 2
- Atena Shiva 3, 2
- Tahura Etezadi 1
- Jamshid YazdaniCharati 4
- Hossein Karami 5
- Sina Iri 6
1 Departmen tof Orthodontics, School of Dentistry, Mazandaran University of Medical Sciences, Sari, Iran
2 Iran Dental Research Center, Mazandaran University of Medical Sciences, Sari, Iran
3 Department of Oraland Maxillofacial Pathology, Faculty of Dentistry, Mazandaran University of Medical Sciences, Sari, Iran
4 Department of Biostatistics, Faculty of Health, Mazandaran University of Medical Sciences, Sari, Iran
5 Department of Pediatrics Hematology and Oncology, Thalassemia Research Center, Mazandaran University of Medical Sciences, Sari, Iran
6 School of Dentistry, Mazandaran University of Medical Sciences, Sari, Iran
Abstract
Introduction: Iran lies in the world’s thalassemia belt; accordingly, the beta-thalassemia gene is carried by 4% of the Iranian population. Due to the dearth of research and literature available on the prevalence of malocclusions in the Iranian population with beta-thalassemia major, this study was conducted to determine the prevalence and severity of facial abnormalities among patients who were referred to Bu-Ali Sina Hospital, Sari, Iran.
Methods: This descriptive cross-sectional study was conducted on 200 patients with thalassemia major who were referred to the care unit of Bu-Ali Sina teaching and therapeutic Hospital, Sari, Iran, in 2018. The patients were then visited by a trained dentist who had been given the necessary theoretical and practical training. Malocclusion was classified based on Angle’s classification. Spacing, overcrowding, overjet, and overbite were measured, and the distances were recorded based on a checklist.
Results: The prevalence of malocclusions obtained was 87.5%, which includedmalocclusions of Class I (34%), Class II (31%), and Classes III (22%) amongst patients. There was no significant relationship between the type of malocclusion and gender (P = 0.77). Moreover, no significant difference was observed among patients with thalassemia major and different classes of malocclusions in terms of age both in males (P = 0.49) and females (P = 0.58).
Conclusions: Malocclusions are common among adolescents and adults with thalassemia, which is not associated with age or gender. Therefore, patients should be regularly visited and followed up by a dentist to manage and control their dental problems. In addition, effective and preventive measures, as well as health education should be seriously considered in these patients.
Keywords
Introduction
Thalassemia is an inherited blood disorder involving abnormal hemoglobin formation due to decreased synthesis of different types of polypeptide chains. The most severe form of this disorder is beta-thalassemia, which arises from mutations in the HBB gene on chromosome 11 (1-3). Alpha/beta imbalance, ineffective erythropoiesis, and chronic anemia in patients with thalassemia occur due to the defect in the synthesis of the beta-globin chains (4).
The prevalence of beta-thalassemia is 1.5%, and its annual incidence has been estimated at 1 per 100,000 population (2). Iran lies in the world's thalassemia belt; accordingly, the beta‐thalassemia gene is carried by 4% of the Iranian population. About three million thalassemia carriers and more than 25,000 patients with thalassemia major have been currently identified in Iran (5).
Thalassemia major is the most severe form of beta-thalassemia. There is great clinical variability in the systemic signs and symptoms of patients with beta-thalassemia major. Bone changes, retardation of growth, and splenomegaly are the consequences of the disease, which occur due to severe anemia in childhood (6). The patients with thalassemia major are at risk of osteoporosis; therefore, they can experience a lot of discomforts associated with bones and teeth (7). The chances of enlargement of the upper jaw (chipmunk face), malocclusion, migration, and spacing of upper anterior teeth, short crowns, and root teeth, as well as discolored teeth, are increased in patients with thalassemia (8-10). Moreover, dental decay is higher among patients with thalassemia, compared to the normal population (10).
The access of special patients with beta-thalassemia major to oral and dental care is a main concern of the dental health care providers. However, the patients refer to dentists when their teeth are severely damaged and require emergency dental services. It is because patients are involved in serious medical complications of thalassemia, which may lead to neglect issues related to the health of their teeth (9, 11). The risk of abscess and infection, as well as its spreading into the tissues of the neck and face is higher during the advanced stages of dental decay. In these stages, there is no other way but to extract the teeth.
Due to the dearth of research and literature available on the prevalence of the severity and types of malocclusions in adolescent and adult patients with beta-thalassemia major, this study was conducted to find out the prevalence of facial abnormalities and malocclusion in patients with thalassemia major referred to Bu-Ali Sina Hospital in Sari, Iran.
Methods and Materials
This descriptive cross-sectional study was conducted on the patients with thalassemia major who were referred to the care unit of Bu-Ali Sina teaching and therapeutic Hospital, Sari, Iran, in 2018.
Study Design
In total, 200 cases were selected using simple random sampling from all patients with thalassemia major aged between 13-39 years who were referred to the care unit of Bu-Ali Sina Hospital for routine examinations, blood infusion, and treatment. The sample size was determined considering α=0.05, β=0.2, d=0.08, and P=84% (12). The patients were visited by a trained dentist who had been given the necessary theoretical and practical training. Demographic characteristics and clinical data were gathered and recorded in a checklist.
In this study, normal occlusion was defined as the presence of all teeth; normal shape, size, and location of teeth; proper molar-overbite relationship (maximum 3 mm) and proper overjet (maximum 2 mm); no space between the teeth; and lack of rotation, overcrowding, and crossbite.
On the other hand, malocclusion was classified based on Angle's classification as follow:
Class I (neutral occlusion): The mesiobuccal cusp of the upper first permanent molar is placed in the mesiobuccal groove of the first lower permanent molar.
Class II (distocclusion): The first permanent molar mesiobuccal groove is placed after the mesiobuccal cusp of the upper first permanent molar.
Class III (mesiocclusion): The first permanent molar mesiobuccal groove is placed before the mesiobuccal cusp of the upper first permanent molar.
In the absence of maxillary and mandibular first molars, occlusion is assessed according to the following criteria:
Class I: Tip of the canine tooth is placed between the canine teeth and the mandibular first premolar.
Class II: Tip of the canine tooth is placed between the canine teeth and the mandibular lateral incisor.
Class III: Tip of the canine tooth is placed between the canine teeth and the mandibular lateral first and second premolars.
The distance between the most prominent labial margins of the incisal edge of the maxillary to the labial surface of the mandibular teeth was calculated for determining the overjet. Furthermore, the vertical relationship between the upper and lower incisors was calculated by the overbite of the vertical distance between the edge of the upper and lower central incisor when they were in contact with posterior teeth. Following that, the distances were calculated in millimeters, and the values more than 2 mm were considered overbite.
Ethical Considerations
The study protocol was approved by the Ethics Committee of Sari University of Medical Sciences, Sari, Iran IR.MAZUMS.REC.1398.492 Before the study, the research objectives and procedures were explained to each case or his/her parents separately, and if the patient showed willingness, the examination was performed. They were then assured that their information would remain confidential.
Statistical Analysis
The obtained quantitative and qualitative data were analyzed in SPSS software (version 25) through the chi-square and ANOVA. A p-value less than 0.05 was considered statistically significant.
Results
In total, 200 patients with thalassemia major and the mean age of 27.04±6.1 years (age range: 13-39 years) were investigated in this study. It should be mentioned that the majority (n=104; 52%) of the patients were male. Tooth condition was normal in 12.5% (n=25) of patients with thalassemia major, and the prevalence of malocclusion was obtained at 87.5%. Furthermore, 69 (34%) patients had malocclusion of Class I, and 62 of them had malocclusion of Class II. Moreover, malocclusion of Classes III were reported in 22% (n=44) of patients with thalassemia major. Table 1 tabulates the malocclusion class of patients with thalassemia major based on gender. According to the obtained results, there was no significant relationship between type of malocclusion and gender (P=0.77).
Moreover, the frequency of males and females was statistically similar in patients with normal teeth. The mean age of thalassemia major patients with various malocclusion classes is shown in Table 2, which showed no significant difference among the patients with thalassemia major and different classes of malocclusion in terms of age both in male (P =0.49) and female (P = 0.58).
Spacing was reported in 13% (n=26) of patients with thalassemia major. However, there was no significant difference between the patients with spacing and those without spacing in terms of gender (P=0.206). The mean ages of the patients with and without spacing were estimated at 28.5±6.5 and 26.8±6.06 years, respectively. Furthermore, the comparison of patients with and without spacing showed no relationship between spacing and age (P=0.18). The frequency of crowding was determined at 28.5% (n=57) in patients with thalassemia major, 59.6% (n=34) of whom were female. There was no significant difference between the patients with and without crowding in terms of gender (P=0.21). Moreover, the mean age of the patients with (26.7±5.8 years) and without crowding (27.1±6.2 years) showed no relationship between crowding and age (P=0.66).
In addition, 30% of patients with thalassemia major had increased overjet (n=60), and 20% of them had overbite (n=40). Increased and decreased overbite were also reported in 15.5% (n=31) and 4.5% (n=9) of the patients, respectively. There was no significant difference between the patients with (26.6±6.1) and without increased overjet (27.8±6.1) in terms of age (P=0.22). The mean age of the patients with increased or decreased overbite was obtained at 27.6±6.8 years, which showed no relationship between overbite and age (P=0.44).
Discussion
Thalassemia can affect the health-related quality of the patients and their families. Knowledge about the oral manifestations of this disease helps to provide clinical, psychological, and social support in order to achieve better treatment outcomes. This descriptive study was an attempt to compare the prevalence of malocclusion degrees and types of malocclusions including spacing, overcrowding, overjet, and overbite, among patients with beta-thalassemia major. The sample population was relatively young (age range: 13-39 years) and the female/male ratio was statistically similar. No association of malocclusion was reported with age and gender.
In general, malocclusion in various degrees was observed in the majority of thalassemia patients in our study. Our findings were supported by the results of other studies indicating that thalassemia patients had higher dental caries scores, compared to the healthy controls (13-15). A study conducted by Elangovan et al. showed that the prevalence of prominent extraoral abnormalities was about 57% in the beta-thalassemia major patients. Consistent with our findings, the Class I occlusion, followed by Class II occlusion, were the most common occlusions (16). However, the prevalence of occlusion with various severity was higher in our study, compared to that in the aforementioned study (87.5% versus 57%). The Class III occlusion was reported in 22% of our patients, while they found no Class III occlusion.
In another study, Sobouti et al. assessed the prevalence of different malocclusions among Iranian adolescents. According to the results, 53%, 19.4%, and 15.6% of the patients had Class I, II, and III malocclusion, respectively. Although the mean age in our study was higher than that in the aforementioned study, Sobouti et al. obtained a higher Class I malocclusion within the age range from 13 to 15 years. On the other hand, similar to our study, the aforementioned study showed higher prevalence of Class I malocclusion among young Iranian population (17). The findings rejected the relationship between the presence of malocclusion and beta-thalassemia major in young people.
The hyperplasia of bone marrow due to rapid red cell turnover leads to changes in bony structure in thalassemia patients, and its incidence is more reported in the maxilla, compared to the mandible (18, 19). This can explain the low prevalence of Class III occlusion in these patients. Due to anemia, gums and the lining of patients with thalassemia major become pale. In addition, dry mouth and painful swelling of salivary glands lead to decreased salivary protection in the patients (11). For this reason, they are more prone to dental decay (9). Negligence of the teeth due to the involvement of these patients in serious medical complications of thalassemia may be the other reason for the increased risk of dental problems in this population (9, 11).
On the other hand, we found no relationship between age and dental lesions in patients with thalassemia major, which was inconsistent with the results of other studies (20, 21). The discrepancies may be due to differences in samples. The sample population was relatively young (age range: 13-39 years) in this study, while other studies were performed on older patients. Pedullà et al. showed that severe gingivitis and probing pocket depth scores were worse in older patients with severe beta-thalassemia major, compared to those with beta-thalassemia intermedia and the general population. Moreover, they reported a higher rate of decayed-missing-filled teeth patients with beta-thalassemia major. It is worth mentioning that the dental problems, including gingival and periodontal status, were affected by thalassemia major only in older cases, whiles it had no effect on younger patients. These findings indicate that age plays an important role in the oral compliance and formation of plaque deposits. They also compared two subgroups of beta-thalassemia major and intermedia in terms of dental problems and indicated no relationship between age and dental problems in patients with beta-thalassemia intermedia (4).
Some problems existed when recruiting a higher number of patients in the older age range in this study. Moreover, the recruiting process lasted almost one year; however, the evaluation of oral hygiene level showed that types of malocclusions (spacing, overcrowding, overjet, and overbite) had no significant association with age and gender. Similar to our study, another study showed a higher rate of spacing, openbite, crowding, mouth breathing, and increased overjet in thalassemia patients, compared to healthy controls (22). In general, the Class II malocclusion is associated with prominent maxillary anterior teeth, spacing, increased overjet, and decreased overbite (23). The most common type of malocclusion is crowding, which occurs in thalassemia patients due to discrepancies between tooth size and arch length (24). Similarly, a higher rate of increased overjet and decreased overbite in thalassemia patients, compared to healthy control, was confirmed in a study performed by Alhaija et al. (23).
The results of the present study highlight the importance of dental treatment care in thalassemia patients. Moreover, facial appearance of patients with βT is unique because of the increased formation of red blood cells caused by erythroid hyperplasia in the bone marrow. Due to the increased malocclusion in the patients, orthodontic treatment is affected by these conditions. Early orthodontic diagnosis and management enable favorable prognosis and minimize the subsequent complications (25). Since infection is one of the main concerns of thalassemia patients, preventive measurements, including the implementation of oral hygiene instructions, diet counseling, and the use of topical fluoride are of critical importance. Finally, further studies with larger sample sizes and control groups are recommended to be conducted on the malocclusion of patients affected with beta-thalassemia major to check the present findings.
Limitations and weaknesses
The obtained results of the present study cannot be generalized to other populations due to the lower sample size and single-centered nature of the study. The incompleteness of some medical records and inaccessibility were other important limitations of this study. Therefore, it is suggested that further multicenter studies with larger sample sizes and control groups be performed on the malocclusion in patients affected with beta-thalassemia major.
Conclusion
The high prevalence of malocclusion is common among adolescents and adults with thalassemia, which is not associated with age or gender. The patients should be regularly visited and followed up by dentists to control and manage their dental problems. According to the high incidence of malocclusion in older patients with thalassemia major, effective preventive measures, health education, and dental treatment are required for this group.
Table 1. Malocclusion classes of patients with thalassemia major based on gender
|
Malocclusion condition |
Male |
Female |
Total |
χ2 |
P-value |
|||
|
No |
% |
No |
% |
No |
% |
|||
|
Normal |
11 |
10.6 |
14 |
14.6 |
25 |
12.5 |
1.77 |
0.77 |
|
Class I |
34 |
32.7 |
35 |
36.5 |
69 |
34.5 |
||
|
Class II div 1 |
33 |
31.7 |
29 |
30.2 |
62 |
31 |
||
|
Class II div 2 |
16 |
15.4 |
11 |
11.5 |
27 |
13.5 |
||
|
Class III |
10 |
9.6 |
7 |
7.3 |
17 |
8.5 |
|
|
Table 2: Mean age of thalassemia major patients with various malocclusion classes
|
Malocclusion condition |
Male |
Female |
||
|
Mean |
SD |
Mean |
SD |
|
|
Normal |
24.64 |
5.67 |
23.95 |
5.02 |
|
Class I |
28.42 |
6 |
27.88 |
5.55 |
|
Class II div 1 |
27.53 |
6.48 |
26.24 |
6.11 |
|
Class II div 2 |
27.03 |
5.82 |
26.39 |
5.29 |
|
Class III |
23.11 |
4.16 |
22.61 |
4.12 |
|
Analysis of variance |
P=0.49 |
P=0.58 |
||
|
Reviewers' Comments: |
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Comments |
Response |
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Reviewer 1: Please correct the following with the help of a statistical consultant |
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1. At the end of the first paragraph in the results section, the significant level should be reported as (P<0.05) (if it is significant). In the table 1 why are designed a separate test for each Malocclusion classes. Malocclusion classes compared with the sex variable using the Chi-square test, so we have a P-Value to report the result. |
It was considered and edited in the text. Table 1 and the text were revised. |
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2. Table 2 shows that mean age changes based on various malocclusion classes were reported only for men if it should be reported for both men and women please correct it |
It was considered and edited in the text.
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Reviewer 2: This study seems to be well structured and is well written. Nevertheless, there are some issues that need to be addressed before the study is published. Point by point review of this study is mentioned below: |
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1. The abstract, results and the tables mention Class IV malocclusion while methods and materials do not mention this malocclusion which is not part of the angle malocclusion classification. Please correct the instances when this malocclusion is mentioned. |
It was considered and edited in the text. We edits data based on angle malocclusion classification.
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2. In the “Study Design”, why random number tables were used to select cases? Cross sectional studies without control groups don’t need randomization for study selection. |
It was considered and edited in the text and highlighted. Sample were selected using simple random method from all patients with thalassemia major. |
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3. What does “d=0.08” in the sample size calculation refer to? Does it stand for absolute error (precision) of measurements or does it refer to the expected differences between different age groups or genders? |
It means absolute measurement error. |
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4. In the study design please mention that if the occlusion was evaluated when the dentition was in CO or CR? |
All details are reported in methods: The distance between the most prominent labial margins of the incisal edge of the maxillary to the labial surface of the mandibular teeth was calculated for determining the overjet. Furthermore, the vertical relationship between the upper and lower incisors was calculated by the overbite of the vertical distance between the edge of the upper and lower central incisor when they were in contact with posterior teeth. |
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5. The “Discussion” section mentions and compares dental lesion and periodontal problems of thalassemia patients. Please combine and summarize these two paragraphs into one paragraph and also further discuss what effects these conditions could have on orthodontic treatment (1). 1) Einy S, Hazan-Molina H, Ben-Barak A, Aizenbud D. Orthodontic Consideration in Patients with Beta-Thalassemia Major: Case Report and Literature Review. J Clin Pediatr Dent. 2016;40(3):241-6. doi: 10.17796/1053-4628-40.3.241. PMID: 27472573. |
It was considered and edited in the text and highlighted. The suggested reference was used and cited in the article. |
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6. In the “Discussion” section compare the malocclusion results of these patients with the malocclusion prevalence in normal Sari’s population (2) and explore what differences in terms of prevalence of different types of malocclusions between healthy and thalassemic patients exist. 2) Sobouti F, Ebrahimi nezhad M, Namadar P, Behzadi Y, Motevalli S, Armin M. Prevalence of Dental Malocclusion among 13-15 year Old Girls . J Mazandaran Univ Med Sci. 2016; 25 (132) :300-303 |
It was considered and edited in the text and highlighted. The suggested reference was used and cited in the article. |
References
- Xu L, Mao A, Liu H, Gui B, Choy KW, Huang H, et al. Long-Molecule Sequencing: A New Approach for Identification of Clinically Significant DNA Variants in α-Thalassemia and β-Thalassemia Carriers. The Journal of Molecular Diagnostics. 2020;22(8):1087-95.
- Vichinsky EP. Changing patterns of thalassemia worldwide. Annals of the New York Academy of Sciences. 2005;1054(1):18-24.
- Joly P, Pondarre C, Badens C, editors. Beta-thalassemias: molecular, epidemiological, diagnostical and clinical aspects. Annales de biologie clinique; 2014.
- Pedullà E, Scibilia M, Saladdino G, Colletta G, Rapisarda S, Terranova M, et al. Dental and periodontal condition in patients affected by β-thalassemia major and β-thalassemia intermedia: a study among adults in Sicily, Italy. J Dent Health Oral Disord Ther. 2015;3(1):81-5.
- Esmaeilzadeh F, Azarkeivan A, Emamgholipour S, Sari AA, Yaseri M, Ahmadi B, et al. Economic burden of thalassemia major in Iran, 2015. Journal of research in health sciences. 2016;16(3):111.
- Gupta SK, Sharma M, Tyagi S, Pati HP. Transfusion-induced hemoglobinopathy in patients of beta-thalassemia major. Indian Journal of Pathology and Microbiology. 2011;54(3):609.
- Rossi F, Perrotta S, Bellini G, Luongo L, Tortora C, Siniscalco D, et al. Iron overload causes osteoporosis in thalassemia major patients through interaction with transient receptor potential vanilloid type 1 (TRPV1) channels. Haematologica. 2014;99(12):1876.
- Singh J, Singh N, Kumar A, Kedia NB, Agarwal A. Dental and periodontal health status of Beta thalassemia major and sickle cell anemic patients: a comparative study. Journal of international oral health: JIOH. 2013;5(5):53.
- Hattab FN. Patterns of physical growth and dental development in Jordanian children and adolescents with thalassemia major. Journal of oral science. 2013;55(1):71-7.
- Hattab FN. Mesiodistal crown diameters and tooth size discrepancy of permanent dentition in thalassemic patients. Journal of clinical and experimental dentistry. 2013;5(5):e239.
- Helmi N, Bashir M, Shireen A, Ahmed IM. Thalassemia review: features, dental considerations and management. Electronic physician. 2017;9(3):4003-8.
- Hashemipour M, Rad M, Ebrahimi Meimand S. Orofacial disformation in thalassemia patients refered to Kerman special disease center in 2007. Scientific Journal of Iran Blood Transfus Organ. 2008;5(3):185-93.
- Mehdizadeh M, Mehdizadeh M, Zamani G. Orodental complications in patients with major beta-thalassemia. Dent Res J. 2008;5(1):17-20.
- Gomber S, Dewan P. Physical growth patterns and dental caries in thalassemia. Indian pediatrics. 2006;43(12):1064.
- Salehi M, FARHOUD D, TOHIDAST EZ, SAHEB JM. Prevalence of orofacial complications in Iranian patients with b-thalassemia major. 2007.
- Elangovan A, Mungara J, Joseph E, Guptha V. Prevalence of dentofacial abnormalities in children and adolescents with β-thalassaemia major. Indian Journal of Dental Research. 2013;24(4):406.
- Sobouti F EnM, Namadar P, Behzadi Y, Motevalli S, Armi M. Prevalence of Dental Malocclusion among 13-15 year Old Girls. J-Mazand-Univ-Med-Sci. 2016;25(132):300-3.
- Piga A. Impact of bone disease and pain in thalassemia. Hematology 2014, the American Society of Hematology Education Program Book. 2017;2017(1):272-7.
- Origa R. β-Thalassemia. Genetics in Medicine. 2017;19(6):609-19.
- Kaur N, Hiremath S. Dental caries and gingival status of 3-14 year old beta thalassemia major patients attending paediatric OPD of vanivilas hospital, Bangalore. Arch Oral Sci Res. 2012;2(2):67-70.
- Veena R. Dental caries and periodontal health status in thalassemia-major patients 2006.
- Shahsevari F, Eslami M, Ferhvesh M. Malocclusion in subjects with beta-thalassemia major. Koomesh. 2007;8(4):211-6.
- Alhaija ESA, Hattab FN, Al‐Omari MA. Cephalometric measurements and facial deformities in subjects with β‐thalassaemia major. The European Journal of Orthodontics. 2002;24(1):9-19.
- Hattab FN, Yassin OM. Dental arch dimensions in subjects with beta-thalassemia major. J Contemp Dent Pract. 2011;12(6):429-33.
- Einy S, Hazan-Molina H, Ben-Barak A, Aizenbud D. Orthodontic consideration in patients with beta-thalassemia major: case report and literature review. Journal of Clinical Pediatric Dentistry. 2016;40(3):241-6.
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