|Year : 2018 | Volume
| Issue : 3 | Page : 186-191
The impact of β-thalassemia major on dental maturity in children at different stages of dental development (In TDJ, we do not quey for manuf details)
Gehan L Abdel Hakeem1, Ashraf M Abdel Fadil1, Amro Moness M. Ali2, Tarek H Abu El Qasem1
1 Department of Paediatrics, Faculty of Dentistry, Minia University, El Minya, Egypt
2 Department of Pediatric and Community Dentistry, Faculty of Dentistry, Minia University, El Minya, Egypt
|Date of Submission||14-Mar-2018|
|Date of Acceptance||10-Jun-2018|
|Date of Web Publication||10-Oct-2018|
Amro Moness M. Ali
Department of Pediatric and Community Dentistry, Faculty of Dentistry, Minia University, Cairo Aswan Road, El Minya
Source of Support: None, Conflict of Interest: None
Assess the dental maturity in B thalassemic children at different stages of dental development.
Patients and methods
Fifty-four β-thalassemia patients were enrolled and classified into: group Ia, 16 patients with age range 3–6 years; group Ib, 18 patients with age 6–12 years; and group Ic, 20 patients older than 12 years. Another 25 healthy children were enrolled as controls. All involved children were subjected to clinical examination stressing on the anthropometric measures, complete blood count, serum ferritin, and oral panoramic radiograph to assess the dental age which is plotted on the charts to assess the dental age centile and dental maturity score.
Significant differences were found between patients and control regarding serum ferritin (P = 0.001), hemoglobin level (P = 0.001), height (P = 0. 001), BMI (P = 0.009), dental age centile (P = 0.02). Dental age was positively correlated with age (P = 0.001, r = 0.9) and serum ferritin level (P = 0.009, r = 0.4). Dental age centile was negatively correlated with age (P = 0.001, r=−0.5) and serum ferritin level (P = 0.001, r=−0.6). Dental maturity score was positively correlated with age (P = 0.001, r = 0.9), age of start transfusion (P = 0.008, r = 0.4) and serum ferritin level (P = 0.002, r = 0.4).
Keywords: children, dental maturity, thalassemia
|How to cite this article:|
Abdel Hakeem GL, Abdel Fadil AM, Ali AM, Abu El Qasem TH. The impact of β-thalassemia major on dental maturity in children at different stages of dental development (In TDJ, we do not quey for manuf details). Tanta Dent J 2018;15:186-91
|How to cite this URL:|
Abdel Hakeem GL, Abdel Fadil AM, Ali AM, Abu El Qasem TH. The impact of β-thalassemia major on dental maturity in children at different stages of dental development (In TDJ, we do not quey for manuf details). Tanta Dent J [serial online] 2018 [cited 2018 Oct 18];15:186-91. Available from: http://www.tmj.eg.net/text.asp?2018/15/3/186/243072
| Introduction|| |
Thalassemia is a hereditary anemia resulting from defects in hemoglobin production . β-thalassemia, which is caused by a decrease in the production of β-globin, affects multiple organs and is associated with considerable morbidity and mortality . Accordingly, lifelong care is required, and financial expenditures for proper treatment are substantial .
β-thalassemia major patient is usually presented at 4–6 months of life, due to the protective effect of high hemoglobin F concentration at birth that slowly declines through the first year of life. Manifestations are those of anemia, failure to thrive and organomegaly. Patients presenting later will have signs of extramedullary hematopoiesis; frontal bossing of the skull, hepatosplenomegaly, thinning of long bones cortices, widening of medullary and diploic spaces; resulting in bossing of the skull, prominence of the upper incisors, and wide separation of orbits .
Thalassemia affection of different tissues is either through chronic hypoxia, iron deposition, complications of blood transfusion, or complication of chelation therapy. Regarding hypoxia, anemia, and/or associated factors depress early teeth eruption, along with body growth and skeletal growth .
Tooth eruption is defined as the movement of the tooth from its site of development in alveolar bone to the occlusal plane in the oral cavity. The tooth eruption is a complex and tightly regulated process which is divided into five stages: pre-eruptive movements, intraosseous stage, mucosal penetration, preocclusal, and postocclusal stages. Pre-eruptive movements occur during crown formation and are so small that they could only be observed by vital staining experiments .
The aim of this study was to assess the dental development and maturity in β-thalassemia major patients with different age groups.
| Patients and Methods|| |
Fifty-four known β-thalassemia major patients recruited in the Hematology Clinic, Pediatric Department, Children's University hospital and insurance hospital were included in this study during the period from March 2014 to February 2015.
The enrolled children were classified into:
- Group I: included 54 β-thalassemic children, their ages ranged from 2 to 16 years divided into three subgroups (according to age):
- Group Ia: 16 β-thalassemic children (primary dentition group): with age range 3–6 years.
- Group Ib: 18 β-thalassemic children (mixed dentition group): with age range, more than 6 years up to 12 years.
- Group Ic: 20 β-thalassemic (permanent dentition group) children age older than 12 years.
Another 25 apparently healthy, age-matched, and sex-matched children were included as controls (group II) collected from school students.
β-thalassemic children (based on hemoglobin electrophoresis) not diagnosed to have or treated from any dental problem.
Patients with congenital and acquired heart disease, hepatitis B or C infection, chronic kidney disease, diabetes mellitus, patients with known odontogenic maldevelopment and patients receiving chronic treatment affecting teeth (i.e. tetracycline) were excluded.
All patients were subjected to the following:
Thorough history taking stressing on age, sex, the age of first transfusion, transfusion frequency, family history, treating modalities, and whether or not splenectomized. Thorough clinical examination including anthropometric measurements: weight, height, head circumference, and BMI calculation. All these measures are plotted on CDC percentile growth charts . Chest, heart, neurologic, and abdominal examination were checked. The radiological investigation included panoramic radiograph to the oral cavity. Laboratory investigations included complete blood count by automated cell counters Sysmex NE (TAO Medical Incorporation, Tokyo, Japan), liver function test: serum glutamic oxalate transaminase, serum glutamic pyruvate transaminase (Konelab 20i, Vantaa, Finland), renal function test: urea and creatinine (Konelab 20i) and serum ferritin by enzyme-linked immunosorbent assay (Accubind, California, USA).
The study was conducted according to the principles of Helsinki declaration and was approved by the faculty of medicine scientific committee (reference number# 23/29.2.2014). An informed written consent from the parents of enrolled children was obtained.
The panoramic radiographs were examined under ideal conditions including the use of subdued ambient room lighting, film masking, and a conventional viewing box (Excel-Type F.I.D-1, Basingstoke, England) with a variable light intensity and a ×2 magnifying lens (X-viewer, Malmo, Sweden).
The panoramic radiographs were assessed in a darkened room with a radiographic illuminator to ensure contrast enhancement of the bone and tooth images . Teeth from the central incisor to the second molar, in the mandibular left quadrant, on a dental panoramic tomography, were analyzed and assigned stages from A to H according to Demirjian's dental age assessment method. These individual stages were later converted into maturity scores based on separate tables for boys and girls. These maturity scores were summed to achieve a total maturity score, which is converted into adental age based on separate male and female tables. To avoid the examiner bias at the time of collecting data, chronological age was first recorded on a data collection sheet and the dental age scores were tabulated later a separate sheet. The panoramic radiographs were used to assess patients dental ages by employing the method of Demirjian et al. .
The radiological appearances of the seven permanent teeth on the left side of the mandible for each patient were evaluated according to developmental criteria. Each tooth was categorized into one of the eight calcification stages (A–H).
Stage A is defined as the start of calcification at the most occlusal part of the tooth crypt in the form of a small inverted cone.
Stage H is defined as the stage in which the apical end of the developing root is complete and the periodontal ligament space has a uniform width around the root and its apex.
The intermediate stages establish a continuum. A numerical score for each tooth was then obtained using standard references for each stage, and the summed scores on all seven teeth give a dental maturity score which is converted directly into a dental age.
The collected data were coded, tabulated, and statistically analyzed using statistical package for the social sciences program for windows software (version 16; IBM Corp., Armonk, NY, USA).
Descriptive statistics were done for numerical data by mean ± SD, while they were expressed for categorical data by number and percentage. Analyses were done for quantitative variables using the Student t test for normally distributed data between the two groups and Mann–Whitney U test for not normally distributed data between the two groups. Analysis of variance test for normally distributed quantitative data between the three groups, post-hoc test for each two groups, Kruskal–Wallis test for non-normally distributed data between the three groups and Mann–Whitney U for each two groups. χ2 test for qualitative data between groups. Pearson's correlation coefficient was used to estimate the correlation between each two variables.
The significance differences were considered when P value less than 0.05.
| Results|| |
Significant decrease in height, weight, and BMI centiles was found in thalassemic patients compared to control group (P = 0.001, 0.001, and 0.009, respectively), while no significant difference between both study groups regarding age, sex, and head circumference centile (P = 0.9, 0.8, and 0.51, respectively) [Table 1].
Highly significant differences in hemoglobin, serum ferritin, serum glutamic oxalate transaminase, serum glutamic pyruvate transaminase, urea and creatinine between patients and control group (P = 0.001, 0.001, 0.003, 0.002, 0.001, and 0.003) respectively [Table 2].
|Table 2: Comparison between the studied groups regarding some laboratory data|
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A significant difference was found in dental age centile (P = 0.02) between patients and control group while no significant difference in dental age (P = 0.9) and dental maturity score (P = 0.7) were found [Table 2].
Significant positive correlations were found between dental age and chronological age (P = 0.001, r = 0.9), HC (P = 0.001, r = 0.5), and serum ferritin level (P = 0.009, r = 0.4) [Table 3] and [Figure 1].
|Table 3: Correlation between dental maturity score and some clinical and laboratory data|
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Significant negative correlations were found between dental age centile and chronological age (P = 0.001, r=−0.5) and serum ferritin level (P = 0.001, r=−0.6) [Table 3] and [Figure 2].
Significant positive correlations between dental maturity score and chronological age (P = 0.001, r = 0.9), age of first transfusion (P = 0.008, r = 0.9), HC (P = 0.003, r = 0.4), and serum ferritin level (P = 0.002, r = 0.4) [Table 3] and [Figure 3].
Significant differences in dental age and dental maturity score between groups Ia and Ib, groups 1a, 1c and between groups 1b and 1c (P = 0.001 for all) [Table 4].
| Discussion|| |
In the present study, β-thalassemic patients demonstrated delayed dentition. Mean dental age centile for thalassemic patients was significantly lower compared to controls. This could be attributed to different tissues pathological changes in thalassemia occurs owed to chronic hypoxia, iron deposition, complications of blood transfusion or complication of chelation therapy in addition to bony deformities. Hypoxia, anemia and/or associated factors depress early teeth eruption, along with body and skeletal growth . Also, chronic tissue hypoxia especially those involved in the dentition process (e.g. components of the periodontal ligament, dental follicle) may be an important factor of retarded dentition in such patients ,.
Chronic hemolysis with consequent iron overload expressed as increased serum ferritin leading to hemosiderosis in different tissues. Iron deposition carries toxic effect on such tissues interfering with the normal metabolism of such tissues ,. Significant negative correlation between dental age centile and chronological age which was markedly obvious in thalassemic patients aging more than 8 years. This was agreeing with the results of Cardoso  where dental maturation is more retarded with age in β-thalassemia patients.
A consequence of chronic hemolysis and iron overload may be transfusion-related viral hepatitis with associated hepatic risk leading to chronic hepatic impairmentwhich may alter the metabolism of many essential elements for adequate teething including fat-soluble vitamins and nutrients. All these may compromise the developing tooth. Nutrients essential for a healthy tooth include calcium, phosphorus, and vitamins (A, C, and D). Calcium and phosphorus are needed to properly form the hydroxyapatite crystals. Their blood levels are maintained by vitamin D. Vitamin A is necessary for the formation of keratin and vitamin C for collagen. Fluoride is incorporated into the hydroxyapatite crystal of a developing tooth and makes it more resistant to demineralization and subsequent decay . Lower vitamin D levels have been reported previously in thalassemia patients by many authors ,,.
Those results could be attributed to hepatic dysfunction which lead to defective hydroxylation of vitamin D and so decreased serum level . Others reported 25 OH-D deficiency may be attributed to hepatic iron overload rather than the dysfunctions of endocrine tissues . Finally, individuals with thalassemia may be at greater risk for vitamin D deficiency leading to many teeth and bone developmental problems.
Calcium homeostasis plays an important role in dental development in thalassemic patients. Iron overload and hemosiderosis are usually targeting on endocrinal glands. Parathyroid endocrinopathies because of iron deposition may share in altered calcium hemostasis and dentition process ,,. Chelation therapy which with associated other mineral chelation is another factor of altered calcium metabolism in thalassemia ,. On the other hand, some authors found no significant difference between thalassemic patients and controls regarding serum calcium level ,. According to Ash and Stanley, permanent teeth eruption usually begins after the age of 8 years (maxillary canine 11–12 years, mandibular canine 9–10 years, etc.) . Most thalassemia complications occur in this age group. Anatomically, thalassemia can affect dentition by different mechanisms. Thalassemia results in medullary cavity expansion on especially in short bone (jaws and maxillae) which depends on several factors such as severity of anemia, age, duration of clinical symptoms duration of therapeutic blood transfusion and presence or absence of splenectomy . These results in dentofacial abnormalities such as distal deviation from the normal anteroposterior molar relation and/or sagittal maxillary overgrowth . In the face, enlargement of jaw and its alveolar process due to medullary expansion with increased over jet and spacing of maxillary teeth with variable degrees of teeth malocclusion ,.
In the present study, the chronological age correlates negatively with the dental age centile. At mid-childhood, most thalassemic patients are transfusion dependent with more risk of longstanding tissue hypoxia, hepatitis-induced chronic liver disease and iron overload inducing premature cellular injury. Subsequently, more interference with normal physical growth including dentition and dental maturation can influence this age group of patients ,,.
| Conclusion|| |
Dental development and maturation is impaired in thalassemic patients which is more with age and permanent dentition. The dental developmental delay in B thalassemic patients is linked to the elevated serum ferritin levels.
All authors equally shared in the explaining results, writing process and reviewing the article.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Higgs DR, Engel JD, Stamatoyannopoulos G. Thalassaemia. Lancet 2012; 379:373–383.
Cunningham MJ, Macklin EA, Neufeld EJ, Cohen AR, Thalassemia Clinical Research N. Complications of beta-thalassemia major in North America. Blood 2004; 104:34–39.
Old JM, Screening and genetic diagnosis of haemoglobin disorders. Blood Rev 2003; 17:43–53.
Kalbassi S, Younesi MR, Asgary V. Comparative evaluation of oral and dento-maxillofacial manifestation of patients with sickle cell diseases and beta thalassemia major. Hematology; 2017:1–6.
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; 40:241–246.
Proffit WR FH. ontemporary orthodontics
ed. St. Louis: Mosby Inc.; 2000.
Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, Flegal KM, Guo SS, Wei R, et al
. CDC growth charts: United States. Adv Data; 2000:1–27.
Uysal T, Sari Z, Ramoglu SI, Basciftci FA. Relationships between dental and skeletal maturity in Turkish subjects. Angle Orthod 2004; 74:657–664.
Demirjian A, Goldstein H, Tanner JM. A new system of dental age assessment. Hum Biol 1973; 45:211–227.
Giglio MJ, Sanz AM, Bozzini CE. Depressed eruption rate of the rat maxillary incisor in a drug-induced uncompensated hemolytic state model. J Dent Res 1990; 69:906–908.
Kjaer I. Mechanism of human tooth eruption: review article including a new theory for future studies on the eruption process. Scientifica 2014; 2014:341905.
Cahill DR, Marks SC Jr. Tooth eruption: evidence for the central role of the dental follicle. J Oral Pathol 1980; 9:189–200.
Smolkin V, Halevy R, Levin C, Mines M, Sakran W, Ilia K, et al
. Renal function in children with beta-thalassemia major and thalassemia intermedia. Pediatr Nephrol 2008; 23:1847–1851.
Mishra AK, Tiwari A. Iron overload in Beta thalassaemia major and intermedia patients. Maedica (Buchar) 2013; 8:328–332.
Cardoso HF. Environmental effects on skeletal versus dental development: using a documented subadult skeletal sample to test a basic assumption in human osteological research. Am J Phys Anthropol 2007; 132:223–233.
Ross MHK, Gordon I, Pawlina W. Histology: a text and atlas: with cell and molecular biology
ed. Baltimore, MD: Lippincott Williams & Wilkins; 2003.
Soliman A, Adel A, Wagdy M, Al Ali M, ElMulla N. Calcium homeostasis in 40 adolescents with beta-thalassemia major: a case-control study of the effects of intramuscular injection of a megadose of cholecalciferol. Pediatr Endocrinol Rev 2008; 6 (Suppl 1):149–154.
Vogiatzi MG, Macklin EA, Trachtenberg FL, Fung EB, Cheung AM, Vichinsky E, et al
. Differences in the prevalence of growth, endocrine and vitamin D abnormalities among the various thalassaemia syndromes in North America. Br J Haematol 2009; 146:546–556.
Pirinccioglu AG, Akpolat V, Koksal O, Haspolat K, Soker M. Bone mineral density in children with beta-thalassemia major in Diyarbakir. Bone 2011; 49:819–823.
Fahim FM, Saad K, Askar EA, Eldin EN, Thabet AF. Growth parameters and vitamin D status in children with thalassemia major in upper Egypt. Int J Hematol Oncol Stem Cell Res 2013; 7:10–14.
Shamshirsaz AA, Bekheirnia MR, Kamgar M, Pourzahedgilani N, Bouzari N, Habibzadeh M, et al
. Metabolic and endocrinologic complications in beta-thalassemia major: a multicenter study in Tehran. BMC Endocr Disord 2003; 3:4.
Vogiatzi MG, Autio KA, Mait JE, Schneider R, Lesser M, Giardina PJ. Low bone mineral density in adolescents with beta-thalassemia. Ann N
Y Acad Sci 2005; 1054:462–466.
Hamed EA, ElMelegy NT. Renal functions in pediatric patients with beta-thalassemia major: relation to chelation therapy: original prospective study. Ital J Pediatr 2010; 36:39.
Goyal M, Abrol P, Lal H. Parathyroid and calcium status in patients with thalassemia. Indian J Clin Biochem 2010; 25:385–387.
Mahachoklertwattana P, Chuansumrit A, Choubtum L, Sriphrapradang A, Sirisriro R, Rajatanavin R. Bone mineral density in children and young adults with beta-thalassemia trait. J Pediatr Endocrinol Metab 2002; 15:1531–1535.
Eren E, Yilmaz N. Biochemical markers of bone turnover and bone mineral density in patients with beta-thalassaemia major. Int J Clin Pract 2005; 59:46–51.
Ash MMN, Stanley J. Wheeler's dental anatomy, physiology, and occlusion
ed. Philadelphia, PA: W.B. Saunders; 2003.
Bassimitci S, Yucel-Eroglu E, Akalar M. Effects of thalassaemia major on components of the craniofacial complex. Br J Orthod 1996; 23:157–162.
De Mattia D, Pettini PL, Sabato V, Rubini G, Laforgia A, Schettini F. Oromaxillofacial changes in thalassemia major. Minerva Pediatr 1996; 48:11–20.
Hazza'a AM, Al-Jamal G. Radiographic features of the jaws and teeth in thalassaemia major. Dentomaxillofac Radiol 2006; 35:283–288
Takriti M, Dashash M. Craniofacial parameters of Syrian children with beta-thalassemia major. J Investig Clin Dent 2011; 2:135–143.
Kassab-Chekir A, Laradi S, Ferchichi S, Haj Khelil A, Feki M, Amri F, et al
. Oxidant, antioxidant status and metabolic data in patients with beta-thalassemia. Clin Chim Acta 2003; 338:79–86.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]