Infantile obesity is a pathology that is generating

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1 ORIGINAL ARTICLE Skeletal maturation in obese patients Maria Rita Giuca, a Marco Pasini, b Simona Tecco, c Enrico Marchetti, c Laura Giannotti, b and Giuseppe Marzo d Pisa and L'Aquila, Italy Introduction: The objective of this study was to compare skeletal maturation in obese patients and in subjects of normal weight to evaluate the best timing for orthopedic and orthodontic treatment. The null hypothesis was that obese and normal-weight patients show similar degrees of skeletal maturation. Methods: The sample for this retrospective study consisted of 50 white patients (28 boys, 22 girls) whose x-rays (hand-wrist and lateral cephalometric radiographs) were already available. The test group included 25 obese patients (11 girls, 14 boys; average age, years), and the control group included 25 subjects of normal weight (11 girls, 14 boys; average age, years). Skeletal maturation was determined by using the carpal analysis method and the cervical vertebral maturation method. Results: According to the carpal analysis, there was a significant difference between skeletal and chronologic ages between the test group ( months) and the control group ( months). Furthermore, the obese subjects exhibited a significantly higher mean cervical vertebral maturation score ( ) than did the control subjects ( ) (P \0.05). Conclusions: Compared with the normal-weight subjects, the obese subjects showed a higher mean discrepancy between skeletal and chronologic ages according to the carpal analysis and had a significantly higher cervical vertebral maturation score. Thus, to account for the growth in obese patients with skeletal discrepancies, it might be necessary to perform examinations and dentofacial and orthopedic treatments earlier than in normal-weight subjects. (Am J Orthod Dentofacial Orthop 2012;142:774-9) Infantile obesity is a pathology that is generating greater interest because of its widespread growth in industrialized countries. Since the 1990s, obesity has been regarded as one of the most serious public health and medical problems of our time. 1 The main causes of obesity are large consumption of highcalorie foods and lack of physical activity; however, obesity can also be the result of genetic conditions, hormone dysfunctions, or even mental disorders. It is possible to distinguish 2 types of obesity: primary and secondary. Primary obesity is caused by an imbalance between food intake and energy expenditure. Secondary obesity is linked to endocrine and genetic pathologies, such as Cushing's syndrome, hyperthyroidism, insulinoma, Stein-Leventhal syndrome, and endocrine hypothalamic disorders. 2 Clinically, the subject's stature is an important element differentiating the 2 a Associate professor, Department of Surgery, University of Pisa, Pisa, Italy. b Resident, Department of Surgery, University of Pisa, Pisa, Italy. c Resident, Department of Health Science, University of L'Aquila, L'Aquila, Italy. d Professor, Department of Health Science, University of L'Aquila, L'Aquila, Italy. Simona Tecco contributed as senior author to the research protocol, literature review, discussion of results, and drafting the manuscript. The authors report no commercial, proprietary, or financial interest in the products or companies described in this article. Reprint requests to: Simona Tecco, Via Le Mainarde 26, Pescara (Pe), 65124, Italy; , simtecc@unich.it. Submitted, June 2011; revised and accepted, July /$36.00 Copyright Ó 2012 by the American Association of Orthodontists. types of obesity. Subjects suffering from primary obesity usually have tall or normal heights, whereas subjects affected by secondary obesity are usually characterized by shorter heights, delayed growth, and dysmorphisms. Genetic factors are an etiologic basis for obesity. Certain monogenic forms of obesity are characterized by defective genes that encode molecules involved in the hypothalamic regulation of energetic balance. 3-5 Also, epigenetic factors play an important role in activating and silencing genes that have their most critical, although not exclusive, expression during the prenatal period and the first few months of a child's life. The etiologic theory that tries to explain the onset of obesity from a genetic point of view is based on the adipostat concept. In other words, an organism has an internal set point that can recognize the amount of adipose deposits and consequently regulate calorie consumption to prevent buildup. Control over an organism's energetic balance is associated with a complex of messenger molecules that connect the hypophysis and the entire endocrine system with the hepatocytes, adipocytes, and muscles. Alterations in this hierarchy can cause a buildup of fat. 6 The consequences of obesity are numerous and include metabolic complications, such as diabetes mellitus, 7 hypertension, dyslipidemia, liver disorders, tooth disorders, 8 and nonalcoholic steatohepatitis; mechanical dysfunctions, such as obstructive sleep apnea; and psychological problems

2 Giuca et al 775 Furthermore, it has been suggested that earlyonset obesity can cause increases in vertebral bone density and bone size, and an acceleration of skeletal growth. In particular, obesity has been hypothesized to impact craniofacial growth and lead to more precocious skeletal maturation of the maxilla and the mandible. 12 The level of body fat can influence the neuroendocrine events that are responsible for the onset of precocious puberty despite low levels of growth hormone. More specifically, leptin, a hormone mainly producedbywhiteadiposetissuetocontrolappetiteand thebuildupofadiposetissuereserves,mightbedirectly involved in this process. 13 Leptin accelerates the production of gonadotropin-releasing hormone by the hypothalamus and affects the adenohypophysis, promoting accelerated pubertal development. 14 Moreover, leptin has been hypothesized to act directly at the level of skeletal growth centers by inducing chondrocyte differentiation and proliferation. 15 In addition, some effects on bone growth might be mediated by other hormones, such as insulin-like growth factor 1, a hormone similar in structure to insulin that is produced in hepatocytes, fibroblasts, and chondrocytes. 16 The biologic aspects of facial skeletal growth are fundamentally important to dentofacial orthopedics. Knowledge of the remaining facial growth potential is essential for correct diagnosis and therapy. Treatment timing can influence therapeutic outcomes aimed to produce orthopedic effects in the craniofacial structures. In particular, the optimal treatment timing for Class II skeletal disharmony with functional appliances is during or slightly after the peak in mandibular growth, because the skeletal responses decrease both before and after maximal pubertal growth. 17 For these reasons, the operator should consider alterations in skeletal maturity when performing orthodontic or orthopedic treatments during the deciduous or mixed dentition period to optimize the therapeutic outcomes. Carpal analysis is a common method used to determine skeletal age. 18 The relationship between chronologic age and skeletal age is called the carpal index. 19 Various methods are used to determine the carpal index. One of the most popular approaches is the Greulich and Pyle 20 method, which consists of a series of standard x- rays (31 for boys, 29 for girls). The x-rays are carried out in chronologic steps that increase gradually from the prenatal stage up to the ages of 19 years in boys and 18 years in girls. These x-rays cover all the phalanx bones of the hand, including the diaphysis and forearm bone. Each x-ray belongs to a subject of a particular age that is characterized by a specific ossification stage. To determine the skeletal age, the x-ray of the carpus must be compared with the corresponding x-ray in the atlas provided by Greulich and Pyle. Measuring cervical vertebral maturation from lateral cephalometric radiographs is an alternative to the handwrist analysis, and it has proven to be an effective way to assess the adolescent growth peak in both body height and mandibular size. 21 One advantage of using the cervical vertebral maturation method is that a lateral radiograph is routinely required for orthodontic treatment planning. Therefore, no additional radiograph is generally required to use this method. Despite this advantage, the cervical vertebral maturation method is not sensitive enough to detect growth maturity outside the growth spurt period. 22 The objective of this study was to compare skeletal maturation in obese patients and normal-weight subjects. The null hypothesis was that obese and normal-weight subjects show similar degrees of skeletal maturation. MATERIAL AND METHODS The sample for this retrospective pilot study consisted of 50 white patients (28 boys, 22 girls) whose x-rays (hand-wrist and lateral cephalometric radiographs) were already available. The subjects were randomly selected from the records at the Department of Paediatrics of the University of Pisa in Italy. The body adiposity status of each subject was evaluated, according to the International Obesity Task Force classification, 23 to allocate the subjects to the test group or the control group: the mean body mass index standard deviations were in the test group and in the control group (Table I). The body mass index is used to assess weight status in children, adolescents, and adults. In adults, the body mass index cutoff points that define obesity and overweight are not linked to age and do not differ for men and women; however, in growing children, body mass index varies with age and sex. For these reasons, each body mass index value was matched to the corresponding percentile on the international charts according to the patient's age and sex to calculate the standard deviation score of the patient's body mass index. The body mass index standard deviation is based on pooled international data that link the accepted adult cutoff points (a body mass index of 25 kg/m 2 for overweight and 30 kg/m 2 for obese) to body mass index percentiles for children. This can be used to establish cutoff points related to the ages of children. 23 The test group included 25 obese patients (11 girls, 14 boys; average age, years), and the control group included 25 normal-weight subjects (11 girls, 14 boys; average age, years). Subjects affected by systemic pathologies or taking medications that might have produced alterations in American Journal of Orthodontics and Dentofacial Orthopedics December 2012 Vol 142 Issue 6

3 776 Giuca et al Table I. Evaluation of auxologic parameters in the test and control groups Auxologic parameter Mean and SD Weight (kg) Obese Control Height (cm) Obese Control BMI SD (percentile) Obese Control BMI, Body mass index. their growth were excluded from the study. The time between the hand-wrist and the lateral cephalometric radiographs did not exceed 1 month. In addition, the bone structures appeared clearly in the radiographs. One operator (M.P.) determined the skeletal age in a blind test by comparing the hand-wrist radiographs with the Greulich and Pyle atlas 20 published in After the skeletal age of each patient was determined, the difference between the skeletal and chronologic ages was evaluated to identify precocious skeletal maturation (positive differences) or delayed maturation (negative differences). Moreover, the same researcher evaluated the cervical vertebral maturation using the method developed by Baccetti et al. 24 This method visually analyzes the morphology of the 3 cervical vertebrae (C2, C3, C4) in terms of 2 parameters: (1) the presence or absence of concavity of the inferior borders of the C2 (odontoid process), C3, and C4; and (2) the differences in the shape of the cervical vertebral bodies with the progression of age, with 4 shapes considered trapezoid, rectangular horizontal, square, and rectangular vertical. The 2 variables were subdivided into 6 consecutive stages of cervical maturation: stage 1, flattened inferior border of the cervical bodies, and the bodies are trapezoid at the superior border; stage 2, a concavity appears at the inferior border of C2 (odontoid process) and increases the anterior vertical height of the bodies, and the bodies are rectangular horizontal in shape; stage 3, a significant concavity appears at the inferior border of C3; stage 4, a concavity appears at the inferior border of C4, and the bodies of all vertebrae are rectangular in shape; stage 5, the concavities are well defined at the inferior borders of all 6 cervical vertebrae, and the bodies are nearly square; and stage 6, there is increased depth in the concavities of all cervical vertebral bodies, and the bodies are rectangular vertical in shape, with no growth remaining. Statistical analysis The data were analyzed statistically. The Student t test for independent samples was used to evaluate the statistical significance of the differences for each analyzed parameter between the test and control groups. The significance of the single tests was evaluated by using the Levene exact test. The level of significance selected was P \0.05. Intraobserver variability was calculated by using Pearson's correlation coefficient between measurements of all subjects with those in the same patients 3 weeks later. The coefficients obtained ranged between 0.99 and 0.97 (P \0.05). RESULTS Carpal assessments with the Greulich and Pyle 20 method showed that the skeletal age exceeded the chronologic age in 23 subjects (13 boys, 10 girls) and was the same in 2 subjects (1 girl, 1 boy) in the test group. In the control group, the skeletal age exceeded the chronologic age in 1 subject (a girl), was less than the chronologic age in 7 subjects (5 boys, 2 girls), and was the same in 17 subjects (9 boys, 8 girls). The subjects in the test group showed a mean precocious skeletal maturation of months. In contrast, the control subjects had a mean delayed skeletal maturation of months (Fig). There was a statistically significant difference (P \0.05) in the discrepancy between skeletal age and chronologic age between the test and control groups. In the test group, there were positive discrepancies between the skeletal and chronologic ages of months in boys and months in girls. In the control group, there were negative mean discrepancies between the skeletal and chronologic ages of months in boys and months in girls. There were no statistically significant differences observed between the sexes. The results of the cervical vertebral maturation analysis are shown in Table II. In the test group, 9 subjects (5 boys, 4 girls) showed stage 2, 13 subjects (8 boys, 5 girls) showed stage 3, and 3 subjects (1 boy, 2 girls) showed stage 4. In the control group, 4 subjects (3 boys, 1 girl) showed stage 1, 16 subjects (8 boys, 8 girls) showed stage 2, and 5 subjects (3 boys, 2 girls) showed stage 3. According to the cervical vertebral maturation analysis, the test group had a higher score ( ) compared with the control subjects ( ), and the difference between the 2 groups was statistically significant (P \0.05). The mean cervical vertebral maturation scores were in obese girls and in obese boys. In the control group, the mean cervical vertebral maturation scores were in girls and December 2012 Vol 142 Issue 6 American Journal of Orthodontics and Dentofacial Orthopedics

4 Giuca et al 777 Fig. Discrepancies between skeletal and chronologic ages in the test and control groups. Table II. Cervical vertebral maturation stages of the subjects in the 2 groups Stage Girls Boys Total Girls Boys Total in boys. No significant difference was found according to sex. DISCUSSION Test Control In orthodontics, the clinical importance of skeletal maturation in growing patients has long been recognized. A patient's growth stage should be evaluated to establish the correct diagnosis and treatment plan. Various methods have been described to determine the degree of maturity. Among these methods, the best indicators of skeletal maturity are the hand-wrist and the carpal analyses. 25 The osseous changes evaluated in handwrist and lateral cephalogram records are indicators of more general skeletal changes, and a close relationship has been established between skeletal maturation and facial maturation. 26 During childhood and adolescence, skeletal growth accelerates, reaches a peak velocity, and then decelerates, with substantial individual variations in the initiation, duration rates, and amounts of growth. 27 Numerous mechanisms regulate the development of the craniofacial complex, including hormonal, genetic, and epigenetic factors; therefore, alterations in these factors can lead to variations in skeletal growth. 28 In the literature, it has been suggested that leptin, produced by the adipose tissue, can stimulate skeletal growth through the activation of various mediators, such as insulin-like growth factor 1 and sex hormones. Alternatively, leptin might act directly on the skeletal growth centers. Leptin receptors have been found in the cartilaginous growth centers that are involved in skeletal maturation. 15 Therefore, an obese subject would have a mechanism of central resistance to leptin and an increased sensitivity to leptin at a peripheral level, causing increased differentiation and proliferation of chondrocytes and resulting in precocious skeletal maturation. The correlation between obesity and precocious skeletal maturation is a controversial subject in the literature. Several studies have shown a positive or moderate correlation 29,30 ; however, increased body weight could be a consequence of puberty, rather than a determining factor. 31 In our study, the skeletal maturity evaluated from hand-wrist and lateral cephalometric radiographs was significantly different between the obese and normal-weight subjects. According to the carpal analysis, the subjects in the test group showed precocious skeletal maturation. In contrast, the subjects in the control group showed a slightly delayed skeletal maturation with respect to their chronologic age. Furthermore, obese subjects had a higher mean cervical vertebral maturation score compared with the controls; this is related to earlier skeletal maturation. In 2004, Ochoa and Nanda 32 analyzed a sample of normal-weight subjects and found that the girls tended to have the greatest skeletal changes between the ages of 10 and 14 years. At age 10, the skeletal age of the girls American Journal of Orthodontics and Dentofacial Orthopedics December 2012 Vol 142 Issue 6

5 778 Giuca et al was 6 months behind their chronologic age. In contrast, boys had no statistically significant differences between their skeletal and chronologic ages in any period, except at age 20 years. 32 Therefore, the results of this study indicated that girls showed pubertal growth almost 2 years earlier than did the boys. 32 In our study, the skeletal age of both obese boys and girls at a mean age of 9.8 was almost 12 months ahead of the chronologic age; however, there was no significant difference in skeletal age between the sexes. Knowledge of skeletal development is essential in orthodontics because early orthodontic treatment carried out during the deciduous or mixed dentition period to improve skeletal discrepancies highly depends on the level of skeletal development. A patient will respond more effectively to the treatment if skeletal development has not yet reached its conclusion. Moreover, dentofacial and orthopedic treatment performed after the growth phase is not effective in improving skeletal discrepancies. Therefore, it is necessary to assess skeletal maturity in growing patients to determine the best timing for orthopedic and orthodontic treatment around the growth spurt. 17 A discrepancy between the skeletal and chronologic ages due to systemic conditions or medications might jeopardize treatment outcomes. According to our results, to account for earlier growth in obese patients with skeletal discrepancies, it might be necessary to perform earlier examinations and treatments than in normal-weight subjects. Body mass index standard deviations are important data that operators should consider in the context of an orthopedic or orthodontic treatment plan. However, the correlation between skeletal maturation, evaluated by carpal analysis or cervical vertebral maturation, and the growth of the maxilla and the mandible is not clearly defined. For this reason, it is difficult to correctly determine the speed of growth of the base of the cranium. Knowing the stage is not sufficient to determine the timing of skeletal maturation accurately, especially in girls, who show a more precocious maturation and a shorter developmental peak than do boys. 33 CONCLUSIONS According to the carpal analysis, obese subjects showed a higher mean discrepancy between skeletal and chronologic ages compared with normal-weight subjects. Furthermore, obese subjects had a significantly higher cervical vertebral maturation score than did normal-weight subjects. Thus, to account for the earlier growth in obese patients with skeletal discrepancies, it might be necessary to perform earlier examinations and treatments than in normal-weight subjects. Further investigations should be carried out with larger samples to confirm these preliminary findings. We thank Drs Rinaldina Saggese and Deborah Bonfigli for their help in preparing the Figure and the Tables. REFERENCES 1. Troiano F, Flegal K. Overweight children and adolescents: description, epidemiology, and demographics. Paediatrics 1998; 101(Suppl): Ogden Cl, Flegal KM, Carroll MJ, Johnson CL. Prevalence and trends in overweight among US children and adolescents JAMA 2002;288: Wardie J, Carnell S, Haworth CM, Plomin R. Evidence for a strong genetic influence in childhood adiposity despite the force of the obesogenic environment. Am J Clin Nutr 2008; 87: Dubern B, Clement K, Pelloux V. Mutation analysis of melanocortin-4 receptor, agouti-related protein, and alphamelanocyte stimulating hormone genes in severely obese children. J Pediatr 2001;139: Farooqui IS, Wangenstess T, Collins S. Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor. N Engl J Med 2007;356: Schuller Perez A. Obesity and thinness in painting. An R Acad Nac Med (Madr) 2004;121: Pinducciu G, Micheletti L, Piras V, Songini C, Serra C, Pompei R, et al. Periodontal disease, oral microbial flora and salivary antibacterial factors in diabetes mellitus type 1 patients. Eur J Epidemiol 1996;12: Costacurta M, Di Renzo L, Bianchi A, Fabiocchi F, De Lorenzo A, Docimo R. Obesity and dental caries in paediatric patients. A cross-sectional study. Eur J Paediatr Dent 2011;12: Caprioglio A, Levrini L, Nosetti L, Berini J, Macchi A, Tagliabue A, et al. Prevalence of malocclusion in preschool and primary school children with habitual snoring and sleep-disordered breathing. Eur J Paediatr Dent 2011;12: Lee YS. Consequences in childhood obesity. Ann Acad Med Singapore 2009;38: Pi-Sunyer F. Medical hazards of obesity. Ann Intern Med 1993; 119: Leonard MB, Shults J, Wilson BA, Tershakovec AM, Zemel BS. Obesity during childhood and adolescence augments bone mass and bone dimensions. Am J Clin Nutr 2004;80: Shalitin S, Phillip M. Role of obesity and leptin in the pubertal process and pubertal growth a review. Int J Obes Relat Metab Disord 2003;27: Halaas JL, Gajiwala KS, Magherita M, Cohen SL, Chait BT, Rabinowitz D, et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 1996;269: Maor G, Rochwerger M, Segev Y, Phillip M. Leptin acts as a growth factor on the chondrocytes of skeletal growth centers. J Bone Miner Res 2002;17: Attia N, Tamborlane WV, Heptulla R, Maggs D, Grozman A, Sherwin RS, et al. The metabolic syndrome and insulin-like growth factor I regulation in adolescent obesity. J Clin Endocrinol Metab 1998;83: Baccetti T. Improving the effectiveness of functional jaw orthopedics in Class II malocclusion by appropriate treatment timing. Orthod Fr 2010;81: December 2012 Vol 142 Issue 6 American Journal of Orthodontics and Dentofacial Orthopedics

6 Giuca et al Abdel-Kader HM. The reliability of dental x-ray film in assessment of MP3 stages of pubertal growth spurt. Am J Orthod Dentofacial Orthop 1998;114: Ozer T, Kama JD, Ozer SY. A practical method for determining pubertal growth spurt. Am J Orthod Dentofacial Orthop 2006; 130:131.e Greulich WW, Pyle SI. Radiographic atlas of skeletal development of the hand and wrist. 2nd ed. Stanford, Calif: Stanford University Press; Al Khal HA, Wong RW, Rabie AB. Elimination of hand-wrist radiographs for maturity assessment in children needing orthodontic therapy. Skeletal Radiol 2008;37: Franchi L, Baccetti T, McNamara JA Jr. Mandibular growth as related to cervical vertebral maturation and body height. Am J Orthod Dentofacial Orthop 2000;118: Cole TJ, Bellizzi MC, Flegal KM, Dietz WH. Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 2000;320: Baccetti T, Franchi L, McNamara JA Jr. The cervical vertebral maturation (CVM) method for the assessment of optimal treatment timing in dentofacial orthopaedics. Semin Orthod 2005;11: Hassel B, Farman AG. Skeletal maturation evaluation using cervical vertebrae. Am J Orthod Dentofacial Orthop 1995;107: Uysal T, Ramoglu SI, Basciftci FA, Sari Z. Chronologic age and skeletal maturation of the cervical vertebrae and hand-wrist: is there a relationship? Am J Orthod Dentofacial Orthop 2006; 130: Mahajan S. Evaluation of skeletal maturation by comparing the hand wrist radiograph and cervical vertebrae as seen in lateral cephalogram. Indian J Dent Res 2011;22: Cali AM, Caprio S. Obesity in children and adolescents. J Clin Endocronol Metab 2008;93(11 Suppl 1):S Karlberg J. Secular trends in pubertal development. Horm Res 2002;57(Suppl 2): Flores-Mir C, Mauricio FR, Orellana MF, Major PW. Association between growth stunting and dental development and skeletal maturation stage. Angle Orthod 2005;75: Akridge M, Hilgers KK, Silveira AM, Scarfe W, Scheetz J, Kinane DF. Childhood obesity and skeletal maturation assessed with Fishman's hand-wrist analysis. Am J Orthod Dentofacial Orthop 2007;132: Ochoa BK, Nanda RS. Comparison of maxillary and mandibular growth. Am J Orthod Dentofacial Orthop 2004;125: Sadeghianrizi A, Forsberg CM, Marcus C, Dahll of G. Craniofacial development in obese adolescents. Eur J Orthod 2005;27: American Journal of Orthodontics and Dentofacial Orthopedics December 2012 Vol 142 Issue 6