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Growth Hormone Deficiency for Oral-Health
Growth hormone (GH) is involved in the regulation of the postnatal dental and skeletal growth, but its effects on oral health have not been clearly defined. This paper aims to provide a review of current clinical knowledge of dental caries, tooth wear, developmental enamel defects, craniofacial growth and morphology, dental maturation, and tooth eruption in growth hormone deficient (GHD) children. A systematic review was carried out using Scopus, MEDLINE-EbscoHost and Web of Science from 2000 to May 2021.
Growth hormone (GH) is a critical regulator of the growth process in children. Both, cell sensitivity to GH and the site of GH action are closely coordinated and affect the odontogenesis. When the new matrix begins to form, GH receptors are expressed in tooth tissues and mediate local growth responses. However, cementocytes and mature odontoblasts in later stages of tooth development do not display expression, which suggests that they become insensitive .
Recent studies have shown that IGF-I and its receptor are expressed in both dental epithelial and mesenchymal tissues of tooth germs, increasing the size of bioengineered tooth germs. In vitro IGF-I signaling promotes cell proliferation, differentiation, and matrix secretion in mouse tooth germs, and so it can be hypothesized that IGF-I regulates tooth morphogenesis .
Oyanagi et al.  showed that the combination of IGF-I and BMP2 promotes odontoblast differentiation and the expression of the ameloblastin enamel matrix gene ( Ambn ) in mice. Their research demonstrated that the expression of Ambn is directly enhanced by IGF-I in dental epithelial cells, so Ambn may play an essential role in normal ameloblast differentiation. It is interesting that at least a hundred genes have been recognized as being expressed during different stages of amelogenesis; this total includes genes that codify sex hormone receptors and growth hormone receptors . Estrogen plays an essential role during tooth formation by influencing the process of enamel and dentin mineralization. An animal model of estrogen deficiency showed a significant reduction in enamel microhardness . The results reported by Arid et al.  in humans have demonstrated that genetic polymorphism in estrogen receptors (rs12154178) and in GH receptors (rs1509460) is associated with alterations in ameloblast function and developmental defects of enamel (DDE). It must be remembered that disturbances in enamel formation are associated with poor esthetics and the higher susceptibility of teeth to harmful local factors. Developmental enamel defects increase the risk of dental caries and noncarious tooth surface loss, which affect long-term dental health . The posteruptive onset of the caries process takes part for as long as three years after permanent tooth eruption . Caries in primary teeth shows a rapid course, due to the specific morphological structure and a lower degree of mineralization. Effective prevention and treatment, especially in the case of primary dentition, can considerably extend the time that a tooth remains in the oral cavity, thus preventing the consequences of its premature loss. In patients with growth hormone deficiencies, missing teeth and tooth-bone discrepancies become risk factors for masticatory organ disorders.
Data from the literature confirm that dental age is delayed with respect to chronological age by up to two years in growth hormone-deficient (GHD) children . It has been reported that tooth eruption, defined as the mucosal penetration of any visible part of a tooth into the oral cavity, is delayed in both primary and permanent dentition . The relationship between the maturation of the skeletal system and the formation of permanent dentition has been confirmed in several studies . There is a relationship between mineralization of the canine and the MP3 stage—one of the stages of ossification of the middle phalanx of the third finger in the development of bones of the wrist . Moreover, the relationship between dental age and maturity in the cervical vertebrae is also determined. A significant association has been confirmed between cervical vertebral maturation (CMV) classification and the development of canine and second premolar teeth . At the same time, it should be remembered that the time for emergence of permanent premolars and canines can be modified by the activity of caries in primary teeth. Several studies have concluded that early extraction of second primary molar or caries in primary molars can accelerate the clinical eruption of permanent second molars .
2. Analysis on Results
2.1. Hard Mineralized Tissue Pathology
2.2. Dental Maturity and Malocclusion
2.3. Craniofacial Growth/Morphology
2.4. Quality Assessment and Risk of Bias
3. Current Insights
There is very little in the literature on oral cavity status in patients with GHD. Our systematic review has shown that some dental topics have not yet been discussed. There has been little to evaluate dental conditions like tooth wear and enamel defects, although we can assume that the effect of growth hormone on the dentition and facial bones is complex . Publications on dental status and craniofacial growth in children with GHD are somewhat confined, and their results are not always concordant .
The size, growth, and osseous maturity of the jaw also play a role in the process of tooth eruption. A strong correlation has been shown between eruption time and dental maturity. The teeth typically erupt when they have reached a 2/3 root length , but individual correlation between chronological age and eruption time is inconsistent . Research has demonstrated that, in GHD patients, dental age (maturity) is significantly delayed . This is consistent with the results of Cantu et al. , which indicated a mean delay in dental age of close to one year. Furthermore, they observed no significant effect of GH treatment on dental maturation. The lack of a subsequent therapeutic response would indicate that dental age is less affected by GH than craniofacial growth.
The studies involved in our systematic review report that not only the height of GHD children, but also their craniofacial morphology and growth, are affected . These studies support the previously demonstrated idea that the linear growth of the body is strongly correlated with jaw growth , and that the growth of craniofacial skeletal structures is poor in periods of slow longitudinal growth .
Birth age does not reflect fully the physiological development of a child. In order to closely evaluate the process of growth, it is necessary to use other criteria, such as dental age and skeletal age. These parameters are essential for dental providers to provide diagnoses and to plan therapy. In clinical practice, evaluation of both dental and skeletal age would be valuable in all children undergoing dental treatment, especially in those with GHD.
The available studies indicate that children with GHD showed abnormal craniofacial morphology with reduced mandibular dimensions, with a resulting tendency to Angle’s Class II occlusion, which affected up to 31% of the patients. Dental age has been shown to be delayed in GHD patients by about 1 to 2 years. Moreover, the risk of dental caries in children with GHD decreases with increasing levels of vitamin D. The data are scarce and further studies would be valuable in evaluating the risk of various oral health problems and in organizing targeted dental care for this vulnerable group.
To gain more of an insight into the effects of this disease and its treatment on oral health and craniofacial structures, data need to be collected both before and after GH administration. Such longitudinal studies could help us to understand the complex endocrine mechanisms regulating the stomatognathic system’s development and functions, in order to provide the optimal treatment of GHD-related disturbances.
The entry is from 10.3390/jcm10163733
- Hikita, Y.; Yamaguchi, T.; Tomita, D.; Adel, M.; Nakawaki, T.; Katayama, K.; Maki, K.; Kimura, R. Growth hormone receptor gene is related to root length and tooth length in human teeth. Angle Orthod. 2018, 88, 575–581.
- Al-Kharobi, H.; El-Gendy, R.; Devine, D.A.; Beattie, J. The role of the insulin-like growth factor (IGF) axis in osteogenic and odontogenic differentiation. Cell Mol. Life Sci. 2014, 71, 469–476.
- Oyanagi, T.; Takeshita, N.; Hara, M.; Ikeda, E.; Chida, T.; Seki, D.; Yoshida, M.; Seiryu, M.; Takano, I.; Kimura, S.; et al. Insulin-like growth factor 1 modulates bioengineered tooth morphogenesis. Sci. Rep. 2019, 9, 368.
- Arid, J.; Oliveira, D.B.; Evangelista, S.S.; Vasconcelos, K.R.F.; Dutra, A.L.T.; de Oliveira, S.S.; de Queiroz, A.M.; Nelson-Filho, P.; Vieira, A.R.; Küchler, E.C. Oestrogen receptor alpha, growth hormone receptor, and developmental defect of enamel. Int. J. Paediatr. Dent. 2019, 29, 29–35.
- Kazoullis, S.; Seow, W.K.; Holcombe, T.; Newman, B.; Ford, D. Common dental conditions associated with dental erosion in schoolchildren in Australia. Pediatr. Dent. 2007, 29, 33–39.
- Opydo-Szymaczek, J.; Gerreth, K.; Borysewicz-Lewicka, M.; Pawlaczyk-Kamieńska, T.; Torlińska-Walkowiak, N.; Śniatała, R. Enamel defects and dental caries among children attending primary schools in Poznań. Poland. Adv. Clin. Exp. Med. 2018, 27, 1535–1540.
- Mejàre, I.; Axelsson, S.; Dahlén, G.; Espelid, I.; Norlund, A.; Tranæus, S.; Twetman, S. Caries risk assessment: A systematic review. Acta Odontol. Scand. 2014, 72, 81–91.
- Cantu, G.; Buschang, H.; Gonzalez, J.L. Differential growth and maturation in idiopathic growth-hormone-deficient children. Eur. J. Orthod, 1997; 19, 131–139.
- Kjellberg, H.; Beiring, M.; Wikland, K.A. Craniofacial morphology, dental occlusion, tooth eruption, and dental maturity in boys of short stature with or without growth hormone deficiency. Eur. J. Oral. Sci. 2000, 108, 359–367.
- Flores-Mir, C.; Mauricio, F.R.; Orellana, M.F.; Major, P.W. Association between growth stunting with dental age development and skeletal maturation stage. Angle Orthod. 2005, 75, 935–940.
- Wites, M.; Kalukin, J.; Niżankowska-Jędrzejczyk, A.; Loster, B.W. Prediction of the growth spurt based on panoramic radiograhps. J. Stomatol. 2011, 64, 875–886.
- Różyło-Kalinowska, I.; Kolasa-Rączka, A.; Kalinowski, P. Relationship between dental age according to Demirjian and cervical vertebrae maturity in polish children. Eur. J. Orthod. 2011, 33, 75–83.
- Kim, C.; Hong, Y.; Han, D.H.; Hong, H.K.; Kim, Y.N.; Bae, K.H. A prospective cohort study on emergence of permanent teeth and caries experience in Korean children. Int. J. Paediatr. Dent. 2011, 21, 254–260.
- Wójcik, D.; Krzewska, A.; Szalewski, L.; Pietryka-Michałowska, E.; Szalewska, M.; Krzewski, S.; Pels, E.; Beń-Skowronek, I. Dental caries and Vitamin D 3 in children with growth hormone deficiency. Medicine 2018, 97, e9811.
- Wójcik, D.; Szalewski, L.; Pietryka-Michałowska, E.; Borowicz, J.; Pels, E.; Beń-Skowronek, I. Vitamin D3 and dental caries in children with growth hormone deficiency. Int. J. Endocrinol. 2019, 5, 1–8.
- Partyka, M.; Chałas, R.; Dunin- Wilczyńska, I.; Drohomyretska, M.; Klatka, M. Influence of growth hormone therapy on selected dental and skeletal system parameters. Ann. Agric. Environ. Med. 2018, 25, 60–65.
- Hodge, N.; Evans, C.A.; Simmons, K.E.; Fadavi, S.; Viana, G. Occlusal characteristics of individuals with growth hormone deficiency, idiopathic short stature, and russell-silver syndrome. J. Den. Child. 2015, 82, 135–140.
- Funatsu, M.; Sato, K.; Mitani, H. Effects of growth hormone on craniofacial growth. Duration of replacement therapy. Angle Orthod. 2006, 76, 970–977.
- Kim, K.B.; Kim, E.K.; Jang, K.M.; Kim, M.S.; Park, E.Y. Evaluation of craniofacial morphology in short-statured children: Growth hormone deficiency versus idiopathic short stature. Yeungnam Univ. J. Med. 2021, 38, 47–52.
- Preda, S.A.; Albulescu, D.M.; Mitroi, M.R.; Popescu, M.; Nechita, F.; Camen, A.; Cotoi, I.A. Craniofacial morphology aspects in children with isolated growth hormone deficiency—A cephalometric study. Rom. J. Morphol. Embryol. 2019, 60, 653–658.
- Choi, S.-H.; Fan, D.; Hwang, M.S.; Lee, H.K.; Hwang, C.J. Effect of growth hormone treatment on craniofacial growth in children: Idiopathic short stature versus growth hormone deficiency. J. Formos. Med. Assoc. 2017, 116, 313–321.
- Segal, D.G.; Pescovitz, O.H.; Schaefer, G.B.; DiMeglio, L.A. Craniofacial and acral growth responses in growth hormone-deficient children treated with growth hormone. J. Pediatr. 2004, 144, 437–443.
- Higgins, J.P.T.; Green, S. Cochrane Handbook for Systematic Reviews of Interventions; Version 5.1.0 (updated March 2011); The Cochrane Collaboration: London, UK, 2011.
- Litsas, G. Growth Hormone and Craniofacial Tissues. An update. Open Dent. J. 2015, 30, 1–8.
- Van Erum, R.; Mulier, G.; Carels, C.; de Zegher, F. Craniofacial growth and dental maturation in short children born small for gestational age: Effect of growth hormone treatment. Own observations and review of the literature. Horm. Res. 1998, 50, 141–146.
- Kjaer, I. Mechanism of human tooth eruption: Review article including a new theory for future studies on the eruption process. Scientifica 2014, 2014, 341905.
- Leroy, R.; Cecere, S.; Lesaffre, E.; Declerck, D. Variability in permanent tooth emergence sequences in Flemish children. Eur. J. Oral Sci. 2008, 116, 11–17.
- Martignon, S.; López-Macías, A.M.; Bartlett, D.; Pitts, N.; Usuga-Vacca, M.; Gamboa, L.F.; O’Toole, S. The use of index teeth vs. full mouth in erosive tooth wear to assess risk factors in the diet: A cross-sectional epidemiological study. J. Dent. 2019, 103164.