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Sunil Kumar Khare, Rajendra Gupta, Amit Prakash Orthodontics ENDOCRINE DISORDERS AND THEIR EFFECTS IN ORTHODONTICS Sunil Kumar KHARE1, Rajendra GUPTA2, Amit PRAKASH3 1. Associate Professor, Dept. Physiology, LN Medical College and Research Centre, Bhopal 2. Associate Professor, Dept. Anatomy, Gaja Raja Medical College, Gwalior 3. Senior Lecturer, Dept. Orthodontics Dentofacial Orthopedics, Rishi-raj Dental College and Hospital, Bhopal Contact person: Amit Prakash – [email protected] Abstract Orthodontic tooth movement results from the response of the periodontal tissue to orthodontic forces, which leads to modeling and remodeling of the surrounding alveolar bone. The endocrine system is responsible for hormonal secretion, being closely related to the central nervous sys‑ tem, as it diversifies its functions through the hypothala‑ mus and pituitary glands. It controls physiological processes and maintains homeostasis. The neuroendocrine system is responsible for adaptation to environmental changes. Also, the nervous system may provide a correct organic response, of primary type, with the release of neu‑ rotransmitters or, if the stimulus prevails, the endocrine system secretes hormones. This is especially important in dentistry because many of the patients attending dental clinics face stressful situations. Awareness is therefore nec‑ essary on the risks and difficulties that may arise during the dental and orthodontic management of patients with endocrine disorders and most common oral manifesta‑ tions. Keywords: endocrine, hormone, orthodontics INTRODUCTION The term ‘endocrine’ refers to endocrine or ductless glands, because they secrete physiolog‑ ically-active substances (hormones) directly into the blood stream. Hormones are secretory prod‑ ucts of the endocrine glands released directly into the circulation in small amounts, in response to a specific stimulus. On their delivery in circu‑ lation, they respond to the target cells or organs [1]. Protein hormones and catecholamines act through intracellular enzymes. The hormone, which acts on a target cell, is called the first mes‑ senger. In combination with the receptor, it forms the receptor-hormone complex. This, in turn acti‑ vates the enzymes of the cell and causes forma‑ tion of another substance, called the second messenger or the intracellular hormonal 280 mediator, making the effects of the hormone to be manifested inside the cells [2]. The most common second messenger is cyclic AMP (cyclic adenosine 3’5’monophosphate or cAMP). On the membrane of most of the target cells, receptor proteins called G-proteins are pre‑ sent. The hormone binds with the receptor cou‑ pled with the G-protein, to form a receptor hormone complex. This complex activates the enzyme adenyl cyclase, which is also present in the cell membrane. Most of the adenyl cyclase protrudes into the cytoplasm of the cell from the inner surface of the cell membrane. The activated adenyl cyclase converts the ATP of the cytoplasm into cAMP, called the second messenger, which performs the hormonal actions inside the cell; by stimulating some enzymes like protein kinase A, it produces the response, as a function of the tar‑ get cells through these enzymes [1-2]. The thyroid and steroid hormones act on the genes of the target cells. As soluble lipids, hor‑ mones can easily enter the target cells and bind with the receptor in either cytoplasm (steroid hormone) or nucleus (thyroid hormone), form‑ ing the hormone receptor complex. This complex enters the nucleus and gets attached to chroma‑ tin. The complex reacts with DNA, stimulates transcription (i.e., formation of mRNA), then it enters the cytoplasm, where it directs the rhibo‑ somes to synthesize specific proteins (transla‑ tion). These proteins may be enzymes, structural proteins and receptor proteins of secretory pro‑ teins. Orthodontic tooth movement results from the response of the periodontal tissue to the ortho‑ dontic force, which leads to modeling and remodeling of the surrounding alveolar bone. The response is considered to occur through the volume 3 • issue 4 October / December 2013 • pp. 280-285 ENDOCRINE DISORDERS AND THEIR EFFECTS IN ORTHODONTICS activation of specific signaling pathways, many of which are known, all acting to ultimately result in tooth movement. The rate at which tooth movement occurs depends on the ability of these pathways to realize bone metabolism by the two main cell types responsible for tooth movement: osteoblasts and osteoclasts [3-5]. GROWTH HORMONE (GH) GH is a protein hormone, secreted by the aci‑ dophils of the anterior pituitary gland. GH secre‑ tion is pulsatile, secretory bursts occurring especially at early hours of sleep and throughout the night. GH has no specific target organ. It is an anabolic hormone to which every organ sys‑ tem responds, considered in the present study being craniofacial growth and its relation with the orthodontic treatment. Apparently, it has no direct action upon bones, acting through a sub‑ stance called somatomedin. GH stimulates the liver to secrete somatomedin and is the main regulator of childhood and adolescent growth. Undersized children secrete less GH than the tall ones. GH pulse amplitude is increased in growth spurt, with simultaneous increase in plasma IGF-I concentrations. These values often increase to as high as 50ng/ml after depletion of the body stores of proteins and carbohydrates during pro‑ longed starvation [1-5]. Dental development Dental delay is always less pronounced than height or bone delay. Dentition seems to be har‑ moniously delayed, so that all studied compo‑ nents of dental development (primary root resorption, secondary tooth formation and erup‑ tive movement) display the same degree of retar‑ dation. GH influence on growth starts after 9 months of age, so that the effect on the growth of primary teeth is very little known. GH deficiency Children show big skull with babyish face, however their intelligence is normal for their age. Cephalometric studies in such children have shown small sizes of the anterior and posterior International Journal of Medical Dentistry cranial bases and smaller mandibular dimen‑ sions, small posterior facial height, and small posterior mandibular height. Hypersecretion leads to gigantism in the young ones and to acro‑ megaly in adults, which is usually caused by a pituitary adenoma. Gigantism A cephalometric study was done on two female patients suffering from gigantism, due to GH excess. The anterior facial heights appeared as the largest cephalometric dimensions, fol‑ lowed by posterior facial height. Acromegalyserum levels of IGF-I in these patients were very high, the mean value being 10-fold higher than in normal adults. Mandibular growth is gradual and often noticed by the dentist when crossbite was developed. The calvarium, hands and feet grow by bone apposition. The tongue grows, and a general visceral growth has been also docu‑ mented. The cartilaginous tissue gets larger, the ribs are thicker and the costochondral cartilage appears hypertrophic. The hypertrophic articu‑ lar cartilage and the growth of chondrocytes in the articular cartilage may cause acromegalic arthropathy. Mandibular growth in acromegaly results from both appositional growth and hypertrophic changes in the condylar cartilage. [6-9] INSULIN Insulin is a polypeptide hormone secreted by the beta cells of the Langerhans islets of the pan‑ creas. A normal non-obese man secretes approx‑ imately 50U/day, with a basal plasma insulin concentration of 10-50 microns/ml. Its main function is to maintain the blood glucose level. Insulin deficiency produces a clinical state called diabetes mellitus, while its excess leads to hypo‑ glycemia. Diabetes mellitus is diagnosed in 3-4% of the population treated in our day-to-day orthodontic practice. The orthodontic practi‑ tioner should have a basic knowledge and under‑ standing of this disease and of its impact on the oral cavity, as well as of its consequences upon the dental treatment. [1,10] 281 Sunil Kumar Khare, Rajendra Gupta, Amit Prakash Orthodontic considerations Informed on the oral complications induced by diabetes mellitus, the dental practitioner should consider them when treating a DM patient; the key to any orthodontic treatment is a good medical control. No orthodontic treat‑ ment should be performed in a patient with uncontrolled diabetes. There is no treatment ref‑ erence with regard to fixed or removable appli‑ ances. A good oral hygiene is especially important when fixed appliances are used, as they may increase plaque retention, which could more eas‑ ily cause tooth decay and periodontal break‑ down. Daily rinses with fluoride-rich mouthwash can provide further preventive benefits. Candida infections may also occur in the oral cavity, so that they should be well monitored. Diabetesrelated microangiopathy can occasionally appear in the periapical vascular supply, resulting in unexplained odontalgia, percussion sensitivity, pulpitis, or even loss of vitality in sound teeth. Especially in orthodontic treatments involving force application for moving teeth over a consid‑ erable distance, the practitioner should regularly check the vitality of the teeth involved. It is advisable to apply light forces and not to over‑ load the teeth [11]. Holtgrave and Donath, who studied the peri‑ odontal reaction to orthodontic forces, evidenced retarded osseous regeneration, weakening of the periodontal fibers and microangiopathies in the gingival areas. In adults, before starting the orthodontic treatment, the orthodontist should obtain a full-mouth (periodontal) examination and evaluation of the need for periodontal treat‑ ment. The periodontal condition should be improved before staring the treatment and should be monitored regularly. Maintaining a strict oral hygiene is important, by a proper use of toothbrush, interdental toothbrush and chlo‑ rhexidine mouthwash. To minimize the neutral‑ izing effect of toothpaste on the chlorhexidine molecule, an at least 30-min interval should be left between tooth brushing and chlorhexidine rinse. As no upper age limit for orthodontic treat‑ ments is any longer valid today, the practitioner will see both type1 and type2 DM patients. Type2 patients can be considered more stable than 282 type1 ones, as hypoglycemic reactions are more frequent in these patients. If a patient is sched‑ uled for a long treatment session, he or she should be advised to eat a usual meal and take the medication as usual. At each appointment, the orthodontist should confirm the meal and medication, to avoid a hypoglycemic reaction in the office. DM patients with good metabolic con‑ trol, without local factors, such as calculus, and with a good oral hygiene, have a similar gingival status as the healthy ones, consequently they can be treated orthodontically [12-14]. THYROXIN HORMONES (TH) TH lack in a specific target organ may affect every organ and system and every biologic pro‑ cess. Thyroid disorders are common and affect craniofacial and dental structures. The dental and craniofacial retardation manifested under prolongued hypothyroid conditions differs from the isolated lack of GH. The main difference is the cranial vault, which shows growth retarda‑ tion in hypothyroidism, and reduced facial height in children with prolongued untreated hypothyroidism. Thyroxin administration seems to lead to increased bone remodeling, increased bone resorptive activity and reduced bone den‑ sity. Thyroid hormones increase osteoclastic bone resorption in neonatal mouse calvarium by stimulation of prostaglandin synthesis [14]. PARATHORMONE (PTH) It is a polypeptide hormone secreted by the parathyroid glands, which increases serum cal‑ cium by releasing calcium from the bone. Pos‑ sibly, it may enhance orthodontic tooth movement by the local use of PTH. The discrete removal of the alveolar bone prior to force application may reduce resistance to tooth movement, permitting a selective tooth movement [15]. CALCITONIN It is a peptide hormone secreted by the inter‑ follicular or C-cells in the thyroid gland, also called thyrocalcitonin. Thyrocalcitonin flows volume 3 • issue 4 October / December 2013 • pp. 280-285 ENDOCRINE DISORDERS AND THEIR EFFECTS IN ORTHODONTICS into the bloodstream and attracts calcium to the bone, thus reducing serum calcium. It also inhib‑ its bone resorption by reducing the number of osteoclasts. Calcitonin is used in the treatment of hypercalcemia and in osteoporosis; because of its physiological role, it is considered as inhibiting tooth movement. consequently, a delay in the orthodontic treatment can be expected [1,15]. VITAMIN-D3 Vitamin-D and its most active metabolite, vitamin-D3, together with parathyroid hormone and Calcitonin, regulate the amount of calcium and phosphorus in the human organism. It pro‑ motes intestinal Ca+2 and PO4-3 absorption. Vita‑ min-D3 increases bone mass and thus reduce fractures in osteoporosis patients. Considering its beneficial effects on bone tissue, it may be assumed that it inhibits tooth movement [16,17]. SEX-STEROIDS A slight increase in the growth rate is seen at the age of 6-8 years in most children, possibly due to an increased GH and IGF-I production, which is stimulated by adrenal androgens. Dur‑ ing puberty, an increase in GH production is seen in boys and girls. Several lines of evidence indicate that this increase is sex-steroid depend‑ ent. The sex-steroids here involved are adrenal and ovarian androgens and ovarian and testicu‑ lar estrogens. Plasma concentration of IGF-I shows a similar increase [18]. Estrogen directly stimulates the bone-forming activity of osteoblasts, so it is reasonably to expect a slower rate of orthodontic tooth move‑ ment. Androgens also inhibit bone resorption and modulate the growth of the muscular sys‑ tem. Thus, the excessive use of these drugs by athletes, in an attempt to achieve better athletic scores, may affect the duration and results of the orthodontic treatment. CORTICOSTEROIDS Hyperglucocorticoidism causes short stature and bone maturation, while increasing relative International Journal of Medical Dentistry weight. Very small amounts of medication can decrease the growth rate. Skeletal IGF-I synthesis is decreased by cortisol, which has an inhibitory effect on bone collagen synthesis. In the process of tooth eruption, however, cortisone has a spe‑ cial effect, the eruption rate being accelerated [19-20]. PROSTAGLANDINS (PGS) The precursor of PGs is the arachidonic acid, which is metabolized by cyclaseoxygenase (cox) enzymes. Experiments have shown that PGs may act as important mediators of mechanical stress during orthodontic tooth movement. They stim‑ ulate bone resorption by increasing the number of osteoclasts and by activating the already exist‑ ing osteoclasts [21]. LEUKOTRIENES These also exist metabolites of the arachidonic acid, produced when metabolized by the lipoxy‑ genase enzyme. Leukotrienes may be also impor‑ tant mediators of orthodontic tooth movement. A study of Mohammed, Takikis and Dziak devoted to the role of inhibitors of leukotrienes synthesis in orthodontic tooth movement showed a significant reduction of orthodontic tooth movement. Consequently, the use of leukotriene inhibitors can delay the orthodontic treatment, whereas leukotrienes and PGs can have future clinical applications, causing enhanced tooth movements [22-23]. BIPHOSPHONATES This class of pharmacological agents is char‑ acterized by their high affinity for calcified tis‑ sues. Biphosphonates are potent blockers of bone resorption, successfully used in the treatment of hypercalcemia, osteoporosis and, generally, in the treatment of metabolic bone diseases involv‑ ing increased bone resorption. Inhibition of the osteoclastic metabolism is caused by a decrease in the number of osteoclasts, which may recom‑ mend it for anchoring and retaining teeth under orthodontic treatment. However, further studies 283 Sunil Kumar Khare, Rajendra Gupta, Amit Prakash are required before any clinical application in orthodontics, for avoiding any possible systemic effects [24]. FLUORIDE It is one of the several trace elements that affect hard tissue metabolism. It stimulates the growth and synthesis activity of osteoblasts and bone formation, and increases bone mass and mineral density. At clinical level, the mentioned findings suggest that the use of fluoride can influence the rate of orthodontic tooth move‑ ment. Even a very active preventive caries treat‑ ment with sodium fluoride (NaF) during orthodontic tooth movement can affect the dura‑ tion of orthodontic therapy [22-24]. NSAIDS (SALICYLATES) These non-steroidal anti-inflammatory drugs inhibit the cyclase -oxygenase (cox) activity. Salicylates’ action can be attributed to their inhi‑ bition of PG synthesis, which seems to play a significant role in bone resorption during ortho‑ dontic therapy. Therefore, it is not recommended to patients undergoing orthodontic treatment to take salicylates for long periods, as this might possibly prolongue the treatment [25]. CONCLUSIONS Most of the studies on hormones have been done on rats, squirrels and monkeys and not on human beings; consequently, very little is still known on the effects of hormones on the devel‑ opment of face and craniofacial skeletal and on the rate of orthodontic tooth movement in humans. The role of endocrine disorders in orthodontics is still a great mystery for an ortho‑ dontic practitioner and further research is required to understand it better. References 1. Brasel JA, Blizzard RM. Textbook of Endocrinology. 5th ed. Philadelphia, Pa: WB Sauders; 1974. 2. Thilander B. Basic mechanisms in craniofacial growth. Acta Odontol Scand. 1995; 53:144–151. 284 3. Pirinen S. Endocrine regulation of craniofacial growth. Acta Odontol Scand. 1995; 53:179–185. 4. Funatsu M, Sato K, Mitani H. 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Effects of drugs and systemic factors on orthodontic treatment. Quintessence International2001; 32:365-371. 25. Tripathi KD. Essentials of Medical Pharmacology, Vedition. Khan R, Antony VV. 285