Impact of Vitamin D Deficiency in Children on the Effectiveness Of

Al gamaa Journal Scientific Journal Court, ISBN: (978-977-85067-4-7). Publisher: Academical International for Studies and Publishing ,in cooperation with a university faculty members, Investment Authority Decision 1270 for the year 2012. The fifth issue - February – 2018.

Impact of Vitamin D deficiency in children on The effectiveness of orthodontic Hanaa abed Alorabi Abdullah abed alorabi Abstract : The current search goal is to clarify the impact of Vitamin D deficiency in children on The effectiveness of orthodontic, By reviewing the literary survey and analysis, the research reached a number of results, the most important of which were the results:intraligamentous injections of a vitamin D metabolite caused an increase in the number of osteoclasts and the amount of tooth movement during canine retraction with light forces in cats, bisphosphonates inhibit orthodontic tooth movement and delay the orthodontic treatment, A serious drawback of long-term use of bisphosphonates is that they can cause osteonecrosis, especially in the alveolar bones of the maxilla and the mandible. Introduction: In childhood, a person needs a variety of vitamins that help him build body parts and rebuild the weakened parts of the main vitamins Vitamin D, Vitamin D Vitamin D is collective name given to anti-rachitic substances synthesized in the body and found in dietary sources activated by UV radiation,which plays an effective role in building bones and teeth in partnership with calcium. Vitamin D deficiency is a direct cause of weakness Teeth Orthodontics are one of the most important methods used by doctors to maintain the strength of the teeth. In the case of vitamin D deficiency in children, orthodontics becomes difficult. The orthodontic process may face the inability of the body to re-fix the teeth . Research problem: The number of children suffering from vitamin D deficiency, the problem of these children in the case of orthodontic, because of the weakness of the ability of teeth to return to normal condition in the absence of vitamin. The problem of research can be framed in the next main question: Whats the impact of Vitamin D deficiency in children on The effectiveness of orthodontic? Definition: Vitamin D is a fat-soluble vitamin that is naturally present in very few foods, added to others, and available as a dietary supplement. It is also produced endogenously when ultraviolet rays from sunlight strike the skin and trigger vitamin D synthesis. Vitamin D obtained from sun exposure, food, and supplements is biologically inert and must undergo two hydroxylations in the body for activation. The first occurs in the liver and converts vitamin D to 25- hydroxyvitamin D [25(OH)D], also known as calcidiol. The second occurs primarily in the kidney and forms the physiologically active 1,25- dihydroxyvitamin D [1,25(OH)2D], also known as calcitriol[1] . Importance of vitamin D: Vitamin D promotes calcium absorption in the gut and maintains adequate serum calcium and phosphate concentrations to enable normal mineralization of bone and to prevent hypocalcemic tetany. It is also needed for bone growth and bone remodeling by osteoblasts and osteoclasts [1,2]. Without sufficient vitamin D, bones can become thin, brittle, or misshapen. Vitamin D sufficiency prevents rickets in children and osteomalacia in adults [1]. Together with calcium, vitamin D also helps protect older adults from osteoporosis.

Vitamin D has other roles in the body, including modulation of cell growth, neuromuscular and immune function, and reduction of inflammation [1,3,4]. Many genes encoding proteins that regulate cell proliferation, differentiation, and apoptosis are modulated in part by vitamin D [1]. Many cells have vitamin D receptors, and some convert 25(OH)D to 1,25(OH)2D.

Vitamin D and Health: Optimal serum concentrations of 25(OH)D for bone and general health have not been established; they are likely to vary at each stage of life, depending on the physiological measures selected [1,2,5]. Also, as stated earlier, while serum 25(OH)D functions as a biomarker of exposure to vitamin D (from sun, food, and dietary supplements), the extent to which such levels serve as a biomarker of effect (i.e., health outcomes) is not clearly established [1].

Furthermore, while serum 25(OH)D levels increase in response to increased vitamin D intake, the relationship is non-linear for reasons that are not entirely

2 clear [1]. The increase varies, for example, by baseline serum levels and duration of supplementation. Increasing serum 25(OH)D to >50 nmol/L requires more vitamin D than increasing levels from a baseline <50 nmol/L. There is a steeper rise in serum 25(OH)D when the dose of vitamin D is <1,000 IU/day; a lower, more flattened response is seen at higher daily doses. When the dose is ≥1,000 IU/day, the rise in serum 25(OH)D is approximately 1 nmol/L for each 40 IU of intake. In studies with a dose ≤600 IU/day, the rise is serum 25(OH)D was approximately 2.3 nmol/L for each 40 IU of vitamin D consumed [1].

In 2011, The Endocrine Society issued clinical practice guidelines for vitamin D, stating that the desirable serum concentration of 25(OH)D is >75 nmol/L (>30 ng/ml) to maximize the effect of this vitamin on calcium, bone, and muscle metabolism [6]. It also reported that to consistently raise serum levels of 25(OH)D above 75 nmol/L (30 ng/ml), at least 1,500-2,000 IU/day of supplemental vitamin D might be required in adults, and at least 1,000 IU/day in children and adolescents.

However, the FNB committee that established DRIs for vitamin D extensively reviewed a long list of potential health relationships on which recommendations for vitamin D intake might be based [1]. These health relationships included resistance to chronic diseases (such as cancer and cardiovascular diseases), physiological parameters (such as immune response or levels of parathyroid hormone), and functional measures (such as skeletal health and physical performance and falls). With the exception of measures related to bone health, the health relationships examined were either not supported by adequate evidence to establish cause and effect, or the conflicting nature of the available evidence could not be used to link health benefits to particular levels of intake of vitamin D or serum measures of 25(OH)D with any level of confidence. This overall conclusion was confirmed by a more recent report on vitamin D and calcium from the Agency for Healthcare Research and Quality, which reviewed data from nearly 250 new studies published between 2009 and 2013 [7]. The report concluded that it is still not possible to specify a relationship between vitamin D and health outcomes other than bone health.

Properties of vitamin D: Serum concentration of 25(OH)D is the best indicator of vitamin D status. It reflects vitamin D produced cutaneously and that obtained from food and supplements [1] and has a fairly long circulating half-life of 15 days [8]. 25(OH)D functions as a biomarker of exposure, but it is not clear to what extent 25(OH)D levels also serve as a biomarker of effect (i.e., relating to health status or outcomes)

[1]. Serum 25(OH)D levels do not indicate the amount of vitamin D stored in body tissues.

In contrast to 25(OH)D, circulating 1,25(OH)2D is generally not a good indicator of vitamin D status because it has a short half-life of 15 hours and serum concentrations are closely regulated by parathyroid hormone, calcium, and phosphate [8]. Levels of 1,25(OH)2D do not typically decrease until vitamin D deficiency is severe [2,5].

There is considerable discussion of the serum concentrations of 25(OH)D associated with deficiency (e.g., rickets), adequacy for bone health, and optimal overall health, and cut points have not been developed by a scientific consensus process. Based on its review of data of vitamin D needs, a committee of the Institute of Medicine concluded that persons are at risk of vitamin D deficiency at serum 25(OH)D concentrations <30 nmol/L (<12 ng/mL). Some are potentially at risk for inadequacy at levels ranging from 30–50 nmol/L (12–20 ng/mL). Practically all people are sufficient at levels ≥50 nmol/L (≥20 ng/mL); the committee stated that 50 nmol/L is the serum 25(OH)D level that covers the needs of 97.5% of the population. Serum concentrations >125 nmol/L (>50 ng/mL) are associated with potential adverse effects [1] (Table 1).

Table 1: Serum 25-Hydroxyvitamin D [25(OH)D] Concentrations and Health* [1] nmol/L** ng/mL* Health status <30 <12 Associated with vitamin D deficiency, leading to rickets in infants and children and osteomalacia in adults 30 to <50 12 to <20 Generally considered inadequate for bone and overall health in healthy individuals ≥50 ≥20 Generally considered adequate for bone and overall health in healthy individuals >125 >50 Emerging evidence links potential adverse effects to such high levels, particularly >150 nmol/L (>60 ng/mL) * Serum concentrations of 25(OH)D are reported in both nanomoles per liter (nmol/L) and nanograms per milliliter (ng/mL). ** 1 nmol/L = 0.4 ng/mL.

An additional complication in assessing vitamin D status is in the actual measurement of serum 25(OH)D concentrations. Considerable variability exists among the various assays available (the two most common methods being antibody

4 based and liquid chromatography based) and among laboratories that conduct the analyses [1,9,10]. This means that compared with the actual concentration of 25(OH)D in a sample of blood serum, a falsely low or falsely high value may be obtained depending on the assay or laboratory used [11]. A standard reference material for 25(OH)D became available in July 2009 that permits standardization of values across laboratories and may improve method-related variability [1,12].

Reference Intakes Intake reference values for vitamin D and other nutrients are provided in the Dietary Reference Intakes (DRIs) developed by the Food and Nutrition Board (FNB) at the Institute of Medicine of The National Academies (formerly National Academy of Sciences) [1]. DRI is the general term for a set of reference values used to plan and assess nutrient intakes of healthy people. These values, which vary by age and gender, include:

 Recommended Dietary Allowance (RDA): average daily level of intake sufficient to meet the nutrient requirements of nearly all (97%–98%) healthy people.  Adequate Intake (AI): established when evidence is insufficient to develop an RDA and is set at a level assumed to ensure nutritional adequacy.  Tolerable Upper Intake Level (UL): maximum daily intake unlikely to cause adverse health effects [1].

The FNB established an RDA for vitamin D representing a daily intake that is sufficient to maintain bone health and normal calcium metabolism in healthy people. RDAs for vitamin D are listed in both International Units (IUs) and micrograms (mcg); the biological activity of 40 IU is equal to 1 mcg (Table 2). Even though sunlight may be a major source of vitamin D for some, the vitamin D RDAs are set on the basis of minimal sun exposure [1].

Table 2: Recommended Dietary Allowances (RDAs) for Vitamin D [1] Age Male Female Pregnancy Lactation 0–12 months* 400 IU 400 IU (10 mcg) (10 mcg) 1–13 years 600 IU 600 IU (15 mcg) (15 mcg) 14–18 years 600 IU 600 IU 600 IU 600 IU

Table 2: Recommended Dietary Allowances (RDAs) for Vitamin D [1] Age Male Female Pregnancy Lactation (15 mcg) (15 mcg) (15 mcg) (15 mcg) 19–50 years 600 IU 600 IU 600 IU 600 IU (15 mcg) (15 mcg) (15 mcg) (15 mcg) 51–70 years 600 IU 600 IU (15 mcg) (15 mcg) >70 years 800 IU 800 IU (20 mcg) (20 mcg) * Adequate Intake (AI)

Sources of Vitamin D Food: Very few foods in nature contain vitamin D. The flesh of fatty fish (such as salmon, tuna, and mackerel) and fish liver oils are among the best sources [1,13]. Small amounts of vitamin D are found in beef liver, cheese, and egg yolks. Vitamin D in these foods is primarily in the form of vitamin D3 and its metabolite 25(OH)D3 [14]. Some mushrooms provide vitamin D2 in variable amounts [15,16]. Mushrooms with enhanced levels of vitamin D2 from being exposed to ultraviolet light under controlled conditions are also available.

Fortified foods provide most of the vitamin D in the American diet [1,16]. For example, almost all of the U.S. milk supply is voluntarily fortified with 100 IU/cup [1]. (In Canada, milk is fortified by law with 35–40 IU/100 mL, as is margarine at ≥530 IU/100 g.) In the 1930s, a milk fortification program was implemented in the United States to combat rickets, then a major public health problem [1]. Other dairy products made from milk, such as cheese and ice cream, are generally not fortified. Ready-to-eat breakfast cereals often contain added vitamin D, as do some brands of orange juice, yogurt, margarine and other food products.

Both the United States and Canada mandate the fortification of infant formula with vitamin D: 40–100 IU/100 kcal in the United States and 40–80 IU/100 kcal in Canada [1].

Several food sources of vitamin D are listed in Table 3.

Table 3: Selected Food Sources of Vitamin D [13] IUs per Percent Food serving* DV** Cod liver oil, 1 tablespoon 1,360 340 Swordfish, cooked, 3 ounces 566 142 Salmon (sockeye), cooked, 3 ounces 447 112 Tuna fish, canned in water, drained, 3 ounces 154 39 Orange juice fortified with vitamin D, 1 cup (check 137 34 product labels, as amount of added vitamin D varies) Milk, nonfat, reduced fat, and whole, vitamin D-fortified, 115-124 29-31 1 cup Yogurt, fortified with 20% of the DV for vitamin D, 6 80 20 ounces (more heavily fortified yogurts provide more of the DV) Margarine, fortified, 1 tablespoon 60 15 Sardines, canned in oil, drained, 2 sardines 46 12 Liver, beef, cooked, 3 ounces 42 11 Egg, 1 large (vitamin D is found in yolk) 41 10 Ready-to-eat cereal, fortified with 10% of the DV for 40 10 vitamin D, 0.75-1 cup (more heavily fortified cereals might provide more of the DV) Cheese, Swiss, 1 ounce 6 2 * IUs = International Units. ** DV = Daily Value. DVs were developed by the U.S. Food and Drug Administration to help consumers compare the nutrient contents among products within the context of a total daily diet. The DV for vitamin D is currently set at 400 IU for adults and children age 4 and older. Food labels, however, are not required to list vitamin D content unless a food has been fortified with this nutrient. Foods providing 20% or more of the DV are considered to be high sources of a nutrient, but foods providing lower percentages of the DV also contribute to a healthful diet.

The U.S. Department of Agriculture’s (USDA’s) Nutrient Database Web site lists the nutrient content of many foods and provides a comprehensive list of foods containing vitamin D arranged by nutrient content and by food name. A growing number of foods are being analyzed for vitamin D content. Simpler and faster methods to measure vitamin D in foods are needed, as are food standard reference materials with certified values for vitamin D to ensure accurate measurements [17].

Animal-based foods can provide some vitamin D in the form of 25(OH)D, which appears to be approximately five times more potent than the parent vitamin in raising serum 25(OH)D concentrations [18]. One study finds that taking into account the serum 25(OH)D content of beef, pork, chicken, turkey, and eggs can increase the estimated levels of vitamin D in the food from two to 18 times, depending upon the food [18]. At the present time, the USDA’s Nutrient Database does not include 25(OH)D when reporting the vitamin D content of foods. Actual vitamin D intakes in the U.S. population may be underestimated for this reason.

Vitamin D Intakes and Status The National Health and Nutrition Examination Survey (NHANES), 2005–2006, estimated vitamin D intakes from both food and dietary supplements [4,19]. Average intake levels for males from foods alone ranged from 204 to 288 IU/day depending on life stage group; for females the range was 144 to 276 IU/day. When use of dietary supplements was considered, these mean values were substantially increased (37% of the U.S. population used a dietary supplement containing vitamin D.) The most marked increase was among older women. For women aged 51–70 years, mean intake of vitamin D from foods alone was 156 IU/day, but 404 IU/day with supplements. For women >70 years, the corresponding figures were 180 IU/day to 400 IU/day [1].

Comparing vitamin D intake estimates from foods and dietary supplements to serum 25(OH)D concentrations is problematic. One reason is that comparisons can only be made on group means rather than on data linked to individuals. Another is the fact that sun exposure affects vitamin D status; serum 25(OH)D levels are generally higher than would be predicted on the basis of vitamin D intakes alone [1]. The NHANES 2005–2006 survey found mean 25(OH)D levels exceeding 56 nmol/L (22.4 ng/mL) for all age-gender groups in the U.S. population. (The highest mean was 71.4 nmol/L [28.6 ng/mL] for girls aged 1–3 years, and the lowest mean was 56.5 nmol/L [22.6 ng/mL] for women aged 71 and older. Generally, younger people had higher levels than older people, and males had slightly higher levels than females.) 25(OH)D levels of approximately 50 nmol/L

(20 ng/mL) are consistent with an intake of vitamin D from foods and dietary supplements equivalent to the RDA [1].

Over the past 20 years, mean serum 25(OH)D concentrations in the United States have slightly declined among males but not females. This decline is likely due to simultaneous increases in body weight, reduced milk intake, and greater use of sun protection when outside [20].

Vitamin D Deficiency Nutrient deficiencies are usually the result of dietary inadequacy, impaired absorption and use, increased requirement, or increased excretion. A vitamin D deficiency can occur when usual intake is lower than recommended levels over time, exposure to sunlight is limited, the kidneys cannot convert 25(OH)D to its active form, or absorption of vitamin D from the digestive tract is inadequate. Vitamin D-deficient diets are associated with milk allergy, lactose intolerance, ovo-vegetarianism, and veganism [1].

Rickets and osteomalacia are the classical vitamin D deficiency diseases. In children, vitamin D deficiency causes rickets, a disease characterized by a failure of bone tissue to properly mineralize, resulting in soft bones and skeletal deformities [22]. Rickets was first described in the mid-17th century by British researchers [22,21]. In the late 19th and early 20th centuries, German physicians noted that consuming 1–3 teaspoons/day of cod liver oil could reverse rickets [21]. The fortification of milk with vitamin D beginning in the 1930s has made rickets a rare disease in the United States, although it is still reported periodically, particularly among African American infants and children [3,22,23].

Prolonged exclusive breastfeeding without the AAP-recommended vitamin D supplementation is a significant cause of rickets, particularly in dark-skinned infants breastfed by mothers who are not vitamin D replete [24]. Additional causes of rickets include extensive use of sunscreens and placement of children in daycare programs, where they often have less outdoor activity and sun exposure [22,23]. Rickets is also more prevalent among immigrants from Asia, Africa, and the Middle East, possibly because of genetic differences in vitamin D metabolism and behavioral differences that lead to less sun exposure.

In adults, vitamin D deficiency can lead to osteomalacia, resulting in weak bones [1,8]. Symptoms of bone pain and muscle weakness can indicate inadequate vitamin D levels, but such symptoms can be subtle and go undetected in the initial stages.

Risk of Vitamin D Inadequacy Obtaining sufficient vitamin D from natural food sources alone is difficult. For many people, consuming vitamin D-fortified foods and, arguably, being exposed to some sunlight are essential for maintaining a healthy vitamin D status. In some groups, dietary supplements might be required to meet the daily need for vitamin D.

Orthodontics Definition: Orthodontia,also called orthodontics and dentofacial orthopedics, is a specialty field of dentistry that deals primarily with malpositioned teeth and the jaws: their diagnosis, prevention and correction. An orthodontist is a specialist who has undergone special training in a dental school or college after they have graduated in dentistry. The field was established by the efforts of pioneering orthodontists such as Edward Angle and Norman William Kingsley. Importance of Orthodontics : The history of orthodontics has been intimately linked with the history of dentistry for more than 2000 years.[25] Dentistry had its origins as a part of medicine. According to the American Association of Orthodontists, archaeologists have discovered mummified ancients with metal bands wrapped around individual teeth.[26] Malocclusion is not a disease, but abnormal alignment of the teeth and the way the upper and lower teeth fit together. The prevalence of malocclusion varies,[27][28] but using orthodontic treatment indices,[29][30] which categorize malocclusions in terms of severity, it can be said that nearly 30% of the population present with malocclusions severe enough to benefit from orthodontic treatment.[31] Orthodontic treatment can focus on dental displacement only, or deal with the control and modification of facial growth. In the latter case it is better defined as "dentofacial orthopedics". In severe malocclusions that can be a part of craniofacial abnormality, management often requires a combination of orthodontics with headgear or reverse pull facemask and / or jaw surgery or orthognathic surgery.[32][33] This often requires additional training, in addition to the formal three-year specialty training. For instance, in the United States, orthodontists get at least another year of training in a form of fellowship, the so-called 'Craniofacial Orthodontics', to receive additional training in the orthodontic management of craniofacial anomalies.[34][35]

When there is a maxillary overjet, or Class II occlusion, functional appliances can be used to correct the occlusion. These may be fixed or removable.[36] Fixed dental braces are wires that are inserted into brackets secured to the teeth on the labial or lingual surface (lingual braces) of teeth. Other classes of functional appliances include removable appliances and over the head appliances, and these functional appliances are used to redirect jaw growth.[37] Post treatment retainers are frequently used to maintain the new position of the dentition. During fixed orthodontic treatment, metal wires are held in place by elastic bands on orthodontic brackets (braces) on each tooth and inserted into bands around the molars. The wires can be made from stainless steel, nickel-titanium (Ni-Ti)[38] or a more aesthetic ceramic material. Ni-Ti is used as the initial arch wire as it has good flexibility, allowing it to exert the same forces regardless of how much it has been deflected. There is also heat activated Ni-Ti wire which tightens when it is heated to body temperature.[39] The arch wires interact with the brackets to move teeth into the desired positions. Fixed orthodontic appliances aid tooth movement, and are used when a 3-D movement of the tooth is required in the mouth and multiple tooth movement is necessary. Ceramic fixed appliances can be used which more closely mimic the tooth colour than the metal brackets. Some manufacturers offer self-litigating fixed appliances where the metal wires are held by an integral clip on the bracket themselves. These can be supplied as either metal or ceramic.[40] The surfaces of the teeth are etched, and brackets are attached to the teeth with an adhesive that is durable enough to withstand the orthodontic forces, but is able to be removed at the end of treatment without damaging the tooth. Currently there is not enough evidence to determine whether self-etch preparations or conventional etchants cause less decalcification around the bonding site and if there is a difference between them in bond failure rate.[41] The bonding material must also adhere to the surface of the tooth, be easy to use and preferably protect the tooth surface against caries (decay) as the orthodontic appliance becomes a trap for plaque. Currently a resin/matrix adhesive which is command light cured is most commonly used. This is similar to composite filling material.[42] Anchorage for the appliance prevents unwanted movement of teeth and it can come from the headgear worn, the palate, or surgical implants.[43] For young patients with mild to moderate Angle Class III malocclusions (prognathism), a functional appliance is sufficient for correction. Examples of functional appliances are: facemask, chin-cup, tandem traction bow or headgear.[44] As the malocclusion increases, orthognathic surgery might be

11 required. This treatment comes in three stages. Prior to surgery there is orthodontic treatment to align teeth into their post-surgery occlusion positions. The second stage is surgery such as a mandibular step osteotomy or sagittal/bilateral sagittal split osteotomy [45] depending on whether one or both sides of the mandible are affected. The bone is broken during surgery and is stabilised with titanium plates and screws, or bioresorbable plates to allow for healing to take place.[46] The third stage of treatment is post-surgical orthodontic treatment to move the teeth into their final positions to ensure the best possible occlusion.[47] A posterior crossbite malocclusion may be corrected using the quad helix appliance or removable appliances during the early mixed dentition stage (eight to 10 years), and more research is required for determining whether any intervention provides greater results than any other for later stages of dentition development. These crossbites are when the maxillary teeth or jaw is narrower than the mandibular, and can occur unilaterally or bilaterally. .[48] Treatment involves the expansion of the maxillary arch to restore functional occlusion, which can either be 'fast' at 0.5mm per day or 'slow' at 0.5mm per week. Palatal expansion can be achieved using either fixed or removable appliances.[48] Banded maxillary expansion involves metal bands bonded to individual teeth which are attached to braces, and bonded maxillary expansion is an acrylic splint with a wire framework attached to a screw in the palatal mid-line, which can be turned and opened to expand the maxilla. Removable functional appliances are useful for simple movements and can aid in altering the angulation of a tooth: retroclining maxillary teeth and proclining mandibular teeth; help with expansion; and overbite reduction.[49] Headgear works by applying forces externally to the back of the head, moving the molar teeth posteriorly (distalising) to allow space for the anterior teeth and relieving the overcrowding [50] or to help with anchorage problems. The facemask aims to pull maxillary teeth and jaw forward and downwards to meet the mandible through a balanced force applied to the upper teeth. The mask rests on the forehead and chin of the wearer, and connects to the maxillary teeth with elastic bands.[44] Some removable appliances have a flat acrylic bite plane to allow full disocclusion between the maxillary and mandibular teeth to aid in movement during treatment. An example of this is the Clark Twin Block. This design has two blocks of acrylic which disocclude the teeth and protrude the mandible. It is used to treat Class II malocclusion. [49]

Vacuum-formed aligners such as Invisalign consist of clear, flexible, plastic trays that move teeth incrementally to reduce mild overcrowding and can improve mild irregularities and spacing. They are not suitable for use in complex orthodontic cases and cannot produce body movement. They are worn full time by the patient apart from when eating and drinking.[50] A large benefit of these types of orthodontic appliance are that they suitable for use when the patient has porcelain veneers: as metal brackets cannot be bonded to the veneer surface.[49] Relationship between orthodontics and vitamine D: Systemic or local application of medications and the intake of dietary supplements, such as vitamins and minerals, intentionally or unintentionally may have an impact on orthodontic tooth movement and orthodontic treatment [51] . Usually the effects are mainly two categories of effects: those related to general bone physiology in terms of bone density, bone mineralization, bone turnover rate, and osteoclast differentiation; and clinical side effects induced by medications, such as gingival hyperplasia, xerostomia, and external root resorption [52] . Vitamin D Vitamin D is collective name given to anti-rachitic substances synthesized in the body and found in dietary sources activated by UV radiation [53] . 1,25 dihydroxycholecalciferol is the most active hormonal form of vitamin D. It regulates calcium and phosphate serum levels by promoting their intestinal absorption and reabsorption in the kidneys. Furthermore, it promotes bone deposition and inhibits PTH release. Italso plays a role in the immune response by promoting immunosuppression [52] . In 1988, Collins and Sinclair demonstrated that intraligamentous injections of a vitamin D metabolite, 1,25- dihydroxycholecalciferol, caused an increase in the number of osteoclasts and the amount of tooth movement during canine retraction with light forces in cats [54] . Similar results were observed by Takano-Yamamoto and colleagues in 1992. [55] . In 2004, Kale and colleagues observed that local applications of vitamins enhanced the rate of tooth movement in rats due to the well-ba lanced bone turnover induced by vitamin D [56] . Stimulatory action of vitamin D on osteoblasts can help stabilize orthodontic tooth movement. In 1976, Bran and colleagues reported that rats treated with vitamin D showed increased bone formation on the pressure side of the periodontal ligament after application of orthodontic forces. In 2004, Kawakami observed an increase in the appositional rate on alveolar bone after orthodontic force application; they suggested that local application of vitamin D could intensify the re-establishment of supporting alveolar bone, after orthodontic treatment [57] . Parathyroid Hormone PTH is secreted by the parathyroid glands. Its main effect is an increase in the concentration of calcium in the blood;

13 consequently, it stimulates bone resorption [58]. More recently, Soma and colleagues observed an increased rate of tooth movement in rats treated with PTH, whether administered systemically [59] or locally [60]. These results indicate that orthodontists should take note of patientsbeing treated with PTH-for example, in cases of severe osteoporosis [61] . Estrogen Estrogen is considered to be the most important hormone affecting the bone metabolism in women. It inhibits the production of various cytokines which are involved in bone resorption by stimulating osteoclast formation and osteoclast bone resorption. It also inhibits osteoblast’s responsiveness to PTH. Estrogens do not have any anabolic effects on bone tissue; they directly stimulate the bone forming activity of osteoblasts [153] . Studies have shown that estrogens decrease the velocity of tooth movement [62]. Estrogen supplementation was used to over overcome postmenopausal problems might slow down the rate of OTM [58] . Corticosteroids Corticosteroids are a class of steroid hormones, produced in the adrenal cortex. They are involved in many physiologic systems, such as stress response, inflammatory and immune responses, carbohydrate metabolism, protein catabolism, and blood electrolyte levels [52] . Evidence indicates that the main effect of corticosteroid on bone tissue is direct inhibition of osteoblastic function and thus decreases total bone formation. Decrease in bone formation is due to elevated PTH levels caused by inhibition of intestinal calcium absorption which is induced by corticosteroids [51] . Corticosteroids increase the rate of tooth movement, and since new bone formation can be difficult in a treated patient, they decrease the stability of tooth movement and stability of orthodontic treatment in a general [63] . Bisphosphonates There are two classes of bisphosphonates: nitrogen containing andnon-nitrogen containing bisphosphonates. They act on different pathways, but their final effect is the same. They all inhibit bone resorption, although their effectiveness differs considerably. They are used primarily for the prevention and therapy of osteoporosis, Paget‘s disease, bone metastases, and bone pain from some types of cancer [64,65]. Studies have shown that bisphosphonates inhibit orthodontic tooth movement and delay the orthodontic treatment [66]. A serious drawback of long-term use of bisphosphonates is that they can cause osteonecrosis, especially in the alveolar bones of the maxilla and the mandible [65]. Calcitonin Calcitonin is a peptide hormone secreted by thyroid in response to hypocalcaemia .It is produced by parafollicular ‘C’ cells of thyroid. Synthesis and secretion of Calcitonin is regulated by plasma calcium concentration. Rise in plasma calcium increases, while fall in plasma calcium decreases Calcitonin release. Calcitonin inhibits proximal tubular calcium and phosphate reabsorption by direct action on kidney. Calcitonin is used in the treatment of hypercalcemia, osteoporosis and paget’s disease of bone. Calcitonin inhibits bone resorption by direct action on osteoclasts, decreasing their ruffled surface which forms contacts with resorptive pit. It also

14 stimulates the activity of osteoblasts. Because of its physiological role, it is considered to inhibit the tooth movement; consequently, delay in orthodontic treatment can be expected [51, 67] . Fluoride Fluoride is one of the trace elements having an effect on tissue metabolism. Fluoride increases bone mass and mineral density, and because of these skeletalactions, it has been used in the treatment of metabolic bone disease, osteoporosis. Even a very active caries treatment with sodium fluoride during orthodontic treatment may delay orthodontic tooth movement and increase the time of orthodontic treatment. Soudium fluoride has been shown to inhibit the osteoclastic activity and reduce the number of active osteoclasts [68] . Paracetamol Paracetamol (acetaminophen) is a commonly used analgesic. It lacks antiinflammatory properties. Therefore, it does not belong with NSAIDs, although their chemical structures are comparable. Other important differences are that paracetamol has almost no effect on blood clotting and no detrimental effects on the stomach lining. These differences are related to its mode of action [52,67] . Paracetamol does not affect the rate of OTM with low dosages, studies suggest that it should be the analgesic of choice for managing pain associated with orthodontic therapy [69,70] .

Orthodontists must know that teeth move at different rates and every individual has differing responses to orthodontic treatment. Many of these differences are caused by changes in bone remodeling process by various drugs and systemic factors. Orthodontists should assume that many patients are taking prescription or medications regularly. The orthodontist must identify these patients by carefully questioning them about their medication history and their consumption of food supplements and it should consider a part of every orthodontic diagnosis [71]. References

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