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Dental Science - Review Article

NSAIDs in orthodontic tooth movement

Muthukumar Karthi, Gobichettipalyam Jagtheeswaran Anbuslevan, Kullampalyam Palanisamy Senthilkumar, Senthilkumar Tamizharsi, Subramani Raja, Krishnan Prabhakar

Department of ABSTRACT Orthodontics, KSR Orthodontic tooth movement is basically a biological response toward a mechanical force. The movement is Institute of Dental induced by prolonged application of controlled mechanical forces, which create pressure and tension zones in Science and Research, Tiruchengode, the periodontal ligament and alveolar bone, causing remodeling of tooth sockets. Orthodontists often prescribe Tamil Nadu, India to manage pain from force application to biologic tissues. Nonsteroidal anti-inflammatory drugs (NSAIDs) are the drugs usually prescribed. NSAIDs block synthesis and result in slower tooth movement. Address for correspondence: have been found to play a direct role in bone resorption. , acetaminophen, , Dr. Muthukumar Karthi, , vadecoxib, and are the commonly prescribed drugs. Acetaminophen is the of choice E-mail: drkarthiortho@gmail. com for orthodontic pain without affecting orthodontic tooth movement.

Received : 01-12-11 Review completed : 02-01-12 Accepted : 26-01-12 KEY WORDS: Acetaminophen, NSAIDs, prostaglandins

rthodontic tooth movement is based on the biologic of prostaglandins (PGs) from in the cellular O principle that prolonged pressure on the teeth results in plasma membrane. PGs such as PGE1 and PGE2 are important remodeling of periodontal structures including the alveolar bone mediators of bone resorption.[6] and periodontal ligament. The early phase of orthodontic tooth movement involves acute inflammatory response characterized Several authors have published on the effects of systemic or by periodontal vasodilatation. There is inflammatory response local application of medicaments and the intake of dietary surrounding the tissues where osteoblastic and osteoclastic supplements, such as vitamins and minerals, during orthodontic activities are carried out.[1,2] Depending on the alterations in the tooth movement.[4] Most reviews did not report the effect of periodontium, pain and discomfort are the common experiences medications or supplements on the rate of orthodontic tooth among orthodontic patients. Reported pain and discomfort is movement. The medications can affect the rate of orthodontic generally the highest during the first 24 h after the application tooth movement.[7] We performed a systematic literature review of an orthodontic force. The periodicity of these complaints on the effects of NSAIDs in particular on orthodontic tooth peaks at 24 h, but decreases to baseline levels by 7 days.[3] movement.

The most common group of medications used in orthodontics Research in molecular biology on orthodontic tooth movement for pain relief consists of nonsteroidal anti-inflammatory drugs has identified the main mediators involved in the complex (NSAIDs).[4,5] These drugs function by inhibition of enzyme process of extravasation, inflammatory cell chemotaxis, and the (COX), which modulates the transformation recruitment of osteoclast and osteoblast progenitors.[8]

NSAIDs have been classified as and anti-inflammatory, Access this article online and analgesic but poorly anti-inflammatory [Table 1].[9] Quick Response Code: Website: Though NSAIDs are chemically disparate, they produce their www.jpbsonline.org therapeutic effects by the common ability to inhibit the activity of the COX enzymes.[10] DOI: 10.4103/0975-7406.100280 Two isoforms of mammalian COX have been described: the constitutive COX1 and the inducible COX2. COX1 is considered

How to cite this article: Karthi M, Anbuslevan GJ, Senthilkumar KP, Tamizharsi S, Raja S, Prabhakar K. NSAIDs in orthodontic tooth movement. J Pharm Bioall Sci 2012;4:304-6.

 S304 Journal of Pharmacy and Bioallied Sciences Vol 4 August 2012 Supplement 2 - Part 3 Karthi: NSAIDs in orthodontics  important in tissue homeostasis. COX2 is transcriptionally are better than in orthodontic tooth movement.[23] induced by cytokines and is important in the development of inflammation.[11-14] NSAIDs have been developed to target The various NSAIDs and their effects on bone metabolism these , including acetylsalicylate (aspirin), and orthodontic tooth movement are given in Tables 2 and 3, ibuprofen, etc.[15] respectively.

Non-selective COX inhibition includes agents such as aspirin, Table 1: Classification of NSAIDs acetaminophen, indomethacin, and , which provide and anti-inflammatory effective pain relief for inflammatory conditions. All NSAIDs have Salicylates Aspirin, salicylamide, benorylate, more or less similar effects and mechanism of action. They suppress the production of (, prostacyclines, derivatives , Indole derivatives Indomethacin, and PGs) because of their inhibition of COX1 and COX2, which derivatives Ibuprofen, naproxen, , are essential in the synthetic pathways of prostanoids. COX1 is a , constitutive form, whereas COX2 is inducible. Acetylsalicylic acid Anthranilic acid derivatives Mephenmic acid, enfenamic acid inhibits both types of COX in a non-competitive and irreversible Arylacetic acid derivatives Diclofenac, way.[16] Thus, it effectively inhibits PG synthesis. derivatives , Pyrrolo-pyrrole derivative Analgesic but poorly anti- In the early 1990s, it became apparent that COX1 mediates inflammatory the synthesis of PGs responsible for the protection of stomach Para-aminophenol derivative (acetaminophen) lining, whereas COX2 is induced during inflammatory reaction, Pyrazolone derivatives Metamizol (dipyrone), thereby mediating the synthesis of PGs responsible for pain. Benzoxazocine derivative Acetylsalicylic acid and flurbiprofen,[17] indomethacin,[18] and ibuprofen[19] have shown reduction in the rate of orthodontic tooth movement.[20] Table 2: Groups and subgroups of NSAIDs, and some well- known brand names Acetaminophen is an NSAID belonging to the family of Group Subgroup Brand names paraminophenols, which by not inhibiting PGs or by inhibiting Salicylates Aspirin Aspirin, Acetal, Acetophen, over them slightly, does not have an effect on orthodontic tooth 100 more movement. Its and analgesic activities are the Diflunisal Dolobid same as aspirin. However, its mechanism of action has not Arylalkanoic acids Diclofenac Voltaren, Voltarol, Diclon, Dicloflex, Difen, Difene, Cataflam, been determined, and it is supposed that its analgesic effect Pennsaid, Rhumalgan, Abitren is produced at the central nervous system level and does not Indomethacin Indocid, Indocid, Indochron act over cell membranes, as those described previously do.[19] Arylalkanoic acids Ibuprofen Nurofen, Advil, Brufen, Dorival, (profens) Panafen, Ibumetin, Ibuprom Acetaminophen is considered to be a very weak PG inhibitor and Flurbiprofen ANSAID Naproxen Aleve, Anaprox, Naprogesic, possesses no significant anti-inflammatory effects. It has no effect Naprosyn, Naprelan on the rate of tooth movement in rabbits undergoing orthodontic Piroxicam Feldene tooth movement. Acetaminophen, a proven analgesic that lacks Movalis, Melox, Recoxa, Mobic the anti-inflammatory properties of NSAIDs, appears to be the Coxibs Celexocib Celebrex, Celebra drug of choice to relieve orthodontic pain.[21-25] Ibuprofen showed Rofecoxib Vioxx, Ceoxx, Ceeoxx Bextra reduced rate of orthodontic tooth movement.[22]

Carlos et al. in their study of orthodontic tooth movement Table 3: Effects of NSAIDs on orthodontic tooth movement after inhibition of COX2 found that both diclofenac and Nonsteroidal anti- Effects on bone Effects on tooth reofecoxib inhibited tooth movement.[23] Coxibs possess inflammatory drugs metabolism movement minimal NSAID typical toxicity with full anti-inflammatory Aspirin Reduced bone Reduced tooth efficacy and have been used for orthodontic treatment of pain.[18] resorption movement Rofecoxib completely inhibited orthodontic tooth movement Diclofenac Reduced bone Reduced tooth [23] resorption movement in rats, whereas celecoxib and did not. Long-term Indomethacin Reduced bone Reduced tooth effect of celecoxib has shown to reduce the rate of orthodontic resorption movement tooth movement.[26] Acetaminophen is still the drug of choice for Ibuprofen Reduced bone Reduced tooth treating the discomfort of tooth movement because no advantages resorption movement are derived from the use of new COX2 inhibiting drugs.[27] Flurbiprofen Reduced bone Reduced tooth resorption movement Naproxen Reduced bone Reduced tooth Recently, rofecoxib and valdecoxib were withdrawn from US resorption movement and European markets by their manufacturer because of reports Celecoxib No effect on bone No influence on of increased cardiovascular events and skin rashes, respectively. resorption tooth movement Another COX2 inhibitor, celecoxib, is currently FDA approved Acetaminophen No effect on bone No influence on resorption tooth movement for treatment of pain syndromes.[28] Celecoxib and parecoxib

Journal of Pharmacy and Bioallied Sciences Vol 4 August 2012 Supplement 2 - Part 3 S305   Karthi: NSAIDs in orthodontics

Conclusion Orthod 1984;6:175-82. 18. Giunta D, Keller J, Nielsen FF, Melsen B influence of in bone turnover related to orthodontic tooth movement in miniature [21-25] [23,26] Acetaminophen and celecoxib are the NSAIDs of pigs. Am J Orthod Dentofacial Orthop 1995;108:361-6. choice for relief of orthodontic pain without affecting the rate 19. Arias OR, Marquez-Orozco MC. Aspirin, acetaminophen, and of orthodontic tooth movement.[29-33] ibuprofen: Their effects on orthodontic tooth movement. Am J Orthod Dentofacial Orthop 2006;130:364-70. 20. Kehoe MJ, Cohen SM, Zarrinnia K, Cowan A. The effect of References acetaminophen, ibuprofen, and on synthesis and the degree and rate of orthodontic tooth movement. 1. Proffit W. Contemporary orthodontics. 3rd ed. St Louis: Mosby; 2000. Angle Orthod 1996;66:339-49. p. 302-5. 21. Roche JJ, Cisneros GJ, Acs G. The effect of acetaminophen on tooth 2. Graber, Vanasdrall, Vig. Orthodontics current principles and movement in rabbits. Angle Orthod 1997;67:231-6. techniques 2009. 22. Reza S, Larry JO, W. Craig, Sheldon MN Comparison of the efficacy 3. Grieve WG, Johnson GK, Moore RN, Reinhardt RA, DuBois LM. of ibuprofen and acetaminophen in controlling pain after orthodontic tooth movement. Am J Orthod Dentofacial Orthop 2009;135:516-2. Prostaglandin E and IL-1β levels in gingival crevicular fluid during human orthodontic tooth movement. Am J Orthod Dentofacial Orthop 23. Felix de Carlos, Juan Cobo Orthodontic tooth movement after 1994;105:369-74. inhibition of cyclooxygenase-2. Am J Orthod Dentofacial Orthop 4. Gameiro GH, Pereira-Neto JS, Magnani MB, Nouer DF. The influence 2006;129:402-6. of drugs and systemic factors on orthodontic tooth movement. J Clin 24. Fidan Alakus S, Elchin Esenlik Pakistan Oral Dent J 2010;30:45-50 Orthod 2007;41:73-8. 25. Carmen G, Hitoshi H, Ken M, Tatsunori S, Joseph HY. Effects of 5. Krishnan V. Orthodontic pain: From causes to management- a review. Steroidal and Non–steroidal drugs on tooth movement and root Eur J Orthod 2007;29:170-9. resorption in rat molar. Angle Orthod 2009;29:715-25. 6. De Carlos F, Cobo J, Diaz-Esnal B, Arguelles J, Vijande M, Costales M. 26. Gustavo HG, Darcy FN, Joao Sarmento PN, Vania CS, Eduardo Orthodontic tooth movement after inhibition of cyclooxygenase-2. DA, Pedro DN, et al. Effects of short- and long-term celecoxib on Am J Orthod Dentofacial Orthop 2006;129:402-6. orthodontic tooth movement. Angle orthod 2008;78:860-5. 7. Krishnan V, Davidovitch Z. The effect of drugs on orthodontic tooth 27. de Carlos F, Cobo J, Diaz Esnal B, Arquelles J, Vijiande M, Costales movement. Orthod Craniofac Res 2006;9:163-71. M. Orthodontic tooth movement after inhibition of cyclooxygenase 8. Krishnan V, Davidovitch Z. Cellular, molecular and tissue level reaction to 2. Am J Orthod Dentofacial Orthop 2006;129:402-6. orthodontic forces. Am J Orthod Dentofacial Orthop 2006;129:469-72. 28. 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