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
Orthodontics, KSR
Institute of Dental
Science and Research,
Tiruchengode,
Tamil Nadu, India
Address for correspondence:
Dr. Muthukumar Karthi,
E-mail: drkarthiortho@gmail.
com
ABSTRACT
Orthodontic tooth movement is basically a biological response toward a mechanical force. The movement is
induced by prolonged application of controlled mechanical forces, which create pressure and tension zones in
the periodontal ligament and alveolar bone, causing remodeling of tooth sockets. Orthodontists often prescribe
drugs to manage pain from force application to biologic tissues. Nonsteroidal anti-inflammatory drugs (NSAIDs)
are the drugs usually prescribed. NSAIDs block prostaglandin synthesis and result in slower tooth movement.
Prostaglandins have been found to play a direct role in bone resorption. Aspirin, acetaminophen, ibuprofen,
diclofenac, vadecoxib, and celecoxib are the commonly prescribed drugs. Acetaminophen is the drug of choice
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

O rthodontic tooth movement is based on the biologic

principle that prolonged pressure on the teeth results in
remodeling of periodontal structures including the alveolar bone
and periodontal ligament. The early phase of orthodontic tooth
movement involves acute inflammatory response characterized
by periodontal vasodilatation. There is inflammatory response
surrounding the tissues where osteoblastic and osteoclastic
activities are carried out.[1,2] Depending on the alterations in the
periodontium, pain and discomfort are the common experiences
among orthodontic patients. Reported pain and discomfort is
generally the highest during the first 24 h after the application
of an orthodontic force. The periodicity of these complaints
peaks at 24 h, but decreases to baseline levels by 7 days.[3]
of prostaglandins (PGs) from arachidonic acid in the cellular
plasma membrane. PGs such as PGE1 and PGE2 are important
mediators of bone resorption.[6]
Several authors have published on the effects of systemic or
local application of medicaments and the intake of dietary
supplements, such as vitamins and minerals, during orthodontic
tooth movement.[4] Most reviews did not report the effect of
medications or supplements on the rate of orthodontic tooth
movement. The medications can affect the rate of orthodontic
tooth movement.[7] We performed a systematic literature review
on the effects of NSAIDs in particular on orthodontic tooth
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
cyclooxygenase (COX), which modulates the transformation recruitment of osteoclast and osteoblast progenitors.[8]

NSAIDs have been classified as analgesic 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
induced by cytokines and is important in the development
of inflammation.[11-14] NSAIDs have been developed to target
these cyclooxygenases, including acetylsalicylate (aspirin),
ibuprofen, etc.[15]
are better than rofecoxib in orthodontic tooth movement.[23]
The various NSAIDs and their effects on bone metabolism
and orthodontic tooth movement are given in Tables 2 and 3,
respectively.

Non-selective COX inhibition includes agents such as aspirin, Table 1: Classification of NSAIDs
acetaminophen, indomethacin, and naproxen, which provide Analgesics and anti-inflammatory
effective pain relief for inflammatory conditions. All NSAIDs have Salicylates
more or less similar effects and mechanism of action. They suppress
Pyrazolone derivatives
the production of prostanoids (thromboxanes, prostacyclines,
Indole derivatives
and PGs) because of their inhibition of COX1 and COX2, which Propionic acid derivatives
are essential in the synthetic pathways of prostanoids. COX1 is a
constitutive form, whereas COX2 is inducible. Acetylsalicylic acid Anthranilic acid derivatives
inhibits both types of COX in a non-competitive and irreversible Arylacetic acid derivatives
way.[16] Thus, it effectively inhibits PG synthesis. Oxicam 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
lining, whereas COX2 is induced during inflammatory reaction, Pyrazolone derivatives
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
paraminophenols, which by not inhibiting PGs or by inhibiting Salicylates Aspirin
them slightly, does not have an effect on orthodontic tooth
movement. Its antipyretic and analgesic activities are the Diflunisal
Arylalkanoic acids Diclofenac
same as aspirin. However, its mechanism of action has not
been determined, and it is supposed that its analgesic effect
is produced at the central nervous system level and does not Indomethacin
act over cell membranes, as those described previously do.[19] Arylalkanoic acids Ibuprofen
(profens)
Acetaminophen is considered to be a very weak PG inhibitor and Flurbiprofen
Naproxen
possesses no significant anti-inflammatory effects. It has no effect
on the rate of tooth movement in rabbits undergoing orthodontic Oxicams Piroxicam
tooth movement. Acetaminophen, a proven analgesic that lacks Meloxicam
the anti-inflammatory properties of NSAIDs, appears to be the Coxibs Celexocib
drug of choice to relieve orthodontic pain.[21-25] Ibuprofen showed Rofecoxib
Valdecoxib
reduced rate of orthodontic tooth movement.[22]
Aspirin, salicylamide, benorylate,
diflunisal
Phenylbutazone, oxyphenbutazone
Indomethacin, sulindac
Ibuprofen, naproxen, ketoprofen,
fenoprofen, flurbiprofen
Mephenmic acid, enfenamic acid
Diclofenac, tolmetin
Piroxicam, tenoxicam
Ketorolac
Paracetamol (acetaminophen)
Metamizol (dipyrone),
propyphenazone
Nefopam
Brand names
Aspirin, Acetal, Acetophen, over
100 more
Dolobid
Voltaren, Voltarol, Diclon,
Dicloflex, Difen, Difene, Cataflam,
Pennsaid, Rhumalgan, Abitren
Indocid, Indocid, Indochron
Nurofen, Advil, Brufen, Dorival,
Panafen, Ibumetin, Ibuprom
ANSAID
Aleve, Anaprox, Naprogesic,
Naprosyn, Naprelan
Feldene
Movalis, Melox, Recoxa, Mobic
Celebrex, Celebra
Vioxx, Ceoxx, Ceeoxx
Bextra

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
Diclofenac Reduced bone Reduced tooth
Rofecoxib completely inhibited orthodontic tooth movement
resorption movement
in rats, whereas celecoxib and parecoxib did not.[23] 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
Acetaminophen[21-25] and celecoxib[23,26] are the NSAIDs of
choice for relief of orthodontic pain without affecting the rate
of orthodontic tooth movement.[29-33]
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Source of Support: Nil, Conflict of Interest: None declared.
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