NSAIDs in orthodontic tooth movement.

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.

Orthodontic 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.[12] 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]

The most common group of medications used in orthodontics for pain relief consists of nonsteroidal anti-inflammatory drugs (NSAIDs).[45] These drugs function by inhibition of enzyme cyclooxygenase (COX), which modulates the transformation 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.

Research in molecular biology on orthodontic tooth movement has identified the main mediators involved in the complex process of extravasation, inflammatory cell chemotaxis, and the recruitment of osteoclast and osteoblast progenitors.[8]

NSAIDs have been classified as analgesic and anti-inflammatory, and analgesic but poorly anti-inflammatory [Table 1].[9]

Table 1

Classification of NSAIDs

Though NSAIDs are chemically disparate, they produce their therapeutic effects by the common ability to inhibit the activity of the COX enzymes.[10]

Two isoforms of mammalian COX have been described: the constitutive COX1 and the inducible COX2. COX1 is considered 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]

Non-selective COX inhibition includes agents such as aspirin, acetaminophen, indomethacin, and naproxen, which provide effective pain relief for inflammatory conditions. All NSAIDs have more or less similar effects and mechanism of action. They suppress the production of prostanoids (thromboxanes, prostacyclines, and PGs) because of their inhibition of COX1 and COX2, which are essential in the synthetic pathways of prostanoids. COX1 is a constitutive form, whereas COX2 is inducible. Acetylsalicylic acid inhibits both types of COX in a non-competitive and irreversible way.[16] Thus, it effectively inhibits PG synthesis.

In the early 1990s, it became apparent that COX1 mediates the synthesis of PGs responsible for the protection of stomach lining, whereas COX2 is induced during inflammatory reaction, thereby mediating the synthesis of PGs responsible for pain. Acetylsalicylic acid and flurbiprofen,[17] indomethacin,[18] and ibuprofen[19] have shown reduction in the rate of orthodontic tooth movement.[20]

Acetaminophen is an NSAID belonging to the family of paraminophenols, which by not inhibiting PGs or by inhibiting them slightly, does not have an effect on orthodontic tooth movement. Its antipyretic and analgesic activities are the 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 act over cell membranes, as those described previously do.[19]

Acetaminophen is considered to be a very weak PG inhibitor and possesses no significant anti-inflammatory effects. It has no effect on the rate of tooth movement in rabbits undergoing orthodontic tooth movement. Acetaminophen, a proven analgesic that lacks the anti-inflammatory properties of NSAIDs, appears to be the drug of choice to relieve orthodontic pain.[21-25] Ibuprofen showed reduced rate of orthodontic tooth movement.[22]

Carlos et al. in their study of orthodontic tooth movement after inhibition of COX2 found that both diclofenac and reofecoxib inhibited tooth movement.[23] Coxibs possess minimal NSAID typical toxicity with full anti-inflammatory efficacy and have been used for orthodontic treatment of pain.[18] Rofecoxib completely inhibited orthodontic tooth movement in rats, whereas celecoxib and parecoxib did not.[23] Long-term effect of celecoxib has shown to reduce the rate of orthodontic tooth movement.[26] Acetaminophen is still the drug of choice for treating the discomfort of tooth movement because no advantages are derived from the use of new COX2 inhibiting drugs.[27]

Recently, rofecoxib and valdecoxib were withdrawn from US and European markets by their manufacturer because of reports of increased cardiovascular events and skin rashes, respectively. Another COX2 inhibitor, celecoxib, is currently FDA approved for treatment of pain syndromes.[28] Celecoxib and parecoxib 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.

Table 2

Groups and subgroups of NSAIDs, and some well-known brand names

Table 3

Effects of NSAIDs on orthodontic tooth movement

Conclusion

Acetaminophen[21-25] and celecoxib[2326] are the NSAIDs of choice for relief of orthodontic pain without affecting the rate of orthodontic tooth movement.[29-33]