This document discusses the role of various drugs used in orthodontic treatment. It covers how prostaglandins and leukotrienes are involved in the inflammatory response and can stimulate bone resorption and tooth movement. It describes how analgesics like NSAIDs can reduce pain but also slow tooth movement by inhibiting prostaglandin synthesis. Specifically, it outlines the effects of aspirin, acetaminophen, Cox-2 inhibitors, and various other NSAIDs. It also discusses how corticosteroids can increase tooth movement but decrease stability, and the side effects of long-term use. Finally, it briefly mentions bisphosphonates and their binding to hydroxyapatite.

1. Dr. DHANASEKARAN.R
FIRST YEAR MDS
Dept. of Orthodontics &
Dentofacial Orthopaedics
ROLE OF DRUGS IN
ORTHODONDICS

2. CONTENTS:
Introduction
Prostaglandins
Analgesics and NSAIDs
Corticosteroids
Bisphosphonates
Interleukin antagonists

3. TNF- α antagonists
Immunosuppresant drugs
Anti cancer drugs
Anti-convulsants
Anti-asthamatic drugs
Conclusion
References

4. Introduction
• DRUG
According to WHO(1966) Drug is any substance or product that is used to
modify or explore physiological systems or pathological states for the
benefit of the recipient.

5. Introduction
• During orthodontic treatment ,often prescribe drugs to manage pain from force
application to biological tissues , manage TMJ problems and tackle some
infections throughout course of treatment.
• Apart from these drugs patients who consume vitamins , minerals, hormonal
supplements and other compounds for the prevention or treatment of various
diseases, can also found in every orthodontic practice.

6. Introduction
• Some of these drugs may have profound effects on the short and long term
outcomes of orthodontic practice. Hence it is necessary to review the mechanism
of action and effects of commonly used drugs on tissue remodeling and
orthodontic tooth movement.

7. Prostaglandins and Leukotrienes
• These are the biologically active derivative of 20 carbon atom polyunsaturated
essential fatty acids that are released from cell membrane phospholipids. They are
the major lipid-derived autocoids.

9. Prostaglandins(PG’s)
• Most of the tissues are capable of synthesizing PG’s from the dietary essential
fatty acids.
• PG’s released due to mechanical,chemical ,thermal & bacterial insults.
• Both PGE 2 and PGI 2 are the potent vasodialators & hyperalgesic agents. PGE2
is also potent pyrogenic substance.
• PG’s play important role in inflammatory response.

10. Actions of PG’s
• PGI2 –Regulation of vascular tone as a vasodilator and exudation at the site of
inflammation.
• PGI2-Anti-aggregatory,TXA2- aggregation of platelets.
• PGE2-mediate bacterial or pyogenic induced fever & malease at the level of
hypothalamus.

11. • PG’s-neuromodulators in the brain by regulating neuronal exitabilty, sympathetic
neurotransmission in periphery.
• PGE2 & PGI2-sensitize afferent nerve endings to induce pain by chemical,
mechanical & thermal stimuli.

12. Effect of PGs on bone & tooth movement
• Experiments have shown that PG’s may be mediators of mechanical stress during
orthodontic tooth movement.
• They stimulate bone resorption,root resorption, decreased collagen synthesis and
increase cyclicAMP.
• They stimulate bone resorption by increasing the number of osteoclasts and
activating already existinng osteoclasts.

13. Effect of PGs on Bone & Tooth Movement
• A lower concentration of PGE2 0.1-1microgram appears to be effective in
enhancing tooth movement.
• Higher concentration leads to root resorption.
• Systemic adminstration is reported to have better effect than local adminstation.

14. Leukotrienes(LT’s)
• Leukotrienes are the metabolites of Arachodonic acid, they are produced when
arachdonic acid is metabolized by the enzyme lipo-oxygenase.
• It is produced by limited number of tissues, mainly by LTB4 neutrophils, LTC4 &
LTD4-cysteinyl – LTs by macrophages.

15. Actions of LT’s
• LTC4 & LTD4 injected i.v. it rises BP fallowed by more prolonged fall in BP.
• It increases capillary permeability –leads edema formation.
• Important mediators of inflammation, produced at the site of inflammation &
causes exudation of plasma.
• It sensitizes afferent carrying pain impulses, causes pain and tendorness at the site
of inflammation.
• It constricts smooth muscle, important mediator in allergic asthma.

16. Effects on bone and tooth movement
• LTs important mediators of orthodontic tooth movement. It stimulates bone
resorption. This role is clearly demonstrated when inhibitors of LTs synthesis are
used in experiment model.

17. Analgesics
• Analgesic is a drug that selectively relieves pain by acting on the CNS or
peripheral pain mechanisms, without significantly altering consciousness.
• Nonsteroid anti-inflammatory drugs (NSAIDs) do not affect the tenderness
induced by direct application of PGs, but block the pain- sensitizing mechanism
induced by bradykinins, tumor necrosis factors (TNFs), interleukins (ILs), etc.

18. • The analgesic action is mainly due to obtunding of peripheral pain receptors and
prevention of PG medicated sensitization of nerve endings.
• NSAIDs are a relatively weak inhibitor of PG synthesis and anti- inflammatory
action may be exerted by reduced generation of superoxide by neutrophils, and
TNF release, free radical scavenging, and inhibition of metalloprotease activity in
cartilage.

19. NSAID Classification

20. ACTIONS OF NSAIDs
• Analgesia
• Anti pyresis
• Anti inflammation
• Dysmenorrhoea
• Ductus arteriosus closure after birth
• Delay in parturition
• Anaphylactoid reaction

21. NSAIDs in Dentistry
• Mild to moderate pain with little inflammation : Paracetamol / low dose ibuprofen
• Post extraction or acute short lasting pain : Ketorolac, diclofenac, aspirin
• Gastric intolerance to conventional NSAIDs : Etoricoxib, paracetamol
• History of asthama / anaphylaxis to aspirin : Nimesulide, COX-2 inhibitor
• Pediatric patients : paracetamol, ibuprofen, naproxen
• Pregnancy : paracetamol, low dose aspirin

22. Effect of NSAIDs on Tooth Movement
• Inhibition of the inflammatory reaction produced by PGs slows the tooth
movement.
• The levels of matrix metalloproteinases (MMP9 and MMP2) increases, along with
elevated collagenase activity,
• A reduction in procollagen synthesis (essential for bone and periodontal
remodelling)

23. • The whole process is controlled by inhibition of cyclooxygenase (COX) activity,
leading to altered vascular and extravascular matrix remodelling.
• causing a reduction in the pace of the tooth movement.

24. Aspirin
• Its action result from inhibition of COX activity, which converts unsaturated fatty
acids in the cell membrane to PGs.
• Orthodontic tooth movement is very slow in patients undergoing long- term
acetylsalicylic therapy.

25. • Salicylate therapy decreases bone resorption by inhibition of PGs’ synthesis and
may effect differentiation of osteoclasts.
• Hence it is advised that patients undergoing orthodontic treatment should not be
advised to take aspirin and related compounds for longer period during
orthodontic treatment.

26. Cox-2 inhibitors
• The drug selectively blocks the COX-2 enzyme and impedes the production of
PGs that cause pain and swelling.
• Because it selectively blocks COX-2 enzyme and not COX-1 enzyme, it was
suggested that the drug can be safely employed during orthodontic
mechanotherapy, without causing negative effects on tooth movement.
• It reduces the amount of root resorption along with control of pain from intrusive
orthodontic forces, without affecting the pace of tooth movement.

27. Acetaminophen
• It is a weak COX-1 and COX-2 inhibitor that also reduces urinary prostaglandin
levels after systemic administration and has shown no effect on orthodontic tooth
movement in guinea pigs and rabbits.
• Comparative studies and clinical experience have shown that acetaminophen is
effective for controlling pain and discomfort associated with the orthodontic
treatment.

28. • 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.

29. other NSAIDs:
• Indomethacin – inhibits osteoclasts
• No significant effects on orthodontic tooth movement.
• Imidazole – Thromboxane A2 synthesis inhibitor.
• Flurbiprofen – Inhibits appearance of osteoclasts.
• No significant effects on orthodontic tooth movement.

30. Corticosteroids
• They are involved in many physiologic systems, such as stress response,
inflammatory and immune responses, carbohydrate metabolism, protein
catabolism, and blood electrolyte levels.
• The main effect of corticosteroid on bone tissue is direct inhibition of osteoblastic
function and thus decreases total bone formation.

31. • Decrease in bone formation is due to elevated PTH levels caused by inhibition of
intestinal calcium absorption which is induced by corticosteroids.
• 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.

32. • Orthodontic treatment in patients undergoing corticosteroid therapy has concerns
for anti-inflammatory and immunosuppressive effects.
• The side effects of long-term steroid therapy include disturbances in mineralized
tissue metabolism and wound healing, discrepancies in chondrogenesis and
osteogenesis, bone loss and osteoporosis.

33. • Force application resulted in a significant increase in the relative extension of
resorption and formation in both groups, indicating that the orthodontic force level
should be reduced and controlled more frequently in patients on chronic steroid
treatment.
• When they are used for longer periods of time, the main side effect is
osteoporosis.

34. • It has been demonstrated in animal models with this type of osteoporosis that the
rate of active tooth movement is greater, but tooth movement is less stable since
little bone is present and there is no indication of bone formation.
• A more extensive retention may be required.
• Yamane et al found lower amount of tooth movement after hydrocortisone
administration at a dose of 10 mg/kg/day for 7 days in rats.

35. • Davidovitch et al showed slower tooth movement in cats treated with cortisone
acetate (12.5 to 25 mg/day).
• Treatment with triamcinolone acetonide is associated with increased tooth
movement in rabbits due to increased resorptive activity in the alveolar bone.
• Another study on rats reported that prednisolone treatment did not affect the
magnitude of orthodontic tooth movement as compared to control group.

36. Bisphosphonates
• Synthetic analogue of pyrophosphates, that bind to hydroxyapatite in bone.
• They inhibit bone resorption and has the ability to prevent osteoporosis, help in
cases of metabolic diseases and hypercalcemia.

37. Classification
• Based on relative potency
• 1st generation : Etidronate
• 2nd generation : Pamidronate (relative potency – 100 times)
Alendronate (relative potency – 100-500 times)
• 3rd generation : Risedronate (1000 times)
Zoledronate (5000 times)
• Based on structure
• Nitrogen containing bisphosphonates
• Non-nitrogen containing bisphosphonates

38. Uses :
1. Osteoporosis
2nd and 3rd generation BPNs are used in cases of post menopausal osteoporosis,
age related osteoporosis, idiopathic and steroid induced osteoporosis.
They conserve the bone mineral density, hence reduces the risk of fractures.
2. Paget’s disease
BPNs arrest osteolytic lesion, reduces the bone pain and improve secondary
symptoms.

39. • Bisphosphonates + calcium ions + Vit D Adjuvant treatment therapy for Paget’s
disease.
3. Hypercalcemia of malignancy.
4. Osteolytic bone metastasis.
5. Bone healing and recovery of bone strength,
SIDE EFFECTS
1. Gastric irritation
2. Esophagitis
3. Osteonecrosis of jaws.

40. Orthodontic implications
1. It inhibits OTM and delays orthodontic treatment
2. Topical application can help in anchorage and retain teeth under the treatment
3. Administering systemic BPN before activation of treatment device results in
formation of atypical hyperplastic cementum, which protects against root resorption.

41. 4. Produces osteoclast inhibitory factors to decrease OTM
5. In high risk patients on BPN therapy, treatment outcome is unpredictable.
(increased treatment duration, reduced OTM, incomplete space closure, poor root
parallelism)

42. Why bisphosphonates are a concern ?
 Association with unusual necrosis of mandible
 After extraction of tooth / bone injury
 Incomplete wound healing
 Results in centre of expanding necrotic area

43. • Occurs mostly in patients with metastatic bone cancer receiving high dose of
bisphosphonates.
• Elective extraction for orthodontic purpose should be avoided in such cases.

44. Slow elimination of drug over a long period of time
• These drugs gets incorporated in one, hence the effects are not immediately
terminated by the stoppage of drug.
• Rates of drug elimination
A. From bone surface (faster)
B. From bone structure (slower)
• In most cases, drug is present only on bone surface, hence orthodontic
treatment can be done after 3 months without any further bisphosphonate
therapy.

45. • Bisphosphonates act by suppressing osteoclastic activity, slowing down the bone
remodeling process, thereby increasing bone mineral density and reducing the risk
of fractures in patients with osteopenia or osteoporosis.
• The drug inhibits resorption of bone, formation of capillaries in the alveolus, and,
consequently, it slows down the velocity of orthodontic tooth movement.

46. • However, by inhibiting bone resorption, this drug may have positive effects on
periodontal health.
• Kim et al demonstrated that the enhancement of anchorage with reduction in tooth
movement was because of the impairment of osteoclast structure, including the
disappearance of ruffled borders and clear zones, formation of irregular borders,
and necrotic degeneration.

47. • Various animal studies support the hypothesis that a reduction in the rate of tooth
movement will occur in patients undergoing bisphosphonate treatment.
• Patients treated with these anti resorptive agents will show reduced tooth
movement between appointments.
• It is further hypothesized that local delivery of these drugs may possibly be used
in human patients in the future for anchorage reinforcement and root resorption
prevention.

48. • Keles et al found that use of pamidronate in mice, decrease osteoclasts on
compression side and reducing tooth movement by 34%.
• Orthodontic treatment is possible in patients taking low dose of bisphosphonates
for short periods (low risk patients).
• Bisphosphonates investigated to use them in orthodontic treatment to enhance
retention, to increase anchorage ability of teeth, to decrease inflammatory root
resorption expected during orthodontic treatment.

49. Inter Leukin Antagonists
• Interleukin antagonists inhibit IL-1, produced by monocytes, macrophages, and
some specialized cells, which are important for the inflammatory response, and
IL-6 and COX-2.
• These drugs influence the inflammatory response following force application,
reducing the pace of tooth movement and bone remodelling.

50. TNF – α Antagonists
• TNF- α antagonists block TNF- α in inflammatory cytokinins released by
activated monocytes, macrophages, and T-lymphocytes, which are essential for
inflammatory responses following force application.

51. Immunosuppresant drugs
• Patients with chronic renal failure or kidney transplants and on
immunosuppressant drugs can encounter some difficulty during orthodontic
treatment.
• Drug consumed for prevention of graft rejection (cyclosporine A) produce severe
gingival hyperplasia, making orthodontic treatment and maintenance of oral
hygiene difficult.

52. • Treatment should be started or resumed after surgical removal of excessive
gingival tissues once there is good oral hygiene, in about 6 months duration.
• Whenever possible, fixed appliances should be kept to a minimum period with
brackets and avoiding the use of cemented bands.
• These drugs are used to treat autoimmune disorders and to prevent graft rejection
during organ transplantation.
• Studies have demonstrated that cyclosporine reduces bone volume, number of
osteoblasts and increases osteoclasts.

53. • Tacrolimus also induced bone loss both in human beings and in experimental
animal models.
• When patients taking these drugs require orthodontic treatment, in the initial stage
of medications usage, it may be advised to delay orthodontic treatment, as there
would be less bone remodelling, or orthodontic activation appointments should be
scheduled at longer intervals.
• Long term medication therapy may accelerate tooth movement, thus orthodontic
appliances must be adjusted customarily, or with greater frequency.

54. Anti-cancer drugs
• These are used for the treatment of childhood cancers. (Sarcomas, Lymphomas,
Leukemias)
• There is every chance of observing disturbances in dental as well as general body
growth and development due to the adverse effects of the chemotherapeutic
agents.

55. • It is clearly stated that patients who had been on chemotherapy with busulfan/
cyclophosphamide belong to the risk group for orthodontic treatment.
• These drugs are known to produce damage to precursor cells involved in bone
remodeling process, thereby complicating tooth movement.

56. Anti-convulsants : (phenytoin)
• It induces gingival hyperplasia due to overgrowth of gingival collagen fibers,
which involve the interdental papilla, making application of orthodontic
mechanics and maintaining oral hygiene difficult.
• If used during pregnancy, it can produce fetal hydantoin syndrome characterized
by hypoplastic phalanges, cleft palate, hare lip, and microcephaly. (Karsten et al,
1997)

57. • Valproic acid has a potential to induce gingival bleeding even with minor trauma,
making orthodontic maneuvers difficult.
• Gabapentin produces xerostomia, making oral hygiene maintenance difficult
during orthodontic treatment.

58. Asthama
• Episodic narrowing of the airways that results in breathing difficulties and
wheezing, characterizes asthma.
• It is highly possible that orthodontists will meet these patients in their routine
clinical practice.
• The immune system of chronic asthmatic patients is always active and there will
be an increased production of osteoclasts and odontoclasts, both multinucleated
cells involved in bone as well as root resorption, respectively.

59. • Moreover, in asthmatic patients, the application of excessive orthodontic force
often results in tissue compression and necrotic areas, which frequently contain
odontoclasts engaged in resorbing the dental roots.
• Primed leukocytes derived from these tissues may travel through the circulation
into the extravascular space of the tissues surrounding orthodontically treated
teeth.

60. • Orthodontic treatment should not be performed in patients who experience very
frequent flare-ups despite being adequately medicated.
• For patients at low to moderate risk, morning appointments with short waiting
times are advised.
• Orthodontists should make sure that the patient has taken adequate medications
and if needed has his/her inhaler present at the time of treatment appointments.

61. Conclusion
• Human beings, in every culture and community on earth, consume a large variety
of molecules in the form of food ingredients, medications, drugs, and remedies.
• Medically related molecules are prescribed and/or provided by physicians,
dentists, other health care providers, and the patients themselves.
• These medications are aimed at specific illnesses, but they always have systemic
effects involving a number of systems, organs, tissues, and cells.

62. • Such alterations may profoundly affect the course and outcome of therapeutic
procedures, such as orthodontic treatment.
• 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 remodelling process by
various drugs and systemic factors.
• Orthodontists should assume that many patients are taking prescription or
medications regularly.

63. • 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.
• Orthodontists need to pay attention to drug consumption and history of each and
every patient, before and during the course of orthodontic treatment, so that the
best treatment strategy (including force control and appointment intervals) can be
selected for each case.

64. References
1. Tripathi KD. Essentials of Pharmacology for dentistry. 2nd ed.
2. Krishnan V, Davidovitch Z. The effect of drugs on orthodontic tooth movement.
Orthod Craniofacial Res. 2006;9:163–171.
3. Krishnan V, Davidovitch Z. Cellular, molecular, and tissue-level reactions to
orthodontic force. Am J Orthod Dentofacial Orthop. 2006;129:469e.1- 469e.32.
4.Diravidamani K, Sivalingam SK, Agarwal V. Drugs influencing orthodontic tooth
movement: An overall review. J Pharm Bioall Sci. 2012;4:299-303.