Orthodontic tooth movement is induced by mechanical stimuli and facilitated by remodeling of the periodontal ligament and alveolar bone. The remodeling activities and the ultimately tooth displacement are the consequence of an
inflammatory process. The cellular, biochemical and molecular events that take place during orthodontic tooth movement have been extensively studied. Although
inflammation is essential in the remodeling activities, it may result in several
undesirable side effects. Thus, not only the aesthetic and functional outcome but also the adverse events for the teeth and the supporting tissue related to the orthodontic tooth movement should be considered.
Orthodontic treatment is very often associated to gingival inflammation, as a result of the local change in the microbial ecosystem and in the composition of the bacterial plaque. Patients with good oral hygiene may develop gingival inflammation during orthodontic treatment. Mild to moderate gingivitis with bleeding on probing and gingival enlargement is evident, especially when fixed orthodontic appliances are used (45-48). Gingivitis does not progress into periodontitis, in terms of loss of attachment and bone probably due to the restriction of plaque-induced inflammatory reaction in the supra-alveolar connective tissue. According to Zachrisson and
Zachrisson (40), 90% of patients acquired little or no periodontal breakdown during orthodontic treatment with fixed appliances, emphasizing the importance of repeated motivation and instructions of oral hygiene. The local changes in the oral ecosysrem and the development of gingivitis during orthodontic treatment are reflected in
changes in the composition of GCF (166, 167). The group of cytokines has attracted particular attention as their levels may increase rapidly with plaque accumulation and before the subsequent visible clinical inflammation, suggesting that they may have a potential role as early markers of gingival inflammatory changes (166). In the studies described in this Thesis on experimental tooth movement (chapters 6 and 7), no significant changes were observed on any of the clinical parameters during the whole experimental period. This is mainly due to the oral hygiene instructions given to each patient before and during the experimental treatment. In fact, meticulous plaque control and motivation for oral hygiene took place every week for all patients. This
allowed our research to focus on the mechanically induced inflammation within the bone and periodontal ligament. Although a weekly visit does not represent a common procedure, orthodontic patients should be aware of the importance of reaching high hygiene levels during orthodontic treatment. Furthermore, for the
clinician it is important to identify patients at risk for periodontal disease and to control the periodontal status before any orthodontic appliance is placed.
Pain is a complex experience which accompagnies orthodontic treatment (50).
It is a subjective response showing large individual variations. The perception of orthodontic pain is part of the inflammatory reaction causing changes in blood flow following orthodontic force application. As a result of the inflammatory reaction, various biochemical mediators are released eliciting an hyperalgaesic response. The painful response during the first days of orthodontic treatment has been related to the release of neuropeptides which in turn evoke the release of pro-inflammatory cytokines, such as IL-6, IL-8 and TNF-α mainly by dental pulp cells and by other cell lines (63, 72). The levels of such mediators return to normal values after 14 days.
Orthodontic pain has a definite influence on compliance and daily activities of the patient. Many patients/parents consider initial lack of information about possible discomfort or pain, to be the major cause of poor compliance. Evaluation of pain is an important part of orthodontic treatment and the patients’ attitude towards orthodontics should be understood and discussed with the patient during the diagnostic phase. In our work described in chapter 3, a baseline interview was established in order to evaluate the patient’s previous experience of general and dental pain as well as the level of dental anxiety. Using the VAS, painful situations were proposed and the subjects had to place a mark on the line at a point that corresponds to the level of pain intensity. Regarding general pain, situations such as “cutting one’s finger”,
“being stung by nettles”, “vaccination” were proposed. Regarding dental pain,
situations such as “polishing”, “injection”, “drilling “ , “scaling “ were proposed. Finally, dental anxiety was assessed based on 4 questions regarding 4 hypothetical dental situations (“how you feel the day before the dental appointement”, “how you feel 5 min before” etc). This questionnary is a very simple and rapid method to evaluate our patient’s perception towards pain. Furthermore, we showed that several biochemical markers detected in GCF, such as PGE2, SP and IL-1β, were associated with pain intensity. The development of a chair-side biochemical test and a baseline interview
may help us to identify patients more “susceptible” to experience not just a discomfort but also high levels of pain during orthodontic treatment. This could further help us to manage pain and distress experienced by the patient. The administration of NSAIDs remains the preferred method for pain control (75). Low doses administered for one or two days in the initial stage of orthodontic treatment, or pre-operative analgesics administered at least one hour before every orthodontic procedure, will help the patient without affecting the tooth movement process.
Root resorption is a common sequela of orthodontic treatment (76-79).
According to its severity, root resortion is classified to cemental or surface resorption, to dentinal resorption and to circumferential root resroption. The last, is clinically the most severe type, it is irreversible and starts at or near the apex and progresses coronally, resulting in root shortening. The most commonly resorbed teeth are the maxillary incisors. In most of the cases, resorption defects are confined to the apical third of the root because the apical third is covered with cellular cementum, which depends on active cells and has more supporting vasculature (207). This makes it more vulnerable to trauma and cell-injury related reactions. Furtermore, there is a decrease in the hardness of the cementum from the cervical to apical regions, making apical areas prone to resorption (208). About 5% of adults and 2% of adolescents are likely to have at least one tooth with resorption of more than 5mm during active treatment. Until now, several factors have been identified as
predisposing factors for root resorption, such as age, gender, pre-existing root condition, type of tooth movement, amount and type of force as well as treatment duration (107-112).
An objective tool to identify teeth at risk of severe resorption is still missing.
Until now, OPT and periapical radiographs are the only tools in the diagnosis of orthodontically induced root resroption. However, a certain degree of resorption is required before being detectable on the radiograph, thus making impossible its detection at an early stage (124, 125). In chapter 7, we showed that digitized
periapical radiographs underestimated apical root resorption. Furthermore, in chapter 8, by using the CBCT as gold standard, we showed that OPT also underestimated orthodontically induced root resorption. We suggested that if signs of moderate root resorption are visible on OPT during the initial or middle phase of orthodontic
help make the decision on continuation and possible modification of orthodontic treatment. Furthermore, in cases of impacted canines, CBCT may be particularly useful in revealing the presence and degree of root resorptions on the adjacent teeth and when orthodontic treatment combined with surgery is required. Otherwise,
periapical radiographs should be obtained 6 months after the beginning of the
orthodontic treatment in order to early detect the occurence of apical root resorption.
Recently, the role of OPG and RANKL in osteoclast genesis and root
resorption- both physiologic and pathologic- procedure has been documented (187, 188). Furthermore, these molecules have been identified in the gingival crevicular fluid mainly in relation to periodontal disease (189, 190). The development of a screen test based on the detection of OPG and RANKL in gingival crevicular fluid, before and during orthodontic treatment, may help to identify patients at risk for root resorption. In our study based on experimental tooth movement, buccal tipping forces were exerted, thus we postulate that the buccal cervical and lingual apical region have undergone tissue compression. The buccal apical and lingual cervical areas were under tension, and the mid-root regions had undergone a mixture of both compression and tension. Based on the hypothesis that the levels of OPG and RANKlL may change in relation to the root resorption defects, the gingival crevicular fluid was collected in the compression areas during the whole experimental period.
Identifying biological markers related to root resorption, may help to the development of a screen test before any changes on root length become obvious in the
radiographs. Recently, research has been focused in identifying genes that control the cellular and ECM components associated with the events taking place during orthodontic tooth movement (115-118). A genetic test that will determine root resorption polymorphisms in patients prior to orthodontic treatment could contribute to the best clinical setting.
At present it is not possible for the clinician to predict patients at risk for severe root resorption during orthodontic treatment. Therefore, gingival crevicular fluid
analysis before or during orthodontic tooth movement, may be useful for the prediction of individual’s response to orthodontic treatment and the related side effects such as root resorption and pain. In particular, the detection of patients at risk and the early detection of root resorption before the radiographic observation are important areas in orthodontics that need to be addressed in order to improve the orthodontic treatment.
13. REFERENCES
1. Proffit WR. (2007) Biologic basis of orthodontic therapy. In: Proffit WR, Fields HW, Sarver D.M. editors. Contemporary Orthodontics, 4th ed. Mosby, St. Louis, pp. 331-358.
2. Mostafa YA, Weaks-Dybvig M, Osdoby P. (1983) Orchestration of tooth movement. Am J Orthod 83:245-250.
3. Wehrbein H, Fuhrmann RA, Diedrich PR. (1994) Periodontal conditions after facial root tipping and palatal root torque of incisors. Am J Orthod
Dentofacial Orthop 106:455-462.
4. King GJ, Archer L, Zhou D. (1998) Later orthodontic appliance reactivation stimulates immediate appearance of osteoclasts and linear tooth movement.
Am J Orthod Dentofacial Orthop 114:692-697.
5. Ashizawa Y, Sahara N. (1998) Quantitative evaluation of newly formed bone in the alveolar wall surrounding the root during the initial stage of
experimental tooth movement in the rat. Arch Oral Biol 43:473-484.
6. Verna C, Melsen B, Melsen F. (1999) Differences in static cortical bone remodeling parameters in human mandible and iliac crest. Bone 1999 25:577-583.
7. Choy K, Pae EK, Park Y, Kim KH, Burstone CJ. (2000) Effect of root and bone morphology on the stress distribution in the periodontal ligament. Am J Orthod Dentofacial Orthop 117:98-105.
8. Murrell EF, Yen EHK, Johnson RB. (1996) Vascular changes in the periodontal ligament after removal of orthodontic forces. Am J Orthod Dentofacial Orthop. 110:280-286.
9. Vandevska-Radunovic V, Kvinnsland S, Kvinnsland IH. (1997) Effect of experimental tooth movement on nerve fibres immunoreactive to calcitonin gene-related peptide, protein gene product 9.5, and blood vessel density and distribution in rats. Eur J Orthod 19:517-529.
10. Vandevska-Radunovic V, Kvinnsland IH, Kvinnsland S, Jonsson R. (1997) Immunocompetent cells in rat periodontal ligament and their recruitment incident to experimental orthodontic tooth movement. Eur J Oral Sci 105:36-44.
11. Vandevska-Radunovic V, Kristiansen AB, Heyeraas KJ, Kvinnsland S.
(1994) Changes in blood circulation in teeth and supporting tissues incident to experimental tooth movement. Eur J Orthod 16:361-369.
12. Hellsing E, Hammarström L. (1996) The hyaline zone and associated root surface changes in experimental orthodontics in rats: a light and scanning electron microscope study. Eur J Orthod 18:11-18.
13. Pavlin D, Goldman ES, Gluhak-Heinrich J, Magness M, Zadro R. (2000) Orthodontically stressed periodontium of transgenic mouse as a model for studying mechanical response in bone: The effect on the number of
osteoblasts. Clin Orthod Res 3:55-66.
14. Reitan K. (1960). Tissue behavior during orthodontic tooth movement. Am J Orthodontics 46:881-890.
15. Heller IJ, Nanda R. (1979) Effect of metabolic alteration of periodontal ligament fibers on orthodontic tooth movement. An experimental study. AmJ Orthodontics 75:239-258.
16. Melsen B. (2001) Tissue reaction to orthodontic tooth movement- a new paradigm Eur J Orthodontics 23:671-681.
17. Van Leeuwen EJ, Maltha JC, Kuijpers-Jagtman AM. (1999) Tooth movement with light continuous and discontinuous forces in beagle dogs. Eur J Oral Sci 107:468-474.
18. Von Böhl M, Maltha JC, Von Den Hoff JW, Kuijpers-Jagtman AM. (2004) Focal hyalinization during experimental tooth movement in beagle dogs. Am J Orthod Dentofacial Orthop 125:615-623.
19. Melsen B. (1999) Biological reaction of alveolar bone to orthodontic tooth movement. Angle Orthod 69:151-158.
20. Von Böhl M, Maltha J, Von den Hoff H, Kuijpers-Jagtman AM. (2004) Changes in the periodontal ligament after experimental tooth movement using high and low continuous forces in beagle dogs. Angle Orthod 74:16-25.
21. Krishnan V, Davidovitch Z. (2006) Cellular, molecular, and tissue-level reactions to orthodontic force. Am J Orthod Dentofacial Orthop 129:469.e1-32.
22. Meikle MC. (2006) The tissue, cellular, and molecular regulation of
orthodontic tooth movement: 100 years after Carl Sandstedt. Eur J Orthod 28:221-240.
23. Midgett RJ, Shaye R, Fruge JF Jr. (1981) The effect of altered bone metabolism on orthodontic tooth movement. Am J Orthod 80:256-262.
24. Ren A, Lv T, Kang N, Zhao B, Chen Y, Bai D. (2007) Rapid orthodontic tooth movement aided by alveolar surgery in beagles. AmJ Orthod Dentofacial Orthop 131:160.e1-10.
25. Kawakami T, Nishimoto M, Matsuda Y, Deguchi T, Eda S. (1996)
Histological suture changes following retraction of the maxillary anterior bone segment after corticotomy. Endodontics and Dental Traumatology 12:38-43.
26. Wilcko WM, Wilco MT, Bouquot JE, Ferguson DJ. (2001) Rapid orthodontics with alveolar reshaping: two case reports of decrowding. Int J Periodontics Restorative Dent 21:9-19.
27. Yamasaki K, Miura F, Suda T. (1980) Prostaglandin as a mediator of bone resorption induced by experimental tooth movement in rats. J Dental Res 59:1635-1642.
28. Yamasaki K, Shibata Y, Imai S, Tani Y, Ahibasaki Y, Fukuhara T. (1984) Clinical application of prostaglandin E1 (PGE1) upon orthodontic tooth movement. Am J Orthodontics 85:508-518.
29. Sekhavat AR, Mousavizadeh K, Pakshir HR, Aslani FS. (2002) Effect of misoprostol, a prostaglandin E1 analog, on orthodontic tooth movement in rats. Am J Orthod Dentofacial Orthop 122:542-547.
30. Seifi M, Eslami B, Saffar AS. (2003)The effect of prostaglandin E2 and
calcium gluconate on orthodontic tooth movement and root resorption in rats.
Eur J Orthod 25:199-204.
31. Chumbley AB, Tuncay OC. (1986) The effect of indomethacin (an aspirin-like drug) on the rate of orthodontic tooth movement. Am J Orthod 89:312-314.
32. Collins MK, Sinclair PM. (1988) The local use of vitamin D to increase the rate of orthodontic tooth movement. Am J Orthod Dentofacial Orthop 94:278-284.
33. Soma S, Matsumoto S, Higuchi Y, Takano-Yamamoto, Yamashita K, Kurisu K, Iwamoto M. (2000) Local and chronic application of PTH accelerates tooth movement in rats. J Dent Res 79:1717-1724.
34. Verna C, Dalstra M, Melsen B. (2000) The rate and the type of orthodontic tooth movement is influenced by bone turnover in a rat model. Eur J Orthod 22:343-352.
35. Bartzela T, Türp JC, Motschall E, Maltha JC. (2009) Medication effects on the rate of orthodontic tooth movement: a systematic literature review. Am J Orthod Dentofacial Orthop 135:16-26.
36. Ren Y, Maltha JC, Kuijpers-Jagtman AM. (2003) Optimum force magnitude to orthodontic tooth movement- a systematic literature review. Angle Orthod 73:86-92.
37. Travess H, Roberts-Harry D, Sandy J. (2004) Orthodontics. Part 6: risks in orthodontic treatment. Br Dent J 196:71-77.
38. Krishnan V (2009) Mechanical and Biological determinants of iatrogenic injuries in orthodontics. In: Vinid Krishnan and Ze’ev Davidovitch editors.
Biological Mechanisms of Tooth Movement, Wiley Blackwell, pp 215-233.
39. Atack NE, Sandy JR, Addy M. (1996) Periodontal and microbiological
changes associated with the placement of orthodontic appliances. A review.
J Periodontol 67:78-85.
40. Zachrisson S, Zachrisson BU. (1972) Gingival condition associated with orthodontic treatment. Angle Orthod 42:26-34.
41. Zachrisson BU, Brobakken BO. (1978) Clinical comparison of direct versus indirect bonding with different bracket types and adhesives. Am J Orthod 74:62-78.
42. Pender N, Samuels RH, Last KS. (1994) The monitoring of orthodontic tooth movement over a 2-year period by analysis of gingival crevicular fluid. Eur J Orthod 16:511-520.
43. Redlich M, Shoshan S, Palmon A. (1999) Gingival response to orthodontic force. Am J Orthod Dentofacial Orthop 116:152-158.
44. Danciu TE, Gagari E, Adam RM, Damoulis PD, Freeman MR. (2004)
Mechanical strain delivers anti-apoptotic and proliferative signals to gingival fibroblasts. J Dent Res 83:596-601.
45. Alexander SA. (1991) Effects of orthodontic attachments on the gingival health of permanent second molars. Am J Orthod Dentofacial Orthop 100:337-340.
46. Huser MC, Baehni PC, Lang R. (1990) Effects of orthodontic bands on microbiologic and clinical parameters. Am J Orthod Dentofacial Orthop 97:213-218.
47. Paolantonio M, di Girolamo G, Pedrazzoli V, di Murro C, Picciani C, Catamo G, Cattabriga M, Piccolomini R. (1996) Occurrence of Actinobacillus
actinomycetemcomitans in patients wearing orthodontic appliances. A cross-sectional study. J Clin Periodontol 23:112-118.
48. Paolantonio M, Festa F, di Placido G, D'Attilio M, Catamo G, Piccolomini R.
(1999) Site-specific subgingival colonization by Actinobacillus
actinomycetemcomitans in orthodontic patients. Am J Orthod Dentofacial Orthop 115:423-428.
49. Kloehn JS, Pfeifer JS. (1974) The effect of orthodontic treatment on the periodontium. Angle Orthod 44:127-134.
50. Oliver RG, Knapman YM. (1985) Attitudes to orthodontic treatment. Br J Orthod 12:179-188.
51. Lew KK. (1993) Attitudes and percpeptions of adults towards orthodontic treatment in an Asian community. Community Dent Oral Epidemiol 21:31-35.
52. Kvam E, Bondevik O, Gjerdet NR. (1989) Traumatic ulcers and pain in adults during orthodontic treatment. Community Dent Oral Epidemiol 17:154-157.
53. Scheurer PA, Firestone AR, Bürgin WB. (1996) Perception of pain as a result of orthodontic treatment with fixed appliances. Eur J Orthod 18:349-357.
54. Firestone AR, Scheurer PA, Bürgin WB. (1999) Patient’s anticipation of pain and pain-related side effects, and their perception of pain as a result of orthodontic treatment with fixed appliances. Eur J Orthod 21:387-396.
55. Stewart FN, Kerr WJ, Taylor PJ. (1997) Appliance wear: the patient’s point of view. Eur J Orthod 19:377-382.
56. Sergl HG, Klages U, Zentner A. (1998) Pain and discomfort during
orthiodontic treatment: causative factors and effects on compliance. Am J Orthod Dentofacial Orthop 114:684-691.
57. Furstman L, Bernick S. (1972) Clinical considerations of the periodontium.
Am J Orthod 61:138-155.
58. Bergius M, Berggren U, Kiliaridis S. (2002) Experience of pain during an orthodontic procedure. Eur J Oral Sci 110:92-98.
59. Ngan P, Kess B, Wilson S. (1989) Perception of discomfort by patients
undergoing orthodontic treatment. Am J Orthod Dentofacial Orthop 96:47-53.
60. Bergius M, Kiliaridis S, Berggren U. (2000) Pain in orthodontics. A review and discussion of the literature. J Orofac Orthop 61:125-137.
61. Erdinç AM, Dinçer B. (2004) Perception of pain during during orthodontic treatment with fixed appliances. Eur J Orthod 26:79-85.
62. Brown DF, Morenhout RG. (1991) The pain experience and psychological adjustment to orthodontic treatment of preadolescents, adolescents and adults. Am J Orthod Dentofacial Orthop 100:349-356.
63. Walker JA Jr, Tanzer FS, Harris EF, Wakelyn C, Desiderio DM. (1987) The enkephalin response in human tooth pulp to orthodontic force. Am J Orthod Dentofacial Orthop 92:9-16.
64. Davidovitch Z, Nicolay OF, Ngan PW, Shanfeld JL. (1988)
Neurotransmitters, cytokines and the control of alveolar bone remodeling in orthodontics. Dent Clin North Am 32:411-435.
65. Davidovitch Z. (1991) Tooth movement. Crit Rev Oral Biol Med 2: 411-450.
66. Nicolay OF, Davidovitch Z, Shanfeld JL, Alley K. (1990) Substance P immunoreactivity in periodontal tissues during orthodontic tooth movement.
Bone Mineral 11:19-29.
67. Saito M, Saito S, Ngan PW Shanfeld J, Davidovitch Z. (1991) Interleukin-1beta and prostaglandine E are involved in the response of periodontal cells to mechanical stress in vivo and in vitro. Am J Orthod Dentofacial Orthop 99:226-240.
68. Grieve WG, Johnson GK, Moore RN, Reinhardt RA, DuBois LM. (1994) Prostaglandin E (PGE) and interleukin-1beta (IL-1beta) levels in gingival crevicular fluid during human orthodontic movement. Am J Orthod Dentofacial Orthop 105:369-374.
69. Alhashimi N ; Frithiof L, Brudvik P, Bakhiet M. (2001) Orthodontic tooth movement and de novo synthesis of proinflammatory cytokines. Am J Orthod Dentofacial Orthop 119:307-312.
70. Giannopoulou C, Dudic A, Kiliaridis S. (2006) Pain discomfort and crevicular fluid changes induced by orthodontic elastic separators in children. J Pain 7:367-376.
71. Awawdeh LA, Lundy FT, Linden GJ, Shaw C, Kennedy JG, Lamey PJ.
(2002) Quantitative analysis of substance P, neurokinin A and calcitonin gene-related peptide in gingival crevicular fluid associated with painful human teeth. Eur J Oral Sci 110:185-191.
72. Lundy FT, Linden GJ. (2004) Neuropeptides and neurogenic mechanisms in oral and periodontal inflammation. Crit Rev Oral Biol Med 15:82-98.
73. Hixon EH, Atikian H, Callow GE, McDonald HW, Tacy RJ. (1969) Optimal force, differential force, and anchorage. Am J Orthod 55:437-451.
74. Jones ML, Richmond S. (1985) Initial tooth movement for application and pain- a relationship? Am J Orthod 88:111-116.
75. Krishnan V. (2007) Orthodontic pain: from causes to management-a review.
Eur J Orthod 29:170-179.
76. Hollender L, Rönnerman A, Thilander B. (1980) Root resorption, marginal bone support and clinical crown lenght in orthodontically treated patients Eur J Orthod 2:197-205.
77. Rönnerman A, Larsson E. (1981) Overjet, overbite, intercanine distance and root resorption in orthodontically treated patients. A ten year follow-up study.
Swed Dent J 5:21-27.
78. Malmgren O, Goldson L, Hill C, Orwin A, Petrini L, Lundberg M. (1982) Root
78. Malmgren O, Goldson L, Hill C, Orwin A, Petrini L, Lundberg M. (1982) Root