Biology of tooth movement /certified fixed orthodontic courses by Indian dental academy


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Biology of tooth movement /certified fixed orthodontic courses by Indian dental academy

  1. 1. Biology of tooth movement INDIAN DENTAL ACADEMY Leader in continuing dental education
  2. 2. Physiologic tooth migration Naturally occurring tooth movements are :    Tooth eruption Migration or drift of teeth Changes in tooth position during tooth movement
  3. 3. Theories of tooth eruption  Bone remodeling.  Root growth.  Vascular pressure.  Periodontal ligament traction.
  4. 4. Biologic control of tooth movement
  5. 5.  Two major theories have been proposed for orthodontic tooth movement: 1. Pressure-tension theory. 2. Biologic electricity.  The bioelectric theory relates tooth movement at least in part to changes in bone metabolism controlled by electric signals that are produced when alveolar bone flexes and bends.  The pressure tension theory relates tooth movement to cellular changes produced by chemical messengers .  The two theories are neither compatible nor mutually exclusive.
  6. 6. Bioelectric theory
  7. 7.  There is a popularly held view that orthodontic forces in vivo produce electric perturbations of the alveolar bone surrounding the teeth.  These transient charges, in turn, mediate cell membrane changes which can be physiologically expressed as bone remodeling- the application of Wolff’s law.  Relatively negatively charged areas are thought to promote bone apposition.  Positively charged areas have been depicted as sites of bone loss.
  8. 8.  Thus by judicious use of applied or induced currents and voltages to discrete anatomical areas , one might expect to promote increased cellular activity and bone turnover, the rate limiting factor of tooth movement.  Alternatively , one might be able to promote retention of teeth in their new positions by an electrically induced deceleration of bone turnover.  It follows that application of direct current or the induction of current in bone may be an efficacious means of controlling tooth movement, depending on the result desired.
  9. 9.  Two types of electric signals have been described that arise in the bone endogenously: 1. Stress generated potential. 2. Bioelectric potential.
  10. 10. Stress generated potential  This is the measurable voltage found when bone is mechanically stressed.  Studies on the origin of this signal clearly determined that the potentials have their origin in the organic part of the bone, with little or no contribution from the mineral component.  When the organic component of bone was disrupted or enhanced by physical and chemical means, the voltage amplitude varied with the amount of cross linked collagen present.
  11. 11.  The physical origin of this stress generated potential appears to be composed of two parts: 1. Piezoelectric potential. 2. Streaming potential.  When a crystalline material such as dried bone is mechanically stressed , the generated electric potential is called piezoelectricity.  Minute voltage elicited when a moist bone is subject to mechanical stress is called streaming potential.
  12. 12. Piezoelectric potential  Was proposed by Bassett (1965)  Piezoelectricity is a phenomenon observed in many crystalline materials in which a deformation of crystal structure produces a flow of electric current as electrons are displaced from one part of the crystal lattice to another.  It is attributed to both organic as well as inorganic materials.  Not only is bone mineral a crystal structure with piezoelectric properties , collagen itself is piezoelectric, and stress generated potentials in dry bone specimens can be attributed to piezoelectricity.
  13. 13. Streaming potentials  Ions in the fluids that bathe living bone interact with the complex electric field generated when the bone bends, causing temperature changes as well as electric signals.  The small voltages that are observed are called “streaming potential”.  These voltages , though different from piezoelectric signals in dry material , have in common their rapid onset and alteration, as changing stresses are placed on the bone.
  14. 14.  Studies done by Ryaby, Jones etal have shown that by adding exogenous electric signals, similar to those generated in vivo, to various cell culture models , it has been shown that cAMP levels and phosphorylation of oncogene proteins can be mediated .  One type of signal has also been shown to inhibit Parathyroid hormone (PTH) induced coupling of adenylate cyclase system.
  15. 15.  Signals generated by the bending of alveolar bone during normal chewing almost surely are important for maintainance of bone around the teeth.  On the other hand sustained force of the type used to induce orthodontic tooth movement does not produce prominent stress – generated signals.
  16. 16.  It appears that stress generated signals, important as they may be for normal skeletal function, probably have little if anything to do with the response to orthodontic tooth movement.
  17. 17. Bioelectric potential  A second type of endogenous signal, which is called bioelectric potential can be observed in bone that is not being stressed.  Metabolically active bone or connective tissue cells (in area of active growth or remodeling ) produce electronegative charges that are generally proportional to how active they are; inactive cells and areas are nearly electrically neutral.  The external electric signals probably effect cell membrane receptors, membrane permeability or both.
  18. 18.  Both animal and human experiments indicate that when low voltage direct current is applied to the alveolar bone, modifying the bioelectric potential, a tooth moves faster than its control in response to an identical spring.  The undermining resorption, soft tissue inflammatory reaction, and tension on the PDL complex, all produce a bioelectric response.
  19. 19. Effect of pulsed electromagnetic fields on orthodontic tooth movement
  20. 20.  In dentistry electromagnetic fields have been used to: 1. Speed the healing of periodontal defects. 2. Reduce the amount of alveolar ridge resorption seen following extractions. 3. Increase the rates of healing of facial fractures. 4. Stimulate the rate of mandibular condylar growth.
  21. 21.  Numerous laboratory studies of the effects of electrical fields on living tissue show that electrical fields: 1. Alter the normal electric states of bone and cartilage. 2. Induce increased rates of cellular division and metabolism. 3. Thus promote increased healing of bone and cartilaginous defects.
  22. 22.  By combining electric stimulation and mechanical stress , Davidovitch has shown both increased cellular activity and accelerated rates of tooth movement.  It was hypothesized that the application of electrical currents during tooth movement potentiated the effect of the mechanical forces, leading to enhancement of cell activation and tissue remodeling.  Davidovitch has suggested that the generation of electric potentials in mechanically stressed bone may be the signal activating the cells that participate in the remodeling process.  Thus it is possible that PEMFs and orthodontic mechanical forces may be capable of functioning together in a synergistic manner.
  23. 23.  Numerous studies have shown increase in the rate and amount of orthodontic tooth movement by using PEMFs.  It can be postulated that: 1. In the presence of a mechanical deformation, the PEMF functions at the cell membrane through an interaction with the calcium ions and cyclic nucleotides to induce within the cells a higher degree of receptivity and reactivity. 2. The PEMF may also be providing the signal for the recruitment of undifferentiated stem cells into the osteoblastic and osteoclastic processes.
  24. 24. 3. the piezoelectric currents generated within the alveolar bone by the pressure and tension of the orthodontic force are thought to provide the signal for the directionality, ie deposition or resorption- of the remodeling process.
  25. 25.  It is believed that the cell membrane represents the interface between the external stimulus, be it mechanical or electrical, and the cell’s specific response.  The nature of effect seen clinically seems to be dependant on such factors as : cell type, cellular environment, and the electrical field parameters used.
  26. 26.  Bassett has suggested that specific parameters of the PEMF, such as waveform and frequency , may be responsible for the activation of a certain group of cells.  It appears that electrical energy, whether applied as a direct current or a PEMF, has the ability to effect both the depository and resorptive activities of bone and the cartilage cells.  Thus there is increased rate of production and action of both osteoclasts and osteoblasts as a result of application of PEMF.
  27. 27. PEMF increased localized calcium deposition neutralizes the tissues net negative charge ( allows) subsequent vascular invasion initiation of osteogenesis
  28. 28. Advantage of PEMF over direct currents  Although both direct current and PEMFs appear to have the ability to stimulate increased rates of tooth movement, it has been suggested that PEMF may eventually prove to be more clinically useful due to: 1. Their ability to alter the PEMF pulse characteristics to achieve specific cellular effects. 2. In addition, the complete non-invasiveness of the technique, 3. the absence of faradic reactions that are potentially tissue damaging, 4. and the ability to generate a predictable current through a more efficient and less cumbersome apparatus , should enhance its potential for clinical use.
  29. 29. Pressure tension theory
  30. 30.  The pressure tension theory , the classic theory of tooth movement , relies on chemical rather than electric signals as the stimulus for cellular differentiation and ultimately tooth movement .  In essence this view of tooth movement shows three stages: 1. Alterations in blood flow associated with pressure within PDL. 2. The formation and release of chemical messengers. 3. Activation of cells.
  31. 31.  The heavier the sustained pressure, the greater should be the reduction in blood flow through compressed areas of the PDL, up to the point that vessels are totally collapsed and no further blood flows.  When light but prolonged forces are applied to a tooth, blood flow through partially compressed PDL decreases as soon as fluids are expressed from the PDL space and the tooth moves in its socket(ie in a few seconds).  Within a few hours , the resulting chemical environment produces a different pattern of cellular activity.  Increased levels of cAMP the “second messenger” are produced after about 4 hours of sustained pressure.
  32. 32. What happens in the first few hours after sustained force is applied against a tooth?  Experiments have shown that prostaglandin and interleukin-1 beta levels increase within the PDL within a short time after the application of pressure, and it is now clear that prostaglandin E is an important mediator of the cellular response.  Changes in cell shape probably play a role.  There is evidence that prostaglandins are released when cells are mechanically deformed (ie pg release might be a primary than a secondary response to pressure).  Mobilization of membrane phospholipids , which leads to the formation of inositol phosphates , is another pathway towards the eventual cellular response.
  33. 33.  Other chemical messengers, particularly members of the cytokine family, also Nitric Oxide and other regulators of cellular activity are also involved.  For a tooth to move osteoclasts and osteoblasts are required for bone resorption and formation on pressure and tension side respectively.  PG-E has the interesting property of stimulating both the osteoclastic and osteoblastic activity, making it particularly suitable as a mediator of tooth movement.
  34. 34. Frontal resorption  When the PDL is mechanically stimulated osteoclasts appear within the compressed PDL within 48 hours.  Osteoclasts arrive in two waves : 1. some (the first wave), maybe derived from a local cell population within the PDL. 2. while others (the larger second wave) are brought from distant areas via blood flow.  Osteoclasts attack the adjacent lamina dura, removing bone in the process of “frontal resorption”, and tooth movement begins soon thereafter.
  35. 35.  Simultaneously osteoblastic activity ensues, but it lags behind a little, so that the PDL space becomes enlarged.  Osteoblasts are recruited locally from progenitor cells in PDL.  Their action is to: 1. form bone on the tension side. 2. and begin remodeling activity on the pressure side.  In frontal resorption a steady attack on outer surface of lamina dura results in smooth continuous tooth movement.
  36. 36. Undermining resorption  The course of events is different if sustained forces against a tooth is great enough to totally occlude blood vessels and cut off the blood supply to an area within the PDL.  Due to its histological appearance as the cells disappear, an avascular area in the PDL has been referred to as hyalinized.  Despite the name , the process has nothing to do with the formation of hyaline connective tissue but represents the inevitable loss of all cells when the blood supply is totally cut off.  When this happens remodeling of bone bordering the necrotic area of the PDL must be accomplished by cells derived from adjacent undamaged area.
  37. 37.  More importantly, osteoclasts appear within the adjacent bone marrow spaces and begin an attack on the underside of the bone immediately adjacent to the necrotic PDL area .  This process is appropriately described as undermining resorption since the attack is from underside of the lamina dura.  When hyalinization and undermining resorption occur , an inevitable delay in tooth movement results.  This is caused by a delay in stimulating differentiation of cells within the marrow spaces , and second because a considerable thickness of bone must be removed from the underside before any tooth movement can take place.
  38. 38.
  39. 39. Time course of treatment with frontal vs undermining resorption
  40. 40.  Not only tooth movement is more efficient when areas of PDL necrosis are avoided but pain is also lessened.  However, even with light forces , small avascular areas are likely to develop in the PDL and tooth movement will be delayed until these can be removed by undermining resorption.  In clinical practice, tooth movement usually proceeds in a more stepwise fashion because of the inevitable areas of undermining resorption.
  41. 41. PDL and bone response to sustained orthodontic force
  42. 42. • The response to sustained force against the teeth is a function of force magnitude: • Heavy forces lead to a rapidly developing pain, necrosis of cellular elements within the PDL, and the phenomenon of “undermining resorption”, of alveolar bone near the effected tooth.  Lighter forces are compatible with survival of cells within the PDL and a remodeling of the tooth socket by a relatively painless “frontal resorption” of the tooth socket.
  43. 43. Phases of tooth movement
  44. 44.  In 1962 Burstone suggested that, if the rates of tooth movement were plotted against time, there would be 3 phases of tooth movement: 1. An initial phase. 2. A lag phase. 3. A postlag phase.
  45. 45.
  46. 46.  Two recent studies done by Pilon etal , and Vas Leeuwen etal have proposed a new time/displacement model for tooth movement.  These studies, performed on beagles, divided the curve of tooth movement into 4 phases.  The first phase lasts for 24 hours to 2 days and represents the initial movement of the tooth inside its bony socket.  It is followed by a second phase, when tooth movement stops for 20 to 30 days.  After the removal of necrotic tissue formed during the second phase , tooth movement is accelerated in the third phase, and continues into the fourth phase.
  47. 47. Initial phase  Cellular and tissue reactions start in the initial phase of tooth movement, immediately after force application.  Events taking place in this phase are:  compression and tension areas develop in the PDL  recruitment of osteoclast and osteoblast progenitors  extravasation and chemoattraction of inflammatory cells  presence of some hyalinized areas was demonstrated even in this early stage
  48. 48. Second phase  Areas of tension are easily recognized by distorted appearance of the normal PDL fiber arrangement.  Disruption of the blood flow due to this distortion leads to development of hyalinized areas and the arrest of tooth movement, which could last from 4 to 20 days.  Only the removal of necrotic tissue, and bone resorption from adjacent marrow spaces, and from the direction of the viable PDL, allow the resumption of tooth movement.
  49. 49.  This process requires the recruitment of phagocytic cells such as macrophages, foreign body giant cells, and osteoclasts.  These cells act in tandem to remove necrotic tissue from compressed PDL sites and adjacent alveolar bone.  In areas of PDL tension, quiescent osteoblasts are enlarged and start producing new bone matrix (osteoid).
  50. 50.  New osteoblast progenitors are recruited from the population of fibroblast-like cells(pericytes) around PDL capillaries.  These preosteoblasts proliferate and migrate toward the alveolar bone surface along the stretched Sharpey’s fibers.  Simultaneously the PDL fibroblasts in tension zones begin multiplying and remodeling their surrounding matrix.
  51. 51.  The third and fourth phases of orthodontic tooth movement , also known as the acceleration and linear phases, respectively, start about 40 days after the initial force application.  They comprise most of the total tooth movement during orthodontic treatment.  The pressure sides of teeth exhibit collagen fibers without proper orientation. Here irregular bone surfaces are found, indicating direct or frontal resorption.  Tension sides during these phases clearly show bone deposition.
  52. 52.  Recent reports by Von Bohl etal demonstrated that teeth subjected to high forces show hyalinization more often than teeth experiencing light forces.  Thus development of hyalinization zones has a definite relationship to force magnitude , but it was found to have no relationship to the rate of tooth movement.  These investigators have concluded that , once tooth movement has started after the second(arrest) phase, bone remodeling takes place at a certain rate, independent of the force magnitude.
  53. 53. Effects of force distribution
  54. 54.  The optimum force levels for orthodontic tooth movement should be just high to stimulate cellular activity without completely occluding blood vessels in the PDL.  Both the amount of force delivered to a tooth and also the area of the PDL over which that force is distributed are important determinants of the biologic effect.  The PDL response is determined not by force alone, but by force per unit area, or pressure.
  55. 55.  Since the distribution of force within the PDL , and therefore the pressure differs with different types of tooth movement, its necessary to specify the type of tooth movement as well as the amount of force in discussing optimum force levels for orthodontic purposes.
  56. 56. Types of tooth movement
  57. 57. Tipping
  58. 58.  Tipping of a tooth leads to concentration of pressure in limited areas of the PDL.  Forces used to tip a teeth must be kept quite low.  Both experiments and experience with humans suggest that the tipping forces should not exceed approximately 50 gm.  Tipping of a tooth by light continuous forces results in greater movement within a shorter time than that obtained by any other method.  Coronal portion of a tooth is chiefly what is moved.
  59. 59.  In most young patients , bone resorption resulting from a moderate tipping movement usually is followed by compensatory bone formation.  The degree of such compensation varies individually and depends primarily on the presence of osteoblasts in the periosteum.  Compensatory periosteal bone apposition in the apical region is also subject to variation, according to whether osteoblasts are present or absent in the periosteum.
  60. 60.  Tipping of adult teeth in a labial direction may result in bone destruction of the alveolar crest , with little compensatory bone formation.  In addition after a prolonged movement of the apical root portion in the opposite direction, resorption of the bone plate in the apical region may occur so rapidly that the root finally is moved through the bone.
  61. 61. Torque  A torquing movement of tooth involves tipping of the apex.  During the initial movement of torque the pressure area usually is located close to the middle region of the root.  This occurs because the pdl is normally wider in the apical third than the middle third.  After resorption of bone areas corresponding to the middle third , the apical surface of bone gradually begins to compress adjacent periodontal fibres and a wider pressure area is established.  Tipping forces of 50-60 gm in the anterior teeth of humans are sufficient.
  62. 62. Bodily movement (Translation)  If two forces acting along parallel lines and distributed over the whole alveolar bone surface are applied simultaneously to the crown of a tooth, the tooth can be bodily moved.(ie the crown and the root apex move in the same direction and the same amount.)  Slight tipping movement also occurs during translation of a tooth.  In translation the total PDL area is loaded uniformly.  Forces in the range of 70-120 gm are sufficient for this purpose.
  63. 63. Extrusive movements during tipping and translation.  A tooth that is moved by tipping is also frequently somewhat extruded, which is a direction of fiber stretching that facilitates further tipping.  Even a tooth moved bodily may become slightly extruded unless the archwire has been adjusted to compensate for any tendency to extrusion.
  64. 64. Rotation  In rotation of a tooth, theoretically forces to produce rotation around its long axis could be much larger than those to produce other tooth movements, since the force would be distributed over the entire PDL rather than a narrow vertical strip.  In fact, however , it is essentially impossible to apply a rotational force so that the tooth also does not tip in its socket, and when this happens an area of compression is created just as in any other tipping movement.  For this reason, appropriate forces of rotation are similar to those for tipping, ie 50-60 gm.
  65. 65. Retention considerations after rotation of teeth  The elongation and oblique arrangement of the supporting fiber bundles necessitate a retention period after treatment has been completed.  In the marginal region rotation usually causes considerable displacement of fibrous structures.  The free gingival fiber groups arranged obliquely from the root surface, interlace with the periosteal structures and the whole supra alveolar fibrous system.  Thus rotation also causes displacement of fibrous tissues located some distance from the rotated tooth.
  66. 66.
  67. 67.  The fiber bundles and the new bone layers of the middle and apical third rearrange themselves after a fairly short retention period.  However , the free gingival fibers remain stretched and displaced for as long as 232 days and possibly longer.  According to these observations, over-rotation or fiberotomy has been recommended.
  68. 68. Extrusion  Extrusive movements ideally produce no areas of compression within the PDL, only tension.  Even if compressed areas could be avoided, heavy forces risk extraction of the tooth.  Light forces , however, move the alveolar bone with the tooth.  Varying with the individual tissue reaction, fiber bundles elongate and new bone is deposited in areas of alveolar crest as a result of the tension exerted by these stretched fiber bundles.
  69. 69.  The force exerted must not exceed 25 -30 gm, because extrusion constitutes the type of tooth movement that requires minimal force.  The open space in the apical region consists partly of an uncalcified osteoid, which is not perceptible on a radiograph.  After 4-5 weeks, calcified bone starts to become visible in the apical area.
  70. 70.
  71. 71. Intrusion  During intrusion of teeth stretch is exerted primarily on the principal fibers.  Relapse usually does not occur, partly because the free gingival fiber bundles become slightly relaxed.  Due to the stretch of principal fibers an intrusive movement may therefore cause formation of new bone spicules in the marginal region.  Rearrangement of the principal fibers occurs after a retention period of 2-3 months.
  72. 72.
  73. 73.  In a young patient the intruded tooth may remain fairly stable.  In adults, however, relapse after intrusion may occur, particularly when the retention period has been too short.  Intrusion requires careful control of force magnitude.  Light force is required because force is concentrated in a small area at the tooth apex.
  74. 74.  Primarily the anterior teeth are intruded.  A light continuous force has proved favourable for intrusion in young patients.  In other cases the alveolar bone may be closer to the apex, increasing the risk for apical root resorption.
  75. 75.  If the bone of the apical region is fairly compact, as it is in some adults, 1. a light interrupted force may be preferable to provide time for cell proliferation to start, 2. and direct bone resorption may prevail when the arch wire is reactivated after the rest period.
  76. 76. Effect of force duration and force decay
  77. 77.  The key to produce orthodontic tooth movement is the application of sustained force, which does not mean that the force must be absolutely continuous.  It does mean that the force must be present for a considerable percentage of time, certainly hours rather than minutes per day.  Animal experiments suggests that only after force is maintained for approximately 4 hours do cyclic nucleotide levels in the PDL increase, indicating that this duration of pressure is required to produce the “second messenger” needed to stimulate cell differentiation.
  78. 78.  Clinical experience suggests that there is a threshold for force duration in humans in the 4-8 hour range, and that increasingly effective tooth movement is produced if force is maintained for longer durations.  Continuous forces , produced by fixed appliances that are not effected by what the patient does , produce more tooth movement than the removable appliances, unless removable appliance is present almost all the time.  Removable appliances worn for decreasing duration of time produce decreasing amounts of tooth movements.
  79. 79. How force magnitude changes as tooth responds by moving?  Duration of force has another aspect, related to how force magnitude changes as tooth responds by moving.  Some decline in force magnitude (ie force decay) is noted with even the springiest device after the tooth has moved a short distance.  From this perspective, orthodontic force duration is classified by the rate of decay as: 1. Continuous – force maintained at some appreciable fraction of the original from patient’s one visit to the next. 2. Interrupted- force levels decline to zero between activations.
  80. 80.  There is an important interaction between force magnitude and how rapidly the force declines as the tooth responds.  To understand this we consider: 1. The effect of a nearly continuous force. 2. Effect of forces that decay fairly rapidly.  Theoretically there is no doubt that light continuous forces produce the most efficient tooth movement.  Despite the clinicians best efforts to keep forces light enough to produce only frontal resorption, some areas of undermining resorption are probably produced in every clinical patient.
  81. 81.  The heavier forces are physiologically acceptable, only if : 1. Force levels decline so that there is a period of repair and regeneration before the next activation. 2. Force decrease at least to the point that no second and third rounds of undermining resorption occurs.  Heavy continuous forces are to be avoided; heavy intermittent forces though less efficient , can be clinically acceptable.
  82. 82. Reactivation schedule  Experience has shown that orthodontic appliances should not be reactivated more frequently than at 3 week intervals.  A 4-6 week appointment cycle is more typical in clinical practice.  Undermining resorption requires 7-14 days.
  83. 83. Diurnal variation in tooth movement in response to orthodontic forces
  84. 84.  Diurnal rhythms have been found in various parameters related to bone formation and resorption, including plasma calcium and phosphate, calcium regulating hormones, osteocalcin.  Diurnal rhythms have also been found in various local events that influence bone turnover , such as proliferation and matrix synthetic activities of osteogenic cells, osteoclast-bone surface contact, and enzyme activities related to bone formation and resorption.  Kotaro Miyoshi etal conducted a study to investigate whether there is any differnce in orthodontic tooth movement in rats when orthodontic force is applied at different times of the day and night.
  85. 85.  More tooth movement was achieved in the rats that received orthodontic force during day time, than those which received the forces during night time.  Results of their study showed for the first time that the response to orthodontic force varies depending on the time of the day, the force is applied.  Also application of force during animal’s rest period may be more effective than while it’s active.
  86. 86.  In rats both bone formation and bone resorption are most active in the environmental light period, and are minimal in the environmental dark period.  This indicates that a greater bone-formative response can be obtained when orthodontic force is applied during the light period, the period of active bone formation, rather than during the dark period.  Thus the magnitude of the response may depend on the underlying physiologic activity of bone formation , which varies with the time of the day.  Possible explanations of this diurnal rhythm can be: 1. Hormonal variations. 2. Diurnal variation in masticatory function.
  87. 87. Hormonal variation  In rats, rhythms of cell proliferation in cartilage and bone parallel the serum corticosterone level, while the rhythm, of matrix synthesis in bone is parathyroid dependant.  It has been shown that diurnal rhythms in calcium metabolism in both rats and human beings are regulated by undefined serum factors.  Therefore it is reasonable to assume that the observed variation in tooth movement is also caused by these hormonal rhythms.
  88. 88. Diurnal masticatory rhythm  Another possible cause for this diurnal variation may be a bio- mechanical rhythm, ie diurnal variation in masticatory function.  The rats being more active during nocturnal period , consume more food during the dark period than during day time, indicating that their masticatory activities increase during night.  Thus it is conceivable that increased masticatory activities during the dark period might interfere with orthodontic force, and thus may inhibit tooth movement.
  89. 89.  If this is applicable to diurnal human beings, more tooth movement would be expected at night than during the day.  Stutzman and Petrovic have shown that the rate of alveolar bone turnover in human beings is higher in the night-time than in daytime.
  90. 90. Cellular response to orthodontic force
  91. 91.  Tooth movement ultimately depends on specific activation of precursor (osteoprogenitor) cells, which form osteoblasts and osteoclasts.  Understanding these level mechanisms and controlling the bone remodeling response is essential to intelligently evaluating current treatment methods and developing innovative approaches in the future.
  92. 92. Mechanically induced bone remodeling  Remodeling is divided into 3 major categories: 1. Turnover in response to micro fractures. 2. Reorientation of bone mass to optimally resist stress (Wolff’s law). 3. Net change in bone volume related to functional load.  At the tissue level the bone turnover cycle is divided into three phases: 1. Activation – occurs in matter of hours. 2. Resorption- occurs in a month. 3. Formation- occurs in 2-3 months.
  93. 93.  This ARF sequence is basically a repair process, requiring about 4 months in adult human cortical bone.  Stress patterns within the periodontium, resulting from functional and/or orthodontic loads , dictate the form of periodontal bone.
  94. 94. Force system
  95. 95.  Application of a force system to the crown of a tooth produces a cascade of viscoelastic, biochemical, and biophysical effects within the periodontium and supporting bone.  From a cellular point of view, distribution of stress, displacement of the PDL, and bone deformation are critical factors.  The characteristics of force system that relate to its biologic effects are: 1. Magnitude. 2. Frequency. 3. Direction and moment to force ratio. 4. Constancy. 5. Functional modification.
  96. 96. Transduction
  97. 97.  Transduction is the conversion of mechanical energy into a biologic signal affecting a remodeling response.  By stress and strain , the mechanical load of an orthodontic force system is transferred to the periodontium, resulting in: 1. Altered stress patterns. 2. Viscoelastic displacement of the PDL. 3. Bone deformation.
  98. 98.  These biophysical events are currently thought to be transduced into a cellular response by one of the following mechanisms: 1. Cell perturbation. 2. Bioelectric signals. 3. Micro environmental factors. 4. Accumulation of micro fractures.
  99. 99.  Because the PDL is viscoelastic it resists displacement by short acting loads such as mastication and swallowing.  However it is readily displaced by light continuous or even interrupted forces such as orthodontic forces or postural habits.  Displacement results in PDL that is widened in osteogenic areas or compressed in cell free or hyalinized areas.
  100. 100. orthodontic force PDL displacement influx of Na and Ca ( Ca influx) cell perturbation inhibits enzyme Adenylate cyclase slows down the production of 2nd messenger cAMP low levels of cAMP(intracellular) initiation of proliferation in bone and cartilage progenitor cells
  101. 101.  Thus stress/ strain brought about by a c AMP mediated mechanism, involving direct perturbation and/ or a bioelectrical signal, appears to initiate proliferation in osseous progenitor cells, an important aspect in activation of bone remodeling.
  102. 102. Micro-environmental factors  Among the micro-environmental factors implicated in initiation of the response of the PDL are : 1. Vascular flow (partial pressure oxygen and carbon dioxide). 2. Cell density changes (widening of PDL breaks contact inhibition, which induces proliferation). 3. Ground substance -collagen ratio.
  103. 103. During PDL displacement Ground substance (from compression areas) (predominantly negatively charged) (migrates with respect to fixed positively charged collagen) Areas of tension (widened zones)
  104. 104.  Thus it is evident that in the stressed PDL: 1) Osteogenic /Tension areas: high ground substance :collagen ratio net negative charge decreased c AMP levels increased osteoblastic activity 2) Resorptive / Compression areas: low ground substance:collagen ratio net positive charge increased c AMP activity increased osteoclastic activity
  105. 105.  As reviewed by Storrey , bone is an anisotrophic, viscoelastic material progressing from elastic to plastic to disruptive deformation, depending on the magnitude and frequency of the load.  Even light loads, continuously applied, produce progressive deformation and may eventually lead to fracture.  At the histological level, micro fractures are any disruption from a minute crack to a fractured trabeculus.
  106. 106. Remodeling response
  107. 107. Osteoclasts recruitment  Appearance of increased number of osteoclasts occurs within hours of application of orthodontic force.  Even after force is terminated, osteoclasts persist for several days in rats and up to 10 days in humans.
  108. 108.  The important distinction is that active osteoclasts are recruited, and are not dependant on local PDL cell proliferation/differentiation as was previously thought.  A significant factor in the orthodontic response is probably recruitment of previously present inactive osteoclasts into the active fraction that supports tooth movement.
  109. 109. Osteoblast histogenesis  Osteoblasts in response to orthodontic force are produced locally by proliferation and differentiation of PDL fibroblast like cells.  This remarkable potential of PDL is related to a large population of osteoblast(Ob) precursor cells.  More than a third of the fibroblast like population in the PDL are preosteoblasts , the immediate proliferating predecessors of osteoblasts.
  110. 110.  Following three aspects are related to osteoblast histogenesis: 1. Cell cycle analysis. 2. Nuclear morphometry. 3. Photoperiod influence.
  111. 111. Cell cycle analysis
  112. 112. Nuclear volume and photoperiod
  113. 113.
  114. 114. Alveolus translocation  Alveolus translocation is the basic bone forming and resorbing response within and immediately adjacent to the PDL following application of orthodontic force.  Alveolus response is a special case of remodeling in which bone formation and resorption occurs simultaneously on opposite sides of the alveolus resulting in drift of the bony socket.  Movement of one mineralized tissue(root), through another (alveolar bone) reflects the unique transduction and activation properties of the PDL.
  115. 115.  During initiation of tooth movement , the osteogenic reaction is slower(days), than the osteoclastic response (hours), in affecting bone remodeling changes.  Particularly when cell free zones and undermining resorption are involved, the resorptive aspect of alveolar translocation is the rate limiting step in tooth movement.
  116. 116. Alveolar bone remodeling  Turnover in human skeleton varies from 5% per year for long bone cortex to 33% for trabecular bone.  The rate of alveolar bone turnover is intermediate between the two.  Tooth movement is not only a response of PDL but also involves generalized remodeling of the adjacent alveolar process.  Half or more of the entire alveolar bone is remodeled during typical orthodontic treatment.
  117. 117.  Areas of hyalinization and necrosis are noted even during physiologic drift and relapse, it is unlikely that significant orthodontic tooth movement occurs without increased bone deformation and remodeling of adjacent alveolar bone.
  118. 118.
  119. 119. Retention period following remodeling  Reitan observed that newly deposited bundle bone is readily resorbed during relapse or reverse tooth movement  Retention involves not only prevention of relapse but also stabilization of a new functional entity.  Considering 1. orthodontically induced remodeling transients, 2. completion of secondary remineralization, 3. and functional adaptation of the alveolar process, four to six months is a biologically relevant , minimal retention period.
  120. 120. Clinical considerations in bone remodeling  Activation of remodeling pockets in resisting bone may be an important factor in rate of tooth movement. • The burst of resorption (A R) ahead of a moving tooth might be considered “telegraphing” a resorptive signal to decrease bone mass preparatory to complete resorption associated with alveolar translocation.  Typical reactivation interval for devices with relatively short ranges of activation (such as closure loops) is about one month.
  121. 121.  From a biological perspective, modern orthodontics is quite primitive.  For example under ideal conditions, bone resorbed is about 100 microns per day, which would relate to orthodontic translation at a rate of 3 mm per month.  This greatly exceeds the efficiency of any clinical method, indicating a considerable gap between clinical proficiency and biologic potential.
  122. 122. Role of neurotransmitters in tooth movement
  123. 123.  Substance -P like immunoreactive nerve fibers have been shown to be distributed in the dental pulp, and PDL , and in the soft tissue of the TMJ.  A study done by Davidovitch et al revealed that in living animals, sensory nerve fibers in the PDL may provide neurotransmitters, specifically SP, to cells populating and bordering the periodontium.  It suggests that in vivo the peripheral nervous system acts as a possible supplier of a link between physical stimulus and the biochemical response.
  124. 124. Pressure Pain reflex Substance P release from sensory nerve terminals Antidromic vasodilation Migration of leukocytes out of capillaries increased supply of PG’s Secretion of lymphokines interaction with Responsive Paradental cells Synthesis of 2nd messengers
  125. 125. First and second messenger interactions in stressed connective tissue
  126. 126.  Connective tissue cells are capable of responding to a variety of stimuli in a mechanism which involves ligand-receptor interactions.  These stimuli are regarded as “first messengers”, whose interaction with specific cell surface receptors leads to enzymatic activities and formation of “second messengers” intracellularly.  It was postulated that cellular stimulation in mechanically stressed bone may result from the motion of fluids and the generation of endogenous electric potentials, leading to enhanced cellular ionic refluxes.
  127. 127.  First messengers : 1. Mechanical - motion of fluids, endogenous electric potentials 2. Chemical - Substance-P, PGE  Second messengers : cAMP, cGMP, Ca
  128. 128.  Davidovitch etal suggested that connective tissue cells, particularly bone cells, may be activated by stress generated potentials, or streaming potentials resulting from force-induced motion of extracellular fluids which bring a variety of ions and molecules in contact with the plasma membrane of native cells.  Moreover , stretching or compressing cells may alter the permeability properties of their membranes , facilitating ion fluxes.
  129. 129. Reaction of connective tissue cells to mechanical forces
  130. 130.  Thus it appears that physical and chemical first messengers may be operant in the initial stage of connective tissue response to mechanical forces.  The interaction of these signals with cells in the affected areas seems to involve elevations in the cellular content of second messengers such as cAMP, c GMP, and Calcium.
  131. 131. Role of Prostaglandins and Interleukins in tooth movement
  132. 132.  In studies of vascular response done by Kenichi Yamasaki on rats, it was demonstrated that periodontal vascular permeability increased both on pressure and tension sides 15 minutes to 1.5 hours following the application of orthodontic force.  These reports suggest that initiation of inflammation was triggered by chemical mediators such as histamine and bradykinin, and PG’s.  Furstman and Bernick reported that pain reaction associated with OTM was from periodontal inflammation caused by mechanical stress, and was induced by chemical mediators such as histamine,bradykinin, and PG’s.
  133. 133.  Prostaglandins are produced from arachidonic acid .  They are released into the extracellular environment, where they participate in cell-cell communication by interacting with prostaglandin receptors on neighboring cells.  Prostaglandin E is involved in : 1. Bone resorption. 2. Bone stimulation. 3. Cell proliferation. 4. Collagen synthesis.
  134. 134.
  135. 135.  This dual effect of PGE on bone formation and resorption is consistent with increased bone turnover triggered by mechanical stimulation.  Thus PG’s may effectuate part of the coupling observed between bone resorption and bone formation.  Biochemical mechanism for PG mediated bone resorption is not known.  In many systems PGE1 and E2, the most potent bone resorption agents , were shown to stimulate adenylate cyclase activity, which is an enzyme catalyzing synthesis of c AMP.
  136. 136.  In vitro experiments carried out by Rodan etal confirmed that mechanical perturbations , which approach a physiologic range , augment prostaglandin production in the osteoblast –enriched cell population.
  137. 137. Cell types synthesizing PG’s  The precise identity and location of PG synthesizing cells is not known.  Davidovitch etal from their studies elucidated that PG’s do not seem to be synthesized by PDL cells, native or migratory, but to be bound by these cells.  The paradental cells associated with the PDL and the alveolar bone, such as fibroblasts, macrophages, cementoblasts, osteoblasts, and osteoclasts are the potential sources of PGE during tooth movement caused by orthodontic forces.
  138. 138.  William G Grieve etal in their study on PGE, and IL1b levels in GCF during human orthodontic tooth movement found that these bone resorbing factors produced within the PDL are detectable in GCF during early phases of tooth movement, and return to their baseline within 7 days.  IL b stimulates bone resorption and concomitantly inhibits bone formation.  IL 1 b levels increased at – 1 hr, 24 hrs and 1 week.  PGE levels increased at - 24 hrs, 48 hrs , and 1 week.  IL b modulates PGE production.
  139. 139.  Kenichi Yamasaki in an vitro study on rats suggested that orthodontic mechanical stress induces the synthesis of PG’s by localized cells, which, in turn stimulate osteoclastic bone resorption.  Lilja etal investigated the enzymatic profile in periodontal tissues histochemically, and suggested that PG synthetases are found in bone marrow in areas undergoing OTM in rats.  Davidovitch and Shanfeld reported the involvement of PGE2 in the bone remodeling of orthodontically treated cats, showing a rise of PGE2 levels in the alveolar bone.
  140. 140.  The mechanism of synthesis and secretion of PG’s from mechanically stressed periodontal tissues is unknown.  Buck etal found lipids which may be correlated with PG’s in stressed human periodontal tissues, especially in cell-free zones.  Stress could conceivably cause a perturbation of periodontal tissue cell membranes with a resultant increase in the synthesis and secretion of PG’s , since the precursors of PG’s are the lipids which constitute the cell membrane.
  141. 141. Action of PG’s  c AMP and intracellular calcium have been reported to be involved in the action of PG’s.  Action of PG’s is known to cause an increase in concentration of both of them.  These second messengers are involved in the induction of osteoclasts from monocytic cells during bone resorption induced by orthodontic mechanical forces.
  142. 142. Orthodontic mechanical stress damage/perturbation of PDL tissues PG synthesis Tooth movement intracellular c AMP and calcium accumulation by monocytic cells Bone resorption modulation and activation of osteoclastic activity
  143. 143. The second messengers
  144. 144.  The second -messenger hypothesis postulates that target cells respond to external stimuli, chemical or physical, by enzymatic transformation of certain membrane- bound and cytoplasmic molecules to derivatives capable of promoting phosphorylation of cascades of intracellular enzymes.
  145. 145.  The first messenger binds to a specific receptor on cell membrane and produces an intracellular second messenger.  This second messenger then interacts with cellular enzymes, evoking a response, such as protein synthesis or glycogen breakdown.  Two main 2nd messenger systems are now recognized: 1. The cyclic nucleotide pathway. 2. Phosphatidyl inositol(PI) dual signaling system.  These systems mobilize internal calcium stores and activate protein kinase C respectively.
  146. 146. The c AMP pathway  c AMP and c GMP are 2 second messengers associated with bone remodeling.  Bone cells, in response to hormonal and mechanical stimuli, produce c AMP in vivo and in vitro.  Alterations of c AMP levels have been associated with synthesis of polyamines, nucleic acids, and proteins, and secretion of cellular products.
  147. 147.  The action of c AMP is mediated through phosphorylation of specific substrate proteins by its dependant protein kinases.  In contrast to this role, c GMP is considered an intracellular regulator of both endocrine and non endocrine mechanisms.  This signaling molecule plays a key role in synthesis of nucleic acids and proteins as well as secretion of cellular products.
  148. 148. The PI dual signaling systems activation of cell surface receptors by 1st messengers hydrolysis of PI 4,5 biphosphonate inositol triphosphate formation release of calcium ions from intracellular stores mitogenesis in mechanically deformed tissue through an increase in DNA synthesis
  149. 149. Role of calcium in tooth movement
  150. 150. Tension(bone apposition) side Ca influx inhibits intracellular enzyme Adenylate cyclase ( which) slows down production of 2nd messenger c AMP initiation of proliferation among bone and cartilage progenitor cells stimulates bone apposition
  151. 151. Pressure (bone resorption) side membrane deformation Ca influx increases activity of PLA2 enzyme Increase in osteoclasts/bone resorption stimulates release of arachidonic acid from membrane phospholipids synthesis of 2nd messenger c AMP PGE2 synthesis
  152. 152. Role of Vitamin D in Orthodontic tooth movement
  153. 153.  1,25, dehydroxycholecalciferol (1,25, DHCC) has been identified as an important factor in tooth movement.  This agent is a biologically active form of Vitamin D, and has a potent role in calcium homeostasis.  This molecule has shown to be a potent stimulator of bone resorption, by inducing differentiation of osteoclasts from their precursors..  It is also known to stimulate bone mineralization and osteoblastic cell differentiation in a dose-dependant manner.
  154. 154.  Kale et al compared the effects of local administration of 1,25, DHCC , and PGE2 on orthodontic tooth movement in rats, and reported that both molecules enhanced tooth movement significantly.  In this study, 1,25, DHCC was found to be more effective than PGE2 in modulating bone turnover during tooth movement, because of its well balanced effect on bone formation and resorption.
  155. 155. Drug effects on the response to orthodontic force
  156. 156.  Administration of certain pharmacologic agents may: 1. Stimulate tooth movement. 2. Depress tooth movement. in response to orthodontic forces.  It is quite possible that use of these pharmacologic agents to manipulate tooth movement in both directions will come into common use.
  157. 157. Drugs stimulating tooth movement  Vitamin D administration can enhance the response to orthodontic force.  The E series of PG’s appears to be the most potent stimulators of bone resorption.  A series of studies have shown that they produce a dose related increase in calcium release from bone in vitro.  Direct injection of PG into the PDL has shown to increase the rate of tooth movement, but this is quite painful, and not very practical.
  158. 158.  Based on his experiments on OTM in rats Kenichi Yamasaki suggested that it is possible that PG’s may be useful in clinical orthodontic movement in the form of local administration combined with OTM.  He suggested that local administration of PG’s combined with OTM : 1. Reduces the hyalinization areas in PDL. 2. Induces more rapid bone remodeling. 3. Provides continuous tooth movement and accelerates the rate of tooth movement.
  159. 159. Drugs depressing tooth movement  Two types of drugs are known to depress the response to orthodontic force, and may influence current treatment: 1. The bisphosphonates used in treatment of osteoporosis. eg alendronate. 2. Prostaglandin inhibitors. eg indomethacin.  Bisphosphonates act as specific inhibitors of osteoclast -mediated bone resorption
  160. 160.  Drugs that effect PG activity fall into two categories: 1. Corticosteroids, and NSAIDs that interfere with PG synthesis. 2. Other agents that have mixed agonistic and antagonistic effects on various PG’s.  Both children and adults on chronic steroid therapy may be encountered, and the possibility of difficult tooth movement in these patients must be kept in mind.
  161. 161.  Fortunately, although potent PG inhibitors like indomethacin can inhibit tooth movement, the common analgesics (ibuprofen, aspirin) seem to have little effect on tooth movement at the dose levels used with orthodontic patients.  Some other drugs which can effect PG levels, and therefore affect the response to orthodontic force are: Tricyclic antidepressants (amitriptyline) antiarrythmic drugs(procaine) antimalarial drugs (quinine,quinidine) anticonvulsant drugs (phenytoin) some tetracyclines( eg doxycycline)
  162. 162.  Recently, the possibility that locally applied PG inhibitors could be used to decrease the response of specific teeth has been explored.  It is now possible in periodontal therapy to place miniature spheres that release a specific antibiotic into the gingival sulcus and into the periodontal pockets.  If a PG inhibitor was placed in similar mini- spheres , and could be maintained in the sulcus around teeth that were to serve as anchors, the improved anchorage would allow more effective tooth movement of the teeth whose movement was desired.
  163. 163. Apical root resorption associated with otm
  164. 164.  Apical root resorption is one of the most common complications associated with orthodontic treatment.  The general consensus is that apical root resorption of vital teeth occurs to some extent in all orthodontic patients.  Following are some important facts about apical root resorption associated with otm:  Sinclair and Sameshima in their study on apical root resorption reported that : 1. Apical root resorption occurs mainly in the anterior teeth , averaging over 1.4 mm.
  165. 165. 2. The average amount of root resorption found for molars and premolars is very low( less than 1mm). 3. Within the anterior segment maxillary teeth are more affected than mandibular teeth by a factor of 2. 4. Among the maxillary anterior teeth following is the frequency of root resorption : laterals>centrals>canines 5. Asian patients had significantly less root resorption than white patients.
  166. 166. 5. Increased root length and overjet are correlated with greater root resorption for the maxillary anterior dentition. 6. Adults have significantly more resorption than children in the mandibular anterior teeth.  Spurrier etal in their study on comparison of root resorption during otm of vital teeth vs endodontically treated teeth found that endodontically treated incisors resorb with less frequency and severity than vital teeth.
  167. 167. Effect of extraction and orthodontic treatment on dentoalveolar support
  168. 168.  In a study done by David B Kennedy etal on effect of extraction and orthodontic treatment on dentoalveolar support reduced alveolar bone heights were noted : 1. in the extraction sites due to bone loss. 2. in the areas of root resorption due to otm.  The most marked alveolar bone loss was seen interproximally for maxillary and mandibular permanent incisors , and at the pressure side of closed first premolar extraction sites.
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