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Bone metabolism & Biological Theories of Tooth movementPreceptors: Dr. Pavan Kumar Chandra Dr. Piush Kumar Presented by: Dr. Anuja Aggarwal2 Bone is a specialized mineralized connective tissue made up of an organic matrix of collagenfibrils embedded in an amorphous substance with mineral crystals precipitated within the matrix.Matrices

organic inorganic 35 % of dry wt. Type I collagen. 10 % non collagenous proteins.ex:BMP Noncollagenous proteins are PG or GAG Modulate cellular attachment. 60 70 % of dry wt. 99% Ca,85 % P, 40 60 % Na & Mg

5Classification of boneBased on Structure Compact Bone or cortical bone - the dense outer shell of the skeleton.Cancellous Bone or trabecular bone - comprises of a system of plates, rods, arches and strutstraversing the medullary cavity encased within the shell of compact bone.Based on developmentIntramembranous bone Eg., Bones of cranial vault, maxilla, etc.Intracartilagenous bone Eg., Vertebra, ribs, base of the skull, etc6Based on the arrangement of the collagenous matrix.Immature Bone : is subdivided into : Woven Bone : Relatively weak ,disorganized and poorlymineralized. The first bone formed in response to orthodontic loading usually is the woven type.Bundle bone Bundle bone is a functional adaptation of lamellar structure to allow attachment ofSharpey's fibersMature Bone or Lamellar bone Lamellar bone a strong, highly organized, well-mineralizedtissue. Adult human bone is almost entirely of the remodeled variety: secondary osteons andspongiosa..

7W Woven Bone L Lamellar Bone8HISTOLOGY OF BONE9PeriosteumCompact BoneCircumferential lamellae Concentric lamellae Interstitial lamellaeBony trabeculaeBone MarrowHISTOLOGY OF BONE

Bone consists of 4 microstructural components1. Cells 2. Organic matrix 3. Inorganic matrix 4. Soluble signalling factorsOsteoblasts Osteocytes osteoclasts

According to Brighton following fracture with in 12 hrs polymorphic mesenchymal cells appearproviding preosteoblastic cell resource. Depending on the presence of environmental cues such as nutrient supply, specific growthfactors, blood vessels & mechanical stability , they can convert either to cartilage formingchondrocytes or bone forming osteoblasts.

Osteoblasts Round cells with an organelle rich cytoplasm. Form bone by laying down osteoid first and thenmineralizing it. Osteoblasts are metabolically active secretory cells that express soluble signaling factors ex:BMPs, TGF- beta, insulin like growth factor I & II , interleukin 1 & platelet derived growth factor

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& osteoid. Expression of these factors by osteoblasts occurs during bone embryogenesis,maintenance(ex: remodeling) & repair. Osteoblasts are derived from paravascular connective tissue cells. Mesenchymal stem cellsdifferentiate into osteoblasts when they are exposed to bone morphogenic proteins (BMP). Cbfa1 is a transcription factor that is expressed by the cells of osteoblastic lineage and isnecessary for osteoblast differentiation During remodeling , osteoid is produced at the rate of 2 -3 micrometers per day at a thickness of 20 micrometers.

After a maturational period of 10 days, osteoid mineralises at a rate of 1- 2 micro meters perday.Osteocytes Osteocytes are former osteoblasts that have become entrapped in bone matrix. These are relatively inactive cells. Their subdued metabolic activity is crucial to bone viability &to sustain homeostasis. The complex processes of homeostasis are regulated by physiologic interactions among cells,tissues, organs & signaling factors such as harmones & growth factors that meticulously titrateintra & extra cellular levels of cationic & anionic moieties Vitality of bone is maintained through a network of osteocytic cytoplasmic processes thattraverse canaliculi.

This highway system enables osteocytes to interact through gap junctions & permits signaltransmission to osteoblasts from osteocytes & from osteocytes to osteoblasts. Osteocytes,osteoblasts & osteoclasts are the cellular crafts men performing the managerialroles of calcium regulation & bone homeostasis, physiological processes fundamental tomodeling & remodeling.Osteoclasts Granulocytic precursors found in bone marrow enter the circulation asmonocytes , and through asynchronous fusion, produce a multinucleated cell with an average of10 12 nuclei known as osteoclast. They represent the terminal stage of differenciation of thesecells. Osteoclasts have a ruffled border, possess calcitonin receptors. They secrete a lysosomal enzyme, tartrate- resistant acid phosphatase (TRAP), which is alsoused as a marker for osteoclast identification. Differentiation of osteoclasts Osteoclasts differentiate from hematopoietic cells. This pathwayof differentiation is also shared by macrophages. GM-CSF (granulocyte monocyte colonystimulating factor) and M- CSF (macrophage colony stimulating factor) are important in regulatingthese shared stages of development.

Another important discovery of osteopotegerin (OPG) or Osteoclastogenesis inhibiting factoe(OCIF) secreted by osteoblasts and functions to block the formation of osteoclasts and boneresorption. SUDA et al isolated an osteoblast membrane bond molecule called osteoclastdifferentiation factor (ODF). ODF was able to induce osteoclastogenesis in bone organ cultures.

When ODF was cloned, it was found identical to an already cloned member of the TNF ligand

family, called TRANCE (TNF-related activation induced cytokine) or RANKL (receptor activatorof nuclear factor kB ligand) Osteoblast membrane bond RANK ligand interact with developing monocytes to cause them todifferentiate eventually into osteoclasts.

Osteoblast regulates the differentiation of osteoclasts. The TALK between an osteoblast andosteoclast is accomplished through an osteoblast membrane bond RANK Ligand (RANKL)(receptor activator of nuclear factor kB ligand)

In this situation OPG can develop to block RANKL in turn blocking the interaction betweenRANK and RANKL/ODF

Cytokines (TNF, interleukin-1), prostaglandins E and growth factors (TGF-, BMP) areupstream signals which regulate the OPG/ODF ratio.

How do osteoclasts work?Osteoclasts contain large amounts of carbonic anhydrase to facilitate the conversion of CO2 and

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H2O to H2CO3. The degradation of bone matrix is presumably the result of the activity of anumber of lysosomal enzymes which can degrade bone at low pH.There is a correlation between activation of bone resorption and acid phosphatase release andoxygen derived free radicals localized in ruffled border..A variety of cathepsins, superoxide dismutase and other lytic enzymes which are produced bythe osteoclast are able to degrade collagen at low pH.

Decreased blood Ca level

parathyroid kidneyparathormone Vitamin DBone Increase in resorption & release of CaIntestine Increase in absorption of CaIncreased blood Ca levelthyroidcalcitoninBone Inhibition of bone resorption and deposition of CaNormal calcium levelFactors affecting bone metabolism Stimulation InhibitionBone formation GH Calcitonin Insulin Testosterone Estrogen

CortisolMineralization Calcitonin Insulin Vit D

CortisolBone resorption Parathormone Thyroxine Cortisol

TestosteroneTooth Movement

2 types of tooth movements- Physiologic Under the effect of force.Theories explaining orthodontic tooth movement- Pressure tension theory Biologicalelectricity or bioelectric theory Fluid Dynamic TheoryPressure tension theory (Schwartz 1932)Sandstedt (1904), Oppenheim (1911), and Schwarz (1932) hypothesized that a tooth moves inthe periodontal space by generating a pressure side and a tension side.This hypothesis explained that on the pressure side: PDL displays disorganization anddiminution of fiber production, cell replication decreases seemingly due to vascular constrictionon the tension side: stimulation produced by stretching of PDL fiber bundles results in anincrease in cell replication, fiber production.He concluded that the forces delivered as part of orthodontic treatment should not exceed thecapillary bed blood pressure (20-25 g/cm2 of root surface).The third phase of bone remodeling consists of loss of bone mass at PDL pressure areas andapposition at tension areas. This succession of events formed the central theme of the pressure-tension hypothesis.

Why it was rejected?Baumrind, pointed out a conceptual flaw in it.He considered the PDL to be a continuous hydrostatic system and suggested that any forcedelivered to it would be transmitted equally to all regions accoording to Pascals Law.He further stated that the presence of fibers in the PDL does not modify the operation of this law,because of the concomitant existence of a continuous body of liquefied ground substance.He recognized that only part of the periodontium where differential pressures, as mentioned inthe pressure-tension hypothesis, can be developed, is solidbone, tooth, and discrete solidfractures of the PDL.Bone Bending & Bioelectric Theory (Farrar 1876)

Farrar was the first to suggest, that alveolar bone bending plays a pivotal role in orthodontic toothmovement.It has been hypothesized that mechanical deformation of the crystalline structure of thehydroxyapetite and the crystalline structure of collagen induce migration of electrons thatgenerate local electric fields. This phenomenon is called piezoelectricity.

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Zengo et al concluded that the concave side of orthodontically treated bone is electronegativeand favors osteoblastic activity, whereas the areas of positivity or electrical neutralityconvexsurfacesshowed elevated osteoclastic activity.

The 2 unusual properties of piezoelectricity, which seem to not correlate well with orthodontictooth movement are (1) a quick decay rate (2) production of an equivalent signal in the oppositedirection upon force removalFurther, ions in the fluids surrounding the living bone interact with these electrical fields. These

currents of small voltages are called streaming potentials.Davidovitch et al suggested recently that piezoelectric potentials result from distortion of fixedstructures of the periodontium collagen, hydroxyapatite, or bone cell surface. But in hydratedtissues, streaming potentials (the electrokinetic effects that arise when the electrical double layeroverlying a charged surface is displaced) predominate as the interstitial fluid moves.

Fluid Dynamic Theory (Bein 1966)Tooth movement occurs as a result alterations in fluid dynamics in the PDL. When PDL iscompressed due to orthodontic force blood vessels of the PDL get trapped between the principalfibers and this results in stenosis. The vessel above the stenosis then balloons resulting in theformation of an aneurysm.

The process of tooth movement under the effect of force is unique to humans. During theprocess of evolution PDL appeared between the tooth and the alveolar socket. Remodeling changes in paradental tissues are considered essential in effecting orthodontictooth movement. The force-induced tissue strain produces local alterations in vascularity, cellular andextracellular matrix reorganization, leading to the synthesis and release of variousneurotransmitters, cytokines, GFs, CSFs & metabolites of arachidonic acid.How is ortho mvmt diff from physiological TM Orthodontic tooth movement is uniquelycharacterized by the abrupt creation of compression and tension regions in the PDL.Physiological tooth movement is a slow process that occurs mainly in the buccal direction intocancellous bone or because of growth into cortical bone. In contrast, orthodontic tooth movementcan occur rapidly or slowly, depending on the physical characteristics of the applied force, andthe size and biological response of the PDL.Biology of tooth movement due to applied force: Current ConceptsPATHWAYS OF TOOTH MOVEMENT On the basis of research in basic biology and clinicalobservations, Mostafa et al proposed an integrated hypothetical model for tooth movement. Thismodel consists of 2 pathways I ----Physiological response II----Generation of localinflammatory response Pathway I Orthodontic force creates vectors of pressure and tension bonebending, generation of tissue bioelectric polarization, and subsequent bone remodelingact on the cell surface cyclic nucleotide pathway, generating changes in the levels of intracellularsecond messengers cAMP

cell proliferation, differentiation, and activation electrically neutral or positive areas promoteosteoclast activity, whereas electronegativity supporting osteoblastic activity.Pathway II Orthodontic forces trigger inflammatory processes in the involved dental andparadental tissues.Lymphocytes, monocytes, and macrophages invade these tissuesThe local elevation in prostaglandins and a subsequent increase in cellular cAMPconcentrations increase osteoclast activity. Secreted hydrolytic enzymes, such as collagenase,dissolve the mechanically strained ECM.Recent model Recent reports by Jones et al detailed events in bone cells immediately after the

application of mechanical stress.Osteoblasts respond to physiologic levels of stress- increase in intracellular free calcium and

membrane potential through activation of K channels.activation of phospholipase C, which releases inositol triphosphate within 10 seconds.Elevated levels of phospholipase C maintain the high calcium concentration throughout stressapplication by keeping the mechanosensitve ion channels open and by further activation ofprotein kinase C

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Phospholipase A is activatedArachidonic acid

Prostaglandins (10 mins)Release of products of the lipooxygenase pathway (leucotriens and hydroxyeicosatetraenoicacids), followed by an elevation in the concentration of cAMP.

Cellular synthetic and secretory activities.Primary stimulus

Acts on

Pdl and bone cellsInteraction between these cells leads to

Transient increase in the intracellular levels of second messengersCAMP IP3 Ca++Secondary messengerNucleusTakes signal toIn the nucleus of each cell different second messengers account for the differential patterning,protein synthesis and Gene expression.Recently identified Immediate Early Gene expression include Cfos, Cjon mRNA, egr-I, SP1growth differentiation factor 9B, extracellular GLA protein.

These transcription factors can produce either cellular proliferation or cellular differentiationleading to osteoblastic bone formation or osteoclastic bone resorption.PhospholipidsMechanical, hormonal, pathological, electricalPhospholipase A

Arachidonic acidLeucotrienesLipooxygenase pathwayCyclic peroxideCyclooxygenase pathwayPG E PG FRole of Prostaglandins

Are mediators of inflammation cause an increase in intracellular cAMP and calciumaccumulation by monocytes.

Increase the number of osteoclasts as well as stimulate osteoblastic cell differentiation andnew bone formation.

Klein and Riasz in 1970 reported for the first time the involvement of prostaglandins inorthodontic tooth movement.

Yamasaki et al in a rat model of tooth movement, demonstrated that injection of PGs increasedosteoclast numbers & local PG injection could also increase the rate of orthodontic toothmovement in primates

In a study done by Anand K Patil et al- PGE in lesser dosage of 3gm along with lignocaine asa vehicle was injected distal to canine in 14 orthodontic patients and it was found to increase therate of orthodontic tooth movement.Role of cytokines and growth factorsCytokines are the protein factors released from cells, which modulate the activity of other cellsand have multiple actions like bone remodelling, bone resorption & deposition.Prominent cytokines which have been shown to stimulate bone resorption and induce osteoclastproliferation are- Interleukin 1 Interleukin-6 Tumor necrosis factor Granulocyte-macrophagecolony stimulating factor Macrophage colony stimulating factorThe early phase of orthodontic tooth movement involves an acute response causing release ofinflammatory mediators such as prostaglandins and interleukins (IL-1) that interact with bone

cells. Cytokines secreted by leucocytes may interact directly with bone cells or indirectly, vianeighboring cells such as monocytes/macrophages, lymphocytes and fibroblasts. Osteoblasts regulate the activity of existing osteoclasts and the formation of new osteoclaststhrough release of cytokines. (TNF)

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Growth factors are released during inflammation and repair by the cells of PDL and bone. These factors include Fibroblast growth factor Insulin like growth factor (IGF-I, IGF-II)-increase type-I collagen and matrix synthesis by osteoblasts. Transforming growth factor (BMP)- induce mesenchymal progenitors to differentiate into both osteoblasts and chondrocytes Platelet growth factorsRole of neurotransmittersIn areas where tension or compression evolves under the influence of the orthodontic appliance,vasoactive neurotransmitters are released from distorted nerve terminals that interact first with

capillary endothelial cel ls. In response, the endothelial cel ls express receptors that bindcirculating leukocytes, promoting their migration by diapedesis out of the capillaries to secretesignal molecules, including cytokines and growth factors, that stimulate PDL and alveolar bonelining cells to remodel their ECM.The PDL is abundantly supplied with 2 kinds of nerve terminals: Ruffini-like endings &nociceptive endings which change their structures in response to external stimuli, such asorthodontic force.Mechanoreceptors in the apical half of the dental root have a low threshold and respond to evenminor stretching of the PDL. In contrast, nociceptors have a high threshold and are activated byheavy forces, tissue injury, and inflammatory mediators.The mechanoreceptors are silent in physiological conditions but contain various neuropeptides

such as substance P, vasoactive intestinal polypeptide, and calcitonin gene-related peptide(CGRP) released when strained.Increased immunoreactivity (increases PG) of substance P has been demonstrated in the PDL inthe early phases of tooth movement.

Another neurotransmitter involved in orthodontic tooth movement is CGRP.Kvinnsland and Kvinnsland localized CGRP in the PDL and the dental pulp after 3 days of molarmovement in fibroblasts at PDL tension sites.Saito et al reported finding intense reactivity to vasoactive intestinal polypeptide, in thecompressed PDL and in the pulp of moving teeth in cats.Role of neurotransmitters in orthodontic tooth movement Orthodontic forceMovement of tissue fluids inside and out of PDLDistortion of nerve endingsRelease of stored neurotransmitters centrally and peripherallyPressure sensation, painInteraction with PDL fibroblasts and alveolar bone cellsIncreased levels of intracellular 2nd messengersSynthesis and secretion of cell products- cell proliferation etc.Interaction with endothelial cellsvasodilatationExtrusion of plasma (prostaglandins) and leukocytesSynthesis and secretion of cytokines

Pressure/tension-electrical-cell After an orthodontic force is applied, the initial step is the detection of a mechanical strain. Application of small bending force to long bones result in compression on one side and tensionon the opposite side.

This produces a flow of interstitial fluid through the canalicular network, generating streamingpotentials and/or fluid shear stress.Streaming potentials is the electric potential that develops between two components by anelectrolyte flowing between the solid surfaces.Eg: bone is partially composed of proteoglycans, which are entrapped in a collagen network.Because of the negative charge of proteoglycans, there is an excess of positive mobile ions inthe fluid. Such potentials could possibly arise in vascular channels, Haversian systems,

canaliculi, microporosities of the structure and as a result of the blood flow and interstitial fluidmovement.Slow decay of signal due to relaxation of fluid flow in the stressed bone. The cells responsible for sensing mechanical strains in bone have been considered to beosteoblasts, osteocytes or both.

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These cells sense mechanical strain by virtue of Mechanosensitive ion channels (Ca and Kpassage due to streaming potential) Extracellular matrix and cytoskeleton reorganization.Cell to Cell contact

There are two types of cellular adhesions- Cell-to-cell adhesion Cell-to-extracellular matrixadhesion.

Integrins are cell surface receptors that mediate cell-to-cell attachment or cell attachment toECM molecules such as collagen, fibronectin, laminin etc.

The cytoskeleton (Microtubules, microfilaments ,Intermediate filaments) presents a number of

possibil ities for transducing mechanical forces acting on cells and/or their adjacent matrices. Many of the extracellular matrix proteins responsible for cell adhesion contain a commonpeptide sequence Arg-Gly-Asp (RGD) which is essential for the cell- binding properties of theseproteins.

Osteoclasts also express integrin receptors including the vitronectin receptor, which plays animportant role in the adhesion of osteoclasts to bone surface. Peptides containing the RGDmotif has been shown to inhibit osteoclast mediated bone resorption in vitro and preventosteoporosis in vivo. These peptides could potentially aid in the treatment of osteoporosis andpossibly in modulating the orthodontic tooth movement.Second messengers

The behavior of all cells is modulated by internal signaling systems, which translate a wide

array of external stimuli such as hormones or mechanical forces into a narrow range of internalsignals or second messengers.

Classically, the second messenger associated with mechanical force transduction isAdenosine 35 cyclic monophosphate (cAMP). It was first identified in 1960 by SUTHERLANDet al- When liver slices were exposed to adrenalin, free glucose appeared under theseconditions and it was postulated that adrenalin was acting as the first messenger, bindingto a receptor and stimulating the production of a powerful chemical second messenger.

Role of G proteins- Some cell membrane receptors operate by activating membrane boundtransducing proteins which bind guanine nucleotides such as GTP or GDP. These arecommonly referred to as G protiens.

At the surface of the cell the external signal binds to the receptor and induces a conformationalchange in the receptor. This is transmitted through the cell membrane and renders theappropriate G proteins susceptible to GTP binding. The G protein-GTP complex then activateseffector enzymes such as adenylate cyclase which generates cAMP. The activity of thecomplex is ended by hydrolysis of the GTP to GDP thus closing of the signaling reactions.

The G proteins act as intermediaries between receptors and intermediary enzymes. The threeimportant G proteins pertinent to orthodontic tooth movement are Gs- the stimulatory regulator ofadenylate cyclase Gi- the inhibitory regulator of adenylate cyclase Gp-the stimulatory regulatorof the PI pathway.

2 active second messengers are generated Water soluble phosphatidyl inositol triphosphate(IP3) and Hydrophobic diacylglycerol.

In a signaling cascade process- receptor activation is followed by second messengergeneration i.e. cAMP and inositol triphosphate. They advance signals to the nucleus through aseries of kinases.Early gene expression

In the nucleus different second messengers account for the differential pattern of immediateearly gene expression (IEG). IEGs are among the earliest responses that can be measured atthe transcription level.

The transcription of the IEGs has been shown to increase when cells are exposed to cytokines,growth factors or mechanical stimulation. IEGs are- c-fos c-jun and egr-1

Protein products from the c-fos and c-jun genes form a hetrodimeric complex named activatorprotein-1 (AP-1). Depending on the state of the cell or in the presence of various stimuli Ap-1

can produce either cellular proliferation or differentiation. Signal input-genetic output Cytoplasmic signaling proteins such as sonic hedgehog, TGF-superfamily and many transcription factors and ions reach the nuclear matrix and then genome-resulting in enhanced or suppressed gene expression.

Input becomes output as gene expressed proteins Protein synthesis inhibition Mobilize

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mitosis Cell motility Secretion of other proteins Programmed cell death (apoptosis) all ofwhich modify cytoskeleton, cell membrane and ECM. This process is continuous.

Changes in cell environment (development, ageing, external conditions) might change thepattern of gene expression. This epigenetic regulation of gene expression involves heritablechanges not from DNA base sequence changes but from chemical modification of bases ATCGor transcription factors bound with DNA. Such genomic changes can occur throughout life.

Pain & Orthodontic Tooth Movement

Tooth movement-associated tissue remodeling, an inflammatory process, might induce painfulsensations, particularly after activation of the orthodontic appliance. After 24 hours of forceapplication, C-fos (immunoreactive neurons known to be involved in transmission of nociceptiveinformation) expression is noted ipsilaterally in the trigeminal nuclues modulated throughserotonergic and dopaminergic systems.Drug interaction Pharmacological agents manipulate tooth movement in both directions. Factors that enhancetooth movement are vitamin D & direct injection of prostaglandin into periodontal l igament. Drugs that inhibit tooth movement are Bisphosphonates used in the treatment of osteoporosis. Ex: alendronate Prostaglandin inhibitors. Ex : NSAIDS, Corticosteroids , Parathyroid, Thyroxin. Osteoporosis is a problem particularly encountered in post menopausal females but is

associated with aging in both sexes. Estrogen therapy , which is used frequently to prevent lossof bone in older women , has no impact on orthodontic treatment. Bisphosphonates aresynthetic analogues of pyrophosphates that bind to hydroxyapatite in bone & act as specificinhibitors of osteoclast mediated bone resorption. If orthodontic treatment is necessary in olderpatients it is better to switch over to estrogen at least temporarily Or use Raloxifene (estrogen recmodulator). Bartzela et al Am J Orthod Dentofac Orthop 2009;135:16-26Dietary calcium : Adults require 1000 to 1300 mg of calcium in their daily diet. The effect ofdietary supplemental calcium on OTM was studied in dogs that were fed low- or high-calciumdiets for 10 weeks before orthodontic premolar movement was induced with a force of 100 N for12 weeks.From 8 weeks on, the low-calcium regimen led to a signicantly higher rate of OTM than did thehigh calcium diet.These data support bone turnover studies showing increases in the number of osteoclasts andosteoblasts in dogs with a low- calcium diet. The nal outcome was increased bone remodelingphenotype in which excessive bone resorption prevailed over deposition.Bartzela et al Am J Orthod Dentofac Orthop 2009;135:16-26Prostaglandin E inhibitors: Prostaglandin E inhibitors are of two categories: Corticosteroids & NSAIDs. Prostaglandinsare formed from arachidonic acid which in turn is derived from phospholipids. Corticosteroidsreduce prostaglandin synthesis by inhibiting the formation of arachidonic acid. NSAIDs inhibitconversion of archidonic acid to prostaglandins by acting on Cox.

There is evidence that PGs play an important role as balancing agents in bone remodelinginduced by mechanical stress. PGs of the E and F series have been implicated in boneremodeling activities, particularly resorption; they decrease collagen synthesis and increasecyclic adenosine monophosphate (AMP). Animal studies showed that the tooth movement indexsignificantly increases when PGs are injected.

Arias OR ,Orozco MCM Am J Orthod Dentofac Orthop 2006;130:364-70Other classes of drugs which reduce tooth movement are: Tricyclic antidepressants (doxepin,amitriptyline, imipramine.) Anti arrhythmatic agents( procaine) Anti malarial drugs ( quinine,quinidine, chloroquine.) Anticonvulsant drug (Phenytoin.) Tetracyclines ex: doxycycline(inhibit osteoclast recruitment)

Indomethacin and flurbiprofenwhich are specific inhibitors of PGs reduce the amount ofosteoclasts in the alveolar bones of cats and rabbits receiving orthodontic forces and also reducethe dental movement index by 50%. Acetaminophen is the DOC.

Arias OR ,Orozco MCM Am J Orthod Dentofac Orthop 2006;130:364-70 John et al AO, 1996 , Acetaminophen (paraminophenol) is suggested as DOC for relieving the

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discomfort associated with ortho treatment. It is a very weak PG inhibitor & no significant anti-inflamatory effects. Exact mechanism by which i t relieves fever & pain is not known, it isbelieved to act in the CNS. It has no effect on orthodontic tooth movement. Kehoe MJ et al, 1996 suggested Misoprostol (produces analgesia similar to morphine) hasinsignificant inhibitory effect on local PGe2 production. The degree & rate of tooth movementincreased attributed to the enhanced bone resorbing activity of PGe1. It was found ibuprofensignificantly decreases PG synthesis in pdl of guinea pigs. There is a marked decrease in degree& rate of tooth movement. Acetaminophen decreases peripheral PG production. But there is no

significant effect on tooth movement. Thus by prescribing OTC analgesics with minimuminhibition of PG, the treatment time can be reduced.89CONCLUSIONTooth movement is a highly conserved physiological mechanism for continuous adaptation of thedentition. Orthodontic tooth movement is a biomechanical exploitation of the physiologicmechanisms for developing and maintaining optimal occlusal function. The tooth continues tomove until it achieves equilibrium with natural and applied loads. ****************