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Saku /certified fixed orthodontic courses by Indian dental academy
 

Saku /certified fixed orthodontic courses by Indian dental academy

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The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and offering a wide range of dental certified courses in different formats.

Indian dental academy provides dental crown & Bridge,rotary endodontics,fixed orthodontics,
Dental implants courses.for details pls visit www.indiandentalacademy.com ,or call
0091-9248678078

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    Saku /certified fixed orthodontic courses by Indian dental academy Saku /certified fixed orthodontic courses by Indian dental academy Presentation Transcript

    • BIOCHEMICAL MEDIATORS OF ORTHODONTIC TOOTH MOVEMENT www.indiandentalacademy.com INDIAN DENTAL ACADEMY Leader in continuing dental education www.indiandentalacademy.com
    • INTRODUCTION • The essence of orthodontic treatment is the movement of teeth through bone to obtain a more perfect dental occlusion. • An accurate understanding and precise control over the factors responsible for initiating and carrying out the tissue reaction will ultimately optimize the rate of tooth movement. • The intelligent use of this knowledge will permit us to modify the orthodontic appliances and treatment regimen in order to achieve optimum tissue response. www.indiandentalacademy.com
    • BONE REMODELING • Bone is a dynamic tissue that constantly undergoes remodeling. • Bone remodeling is a coupled process: Localized removal of old bone + Replacement with newly formed bone 2/3 mineral phase • Bone 1/3 organic matrix Two principle bone cells – osteoblast osteoclastwww.indiandentalacademy.com
    • BONE REMODELING CYCLE www.indiandentalacademy.com
    • BONE REMODELING COUPLING www.indiandentalacademy.com
    • LOCAL REGULATION OF BONE REMODELING • Bone is rich source of growth factors. • These factors are released from the bone as it resorbs or by activated bone cells. • They may then act in a sequential manner to regulate all the cellular events required for formation of bone. www.indiandentalacademy.com
    • • TGF-β superfamily is particularly important in the coupling, that links bone formation to prior bone resorption. Bone resorption TGF-β from bone osteoblast precursor proliferation BMP’S autostimulatory effect on osteblast & the formation of mineralized nodules www.indiandentalacademy.com
    • • Also , the other growth factors such as IGFs, FGFs & PDGF effects osteoblast proliferation and differentiation. • These factors are all bone growth stimulants. THE COMPLICATED INTERACTION BETWEEN THESE FACTORS RELEASED LOCALLY IN ACTIVE FORM AS A RESULT OF RESORPTION PROCESS ARE RESPONSIBLE FOR CAREFULLY CO-ORDINATED FORMATION OF NEW BONE AT THESE SITES www.indiandentalacademy.com
    • BIOLOGIC PATHWAYS OF ORTHODONTIC TOOTH MOVEMENT • It is known that bone cells (osteoblasts & osteoclasts) respond to orthodontic forces(OF) by proliferation and increased activity; however the mechanism of conversion of OF into biologic activity is not completely understood. • It is proposed that primary stimulus or 1st messenger may alter cell activity through plasma membrane. www.indiandentalacademy.com
    • • The plasma membrane bound enzymes along with ca++ act to elevate cyclic nucleotide molecules (cAMP,cGMP). • Cyclic nucleotides have been characterized as 2nd messenger; ie these molecules convert membrane effects into cellular response www.indiandentalacademy.com
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    • Piezoelectric signals have 2 unusual characters: 1. Quick decay rate 2. Production of an equivalent signal, opposite in direction when force is released www.indiandentalacademy.com
    • BIOCHEMICAL MEDIATORS OF ORTHODONTIC TOOTH MOVEMENTS • Biochemistry is described as the science concerned with chemical constituents of living cells and with reactions and processes they undergo. • Various biochemical substances play important role in remodeling of tissues , during OTM. • They can be categorized under following - 1. HORMONES 2. ENZYMES 3. PGs & LTs 4. NEUROTRANSMITTERS & CYTOKINESwww.indiandentalacademy.com
    • HORMONES • Hormones are main chemical regulators of body mechanism . • These are usually directly released into the blood stream from specific glands . • These elicit different reactions in different tissues with only certain tissues responding to a given hormone. • As specific tissue cells may respond selectively to a hormone , these are called as Target cells. www.indiandentalacademy.com
    • • Hormones may directly enter the cells and regulate the mechanism or bind to the cell membrane and elicit a 2nd messenger response from cytoplasm. • cAMP is designated as a second messenger. 1st messenger GLAND TARGET CELL hormone 2nd messenger TARGET CELL METABOLIC EFFECTS cAMP www.indiandentalacademy.com
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    • PARATHROMONE • PTH causes a rise in blood calcium level by following mechanism – 1. It causes bone resorption. 2. It converts vit D into its active form 1,25- dihydroxycholecalciferol. 3. It causes reabsorption of calcium from the distal segment of nephron. • PTH acts by stimulating adenyl cyclase and cAMP production www.indiandentalacademy.com
    • Action may be divided into – • INSTANTANIOUS REGULATION of calcium is accomplished in seconds by selective transfer of calcium ions into and out of bone fluid. www.indiandentalacademy.com
    • • Bone fluid is seperated from extracellular fluid by osteoblasts or relatively thin bone lining cells. • A decrease in the serum calcium level stimulates secretion of PTH, which enhances transport of ca+2 from bone fluid into osteocytes and bone- lining cells. • The active metabolite of vit D(1,25 D) enhances the pumping of calcium ions from bone-lining cells into extracellular fluid. • Thus Ca+2 is transported across bone-lining cells, resulting in a net flux of calcium ions from bone fluid to extracellular fluid. www.indiandentalacademy.com
    • • SHORT TERM CONTROL of calcium levels affects rates of bone resorption and formation within minutes. • PTH acting in concert with 1,25 D accomplishes these important tasks- 1. Enhances osteoclast recruitment from promonocyte precursors. 2.Increase the resorption rate of existing osteoclasts. 3.It may supress the rate at which osteoblast form bone. www.indiandentalacademy.com
    • • LONG TERM REGULATION of metabolism has profound effects on skeleton. • Mass and geometric distribution of bone are strongly influenced by load history (biomechanics) and sex hormone status. • PTH is primary mediator of frequency of remodeling. • PTH mediated activation frequency determines mean bone age. www.indiandentalacademy.com
    • • Surprisingly , however PTH receptors are not found on cell membranes of osteoclast but are found on osteoblast and osteocytes. • This indicates that control of osteoclasts is via paracrine agents secreted by other cells, probably by preosteoblast and mesenchymal cells. www.indiandentalacademy.com
    • • Midgett et al (1981) studied the effect of altered bone metabolism on OTM. • Experimental dogs fed with a low calcium diet showed elevated endogenous PTH levels(state of hyper parathyroidism). • The resulting high turnover osteopenia contributed to enhanced rate of OTM because of lower bone density and elevated remodeling rate. • (unfortunately this approach is not applicable for clinical use because of considerable amount of systemic bone loss ) www.indiandentalacademy.com
    • VITAMIN D • Cholecalciferol is synthesised in skin irradiated by UV light, hydroxylated in liver at #25 position and then hydroxylated in kidney at #1 position to produce the active metabolite 1,25 dihydroxycholecalciferol. • Biochemical effects of vit D – a) intestinal villi – promotes absorption of ca++. b) bone – mineralisation of bone is by increasing the activity of bone osteoblast . - it coordinates the remodeling action of osteoblast and osteoclast. c) Renal tubules- reabsorption of ca++ and phosphorous. www.indiandentalacademy.com
    • • Monte k collins and Peter M sinclair (1988) studied the local use of vit D to increase the rate of OTM. • They concluded that – 1) a weekly intraligamentous injection of 1,25 D soln. produced significantly increased amount of OTM after 21 days of experimental period. 2) there was increased rate of recruitment and activation of mononuclear osteoclast resulting in greater bone resorption. 3) no obvious clinical, microscopic and biochemical side effects were noted. www.indiandentalacademy.com
    • • Local injection of 1,25 D significantly increased the rate of OTM. • Although similar findings have been reported with the use of pulsed electromagnetic fields, direct currents and PGs, but these techniques represent completely different mechanism of action from 1,25 D. • Pulsed fields and direct electric currents activate osteoclasts by increasing the levels of cAMP and cGMP which acts as 2nd messenger at the level of cell membrane. PGs have been shown to act in the similar fashion. www.indiandentalacademy.com
    • However 1,25 D acts directly on nucleus of circulating monocytes and progenitor cells. This allows a cellular activation that is totally independent of cyclic nucleotide cascade. www.indiandentalacademy.com
    • • Microscopically, the experimental teeth displayed faster than normal recruitment of resorptive cells. • Among the local changes that are known to contribute to the fusion of mononuclear osteocyte cells are an increase in the ca++ concentration and decrease in pH, both of which occur only after bone resorption has preceded for a while. • Therefore , the rate limiting step in OTM may be the time required for adequate recruitment of osteoclast precursor cells. • In this regard 1,25 D seemed to be efficatious in increasing the rate of alveolar resorption. www.indiandentalacademy.com
    • SEX HORMONES • Sex hormones have profound effect on bone. • Androgens build and maintains musculoskeletal mass. • The primary hypertrophic effect of androgen is to increase the muscle mass. • The anabolic effect on bone is a secondary biomechanical response to increase loads generated by the enhanced muscle mass. www.indiandentalacademy.com
    • • ESTROGEN, on the other hand has direct effect on bone; it conserves skeletal calcium by suppressing the activation frequency of bone remodeling. • At menopause, enhanced remodeling activation increases turnover. • Because a slight negative calcium balance associated with each remodeling event, a substantial increase in the turnover rate can result in a rapid bone loss, leading to symptomatic osteoporosis. • Thus, orthodontist should avoid a treatment plan that is overly dependent on orthodontically induced anabolic remodeling in post menopausal females. www.indiandentalacademy.com
    • ENZYMES • Enzymes in blood serum are either normal or abnormal constituents. • Enzymes not normally found in serum are derived from tissue damage. • The abnormal serum enzymes ie non- plasma specific enzymes are of 2 types- 1. secretory – function in digestion 2.intracellular – perform role in metabolism www.indiandentalacademy.com
    • • Different type of intracellular enzymes are alkaline phosphatase, acid phosphatase, creatinine kinase, serum transaminase, lactate dehydrogenase etc. • Out of these alkaline phosphatase , AP and LDH are the ones which plays important role in metabolism and tissue degradation incident to OTM. www.indiandentalacademy.com
    • • Phosphatase changes have been described in orthodontically treated tissues. • Few investigators have reported increased AP and decreased Alkaline Phosphatase activity on the pressure side & increased Acid and Alkaline Phosphatase activities on the tension side of orthodontically treated tooth upto 7 days after appliance activation in rats. As no description past 7 days was made, it is likely that reversal in activity of these enzymes was missed in these studies. www.indiandentalacademy.com
    • • A study was done by Keeling and King (1993) to examine time course of phosphatase changes during an entire tooth movement cycle in both the serum and alveolar bone. • During OTM in rodent model- - early wave of resorption (3 to 5 days) - reversal (5 to 7 days) - late wave of formation (7 to 14 days) • Resorbing cells (osteoclasts and macrophages) - high AP & TRAP activities. • Bone forming cells (osteoblasts) - high Alkaline Phosphatase activities.www.indiandentalacademy.com
    • • AP, TRAP and Alkaline Phosphatase changes in serum and alveolar bone clearly demonstrated that bone turnover is not balanced in short term during OTM. • Instead there seems to be an early preponderance of bone resorption followed by later period when bone formation is primary. • This finding confirms earlier reports of bone turnover characterized by tandem periods of activation, resorption , reversal and formation, occurring after orthodontic force application. www.indiandentalacademy.com
    • • The early peak in serum AP & TRAP preceded the peak in bone. • This early serum peak occurred during the induction (activation) phase of bone turnover cycle during which no bone changes could be quantified. • The serum peak fell of early (day 3) and remained depressed until the end of observation period. • The peak in bone AP & TRAP activities lasted longer (from day 3 to 7) and reversed between days 7 & 10, remaining depressed at 10 & 14 days. • The finding that the serum peak in these enzyme activities preceded their appearance in bone suggests that osteoclasts and preosteoclasts may be detectable during their migration to the treated PDL. www.indiandentalacademy.com
    • • There was a peak in Alkaline Phosphatase activity in both serum & alveolar bone at day 7, reflecting formation that occurred between 7 and 10 days. • In addition, a second , but significant , late peak at day 14 was observed in serum but not in bone. • The timing of serum Alkaline Phosphatase changes in bone , confIrms previous observations that osteoblasts are present locally without a requirement for significant blood borne migration. www.indiandentalacademy.com
    • Histochemistry of enzymes associated with tissue degradation incident to OTM (Lilja et al ) • Study was done on the activity of AP & LDH in PDM and alveolar bone as indicators of bone resorption and tissue damage during OTM. • Non treated rats – cells with high AP activity were randomly distributed along the bone surface. • Low orthodontic force – rapid redistribution of cells with high AP activity to the pressure zones. • Low forces caused no change in distribution and activity of LDH www.indiandentalacademy.com
    • • High forces - changes in enzyme activity similar to those induced by low forces. • However there was one definite difference - a zone lacking both AP & LDH developed in compressed parts of PDM. www.indiandentalacademy.com
    • • It was concluded, 1) high activities of AP & LDH in PDM reflects a high metabolic activity and a rapid turnover of connective tissue. 2)AP is a lysosomal enzymes which has a high activity and bone resorbing cells. During 1st 10 hrs of orthodontic treatment the distribution of AP containing cells change from a non specific distribution to local accumulation in the pressure zone. The mechanism which direct osteoclastic resorbtive activity to specific site on bone surface is not known. Piezoelectricity, streaming potential and chemotaxis due to local tissue damage have been proposed. www.indiandentalacademy.com
    • 3)Compression of PDM to a certain degree induces hyalinization of most compressed areas. Neither LDH nor AP activity was demonstrated in these areas. The hyaline zone is area of aseptic necrosis . This hyaine zone is resistant to degradation and persist for long time in the pressure zone, depending on the magnitude of force. The lack of lysosomal enzymes in hyaline zone explains why the elimination of the hyaline zone is a slow process . www.indiandentalacademy.com
    • PROSTAGLANDINS AND LEUKOTRIENES • PGs and LTs are modulators of adenyl cyclase. • Effects restricted to cell of origin and neighbouring cells. • Action depends on modulating cAMP levels and intracellular flow of Ca+2 www.indiandentalacademy.com
    • PROSTAGLANDINS Parent compound – Prostanoic acid. www.indiandentalacademy.com
    • PGs are not stored in tissues,rather they are produced from membrane phospholipid stores. www.indiandentalacademy.com
    • Mechanical distortion of cell PGE2 from membrane phospholipids Subseqent binding of extra-cellular PGE2 to cell surface receptors Activation of adenyl cyclase & cAMP pathway www.indiandentalacademy.com
    • • PGs secretion regulated by FEED-BACK mechanism. • PGs promote bone resorption by: - number & size of osteoclasts. - Activation of existing osteoclasts. - Induction of collagenase production by mechanically deformed cells. • PGs of E & F series are powerful mediators of bone resorption www.indiandentalacademy.com
    • LEUKOTRIENES • LTs are compounds closely related to PGs,that are produced by conversion of arachadonic acid via lipo-oxygenase pathway. • There is interaction b/t cyclo-oxygenase & lipo-oxygenase pathway. • Inhibition of one pathway of arachadonic acid will shunt the effect into increase in the conversion via the other pathway. www.indiandentalacademy.com
    • • BUT inspite of PGs levels ,a selective inhibition of LTs synthesis cause significant reduction in tooth movement. www.indiandentalacademy.com
    • There are several mechanisms through which LTs might affect tooth movement: 1. Mediator of inflammatory response. 2. Collagenase systhesis. 3. Facilitate Ca+2 movement during chemotactic activity of neutrophils. www.indiandentalacademy.com
    • NEUROTRANSMITTERS • Physical distortion imposed by Orthodontic forces on paradental tissues,has effects on peripheral nerve fibres and terminals. • Neuropeptides stored in nerve terminals within the PDL either may be released into the extracellular space or streamed towards the ganglion. www.indiandentalacademy.com
    • Neuropeptides, particularly SP, VIP & cGRP have been shown to affect bone cells directly or through their effects on vascular system. www.indiandentalacademy.com
    • SUBSTANCE P (SP) • First peptide to be proposed as neurotrasmitter. • Synthesised ribosomally in the cell bodies of small diameter primary afferent neuron, then transported by axoplasmic flow to terminals centrally or peripherally. • There it is stored & released on neuronal stimulation. • Peripherally released SP interacts with blood vessel cells, causing vasodilation, which results in extravassation of plasma & migration of leukocytes into extravascular tissues. www.indiandentalacademy.com
    • • SP has been identified in dental tissues (in fibres around blood vessels in dental pulp & PDL) • Role of SP in bone remodeling was studied in arthritic joints. Severe arthritis more SP containing primary afferent less severe arthritis less SP containing primary afferent www.indiandentalacademy.com
    • • When SP incubated for 48 hrs with cultured human stnoviocytes from arthritic patient : - PGE2 & collagenase release - cell proliferation VASOACTIVE INTESTINAL POLYPEPTIDE (VIP) • First isolated from hog intestinal tissue. • Contains 28 amino acid. • Potent vasodilator – hypotensive effects on most vascular bed. • Shown to stimulate bone resorption in-vitro, in a dose related manner , through c-AMP mechanism. www.indiandentalacademy.com
    • Orthodontic force Movt. Of tissue fluid in and out of pdl Distortion of nerve endings Release of stored neurotransmitter Pressure sensation,pain Interaction with endothelial cells vasodilation Extrusion of plasma,PGs & leucocytes Synthesis and secretion of cytokines Interaction with pdl fibroblasts & alveolar bone cells Incresed level of intracellular 2nd messengers(Ca++,cAMP,cGMP) Synthesis & secretion of Cell products,cell proliferation, Motility etc. ROLE OF NEUROTRANSMITTERS IN OTM www.indiandentalacademy.com
    • CYTOKINES • Cytokines are small proteins produced by cells which modify the behavior of other cells. • Inflammatory cell produces numerous cytokines. • Some cytokines particularly IL-1α,IL-1β,TNF- α and γ-INF have been implicated in mediation of bone remodeling process. www.indiandentalacademy.com
    • • Source of IL-1:Mononuclear phagocytes keratinocytes fibroblasts endothelial cells 2 distinct gene products cloned in humans: IL-1α and IL-1β www.indiandentalacademy.com
    • How do CYTOKINES induce mechanically induced bone remodeling? www.indiandentalacademy.com
    • Although effective cell of bone resorption is osteoclast,studies demonstrate that osteoblast and not osteoclast exhibit receptors for PTH, Vit-D metabolites and PGs, indicating that osteoclast recruitment and activity involves cells of osteoblast lineage. www.indiandentalacademy.com
    • How osteoblasts transmits signals?? www.indiandentalacademy.com
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    • ROOT RESORPTION • OTM is possible because of greater resistance of cementum than bone to resorption. • However, its proved that most teeth moved orthodontically undergo some minor degree of root resorption followed by repair. • The initial breakthrough of cementum is connected with removal of hyalinized parts of PDL. www.indiandentalacademy.com
    • • Macrophages in various stages of maturation accumulates around the hyalinized zone & remove necrotic tissue. • The barrier effect of the cementoid tissue behind the hyalinized zone seems to be reduced or gone, and macrophages fuse & become resorbing cells (clasts) . • A small breakthrough is adequate to start the process. www.indiandentalacademy.com
    • • When a resorption lacuna has been formed , the ensuing events will depend on whether application of force is continued. • If it is, resorption will continue. • If application of force is absent or below certain level, repair will commence in resorption lacunae with the deposition of cementum. • Thus, rest periods without force application should be included in treatment of patients with a tendency for root resorption. www.indiandentalacademy.com
    • PHARMACOLOGICAL CONTROL OF TOOTH MOVEMENT 2 Types of drugs are known to depress the response to orthodontic force - 1. Bis-phosphonates eg: alendronate(fosamax) 2. Prostaglandin inhibitors eg: indomethacin www.indiandentalacademy.com
    • Drugs that affect PG activity falls in 2 categories: 1. Corticosteriods & NSAIDs. 2. Agents that have mixed agonistic and antagonitic effects on various PGs. www.indiandentalacademy.com
    • Any drugs that accelerate tooth movement?? • Relaxin • Substances with angiogenic activity -estrogen -NO -Naltrexone • Collagenase www.indiandentalacademy.com
    • conclusion The next major change in the way orthodontics will be practised in future, is in clinicians ability to change the host to respond to – mechanical forces applied to the teeth or propensity for teeth in new position to relapse. The means of doing so is through expanding the understanding of BASIC BIOLOGY OF TOOTH MOVEMENT www.indiandentalacademy.com
    • REFERENCES 1. The biology of tooth movement -Norton and Burstone 2. Orthodontics -current principles and technique -Graber and Vanarsdal 3.Contemporary Orthodontics -William R.Proffit www.indiandentalacademy.com
    • For more details please visit www.indiandentalacademy.com www.indiandentalacademy.com