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MECHANISM OF BONE LOSS

GUIDE BY: PRESENTED BY:DR DIVYA JAGGI DR ANKITA DADWAL

MDS 2ND YEAR

CONTENTS

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INTRODUCTION ETIOLOGY OF BONE LOSS PATHWAYS OF INFLAMMATION MECHANISM OF BONE DESTRUCTION RANK, RANKL AND OPG RANK/OPG RATIO ROLE OF IMMUNE CELLS , TLRs AND PAMPs BACTERIAL INFLUENCE FORMATION OF ACTIVATED OSTEOCLASTS INTRACELLULAR SIGNALS IN OSTEOCLAST AND

PRECURSORS DEGRADATION OF MINERAL AND ORGANIC MATRIX MEDIATORS OF INFLAMMATION CONCLUSION REFRENCES

INTRODUCTION

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The height and density of alveolar bone are normally maintained by an equilibrium.

Regulated by local and systemic influences , between bone formation and resorption.

When resorption exceeds formation, both bone height and density is reduced.

ETIOLOGY OF BONE LOSS

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EXTENSION OF GINGIVAL INFLAMMATION

BY TRAUMA FROM OCCLUSION

INFLUENCE OF SYSTEMIC DISEASES

PATHWAYS OF INFLAMMATION

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After inflammation reaches the bone, it spreads into the marrow spaces and replaces the marrow with a leukocytic and fluid exudate, new blood vessels and proliferating fibroblasts.

Multinuclear osteoclasts and mononuclear phagocytes

increase in number, and the bone surfaces appear, lined with Howship lacunae

In the marrow spaces, resorption proceeds from within, causing a thinning of the surrounding bony trabeculae and enlargement of the marrow spaces, followed by destruction of the bone and a reduction in bone height

MECHANISM OF BONE DESTRUCTION

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1. Direct action of plaque products on bone progenitor cells induces the differentiation of these cells into osteoclasts.

2. Plaque products act directly on bone, destroying it through a non cellular pathway.

3. Plaque products stimulate gingival cells causing them to release mediat0rs, which in turn induce bone progenitor cells to differentiate into osteoclasts.

4. Plaque products cause gingival cells to release agents that act as cofactors in bone resorption.

5. Plaque products cause gingival cells to release agents that destroy bone by direct chemical action , without osteoclasts.

Hausman 1970

RANKL , RANK AND OPG

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RANKL/OPG RATIO IN ASSESSMENT OF THECLINICAL

SEVERITY OF PD

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BACTERIAL INFLUENCE

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Harmful pathogenic products and enzymes such as hyaluronidases, collagenases, and proteases break down extracellularmatrix components in order to produce nutrients for their growth.

Once immunoinflammatory processes begin, various molecules (e.g., proteases, MMPs, cytokines, prostaglandins, and host enzymes) are released from leukocytes and fibroblasts.

An imbalance between the level of activated tissue destroying MMPs and their endogenous inhibitors (TIMPs). Thus, the connective tissue attachment and alveolar bone are destroyed, and the junctional epithelium and the inflammatory infiltrate migrate apically.

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Porphyromonas gingivalis produces a fimbrial protein that is a potent osteoclast stimulator via a tyrosine kinase mechanism.

Aa produces a 62 kDa heat shock protein associated with the ability to stimulate bone resorption, as well as a peptide that acts as a potent IL-6 inducer in fibroblasts and monocytes.

T. denticola has been shown to produce cystalysin, an enzyme that catalyzes the , elimination of L-cysteine to produce 𝛼 𝛽pyruvate, ammonia, and sulfide, which in turn enables the bacterium to produce sulfide.

TLRs AND PAMPs

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TLRs AND OSTEOBLASTS

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TLRs AND OSTEOCLASTS

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ROLE OF INFLAMMATION IN BONE RESORPTION

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OSTEOIMMUNOLOGY

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The relationship between the immune system and bone metabolism has been termed osteoimmunology.

Osteoimmunology seeks to define and understand the interactions of immune cells and their cytokines with skeletal cells.

Both the immune system and bone share a large number of regulatory cytokines and other molecules in common.

ROLE OF SPECIFIC IMMUNE CELLS

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FORMATION OF ACTIVATED OSTEOCLATS

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INTRACELLULAR SIGNALS IN OSTEOCLASTS AND PRECURSORS

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DEGRADATION OF MINERAL AND ORGANIC MATRIX

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One of the first events in the triggering of preosteoclasts is the contraction of the osteoblast actin and myosin cytoskeleton inresponse to local and systemic influences, forexample, parathyroid hormone (PTH), retinoid acid, and vitamin D3 stimulation.

This increases the width of intercellular spaces, exposing more osteoid to interstitial fluid.

Osteoclasts resorb bone in resorption lacunae by generating a pH gradient between the cell and bone surface, favouring the mineral-dissolving action of the osteoclast proteinases.

Carbonic anhydrase (CA) II is the main cytoplasmic source of protons for the acidification of the lacuna. This hydrates carbon dioxide to carbonic acid, which ionizes into carbonate and hydrogen ions.

REGULATION OF OSTEOCLASTIC BONE RESORPTION

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These cysteine proteases are secreted by osteoclasts to degrade native collagen at an acidic pH of 4.5 .

The dissolution of the mineral phase in the acidic microenvironment below the RB exposes collagen fibrils to the enzymatic attack of cathepsins B, E, K, S, and L.

Thereafter, matrix metalloproteinases (MMPs), such as gelatinase A (MMP-2), stromelysin (MMP-3), and collagenase (MMP-1), continue with the matrix degradation process.

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Osteoclasts contain the highest concentration of mitochondria of any cell type, thus generating the ATP required for the carbonic anhydrase-catalysed production of hydrogen ions .

Systemic influences on bone resorption may be exerted by several mediators, including PTH, IL-1, TNF, TGF, and 1,25-dihydroxyvitaminD3.

Calcitonin, interferon gamma (IFN ), and TGF are potent 𝛾 𝛽inhibitors of osteoclast activity and differentiation

MEDIATORS OF BONE RESORPTION

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Interleukin-1Interleukin-6Tumor Necrosis

FactorParathyroid hormonePTH related proteinM-CSFPGE2RANKLRANKVitamin D

Interferon gammaOPGEstrogenAndrogenCalcitonincyclosporin

SUMMARY

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REFRENCES

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CARANZZA clinical periodontology 8th edition.Carranza’s clinical periodontology- 10 th editionMechanisms of Bone Resorption in Periodontitis:

StefanA.Hienz,SwetaPaliwal,andSasoIvanovski Journal of Immunology Research Volume 2015, Article ID 615486.

Inflammation and Bone Loss in Periodontal Disease David L. Cochran J Periodontol • August 2008 (Suppl.)

Osteoclastic bone resorption induced by innate immune responses MASANORI KOIDE,SAYA KINUGAWA,NAOYUKI TAKAHASHI & NOBUYUKI UDAGAWA Periodontology 2000, Vol. 54, 2010, 235–246.

Mechanisms and control of pathologic bone loss in periodontitisP. MARK BARTOLD,MELISSA D. CANTLEY &DAVID R. HAYNES

Periodontology 2000, Vol. 53, 2010, 55–69 .