mechanism of bone loss

1. MECHANISM OF BONE
LOSS1
GUIDE BY: PRESENTED BY:
DR DIVYA JAGGI DR ANKITA DADWAL
MDS 2ND YEAR

2. 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

3. 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.

4. ETIOLOGY OF BONE LOSS
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 EXTENSION OF GINGIVAL INFLAMMATION
 BY TRAUMA FROM OCCLUSION
 INFLUENCE OF SYSTEMIC DISEASES

5. PATHWAYS OF INFLAMMATION
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6. 6/25
 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

7. 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

8. RANKL , RANK AND OPG
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9. RANKL/OPG RATIO IN ASSESSMENT
OF THECLINICAL SEVERITY OF PD
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10. 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.

11. 11/25
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 𝛼,𝛽 elimination of L-cysteine to produce
pyruvate, ammonia, and sulfide, which in turn enables the
bacterium to produce sulfide.

12. TLRs AND PAMPs
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13. TLRs AND OSTEOBLASTS
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14. TLRs AND OSTEOCLASTS
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15. ROLE OF INFLAMMATION IN BONE
RESORPTION
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16. 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.

17. ROLE OF SPECIFIC IMMUNE CELLS
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18. FORMATION OF ACTIVATED
OSTEOCLATS
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19. INTRACELLULAR SIGNALS IN
OSTEOCLASTS AND PRECURSORS
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20. 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.

21. 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 𝛾), and TGF 𝛽 are potent
inhibitors of osteoclast activity and differentiation

23. MEDIATORS OF BONE RESORPTION
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 Interleukin-1
 Interleukin-6
 Tumor Necrosis Factor
 Parathyroid hormone
 PTH related protein
 M-CSF
 PGE2
 RANKL
 RANK
 Vitamin D
 Interferon gamma
 OPG
 Estrogen
 Androgen
 Calcitonin
 cyclosporin

24. SUMMARY
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25. REFRENCES
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 CARANZZA clinical periodontology 8th edition.
 Carranza’s clinical periodontology- 10 th edition
 Mechanisms 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 periodontitis
 P. MARK BARTOLD,MELISSA D. CANTLEY &DAVID R. HAYNES
Periodontology 2000, Vol. 53, 2010, 55–69 .