alveolar bone

MECHANISM OF ALVEOLAR BONE
DESTRUCTION IN PERIODONTITIS
PRESENTED BY :
SONAL GOYAL
1st YEAR POSTGRADUATE
DEPARTMENT OF PERIODONTOLOGY
A.E.C.S. MAARUTI COLLEGE OF DENTAL
SCIENCES

CONTENTS
 Introduction
 Alveolar bone
 Bone structure
 Bone Remodeling
 Factors regulating bone destruction
 Factors regulating bone formation
 Ultrastructural changes in periodontal diseases
 Factors involved in bone destruction during
periodontal diseases.
 Conclusion
 References

INTRODUCTION
 Periodontal diseases are chronic inflammatory disorders
involving the supporting structures of the teeth.
 Changes in the normal balance of the bone modelling and
remodeling causes diseases such as periodontitis.
Schwartz ZV, Goultschin J, Dean DD, Boyan BD. Mechanisms of alveolar bone destruction in
periodontitis. Periodontology 2000. 1997 Jun 1;14(1):158-72.

 The height and density of the 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 may be
reduced.
Newman MG, Takei H, Klokkevold PR, Carranza FA. In: Carranza's clinical
periodontology.11.Elsevier health sciences; 2011. 185-96.

ALVEOLAR BONE
 Alveolar bone is a specialized part of the mandibular and
maxillary bones that forms the primary supporting structure
for tooth.
 It develops from the osteoblasts derived from dental follicle
surrounding the tooth germ.
 It consists of outer cortical plate made-up of compact bone, a
central spongiosa, and bone lining the alveolus.
 The cortical plate and bone lining the alveolus meets at the
alveolar crest.

 Alveolar bone is divided into two parts :-
1. The alveolar process is the portion of the maxilla and
mandible that forms and supports the tooth sockets.
2. The basal body.
 Forms when the tooth erupts to provide osseous attachment to
the forming PDL.
 Tooth- dependent bony structures.
periodontology.11.Elsevier health sciences; 2011. 12-51

Bone structure
 The alveolar wall is surrounded by the supporting bone with
which it forms anatomical unit.

Tencate R. Periodontium. In : Textbook of Oral Histology.8.Elsevier;2015:205-232.
bone
Inorganic
content- 67%
hydroxyapatite
Organic content-
33%
28% collagen
5%
noncollagenous
proteins

1.Mineral phase
 Composed mainly of calcium and phosphate
 Also present are, hydroxyl, carbonate, citrate and trace
amounts of other ions- Na, Mg, F.

Cancellous bone
 20% of the total bone.
 Like cortical bone, shows well-defined lamellar pattern.
 Consist of trabeculae that enclose irregularly shaped marrow
spaces lined with a layer of thin, flattened endosteal surface.
 Cells in the Haversian system occupies larger area higher
metabolic activity than cortical bone.
 Found mostly in interradicular and interdental space.

Cortical Bone
 Makes up of 80% of bone.
 Made up of Haversian System-

 Confined by periosteum on the outside and endosteum on the
inside.
 Well defined lamellar pattern, seen in polarized light

Each type of bone is tightly regulated and
responds differently to hormones, growth
factors and various treatment modalities.
Changes in this balance, either systemically
or locally, results in diseases due to
increased or decreased bone mass.
Lamellar bone disappears and woven bone
or primary bone is formed.

 Consists primarily of collagen.
 Small amounts of proteoglycans and lipids
 Noncollagenous proteins- osteopontin, osteonectin,
osteocalcin (bone gla-protein) and matrix gla-protein.
2. Organic Phase
Cell types
Osteoblasts
Osteoclasts

1.Osteoblasts
 Mononucleated cells involved in the synthesis of collagenous
and non-collagenous proteins.
 Functions-
 Synthesize the organic matrix components.
 Direct the events in mineralization.
 Production of paracrine and autocrine factors (cytokines and
growth factors) influences bone resorption and bone
formation.

Osteoblasts
and
Osteocytes
Proteases
Degrading and
remodeling the
extracellular
matrix
Maturation and
mineralization

Osteocytes
 As the osteoblasts form bone, some osteoblasts become
entrapped within the matrix they secrete, these cells are then
called osteocytes.
 They may be mineralized or unmineralized.
 Maintains the mineralized matrix.
 Responds most rapidly to calciotropic hormones, moving Ca
and inorganic phosphates into and out of the bone mineral
pool.

2. Osteoclasts
 Highly specialised motile migratory bone resorptive cells,
deerived from haematopoietic stem cells.
 Cells responsible for bone resorption.
Heinz SA, Paliwal S, Ivanovski S. Mechanisms of bone resorption in periodontitis. Journal of
Immunology 2014; 2015:1-10.

 In response to key factors such as M-CSF/CSF-1, osteoclast
differentiation factor, interleukins, tumor necrosis factor and
contact with mineralized bone particles containing
osteocalcin, haematopoietic precursors may undergo
differentiation into monocyte and macrophages derived
colony-forming unit.
 Also differentiates into peripheral blood monocytes and tissue
macrophages.
 Finally fuse into mature multicellular osteoclasts.
Immunology 2014; 2015:1-10.

 In bone remodeling, the bone is constantly resorbed on a
particular bony surface, followed by a phase of bone
formation.
 The ability of the alveolar bone to remodel rapidly facilitates
positional adaptation of teeth in response to functional forces
and in the physiological drift of teeth that occurs with the
development of jaw bones.
Bone remodeling/ coupling

 Bone remodeling involves the co-ordination of activities of
cells from two distinct lineages, the osteoblasts and the
osteoclasts, which form and resorb the mineralized connective
tissues of bone, respectively
Osteoclastic precursors become activated and
differentiate into osteoclasts, and this begins the process
of bone resorption, followed by bone formation.
Sodek J, McKee MD. Molecular and cellular biology of alveolar bone.Perio2000, 2000;24:99-
126

Bone remodelling

Bone modeling
 It is the process used by the bone to shape itself, creating an
organ with maximal compressive strength, associated with the
formation and growth of the bones in childhood and
adolescence.

Bone is formed rapidly , primarily on the
periosteal surface
Bone is destroyed on the
endosteal surface, at the focal
points along the endosteal
surfaces, and within osteon of
the compact bone.

Release of
Ca
PTH
Breakdown
of collagen
Release of
osteogenic
substrates
Stim & diff
of
osteoblasts
Deposition
of bone

Factors regulating bone resorption
 The cellular events involved in resorption of bone are
modulated by a group of local osteotropic factors which may
have extremely potent effects on bone cell both in vitro and in
vivo.
 A disturbance in homeostatic balance that is essential for
functional bone turnover results in destructive osteolytic
process.
Immunology 2014; 2015:1-10.

 Phases of bone resorption :-
1st phase Formation of osteoclasts
progenitor in the
haematopoeitic tissues followed
by their vascular dissemination
and generation of preosteoclasts
and osteoblasts in bone itself.
2nd phase Activation of osteoclasts at the
surface of mineralized bone.
3rd phase Resorption of the bone via
activated osteoclasts.

Local factors Systemic factors
IL-1
IL-6
TNF
Lymphotoxin
Gamma interferon
CSF
prostaglandins
Parathyroid hormone
Calcitonin
Vitamin D3
Immunology 2014; 2015:1-10.

1.Cytokine
 Osteotropic cytokines such as IL-1. IL-6, TNF-α and TNF-β
mediate a multitude of effects in body in addition to their
effects on bone cells.
 It is more important for trabecular bone (closer to cytokine
rich marrow), than cortical bone.
Heinz SA, Paliwal S, Ivanovski S. Mechanisms of bone resorption in periodontitis. J Immunology
2014; 2015:1-10.

 PTH, calcitriol, PTH- related protein, PGE-2, thyroxine, IL-
11, bacterial lipopolysaccharide.
 Cytokine release by osteoblasts
 Modulates differentiation, activation, life span and function of
osteoclasts. + Local factors
 Bone homeostatic balance.
Heinz SA, Paliwal S, Ivanovski S. Mechanisms of bone resorption in periodontitis. J Immunology
2014; 2015:1-10.

Interleukin-1
 Key regulatory role in bone resorption in diseases such as
rheumatic arthritis and periodontitis.
 Powerful and potent bone-resorbing cytokine.
 By direct or indirect mechanisms, IL-1 can induce the
proliferation of osteoclast precursors and the differentiation
and activation of mature osteoclasts.
Assuma R, Oates T, Cochran D, et al. IL-1 and TNF antagonists inhibit the inflammatory
response and bone loss in experimental periodontitis. J Immunol 1998; 160: 403-409.

Bone
resorption
Indirect mechanism-
stimualtes the production of
PGE-2
Effects osteoclast
number and activity,
directly influence
osteogenic cells to cause
cytoplasmic contraction
and secretion of
collagenase. Tissue
plasminogen activator
and RANK-L.

 Active forms of IL-1 : IL-1α and IL-1β.
 Binds to type 1 and type 2 IL-1R.
 IL-1R type 1 receptor capable of transduction of signals and
mediates the biological effects of IL-1.

 Type-2 receptors (membrane bound or soluble form) serves
as IL-1 binding protein and thus antagonizes IL-1.
 IL-1α and IL-1β increase the binding of PMNs and
monocyte/macrophages to endothelial cells, stimulate the
production of PGE-2 and release of lysosomal enzymes and
stimulates bone resorption.

Interleukin-6
 Responsible for the formation of cells with an osteoclastic
phenotype.
 Produced by osteoblasts.
 Increases in response to cytokines and hormones.
 When stimulated by PTH, osteoblasts produce IL-6, which
increases osteoclastic differentiation, causes osteoblasts to
contract making the bone surface more susceptible to
resorption.

Tumor necrosis factor-α and Lymphotoxin
 Multifunctional cytokines produced by activated
lymphocytes.
 Major function- stimulates osteoclastic bone resorption
 Tumor necrosis factor-α :-
1. Effect is mediated by PGE-2 and IL-6.
2. Affects cell with osteoblast phenotype.
3. Inhibits differentiation function.
4. Stimulates cell proliferation.

Osteoclastogenesis
inducers- RANKL,
RANK, OPG.
Expressed by
osteoblasts,
fibroblasts, T-
cells.
Activation and
differentiation of
osteoclasts.
Modulators of
bone
metabolism-
PTH, Vit- B3,
IL-11
Bartold PM, Cantley MD, Haynes DR. Mechanism and control of pathologic bone loss in
periodontitis. Periodontology 2000, 2010; 53:55-69.

RANK AND RANK-L
 Key mediator in the process of osteoclast formation.
 This membrane-bound protein is a member of the tumor
necrosis factor superfamily and is expressed by a variety of
cells, including osteoblasts, fibroblasts and T-cells.
Bartold PM, Cantley MD. Mechanisms and control of pathological bone loss in periodontitis.
Perio 2000, 2010;53:55-69

 During normal bone metabolism, RANKL is expressed by
osteoblasts. However, at inflammatory sites RANKL is also
expressed by immune cells such as T-lymphocytes .
 The expression of RANKL is also regulated by other
modulators of bone metabolism including parathyroid
hormone, vitamin D3 and interleukin-11.
Perio 2000, 2010;53:55-69

Osteoprotegerin
 Osteoprotegerin is a natural inhibitor of RANKL.
 It is a soluble tumor necrosis factor receptor-like molecule
that
 acts as a decoy and blocks the binding of RANKL to RANK
 and thus prevents osteoclastogenesis.
Perio 2000, 2010;53:55-69

 RANKL ⁄ osteoprotegerin ratio:
 The RANKL ⁄ osteoprotegerin ratio in inflamed periodontal
tissues has been found to increase either because of an
increase in RANK or a decrease in osteoprotegerin, or both.
 Not only is the RANKL ⁄ osteoprotegerin ratio increased at
sites of periodontal inflammation, but recent reports suggest
that this ratio also correlates with disease severity.
Perio 2000, 2010;53:55-69

RANKL binds to RANK on the surface of pre-osteoblasts
Activation of c-jun terminal kinase
Activation of nuclear factor-kappaB
Osteoclast formation

Gamma interferon
 Multifunctional cytokine.
 Inhibits bone resorption induced by IL-1 and TNF-α than
systemic hormones like parathyroid hormones or 1,25-
(OH)2D3.

2.Colony stimulating factor
 Produced mainly by osteoblasts or bone stromal cells
 Stimulates differentiation of osteoclast precursors into mature
osteoclasts.
 Effect on osteoclast is indirect- it stimulatees IL-1 production,
which in turn stimulates prostaglandin synthesis.

Binds to receptor on pre-
osteoblasts, cFMS
Activation of transcription
factors: c-fos
Initiation of
osteoclastogenesis
Proliferation and survival of
pre-osteoclasts and mature
osteoclasts

3. Prostaglandins and Arachidonic acid metabolites
 Produced by immune, marrow and bone cells.
 Prostaglandins of E-series:
1. First described stimulators of osteoclastic bone resorption.
2. Slow-acting but powerful mediators.
3. Affect both active mature osteoclasts as well as
differentiated osteoclasts precursors.

4. Local effect.
5. Mediates the effects of epidermal growth factor and
transforming growth factor β.
6. Causes both bone resorption and formation.
7. High doses- inhibitory action
8. Low doses- stimulatory action (periosteal bone formation).

 Arachidonic acid-
1. Stimulates bone resorption.
2. 5- lipoxygenase metabolizes arachidonic acid and produces
metabolites which are capable of stimulating bone
resorption.
3. This also stimulates bone formation.

Effect of parathyroid hormones on Ca metabolism
 When there is a decrease in blood Ca levels, PTH stimulates
osteoblasts to release IL-1 and IL-6 which stimulates the
monocytes into the bone area.
 PTH simulates the mature osteoclasts to resorb bone.
 It indirectly increases Ca absorption from gut via increased
Vit D synthesis in kidneys.
Immunology 2014; 2015:1-10.

 Cause osteoblast retraction and secretion of collagenase and
plasminogen activator from osteoblasts, which releases
osteocalcin – helps in chemotactic for osteoclast precursors.
Calcitonin-
 Inhibits bone resorption and promotes Ca deposition in bone
matrix and increase cAMP.
 Decreases size of ruffled border.
 Decreases blood Ca level.
Immunology 2014; 2015:1-10.

 Vitamin D metabolites-
 Causes bone formation as well as resorption.
 Bone resorption is by differentiation of committed
progenitor cells into mature cells.
 It also stimulates osteoclastic bone resorption in high
concentration. It has a slow onset of action.
 It stimulates the fusion or differentiation of the osteoclast
precursor cells.

4. Sex steroids
 Androgens affects osteoclastic bone resorption in a manner
similar to that of the estrogens.

Factors regulating bone formation
 New bone formation takes place by (1) short reversal phase:
Production of new organic matrix by osteoblasts. (2)
Mineralization of the matrix.
 Bone formation is controlled by systemic hormones and local
factors.
 Local factors- growth factors that act directly on cells of the
osteoblastic lineage, thus acts as autocrine or paracrine
factors.

 Growth factors :-
1. Polypeptides
2. Exert their activity by binding to specific receptors on the
cell surface.
3. Natural products of cell.
4. Stimulates a varity of cellular activities hence are
multifunctional.

1. Platelet-derived growth factor
 PDGF is a potent chemotactic and mitogenic effect on
osteogenic cells, promoting their proliferation and migration
in the healing area.
 Acts synergistically with IGF-1 promoting synthesis and
production of extracellular matrix.

2. Heparin- binding growth factors
 Types - acidic fibroblasts growth factor and basic fibroblasts
growth factors.
 Inhibits alkaline phosphatase activity.
 Bone matrix secrete basic as well as acidic fibroblasts growth
factors.

 Interacts with heparin enhances the effect of
Fibroblast growth factor bone cell replication.
 Acts on distinct stages of cell maturation, hence causes
osteogenesis.

3. Insulin like growth factors
 Non-glycosylated polypeptides.
 Types- insulin-like growth factors- I and Insulin-like growth
factor- II.

Acts as paracrine or autocrine regulators of bone
formation.
Increase preosteoblastic cell replication.
Stimulatory effect on osteoblastic collagen synthesis
and bone matrix apposition.
Decrease the degradation of collagen.
One of the most important bone mass regulator :
synthesized by bone cells and is present in substantial
concentration in bone.
Increases bone cell mitosis and deposition of the
matrix.

4. Transforming growth factor- β
 Though not produced by bone cells, stimulates bone
resorption.
 It is a polypeptide synthesized by skeletal cells.
 Most abundant growth factors in bone matrix.
 Transforming growth factor-β superfamily of polypeptides-
five isoforms, bone morphogenic proteins, activins, inhibins.

 Increases the biosynthesis of type-I collagen, fibronectin and
osteocalcin, as well as bone matrix deposition and chemotaxis
of osteoblasts.
 TGF-β is synthesized by osteoblasts in latent (inactive) form
and released during the phase of bone resorption.
 PTH and other bone resorbing hormones act on osteoblasts to
release Plasminogen activator which activate latent TGF- β.

TGF-β messenger RNA levels are increased by fibroblast
growth factors.
It decreases platelet- derived growth factor AA binding to its
bone cell receptor.
It inhibits 1,25-(OH)2D3- dependent stimulation of osteocalcin
production, indicating that it is important for proliferation and
initial stages of osteogenic differentiation, however, it delays
terminal differentiation.

Bone morphogenetic protein
Produced during bone
repair, it has
osteoinductive
activity. Morphogenic
protein- causes
bone to form when
implanted in tissues
that would
otherwise not form
bone.
On implantantion
in bone, it induces
the production of
new bone through
an endochondral
pathway.
BMP induces
chondrocyte
differentiation and
matrix
mineralization.
Stimulates
differentiation
precursor cells into
more mature
osteoblasts and
collagen production
by osteoblasts.

Ultrastructural changes in periodontal diseases
 Page and Schroeder :
 Subclinical gingivitis develops
 Acute inflammatory response begins at the base of the
gingival sulcus (within 2-4 days of plaque accumulation).

 Recruitment of neutrophils, lymphocytes, mononuclear
cells.
 These produces local factors.
 Causes Bone remodelling.
 Upto 70% of collagen degrades within 4-7 days of
inflammation.

 Chronic gingivitis-
 Further accumulation of inflammatory cells.
 Destruction of connective tissue.
 No ultrastructural changes seen.

 Periodontitis-
 Apical progression of cellular infiltrate and collagen
degradation close to bone surface.
 Osteoclasts appears and resorbs the crest of the bone.
 Loss of anchorage of principal fibres.

Garant and Cho in 1979 suggested that locally produced bone
resorption factors may need to be present in the proximity of the
bone surface to exert their action.
Page and Schroeder in 1982 ,
on the basis of Waerhaug’s
measurement made an human
autopsy, postulated a range of
effectiveness of about 1.5 –
2.5 mm within which bacterial
plaque can induce loss of
bone.
Large defects greatly
exceeding a distance of 2.5
mm from the tooth surfaces (as
described in aggressive types
of periodontitis) may be
caused by the presence of
bacteria in the tissues.
Radius of action:

Bone factor concept:
 By Glickman, in 1951.
Local and systemic factors regulate the physiologic equilibrium
of bone.
When there is general tendency toward bone resorption, bone
loss initiated by local inflammatory processes may be
magnified.
This systemic influence on the response of alveolar bone has
been termed the bone factor in periodontal disease
Glickman I. The experimental basis for the “bone factor” concept in periodontal diseases.
Journal of Periodontol 1949; 20: 7-22.

 The destructive effects of inflammation and trauma from
occlusion varies with the status of the individual “bone
factor”.
 It is less severe in a healthy individual in the presence of a -
POSITIVE Bone Factor
 than when superimposed upon a systemically induced bone-
destructive tendency -NEGATIVE Bone Factor.
Glickman I. The experimental basis for the “bone factor” concept in periodontal diseases.
Journal of Periodontol 1949; 20: 7-22.

 In periodontitis, bacterial products such as
lipopolysaccharide and factors produced during the
inflammatory process, affects bone remodeling.
 These local factors are produced from lymphocytes and
monocytes, along with cells of mesenchymal origin:
osteoblasts and fibroblasts.
 Goodson et al, in 1974, suggested that host- mediated PGE-2
mediates tissue destruction.
Factors involved in bone destruction during
periodontal diseases

 Prostaglandin E-2 :-
 an increased level seen in PGE-2 in GCF.
 Produced by lipopolysaccharide-activated gingival
macrophages.
 Also cytokines which causes stimulation of mesenchymal
cells and osteoclasts produce PGE-2.
 Thus, there is an total increase in local concentration of
eicosanoid.

 With increasing levels of PGE-2, there is an increase in
severity and aggressiveness of disease.
 Increased rate of attachment loss.
 Further studies have shown that, disease progression was
treatable by inhibiting PGE-2 synthesis
1. NSAIDS (Fluriprofen and Ibuprofen)
Jeffcoat et al Bone loss is arrested by
NSAIDS

 In contrast,
 Total inhibition of PGE-2 may not be necessary for disease
control.
 Biochemical mediators, IL-1αand TNF-α, depends on a small
amount of PGE-2 to augment their bone-resorbing activity.

 Interleukin-1 :
 IL-1β are present at a higher level in periodontal diseases.
 Produced by lymphocytes and macrophages from inflamed
periodontal tissues.
 Gingival mononuclear cells and macrophages produce IL-1
after stimulation with periodontopathic bacteria.
 This is found in tissues around active sites of bone loss.
 Presence of high levels of IL-1α and IL-1β in GCF of patients
with periodontal diseases.

Massada et al Decrease in both IL-1 α and
IL-1β levels in GCF after scaling
and root planing.
Reinhardt et al Decreased levels of IL-1 α and
IL-1β in shallow pockets and
moderate pockets after
nonsurgical treatment.
Reinhardt et al Continued elevated levels of
IL-1 α and IL-1β after papillary
flap debridement.

 Interleukin-6 :
 Present in GCF in periodontal diseases.
 Derived from gingival lymphocytes and macrophages.
 IL-1β induces the production of IL-6 in gingival fibroblasts.

 Tumor necrosis factor- α –
 cytokine associated with bone resorption in periodontal
diseases.
 Found in higher levels in GCF of periodontitis patients than
in healthy patients.
 Produced by PMNL, lymphocytes and macrophages from
inflamed periodontal tissue.
 Mediates the effects of lipopolysaccharides on other cells in
disease.

Conclusion
 Plaque and its associated bacteria, which populate the
periodontal pockets, release lipopolysaccharides and other
bacterial products to the sulcus, affecting both the immune
cells in the connective tissue as well as in osteoblasts.
 They produce local factors which increases osteoclast
formation and activation as well as inhibit osteoblasts
function.
 Eventually causing bone resorption in patients with
periodontitis.

 Bone remodeling is a complex process involving a number of
cellular functions directed towards the coordinated resorption
and formation of new bone.
 It is regulated by systemic hormones and local factors.

References
1. Schwartz ZV, Goultschin J, Dean DD, Boyan BD.
Mechanisms of alveolar bone destruction in periodontitis.
Periodontology 2000. 1997; 14(1): 158-72.
2. Newman MG, Takei H, Klokkevold PR, Carranza FA. In:
Carranza's clinical periodontology.11.Elsevier health
sciences; 2011. 185-96
sciences; 2011. 12-51

4. Heinz SA, Paliwal S, Ivanovski S. Mechanisms of bone
resorption in periodontitis. Journal of Immunology 2014;
2015:1-10.
5. Assuma R, Oates T, Cochran D, et al. IL-1 and TNF
antagonists inhibit the inflammatory response and bone loss
in experimental periodontitis. J Immunol 1998; 160: 403-
409.
sciences; 2002. 354-71.

8. Bartold PM, Cantley MD, Haynes DR. Mechanism and
control of pathologic bone loss in periodontitis.
Periodontology 2000, 2010; 53:55-69.
9. Tencate R. Periodontium. In : Textbook of Oral
Histology.8.Elsevier;2015:205-232.
10. Bartold M, Cantley MD. Mechanisms and control of
pathological bone loss in periodontitis. Perio 2000,
2010;53:55-69.
11. Glickman I. The experimental basis for the “bone factor”
concept in periodontal diseases. Journal of Periodontol
1949; 20: 7-22.

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