Osteogenesis &

Osteolysis
Of Alveolar Bone In
Health & Disease
Dr. Sandip Ladani
Guided by,
Dr. Mihir N. Shah
Dr. Archita Kikani
Dr. Hiral Parikh
Dr. Niraj Motwani
 Contents
• Introduction
• Development
• Bone formation
• Regulation of bone formation
• Bone resorption
• Regulation of bone resorption
• Bone Modeling Vs Bone Remodeling
• Ageing & Bone
• Bone’s Role in Calcium Homeostasis
• Alveolar Bone in Disease
• Clinical Implication
 Introduction
• BONE:
– Bone is a mineralized
connective tissue that
performs the function of
support, protection and
locomotion.

• ALVEOLAR PROCESS :
- It is defined as the parts of
the maxilla and mandible that
support the sockets of the teeth.
 Development of Alveolar
Process
• Tooth-dependent bony structures.
- Schroeder HE, 1991.
• The alveolar process consists of bone which
is formed both by cells from
– the dental follicle (alveolar bone proper) and
– cells which are independent of tooth
development.
 Development of the alveolar bone
proper
• Late bell stage:
– Bony septa and bony bridge start to form.
• Dental Follicle surrounds each tooth germ.
• Continued bodily movement.
• Major changes in alveolar process.
• Height
• Cell differentiation from dental follicle
– Fibroblast, cementoblast, osteoblast.
• Osteoblast: Alveolar bone proper –Ten Cate, Hoffman
• Size & Shape : Alveolar Bone proper
• Rest of bony structure: periosteal bone formation - Schroeder
 Remodeling of the alveolar
processes during tooth
eruption
• The alveolar processes - already grown over the occlusal plane of the developing tooth.
• Gubernacular canal must be widened by osteoclastic bone resorption.
• New bone formation at the base of the bony crypt – outward eruption force
• Dental Follicle – Key structural component responsible for regulating eruption - Eskici, Larson
EK.
• Monocytes containing tartrate-resistant acid phosphatase, an indicator of lysosyme activity –
Osteoclast precursors.
• Recent: Factors: - Wise GE
– Colony stimulating factor-1 : recruitment & differentiation of preosteoclasts
– Epidermal growth factor : upregulates the production of CSF-1 via its ability to stimulate the cells of
the reduced enamel organ to make interleukin – 1 α
BONE FORMATION
 BONE FORMATION

Cellular Differentiation

Stromal stem cell Osteogenic

Pathway Osteoblast

Controlled by cascade
of events involving
genetic programming
and gene regulation
by various hormones,
cytokines and growth
factors.
 BONE FORMATION

• Collagen type I and Alkaline Phosphatase –

characteristic of osteogenic lineage.
• Type II collagen – Lost
• Type III collagen – Diminishes progressively.
steogenic Master Gene
BONE FORMATION

Re α2 β
ce 1
pt
or
 BONE FORMATION

su
bs
eq
ue
on nt
em
si
er
es

ge
pr

n ce
ex
s
ce
du
in

in vivo
BONE FORMATION
 BONE FORMATION

• Various developmentally regulated genes:

• Homeobox genes – hoxa-2, hoxd-13 and hoxa-
13, dlx-5, msx-1 and msx-2
 BONE FORMATION

Osteogenic Master Gene

Cbfa1

Functional role in the

differentiation of all Complete absence of
mineralizing tissue cells. ossified tissues.
For eg. Odontoblasts, - Komori T et al,
Cementoblasts, 1997
Ameloblasts
 BONE FORMATION

• BMP-2
– Upregulates Cbfa1 & Msx-2 leading to osteogenic
differentiation.
• TGF-ß
– Increases Cbfa1
– No osteogenic differentiation

Therefore, other factors induced by BMP are

necessary for complete expression of the
osteoblastic phenotype.
 BONE FORMATION

nti
te
Po
al r BMP-4
c to
fa
Induc
es

Regula
tes
REGULATION OF BONE
FORMATION
REGULATION OF BONE FORMATION

Production Activity of
of Osteoblastic
Osteoblastic cells
cells
REGULATION OF BONE FORMATION

• Parathyroid Hormone:
– Regulates serum calcium levels
– Stimulates bone resorption
– But also – anabolic effects mediated
through TGF-β and Insulin like Growth
Factor-I.

Thus affects Bone remodeling

REGULATION OF BONE FORMATION

• Vitamin D3:
– Stimulates bone resorption.
– Essential for normal bone growth and
mineralization.
– Calcium absorption from the intestine.
– Strongly stimulates the synthesis of
osteocalcin and osteopontin by osteoblasts.
– Suppresses collagen production.
REGULATION OF BONE FORMATION

• Insulin: (Anabolic effect)

– Targets osteoblasts directly.
– Stimulates bone matrix formation
and mineralization.
– Indirectly affects bone formation by
a stimulation of IGF-I produced in
the liver.
REGULATION OF BONE FORMATION

• Growth Hormone: (Anabolic

effect)
– Required for attaining normal bone
mass
– Anabolic effect through IGF-I
production.
REGULATION OF BONE FORMATION

• Glucocorticoids: (in vitro)

– promotes differentiation of osteoblasts and
stimulate bone matrix formation.
REGULATION OF BONE FORMATION

• Glucocorticoids: (in vivo)

REGULATION OF BONE FORMATION

• Bone Morphogenetic Proteins:

– Belong to TGF-β family.
– Can induce chondrogenic and osteogenic differentiation in
undifferentiated mesenchymal cells.
– Stimulating differentiation of more mature osteoblasts.
– Stimulate collagen production.
– No marked effects on bone matrix formation.
REGULATION OF BONE FORMATION

• TGF-β:
– Can act as a potent inhibitor of
osteogenic induction by BMP.
– Strongly stimulates expression of
matrix proteins by osteoblastic cells.
REGULATION OF BONE FORMATION

TGF-β:
•
REGULATION OF BONE FORMATION

• IGF-I and II: (Potent Anabolic

Agents)
– Similar effects like TGF-β on matrix
proteins and matrix
metalloproteinases.
– Also stimulates proliferation of
Osteoblastic cell precursors.
REGULATION OF BONE FORMATION

• Fibroblast growth factors : (Basic)

– Increased proliferation of osteoprogenitors.
– Promote osteogenic differentiation.

• PDGF:
– Promotes osteogenesis as Fibroblast growth
Factors.
– Also influences the expression of other cytokines.

31
 BONE
RESORPTION
 BONE RESORPTION

• Specialized cell : Osteoclast

• Produced by the monocyte/macrophage
lineage of hematopoietic cells.
Receptor Activator of Nuclear Factor κB / Ligan
Osteoprotegerin Ligand
 BONE RESORPTION
u ro
y al
H nan or
e pt
c
re D44
C
Fusion of monocytic precursors
occurs at the site of bone
resorption to form osteoclasts.
Signaling cell
attachment and
Highly also possibly for
αvß 3 expressed in osteoclast
integrin osteoclasts chemotaxis
with CD44 and (haptotaxis) &
osteoclasts migration
precursors
 BONE RESORPTION

1. Demineralization Phase

2. Degradation of
matrix
 BONE RESORPTION

1. Demineralization Phase
 BONE RESORPTION

2. Degradation of
matrix
1. Demineralization Phase
Matrix
Lysosomal metalloproteinases
enzymes activated under
acidic conditions
observed in
resorption lacunae

Can degrade
matrix
macromolecule
BONE RESORPTION

Me
ch
m ani
lim for s
re
s o itin g
ac rpt
tiv ive
ity
.
REGULATION OF BONE
RESORPTION
REGULATION OF BONE RESORPTION

Calcito
nin: Ca
cytopla uses
smic
contra
ction o
membr f t he c e
ane in ll
osteoc mature
lasts a
dissoci nd
Stimula ation in their
t es monoc to
prolife ytic ce
ration lls
precur of
sor cel
Indirec ls.
tly via
Regula PG E
te 2
Osteoc
last
develo
pment
throug
ht
OPG/OP he
G
pathwa L/RANK
y
 BONE
MODELING

V
s BONE
REMODELI
NG
 BONE MODELING

• Modeling is the process used by bone to shape

itself, rating an organ with maximal
compressive strength, which is associated with
the formation and growth of bones in
childhood and adolescence.

Periodontology 2000, Vol.

 BONE REMODELING
• Remodeling represents a change that occurs within the
mineralized bone without a concomitant alteration of the
architecture of the tissue.
Why Remodel Bone ???
• Allows bone to respond to loads
(stresses)
• Allows repair of microdamage
• Participates in serum Ca2+ regulation
• Replacement of old bone with new bone
 BONE REMODELING

COUPLING

IN NORMAL
ADULTS

Osteoblasts Osteoclasts

– Forst HM-
1964
BONE REMODELING HYPOTHESIS
 ACTIVATION FREQUENCY

• The number of sites entering the bone formation

phase, called the activation frequency, together
with the individual rates of the two processes,
determines the rate of tissue turnover.
• Significance:
– Resorption depth and mean wall thickness may vary by on
10-20% of normal in different diseases
– Activation frequency may vary by upto 50-100%.
• Thus, in most diseases, the activation frequency is
the most important regulator of bone turnover and
changes in the bone mass.

- Ericksen Ef,
1986
BONE MULTICELLULAR UNITS (BMUs)
A BMU is comprised of
(1) a front osteoclast residing on a surface of newly resorbed bone (the
resorption front),
(2) a compartment containing vessels and pericytes, and
(3) a layer of osteoblasts present on a newly formed organic matrix (the
deposition front).
•Becomes “machinery” that remodels bone.
•Forms in response to molecular signaling.
•Functions over a period of weeks to months (10 µ m/day).

Osteoclast (OC)
Osteoblasts (OB)
Osteoid (OS)
Vascular structures (V)
RL = reversal line
LB = lamellar bone
 AGING & BONE

•Starts at the age of approximately 25-30 years, when maximal

bone formation is achieve.

•From that age, a steady decline in bone mass begins for both
men and women. (more severe in females)

•The decrease in bone mass leads to:

•Thinning of cortical bone due to tunneling or trabeculation of
the endosteal cortical envelope, with expansion of the marrow
cavity accompanied by some gain in diameter.
Bone’s Role in Calcium
Homeostasis
Bone’s Role in Calcium Homeostasis
Bone’s Role in Calcium Homeostasis
Some
stimulus Increase
causes production of More
blood cAMP in PTH is
calcium Parathyroid secrete
level to Gland d
decrease
a ck
d b
e Stimulates
fe osteoblast to
e
it v ff release IL-1 & IL-6
a O
eg s
N
u rn
T
Causes LIF
bone Migration
secreted of
resorptio by
n& monocyte
osteoblas to bone
release t
of areas
coalesces
calcium monocyte
in blood. s to form
osteoclast
Alveolar Bone in
Disease
Alveolar Bone in Disease
 Clinical
Implications
 Clinical Implications

• Alveolar bone is dependent upon the

presence of teeth for its preservation.

• Maintenance is also compromised by

trauma and inflammatory episodes
associated with periodontal disease.

• Rapid remodeling – important for

movement of teeth in response to
occlusive and orthodontic forces.
Clinical Implications

Site
specific
remodeling
in the
absence of
inflammati
on.
Potential Therapeutic Strategies To Treat
Bone Resorption
Potential Therapeutic Strategies To Treat
Bone Resorption
Increases
apoptosis of
osteoclasts thus
Flurbiprofen & Promotes
reducing life
Ibuprofen
span apoptosis
Current therapeutic
agents for
osteoporosis.
Also is used for
coating implant
surface.
Block the initial
osteoclast
adhesion to the
matrix.

Reduce the
protease
degradation of
the organic
matrix.
Conclusion
 Conclusion
•Alveolar bone has interdependence with dentition.

•Constant state of Flux.

•Rate of remodeling is unique to alveolar bone and is

important for its adaptability.

•Many of the factors that regulate bone remodeling like,

Cbfa1 & Osteoprotegrin, appear to exert their effects either
directly or indirectly through these genes, which have
become important targets for developing pharmacological
and clinical strategies to regulate the rate of bone
formation and resorption that will be important for
maintenance of a healthy periodontium.
 References
• Carranza’s Clinical Periodontology, 10th edition.
• Periodontology 2000 Vol. 3, 1993
• Periodontology 2000 Vol. 13, 1997
• Periodontology 2000 Vol. 14, 1997
• Periodontology 2000 Vol. 24, 2000
• Periodontology 2000 Vol. 41, 2006
• Principles of Anatomy & Physiology, 11th edition, by
Tortora & Derrickson.
• Clinical Periodontology & Implant Dentistry, 5th
edition, Jan Lindhe
Thank You