Basic bone biology

How bone response in orthodontic force

1. Om Shree Ganapati namah
Basics of bone biology / Role of
inflammation / Relevance to orthodontics
Dr. Sangamesh B. M.D.S., MOrth RCS(Edinburgh)
Assistant Professor

2. Contents
Gross bone anatomy
Bone cells
Periodontal ligament
Functional histology
Bone turnover
Bone modeling and remodeling

3. Bone
Highly specialized support
tissue characterized by
Rigidity
Hardness

4. The bones in the
skeleton are not all solid
Strength to act as levers
for muscles
Give form to soft tissues
Provide protective
cavities for the vital
organs

5. Outer cortical or compact bone
Inner trabecular or spongy bone
Periosteum
Endosteum
Structure of the bone

6. Types of bone
Primary bone or the
woven bone
Secondary bone or the
lamellar bone
Trabecular /
cancellous / spongy
Cortical / compact /
dense

7. Woven (immature, fracture) Large, rounded osteocytes
Osteocytes irregularly spaced
Randomly oriented collagen fibres
Variable collagen fibre diameter
Rapid matrix mineralisation
Forms rapidly
Rapid turnover
Lamellar (mature, adult)
Smaller, flattened osteocytes
Osteocytes regularly spaced
Collagen fibers show regular,
“plywood” orientation – confers strength
Regular collagen fiber diameter
Delayed matrix mineralisation (few days)
Forms slowly
Slow turnover

8. Types of bone formation

9. Endochondral ossification formation of long bones from cartilage model
Albert
s

et
al
Molecu
lar –
M
ol
e
c
ular Bio
log
y o
f
t
he Cell
Growing knee joint (cat) growth plate
Endochondral bone formation
is by the replacement
of the hyaline
cartilage model with
bone tissue.

10. Intramambranous bone formation
is the replacement of
the connective tissue
membrane sheets
and results in the
formation of flat
bones.
Intramembranous ossification
Calvarium
Periosteum

11. Outer Cortical bone is
solid with few small
canals
Inner trabecular bone is
like scaffolding or a
honey-comb
Spaces between the
bone are filled with fluid
bone marrow cells and
some fat cells
Alveolar Bone

12. Tooth eruption (cat) ultra-low power section of
developing jaw
1 mm

14. Supporting the teeth
Alveolar bone
Periodontal ligament

15. Alveolar bone proper /
Bundle bone
Central spongiosa
Outer cortical plates

17. Alveolar bone proper /
Bundle bone
Because alveolar process is
regularly penetrated by collagen
fiber bundles, it is also called
bundle bone
It appears more radiodense
than surrounding supporting
bone in X-rays called lamina
dura

18. Alveolar bone proper /
Bundle bone
Because alveolar process is
regularly penetrated by collagen
fiber bundles, it is also called
bundle bone
It appears more radiodense
than surrounding supporting
bone in X-rays called lamina
dura

19. Low-power scanning electron mi
croscope image of
nor
m
al bone
architecture in the 3
rd
lumbar
ver
tebra of
a 30 year
old woman
m
a
rrow and other cell
s rem
o
ved to reveal
t
h
ic
k
,
int
e
r
c
onnec
t
ed plat
es
of
bone
Trabecular
bone

21. Relevance of
Architecture and Geometry
Normal Loss of Loss of
Quantity and Quantity Architecture
Architecture

22. Trabcular bone element perforated by osteoclast action
Low-power scanning electron mi
croscope image of
osteoporot
ic
bone ar
chitecture in the 3
rd
lumbar
vertebra of
a 71 year
old woman
m
a
rrow and other cell
s rem
o
ved to re
veal eroded, fragi
le
rods of
bone
Trabcular bone element eroded by osteoclasts

23. Normal
Moderate Osteoporosis
Severe Osteoporosis
Courtesy Dr. A. Boyde

24. Compact bone

30. Mineral deposition

31. Composition of the bone
Inorganic bone - 67%
65-70% inorganic mineral
(hydroxyapatite)
Crystalline complex of
Calcium and phosphate
(hydroxyapatite)
Ca
5(PO
4)
3(OH)
2
Organic bone - 33%
Collagen - 28%
Cells - 5%
Osteocalcin
Sialoprotein
Phosphoprotein
Osteonectin
Bone specific protein

32. Water 45 - 50%
Ash 30 - 35%
Protein 10 - 15%
Fat 5 - 10%

Composition of Ash:
Calcium 36%
Phosphorus 17%
Magnesium 0.8%

33. Structural and Metabolic Bone
Fractions
• Cortical
– outer half provides strength – Inner half provides metabolic Ca
++
• Trabecular
– High turnover rate – Major source of metabolic Ca
++

34. Calcium
Electrical- carries current during an action potential across
membranes, and can result in changes in intracellular free Ca2+
Cofactor for extracellular enzymes and regulatory proteins -
stability or maximal activity
Intracellular regulator - as a result of change in [Ca2+] inside
cells
Structural (bones, tissues)

Vitamin D
1,25-dihydroxyvitamin D is thought to be the biologically active
form which upregulatores calcium binding proteins to enhance
calcium absorption
conserves calcium at the kidney and increases bone resorption

35. Phosphorus
Structural in bone, phospholipids
Buffer and regulator of acid-base balance
Energy currency of cells


Magnesium
Magnesium is thought to enhance bone quality by
influencing hydroxyapatite crystal growth.

36. Collagen
Fiber
Orientation
Alternate
Parallel
Twisted Plywood

37. Cells of the bone

38. Osteoblasts are derived from
the mesenchymal stem cells

39. Transcription Factors & Differentiation
of Mesenchymal Progenitors
T Katagiri & N Takahash
i. Oral Diseases. 2002

40. Primitive
progenitor
Preosteoblast
Osteoblast
Osteocyte
Regulated self-renewal,
Choice of cell fate
Commitment, differentiation
Extracellular matrix
synthesis & mineralization
C3HT101/2
MC3T3.E1
Metaphyseal bone cells
Diaphyseal bone marrow stromal cells

41. BONE
Osteoblast T issue Matrix
Cell adhesion molecules Cell membrane Cytoskeleton
Nuclear Matrix
nuclear pore
nucleolus
nucleoskeleton
Integrins ECM
The Osteoblast Tissue Matrix

42. Osteocytes
osteoblast
osteocyte

43. Osteocytes

44. 3
Inhibitors of Osteoclast Formation
OPG
sRANK-Fc
GM-CSF
IFN!
IFN"
IL-18
IL-12
OCIL
TSA-1
Legumain
sFRP-1
IL-4
IL-13
IL-10
-binds RANKL
-binds RANKL
-direct
-direct
-direct (feedback loop?)
-indirect via T-cells
-indirect via T-cells
-direct
-direct
-direct
-?
Th2 cytokines}
Dr. Jack Martin
Osteoclast Differentiation
OPG
RANKL
RANK
Activated
Osteoclast
Hematopoietic
Stem Cells
Mononuclear
Osteoclast
Osteoclast
Progenitor
Inactive
Osteoclast
1,25(OH)
2
D
3
Osteoblasts
Bone
Characteristics of Osteoclasts
!Multinucleated Cells-contain 4-20 nuclei in
vivo
!Tartrate-resistant acid phosphatase
positive
!Calcitonin receptor positive
!Vitronectin receptor positive
!Positive for cathepsin K
!Resorb bone
Ultrastructural Features
!Highly vacuolated “foamy” cells
!Polarized cells have ruffled border and
sealing zone
Ultrastructural Characteristics of
the Osteoclast
BONE
Clear Zone
Resorption Lacuna/ Pit
Vitronectin
Receptors (VNR, !
v
"
3
)
Calcitonin
Receptors (CTR)
Ruffled Border
H
+
H
+
H
+
Cl
-
Cl
-
Cathepsin K
TRAPLysosomal
enzymes
Proton pump
V-ATPase
VNR and collagen
receptors(!
2
b
1
)
Carbonic
Anhydrase II
H
+HCO
3
-
Drs. Quinn/Martin 2002
Transmission Electron Micrograph of a
Human Osteoclast
Stenbeck, Seminars Cell Developmental Biol 2002
1
The Osteoclast
!Multinucleated giant cell found in bone
!Found in contact with calcified bone
surface
!Function is bone resorption
!Life span in vivois up to 2 weeks with a
half-life around 6-10 days
Osteoclasts on Bone
Dr. Ott’s Web Site 2002
Osteoclast on Bone
Dr. Ott’s Web Site 2002
In vitroGenerated Murine
Osteoclast
Galvin et al BBRC
Location of Osteoclasts
!Attached to or at the bone surface
!BMU-basic multicellular unit
!Howship’s lacunae-generally 2
osteoclasts/lacunae, but can be up to 5
Bone Remodeling
Osteoblast
Reversal/ FormationReversal/ Formation
New Bone
Osteoclast
ResorptionResorption

45. 3
Inhibitors of Osteoclast Formation
OPG
sRANK-Fc
GM-CSF
IFN!
IFN"
IL-18
IL-12
OCIL
TSA-1
Legumain
sFRP-1
IL-4
IL-13
IL-10
-binds RANKL
-binds RANKL
-direct
-direct
-direct (feedback loop?)
-indirect via T-cells
-indirect via T-cells
-direct
-direct
-direct
-?
Th2 cytokines}
Dr. Jack Martin
Osteoclast Differentiation
OPG
RANKL
RANK
Activated
Osteoclast
Hematopoietic
Stem Cells
Mononuclear
Osteoclast
Osteoclast
Progenitor
Inactive
Osteoclast
1,25(OH)
2
D
3
Osteoblasts
Bone
Characteristics of Osteoclasts
!Multinucleated Cells-contain 4-20 nuclei in
vivo
!Tartrate-resistant acid phosphatase
positive
!Calcitonin receptor positive
!Vitronectin receptor positive
!Positive for cathepsin K
!Resorb bone
Ultrastructural Features
!Highly vacuolated “foamy” cells
!Polarized cells have ruffled border and
sealing zone
Ultrastructural Characteristics of
the Osteoclast
BONE
Clear Zone
Resorption Lacuna/ Pit
Vitronectin
Receptors (VNR, !
v
"
3
)
Calcitonin
Receptors (CTR)
Ruffled Border
H
+
H
+
H
+
Cl
-
Cl
-
Cathepsin K
TRAPLysosomal
enzymesProton pump
V-ATPase
VNR and collagen
receptors(!
2
b
1
)
Carbonic
Anhydrase II
H
+HCO
3
-
Drs. Quinn/Martin 2002
Transmission Electron Micrograph of a
Human Osteoclast
Stenbeck, Seminars Cell Developmental Biol 2002

46. 3
Inhibitors of Osteoclast Formation
OPG
sRANK-Fc
GM-CSF
IFN!
IFN"
IL-18
IL-12
OCIL
TSA-1
Legumain
sFRP-1
IL-4
IL-13
IL-10
-binds RANKL
-binds RANKL
-direct
-direct
-direct (feedback loop?)
-indirect via T-cells
-indirect via T-cells
-direct
-direct
-direct
-?
Th2 cytokines}
Dr. Jack Martin
Osteoclast Differentiation
OPG
RANKL
RANK
Activated
Osteoclast
Hematopoietic
Stem Cells
Mononuclear
Osteoclast
Osteoclast
Progenitor
Inactive
Osteoclast
1,25(OH)
2
D
3
Osteoblasts
Bone
Characteristics of Osteoclasts
!Multinucleated Cells-contain 4-20 nuclei in
vivo
!Tartrate-resistant acid phosphatase
positive
!Calcitonin receptor positive
!Vitronectin receptor positive
!Positive for cathepsin K
!Resorb bone
Ultrastructural Features
!Highly vacuolated “foamy” cells
!Polarized cells have ruffled border and
sealing zone
Ultrastructural Characteristics of
the Osteoclast
BONE
Clear Zone
Resorption Lacuna/ Pit
Vitronectin
Receptors (VNR, !
v
"
3
)
Calcitonin
Receptors (CTR)
Ruffled Border
H
+
H
+
H
+
Cl
-
Cl
-
Cathepsin K
TRAPLysosomal
enzymes
Proton pump
V-ATPase
VNR and collagen
receptors(!
2
b
1
)
Carbonic
Anhydrase II
H
+HCO
3
-
Drs. Quinn/Martin 2002
Transmission Electron Micrograph of a
Human Osteoclast
Stenbeck, Seminars Cell Developmental Biol 2002

47. Osteoclast differentiation
Osteoclast migration
Osteoclast polarization
Ruffled border formation
Osteoclast actin ring formation
Dissolution of bone
Osteoclast bone resorption
Osteoclast apopotsis

48. Functions of bone
Provide structural support to the body
Provide protection of vital organs
Provide an environment for marrow (Blood
forming and fat storage)
Act as mineral reservoir for calcium
homeostasis in the body

49. Periodontal Ligament

50. Periodontal Ligament
PDL is the soft specialized connective tissue situated between
cementum and alveolar bone proper
Ranges in thickness between 0.15 and 0.38 mm and is thinnest
in the middle portion of the root
The width decreases with age
Tissue with high turnover rate
Contains fibers, cells and intercellular substance

51. Embryogenesis

The PDL forms from the dental follicle shortly after root development begins

52. Cells
Osteoblasts
Osteoclasts (critical for periodontal disease and tooth movement)
Fibroblasts (Most abundant)
Epithelial cells (remnants of Hertwig’s epithelial root sheath-epithelial cell
rests of Malassez)
Macrophages (important defense cells)
Undifferentiated cells (perivascular location)
Cementoblasts
Cementoclasts (only in pathologic conditions)

53. Ground Substance
Amorphous background material that binds tissues and fluids - major
constituent of the PDL
Similar to most connective tissue ground substance
Dermatan sulfate is the major & glycosaminoglycan
70% water; critical for withstanding forces
When function is increased PDL is increased in size and fiber thickens, bone
trabeculae also increase in number and thicker
However, in reduction of function, PDL narrows and fiber bundles decreases
in number and thickness (this reduction in PDL is primarily due to increased
cementum deposition)

54. PDL fibers
Collagen fibers: I, III and XII. Groups of fibers that are
continually remodeled. (Principal fiber bundles of the PDL).
The average diameter of individual fibers are smaller than other
areas of the body, due to the shorter half-life of PDL fibers (so
they have less time for fibrillar assembly)
Oxytalan fibers: variant of elastic fibers, perpendicular to
teeth, adjacent to capillaries
Eluanin: variant of elastic fibers

55. Dentoalveolar group
Alveolar crest group (ACG): below CE junction, downward, outward
Horizontal group: apical to ACG, right angle to the root surface
Oblique group: most numerous, oblique direction and attaches coronally to
bone
Apical group: around the apex, base of socket
Interradicular group: multirooted teeth. Runs from cementum and bone ,
forming the crest of the interradicular septum
At each end, fibers embedded in bone
and cementum: Sharpey’s fiber

Principal Fibers
Run between tooth and bone.
Can be classified as dentoalveolar and gingival group

56. Gingival ligament fibers
The principal fibers in the gingival area are referred to as
gingival fibers. Not strictly related to periodontium. Present in
the lamina propria of the gingiva.
Dentogingival: most numerous; cervical
cementum to f/a gingiva
Alveologingival: bone of the alveolar crest
to f/a gingiva
Circular: around neck of teeth, free
gingiva
Dentoperiosteal: runs apically from the
cementum over the outer cortical plate to
alv. process or vestibule (muscle) or floor
of mouth
Transseptal: cementum between
adjacent teeth, over the alveolar crest

59. The PDL gets its blood supply from perforating
arteries (from the cribriform plate of the bundle
bone).
The small capillaries derive from the superior &
inferior alveolar arteries.
The blood supply is rich because the PDL has a very
high turnover as a tissue.
The posterior supply is more prominent than the
anterior.
The mandibular is more prominent than the maxillary

62. Interstitial Space
Present between each bundle of ligament fibers
Contains blood vessels and nerves
Designed to withstand the impact of masticatory forces

63. Nerve supply
The nerve supply originates from the inferior or
the superior alveolar nerves.
The fibers enter from the apical region and
lateral socket walls.
The apical region contains more nerve endings
(except Upper Incisors)

64. Tooth support
Shock absorber: Withstanding the forces of
mastication
Sensory receptor necessary for proper
positioning of the jaw
Nutritive: blood vessels provide the essential
nutrients to the vitality of the PDL
FUNCTIONS OF PERIODONTIUM

65. Bone turnover
Bone modeling

66. Technique for quantifying the
remodeling process
How much (static)
How long (dynamic)
Cell activity

68. “ . . . the origin or causation of the
phenomenon would seem to lie partly
in the tendency of growth to be
accelerated under strain. . . .
accounting therefore for the
rearrangement of . . . the trabeculae
within the bone.”
D’Arcy Thompson, 1917

69. Rules for Bone Adaptation
Bone responds only to dynamic loads
The loading period can be short
Rate related phenomena are critical to
response

71. The Mechanostat: Essential Principles
Threshold-driven
Modeling and Remodeling are antagonistic
Operate within different strain ranges
Architecturally antagonistic
Bone envelopes are controlled by local conditions

72. Signal Transduction
External signals
Odorants
Chemicals that reflect metabolic status
Ions
Hormones
Growth factors
Neurotransmitters
Light
Mechanical forces

73. Signal Transduction Steps
Recognition
Ionic bonds
Van der Waals interactions
Hydorphobic interaction
Transduction
Transmission
Modulation of the Effectors
Response
Termination

74. Bone modeling

75. Modeling
Activation – Resorption (A-R)
Activation – Formation (A-F)

76. Drift (Cortical and Trabecular)
Occurs through Modeling Processes

78. Old bone New bone Osteoid
3. Resorption
4. Reversal
5. Formation
6. Quiescence
1. Quiescence
2. Activation
LC
POC
OB
LC
OC
HL
?
CL
CL
BSU
CL
The Quantum
Concept of
Bone
Remodeling

81. Gene 1
Environment 2
Phenotype
Gene 2 Gene 3Gene 4
Environment 1
Gene x Environment Interactions
Underlying Complex Disease

82. Role of inflammation
Dr Anand K. Patil