BONE

BY:
E P E D
AR RANAS
REMODELIN
G
PR
E M ACA
N
DIVI
- 2 017
2- 8
 I. BONE REMODELING

BONE RESORPTION
BONE DEPOSITION
ADDITIONAL TOPICS:

II. BIOLOGY OF TOOTH MOVEMENT BOOK

CHAPTERS 8, 10 AND 11

III. BONE PATHOLOGY NOTES

HEALING OF FRACTURES
BONE REMODELING
 INTRODUCTION
Bone
Undergoes constant renewal in response to chemical,
mechanical, nutritional, and hormonal influences.

A balance between the processes of bone

resorption by osteoclasts and bone deposition by
osteoblasts is required in a healthy adult
 DEFINITION OF TERMS
Tooth movement involves both bone modeling and remodeling

Bone Modeling
-independent sites of resorption and deposition change the form of a bone
-uncoupled
-craniofacial growth of child and adolescent

Bone Remodeling
-specific, coupled sequence of resorption and deposition occurs to replace
existing bone
 DEFINITION OF TERMS

BONE RESORPTION - is the process by which osteoclasts break

down bone and release the minerals, resulting in a transfer of
calcium from bone fluid to the blood

BONE DEPOSITION - The osteoblasts secrete an organic matrix

composed largely of collagen protein, which becomes hardened by
deposits of hydroxyapatite.
 DEFINITION OF TERMS

Undermining Resorption
– osteoclasts from adjacent marrow
spaces attack the underside of the
lamina dura. Produced by heavy forces
with pain, necrosis of cellular elements
within the PDL.
 DEFINITION OF TERMS

Frontal Resorption
– osteoclasts from the involved PDL and
attack the adjacent lamina dura.
Produced by light forces with less pain
and survival of the cellular elements
within the PDL. Ideal for orthodontic
tooth movement.
 BONE REMODELLING UNIT
BONE REMODELLING UNIT (BRU) –FROST
volume of bone in which surface resorption or formation is
taking place
has primary importance in skeletal homeostasis due to
functional needs
last for months
life cycle of this has been designated as the :

ACTIVATION –RESORPTION- REVERSAL- FORMATION

 DEFINITION OF TERMS
OSTEOPROGENITOR CELLS
are undifferentiated mesenchymal cells and
hemotopoetic stem cells

under certain circumstances they divide and transform in

to osteoblasts and osteoclasts
 DEFINITION OF TERMS
OSTEOBLASTS
FUNCTIONS :
 Regulation of osteoclasts and deposition of
bone matrix
 Bone remodeling and mineral metabolism
 Mineralization of new bone
 Secrete type I collagen ,type V collagen,
osteonectin, osteopontin, RANKL,
osteoprotegerin, growth factors Osteocalcin
and CBFA1
 Express alkaline phosphatase
OSTEOCLAST
DEFINITION OF TERMS
 Generally occur in clusters.       
 They have prominent mitochondria,
  lysozomes, vacuoles and 
few endoplasmic reticulum
 Activity is controlled by Parathyroid
Hormone
 occupying shallow  depressions
called Howship’s lacunae
surfaces or in resorption cavities
  called  cutting cones
 DEFINITION OF TERMS
OSTEOCYTES
Most abundant bone cells 
Communicate with each other and with other
 cells on surface  of the bone via dendritic
process encapsulated in canaliculi
Play role in calcium homeostasis
Exchange of metabolic and  biochemical
 messages occurs  between blood stream and 
canaliculi  
 Acts as  mechanosensors instructing osteoclasts whe
re  to resorb and osteoblasts where and 
when to form
 BONE REMODELLING UNIT
BONE METABOLIC UNIT (BMU)

 Functional unit of bone that results from bone

remodelling process.
 The principle importance is in mineral homeostasis and
balance .(metabolic balance)
 The process can be from months to 10 years.
 DEFINITION OF TERMS
RANKL
RECEPTOR ACTIVATOR OF NUCLEAR FACTOR KAPPA-B
LIGAND
Member of the tumor necrosis factor (TNF) cytokine family.
it plays a critical role for adequate bone metabolism, this
surface-bound molecule (also known as CD254) found on
osteoblasts serves to activate osteoclasts, which are
critically involved in bone resorption.
stimulation of osteoclast differentiation and bone
resorption
 DEFINITION OF TERMS
OSTEOPROTEGERIN
a cytokine receptor, and a member of the tumor necrosis
factor (TNF) receptor superfamily
Acts as a decoy and blocks the binding of RANKL to RANK
and thus prevents Osteoclastic activity
 DEFINITION OF TERMS

RANK is the receptor for RANK-Ligand (RANKL) and part of the

RANK/RANKL/OPG signaling pathway that regulates osteoclast differentiation
and activation. It is associated with bone remodeling and repair, immune cell
function, thermal regulation and other physiologic activities

Osteoprotegerin- and blocks the binding of RANKL to RANK

 DEFINITION OF TERMS
PARATHYROID HORMONE
It acts to increase the concentration of calcium (Ca2+) in
the blood, whereas calcitonin (a hormone produced by the
parafollicular cells (C cells) of the thyroid gland) acts to
decrease calcium concentration.

PTH acts to increase the concentration of calcium in the

blood by acting upon parathyroid hormone receptor in
three parts of the body
 DEFINITION OF TERMS
CALCITONIN
 Functionally, Calcitonin decreases the rate of bone
resorption by promoting accumulation of organically
derived phosphorus from area next to the bone.
 This attracts calcium and favors bone deposition.
 Calcitonin decreases the function of the osteoclast
FACTORS AFFECTING BONE RESORPTION AND DEPOSITION
1.Platelet derived growth factor
2. Heparin binding growth factor 1. IL 1
3. Insulin like growth factor 2. IL 6
4. Transforming growth factor 3. TNF
5. Bone morphogenic protein 4. Gamma interferon
6. Estrogen
5. Colony stimulating factors
7. Calcitonin
6. Prostaglandin & other
8. Nitrous Oxide
9. 1,25 Dihydroxy vit D3/Calcitriol
Arachidonic Acid
10. Vit. A metabolites
11. Vit. C 7. PTH
12. Zinc
13. Manganese
14. Phosporus
>>>DEPOSITION <<<RESORPTION
 CHAPTER 8:

MOLECULAR MECHANISMS
OF TISSUE REPAIR

Charles Bertolami and Rebecca Bronson

 REMODELLING PROCESS
CELLULAR
PROLIFERATIO
N

MATRIX
SYNTHESIS MIGRATION
/DEGRADATION

DIFFERENTIATION
REVIEW OF THE REPAIR PROCESS

A. Injury, Inflammation, And Repair

B. Interactions Between Matrix Constituents And Cells

INJURY, INFLAMMATION, REPAIR
INFLAMMATION- response of tissue to injury or
infection

migration of leukocytes
macrophages become predominant/phagocytosis
release of chemotactic and mitogenic factors for both
fibroblasts and endothelial cells
INJURY, INFLAMMATION, REPAIR
INJURY- Too much stress exceeds the cell’s adaptive capacity
-irreversible/reversible

-some events in both acute and chronic injuries:

reduced ATP synthesis
release of different enzymes
disruption of cell membrane
free radical production
loss of calcium homeostasis
INJURY, INFLAMMATION, REPAIR
REPAIR-restoration of tissue architecture and function after an
injury

12 hours after injury fibroblasts are observed in the area

extracellular matrix synthesis
Production of new connective tissue (granulation tissue)
INFLAMMATORY AND ACUTE-PHASE MEDIATORS
A. The role of platelets

Blood plasma was adequate to maintain fibroblast viability

and factors present in serum were necessary to promote
proliferation.
PLATELET-DERIVED GROWTH FACTOR
-a required element in cell division of fibroblasts
stimulates tissue remodelling and cell proliferation
-regulates bone formation
INFLAMMATORY AND ACUTE-PHASE MEDIATORS

B. The role of macrophage

Transformed from monocytes

a type of phagocyte, which is a cell responsible for detecting,
engulfing and destroying pathogens and apoptotic cells
Some macrophages act as scavengers, removing dead or
necrotic cells while others provide host immunity by
engulfing microbes.
INFLAMMATORY AND ACUTE-PHASE MEDIATORS

C. INTERLEUKIN -1

cytokine derived from mononuclear phagocytes

 modulates the metabolism of several types types of
mesencymal cells including fibroblasts, synoviocytes,
osteocytes and chondrocytes
Synthesize prostglandins, neutral proteases and
collagenase
Stimulates bone resorption, inhibits bone formation
INFLAMMATORY AND ACUTE-PHASE MEDIATORS
D. OTHER MEDIATORS

MACROPHAGE-DERIVED GROWTH FACTOR

Stimulates cellular proliferation and synthesis of

extracellular components
Has the same activities as with the platelet-
derived growth factor during infammation
regulates bone formation
B. INTERACTIONS BETWEEN MATRIX CONSTITUENTS AND CELLS
 EXTRACELLULAR MATRIX

Components:
a. Collagen
b. Fibrin and fibronectin
c. Glycosaminoglycans

Functions:
Adhesion/structural integrity, migration,
proliferation, differentiation and synthesis
 EXTRACELLULAR MATRIX
Components:

a. Collagen-influence cellular shape, growth and

differentiation
-influence collagenase production by fibroblasts
b. Fibrin and fibronectin
fibrin-resulted from the conversion of fibrinogen
-interacts with both fibronectin and hyaluronate to
form an extensive matrix
fibrinectin-fibroblastic cell product
 EXTRACELLULAR MATRIX
Components:

c. Glycosaminoglycans/Proteoglycans

 Accumulate along with collagen at sites of injury and contribute

to the structural constituents of healing tissues
 Involved in the regulation of cellular proliferation, migration,
differentiation, and synthesis/secretion of collagen

Example of glycosaminoglycan: hyaluronic acid

 EXTRACELLULAR MATRIX

Hyaluronic acid

 Natural substance found in the human body

 Produced also by fibroblasts
 Stabilizers of extra-cellular matrix
 Helps in the regulation of the healing process
 HEALING ABNORMALITIES

HYPERTROPHIC SCARS AND KELOIDS

 These aberrations result from a disequilibrium between matrix
synthesis and catabolism
-this disequilibrium maybe seen as the alteration in the
normal remodeling of wound tissue
 IMPLICATION IN ORTHODONTICS

RELAPSE IN ORTHODONTICS ARE DUE TO:

 Failure in periodontal remodeling
 Inadequate activation of normal adaptive mechanisms

-it is important to know the underlying principles of tissue

remodeling basic to reparative and tooth movements as well as soft
tissue repair
 CHAPTER 10

COLLAGEN TURNOVER IN PERIODONTAL LIGAMENT

Jaro Sodek
 COLLAGEN TURNOVER
DEFINITION:

 Renewal of a given substance or component by synthesis or

exchange, or by replacement with a radiolabeled molecule in a
tissue or a tissue compartment

 Time interval required for the amount of a substance

transferred out of a compartment

 HYDROXYPROLINE CONTENT in urine-indication of collagen

turnover
 COLLAGEN TURNOVER IN PERIODONTAL TISSUES
PROOF/STUDIES:
 VITAMIN C DEFICIENCY STUDIES
 Various rodent and primate periodontal tissues (Orlowski et al.)
-There were significant errors in calculations of collagen half lives
-There were contaminated proteases
-Discrimination between matrix proteins, cellular proteins and tissue fluid
proteins was difficult
-But can provide indications of regional differences in turnover rates
within a tissue
Results:
Skin and tissues-similar rates of collagen synthesis
Bone- small amount of synthesized collagen
 COLLAGEN TURNOVER IN PERIODONTAL TISSUES
STUDIES:
 Collagen Metabolism in Periodontal Tissues of Marmoset and Beagle Dog
with other connective tissues
-high periodontal tissue collagen turnover rate, but result is not
considered significant because it is of general occurrence in previous
studies
 Type 1 and 3 Collagen in Rat Periodontal Tissues Analysis
-Type 1 and 3 turnover rate is similar
-Consistent results both in vivo and culture
-Type 1 and 3 collagens have found to be produced by periodontal
ligament fibroblasts and are produced simultaneously in skin and gingival
fibroblasts
 FACTORS AFFECTING COLLAGEN TURNOVER IN PERIODONTAL TISSUES

LOW FUNCTIONAL STRESS IN GINGIVAL CONNECTIVE

TISSUE=low turnover of collagen
OSTEOGENIC ACTIVITY=rapid turnover of collagen
REMODELING OF CALCIFIED TISSUE IN ENDOSTEAL
SPACES=lower than remodeling of fibrous tissues in endosteal
spaces
MINERALIZATION OF CONNECTIVE TISSUE OF BONE=low
turnover rate
Bone resorption- high turnover rate
Bone deposition-low turnover rate
 Chapter 11:

EXTRACELLULAR MATRIX AND

SEQUENTIAL REPLACEMENT EVENTS
DURING TISSUE FORMATION,
REMODELLING AND REPAIR

David A Carino and Arnold Caplan

 REPLACEMENT EVENTS DURING TISSUE FORMATION, REMODELING AND REPAIR

REPLACEMENT EVENTS
DEFINITION:

 Cells and tissues are sequentially replaced by the next less developmentally
manipulable and more stringently controlled movement.

 Example for this process is the activity in a

Cartilage proteoglycan-glycosoaminoglycan, keratin sulfate, chondroitin sulfate
 EFFECTS IN TISSUE AND MUSCLES
Chondroitin sulfate- known for water structuring properties
- loss of it will affect tissue resiliency and
eventually a cartilage damage may be seen in osteoarthritis
patients
Elimination of Chondroitin sulfate in muscles will lead to
depletion of extracellular tissue volume=loss of resiliency
In cardiac muscle, effects depends on their molecular structure
 IMPLICATION IN ORTHODONTICS
Recent evidences indicates that glycosaminoglycans and
proteoglycans are present in gingival tissue which health is
important during tooth movement and bone remodeling.
Notes on Pathology of Bone

HEALING OF FRACTURES
 DEFININITION OF TERMS
FRACTURE-break in bone or cartilage from variable causes
1. Traumatic fracture
2. Pathological fracture
3. Incomplete fracture/ greenstick fracture
4. Comminuted fracture
5. Open fracture
6. Closed fracture
 HEALING OF FRACTURE
A. IMMEDIATE DIRECT EFFECT
B. IMMEDIATE DIRECT INJURIES
C. REPAIR
D. REMODELLING OF CALLUS
 HEALING OF FRACTURE
A. IMMEDIATE DIRECT INJURIES (EXTERNAL FORCE)

1. bone broken, fragments separated by varying distance

2. breaking of blood vessels which cross the fracture line
3. Break blood vessels in periosteum, marrow
4. Breakage of blood vessels within the haversian system
5. Clot formed between fragments
6. The more fragments displaced, the greater the blood vessels
broken, more bleeding
 HEALING OF FRACTURE
B. IMMEDIATE INDIRECT INJURIES (INTERNAL FORCE)

1. Death of osteocytes
2. Death of bone marrow and periosteum
3. Distancing of dead osteocytes to fracture sites
4. Death of the ends of bone
 HEALING OF FRACTURE
C. REPAIR
1. Formation of callus
Callus- new tissue formed around and between ends of the bone
fragments of fracture
2. External callus- part of callus around the bone fragments
3. Internal callus- part of callus between ends of fragments and
between the marrow cavity
 HEALING OF FRACTURE
D. REMODELLING OF CALLUS

Occurs periosteally, transosteally and endoesteally

Trabecular space between cortex are replaced by cortical bone
Haversian systems are formed between pieces of cortical bone
after dead bone has been removed