BONE HEALING

IQNASIA WINDY
NOVITASARI
I11111059

BONE COMPOSITION

BONE COMPOSITION
Component

Comment

Bone is composed of multiple components: 1. Organic phase (matrix:

protein, macromolecules, cells); 2. Inorganic phase (minerals, e.g., Ca +
+
); 3. Water
Inorganic phase
Calcium hydroxyapatite
Osteocalcium phosphate

Approximately 60% of bone

weight
Ca10(PO4)6(OH)2. Primary mineral
bone. Adds compressive
strength.
Brushite is a secondary/minor
mineral in bone

BONE COMPOSITION
Component
Organic phase
Collagen

Proteoglycans

Comment
Also known as osteoid before its
mineralization; approximately
35% of bone weight
Type 1 collagen give tensile
strenght and is 90% of organic
phase. Mineralzation occurs at
ends (hole zones) and along
sides (pores) of the collagen
fibers.
Macromolecules made up of
hyaluronic backbone w/ multiple
glycosaminoglycans (GAG)
GAG; made of core protein w/
chondroitin & keratin branches

BONE COMPOSITION
Component
Organic phase
Noncollagen proteins
Cells
Water

Comment
Osteocalcin #1, is indicator of
increased bone turnover (e.g.,
Pagets disease)
Others: osteonectin, osteopontin
Osteoblasts, osteocytes,
osteoclasts
Approximately 5% of bone
weight (varies with age and
location)

Periosteum surrounds the bone, is thicker in children, and responsible

for the growing diameter (width) of long bones.

BON
E
FOR
MATION

BONE FORMATION
Ossification

Comment

Bone formation (ossification) occurs in 3 different ways: enchondral,

intramembranous, appositional
Enchondral

Bone replaces a cartilage anlage

(template). Osteoclasts remove
the cartilage, and osteoblasts
make the new bone matrix,
which is then mineralized.
Typical in long bones (except
clavicle).
Primary ossification centers
occur at various times after
birth, usually in the epiphysis.
Longitudinal growth at the
physis also accurs by enchondral
ossification.

BONE FORMATION
Ossification
Intramembranous

Appositional

Comment
Bone develops directly from
mesenchymal cells without a
cartilage anlage.
Mesenchymal cells differentiate
into osteoblasts, which produce
bone.
Examples: flat bones (e.g., the
cranium) and clavicle.\
Osteoblasts make new
matrix/bone on top of existing
bone.
Example: periosteal-mediated
bone diameter (width) growth in
long bones

FACTORS
INFLUENCING BONE
HEALING (SYSTEMIC)
A. Age
B. Activity level including
C. Nutritional status
D. Hormonal factors
E. Diseases: diabetes, anemia, neuropathies,
tabes
F. Vitamin deficiencies: A, C, D, K

FACTORS
INFLUENCING BONE
HEALING (SYSTEMIC)
G. Drugs: NSAIDs, anticoagulants, factor XIII,
calcium channel blockers (verapamil),
cytotoxins, diphosphonates, phenytoin
(dilantin), sodium fluoride, tetracycline
H. Other substances (nicotine, alcohol)
I.

Hypoxia

J.

Systemic growth factors

K. Environmental temperature
L. Central nervous system trauma

FACTORS
INFLUENCING BONE
HEALING (LOCAL)
A. Factors independent of injury, treatment, or
complications
B. Factors depending on injury
C. Factors depending on treatment
D. Factors associated with complications

PREREQUISITES FOR
BONE HEALING
Adequate blood supply
Adequate mechanical stability

BLOOD
SUPPLY IN
TUBULAR
BONES
Nutrient artery

Periosteal vessels
Epiphyseal and
metaphyseal vessels

MECHANICAL
STABILITY
Early stability promotes
revascularization
After first month, loading
and interfragmentary
motion promotes greater
callus formation

MECHANICAL
STABILITY
Mechanical load and small displacements at the
fracture site stimulate healing
Inadequate stabilization may result in excessive
deformation at the fracture site interrupting tissue
differentiation to bone (soft callus)
Over-stabilization, however, reduces periosteal
bone formation (hard callus)

STAGES OF BONE
HEALING

(a) Haematoma: there is tissue damage and bleeding at the fracture

site; the bone ends die back for a few milimetres. (b) Inflammation:
inflammatory cells appear in the haematoma. (c) Callus: the cell
population changes to osteoblasts and osteoclasts; dead bone is
mopped up and woven bone appears in the fracture callus. (d)
Consolidation: woven bone is replaced by lamellar bone and the

TISSUE
DESTRUCTION AND
HAEMATOMA
FORMATION
Vessels are torn and a haematoma forms around

and within the fracture. Bone at the fracture

surfaces, deprived of a blood supply, dies back for
a millimetre or two.

INFLAMMATION AND
CELLULAR
PROLIFERATION
Within 8 hours of the fracture there is an acute
inflammatory reaction with migration of
inflammatory cells and the initiation of
proliferation and differentiation of mesenchymal
stem cells from the periosteum, the breached
medullary canal and the surrounding muscle.

CALLUS FORMATION
The differentiating stem cells provide
chrondrogenic and osteogenic cell populations;
given the right conditions and this is usually the
local biological and biomechanical environment
they will start forming bone and, in some cases,
also cartilage.
As the immature fibre bone (or woven bone)
becomes more densely mineralized, movement at
the fracture site decreases progressively and at
about 4 weeks after injury the fracture unites.

CONSOLIDATION
With continuing osteoclastic and osteoblastic
activity the woven bone is transformed into
lamellar bone. The system is now rigid enough to
allow osteoclasts to burrow through the debris at
the fracture line, and close behind them.
Osteoblasts fill in the remaining gaps between the
fragments with new bone. This is a slow process
and it may be several months before the bone is
strong enough to carry normal loads.

REMODELLING
The fracture has been bridged by a cuff of solid
bone. Over a period of months, or even years, this
crude weld is reshaped by a continuous process
of alternating bone resorption and formation.

FRACTURE REPAIR

(a) fracture; (b) union; (c) consolidation; (d) bone

remodelling. The fracture must be protected until
consolidated.

MECHANISMS FOR
BONE HEALING
Direct (primary) bone healing
Indirect (secondary) bone healing

DIRECT BONE
HEALING
Mechanism of bone healing seen when there is no
motion at the fracture site (i.e. absolute stability)
Does not involve formation of fracture callus
Osteoblasts originate from endothelial and
perivascular cells

DIRECT BONE
HEALING
A cutting cone is formed that crosses the fracture
site
Osteoblasts lay down lamellar bone behind the
osteoclasts forming a secondary osteon
Gradually the fracture is healed by the formation
of numerous secondary osteons
A slow process months to years

COMPONENTS OF
DIRECT BONE
HEALING
Contact
Healing

Direct contact between the fracture ends allows healing

to be with lamellar bone immediately

Gap Healing
Gaps less than 200-500 microns are primarily filled with
woven bone that is subsequently remodeled into
lamellar bone
Larger gaps are healed by indirect bone healing
(partially filled with fibrous tissue that undergoes
secondary ossification)

DIRECT BONE
HEALING

INDIRECT BONE
HEALING
Mechanism for healing in
fractures that have some
motion, but not enough to
disrupt the healing process.
Bridging periosteal (soft)
callus and medullary (hard)
callus re-establish structural
continuity
Callus subsequently
undergoes endochondral
ossification
Process fairly rapid - weeks

LOCAL REGULATION
OF BONE HEALING
1. Growth factors
2. Cytokines
3. Prostaglandins/Leukotrienes
4. Hormones
5. Growth factor antagonists

FACTORS THAT
NEGATIVELY AFFECT
BONE HEALING
1. Tobacco smoking
2. Nonsteroidal antiinflammatory drugs
(cyclooxygenase-1 and cyclooxygenase-2)
3. The fluoroquinolone family of antibiotics
4. Other factors: weight bearing or muscular
stimulation of the fracture site; diabetes

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