FRACTURE HEALING

Presented by : Dr. momin mohammad farhan

Moderator : Dr. S. jidgekar
 Fracture Healing
 Healing of fracture in many ways similar to the
healing of soft tissue wound, except that soft
tissue heals with fibrous tissue , and end result
of bone healing is mineralised mesenchymal
tissue.
 Bone has a remarkable capacity to regenerate.
 Bone and liver are the only two organs in the
body that repair themselves without scar.
 Healing begins as soon as a bone is broken.
Mechanisms of Bone Formation

 Cutting Cones
 Intramembranous Bone
Formation
 Endochondral Bone Formation
 Cutting Cones
 Primarily a
mechanism to
remodel bone
 Osteoclasts at the
front of the
cutting cone
remove bone
 Trailing
osteoblasts lay
down new bone
 Intramembranous (Periosteal) Bone
Formation
 Mechanism by
which a long bone
grows in width
 Osteoblasts
differentiate directly
from preosteoblasts
and lay down seams
of osteoid
 Does NOT involve
cartilage
 Endochondral Bone Formation
 Mechanism by which a
long bone grows in
length
 Osteoblasts line a
cartilage precursor
 The chondrocytes
hypertrophy,
degenerate and calcify
 Vascular invasion of
the cartilage occurs
followed by
ossification
 Fracture Healing
 Bone healing is divided into two types
I. Primary bone healing
II. Secondary bone healing

Primary 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
 Primary 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
 Components of Direct Bone Healing
 Contact Healing
 When there is direct contact between cortical bone ends,
lamellar bone forms directly across the fracture line,
parallel to the long axis of the bone, by direct extension
of osteons
 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)
 Secondary bone healing

 Healing course
1) Stage of hematoma and Inflammation ( < 7
days)
2) Stage of granulation tissue (up to 2-3 weeks)
3) Stage of callus ( 4~12 weeks )
4) Stage of remodeling ( 1-2 years )
5) Stage of modeling ( many years )
 1) Stage of hematoma and inflamation
 When a bone is fractured,
blood leaks out through
torn vessels in the bone and
forms hematoma between
and around the fracture.
 It results in iscaemic
necrosis of the fracture
ends, Osteocytes near the
fracture surface are starved
of oxygen & die.
 This stage lasts up to 7 days
 1) Stage of hematoma and inflamation

 Hematoma in fracture site brings

hematopoietic cells secreting growth factor
 Growth factors
• Insulin-like growth factor (IGF-1)
• Transforming growth factor (TGF)

• Vascular endothelial growth factor (VEGF)

• Fibroblast growth factor (FGF)

 2) Stage of granulation tissue

 This stage lasts up to (2-3

weeks)
 The sensitised precursor
cells produces cells which
differentiate and organise
to provide blood vessels,
fibroblast, osteoblast etc.
 Collectively they form a
soft granulation tissue in
the space between the
fracture fragment.
 2) Stage of granulation tissue
 The blood clot gives rise to a losse fibrous mesh which
serves as a framework for the ingrowth of fibroblasts and
new capillaries
 The clot is eventually remove by the macrophages, giant
cells and other cells arising in granulation tissue.
 The fracture is still mobile in this stage

Hematoma
Periost Dead osteocytes/empty lacunae

Granulation Angiogenesis
tissue

Endosteum Devitalized marrow

 3) Stage of callus
 This stage lasts for about (4-12
weeks)
 The granulation tissue further
differentiates and creates osteoblasts.
 This cells lay down an intercellular
matrix which soon becomes
impregnated with calcium salts, this
results in formation of callus, also
called woven bone.
 A much wider zone over the cortex
on either side of the fracture ends is
covered by the woven bone callus
and united to bridge the gap
between the ends.
 The fracture is no mobile in this
stage.
 4) Stage of remodelling

 The woven bone is replaced by

mature bone with a typical
lamellar structure.
 The woven bone is cleared
away by incoming osteoclasts
and the calcified cartilage
disintegrates.
 In their place newly formed
blood vessels and osteoblasts
invade, laying down osteoid
which is calcified an lamellar
bone is formed.
 It is a slow process and take
from 1-4 years.
 5) Stage of modelling

 Continues for years after clinical and

radiographic union have occurred.
 The bone is gradually strengthened
 The shapening of the cortices occurs at the
endosteal an periosteal surfaces.
 The major stimulus to this process comes from
local bone strains i.e weight bearing stresses and
muscle forces
 Local Regulation of Bone Healing

 Growth factors
 Cytokines
 Prostaglandins/Leukotrienes
 Hormones
 Growth Factors

 Transforming growth factor

 Bone morphogenetic proteins
 Fibroblast growth factors
 Platelet-derived growth factors
 Insulin-like growth factors
 Transforming Growth Factor

 Acts on serine/threonine kinase cell wall

receptors
 Promotes proliferation and differentiation of
mesenchymal precursors for osteoblasts,
osteoclasts and chondrocytes
 Stimulates both endochondral and
intramembranous bone formation
 Induces synthesis of cartilage-specific proteoglycans
and type II collagen
 Stimulates collagen synthesis by osteoblasts
 Bone Morphogenetic Proteins
 Osteoinductive proteins initially isolated from
demineralized bone matrix
 Induce cell differentiation
 BMP-3 (osteogenin) is an extremely potent inducer of
mesenchymal tissue differentiation into bone
 Promote endochondral ossification
 BMP-2 and BMP-7 induce endochondral bone formation in
segmental defects
 These are included in the TGF-β family
 Except BMP-1
 Sixteen different BMP’s have been identified
 BMP2-7,9 are osteoinductive
 BMP2,6, & 9 may be the most potent in osteoblastic
differentiation
 Involved in progenitor cell transformation to pre-
osteoblasts
 Platelet-Derived Growth Factor
 A dimer of the products of two genes,
PDGF-A and PDGF-B
 PDGF-BB and PDGF-AB are the predominant
forms found in the circulation
 Stimulates bone cell growth
 Increases type I collagen synthesis by
increasing the number of osteoblasts
 PDGF-BB stimulates bone resorption by
increasing the number of osteoclasts
 Insulin-like Growth Factor
 Two types: IGF-I and IGF-II
 Synthesized by multiple tissues
 IGF-I production in the liver is stimulated by
Growth Hormone
 Stimulates bone collagen and matrix
synthesis
 Stimulates replication of osteoblasts
 Inhibits bone collagen degradation
 Cytokines
 Interleukin-1,-4,-6,-11, macrophage and
granulocyte/macrophage (GM) colony-
stimulating factors (CSFs) and Tumor Necrosis
Factor
 Stimulate bone resorption
 IL-1 is the most potent
 IL-1 and IL-6 synthesis is decreased by estrogen
 May be mechanism for post-menopausal bone
resorption
 Peak during 1st 24 hours then again during
remodeling
 Regulate endochondral bone formation
 Prostaglandins / Leukotrienes
 Effect on bone resorption is species dependent
and their overall effects in humans unknown
 Prostaglandins of the E series
 Stimulate osteoblastic bone formation
 Inhibit activity of isolated osteoclasts
 Leukotrienes
 Stimulate osteoblastic bone formation
 Enhance the capacity of isolated osteoclasts to form
resorption pits
 Hormones
 Estrogen
 Stimulates fracture healing through receptor mediated mechanism
 Modulates release of a specific inhibitor of IL-1
 Thyroid hormones
 Thyroxine and triiodothyronine stimulate osteoclastic bone
resorption
 Glucocorticoids
 Inhibit calcium absorption from the gut causing increased PTH
and therefore increased osteoclastic bone resorption
 Parathyroid Hormone
 Intermittent exposure stimulates
 Osteoblasts
 Increased bone formation
 Growth Hormone
 Mediated through IGF-1 (Somatomedin-C)
 Increases callus formation and fracture strength
 Vascular Factors
 Metalloproteinases
 Degrade cartilage and bones to allow
invasion of vessels
 Angiogenic factors
 Vascular-endothelial growth factors
 Mediate neo-angiogenesis & endothelial-
cell specific mitogens
 Angiopoietin (1&2)
 Regulate formation of larger vessels and
branches
Factors affecting fracture healing
Systemic factors
A.Age of the patient
- fracture unites faster in children
- on an average ,bones in children unite in half
the time
compared to that in adults
B.Activity level
1.General immobilization
2.Space flight
C.Nutritional status
- Malnutrition Reduces activity and proliferation
of
osteochondral cells and decreased callus
formation
 Factors affecting fracture healing
Systemic factors
D.Hormonal factors
1.Growth hormone
2.Corticosteroids (microvascular avascular necrosis)
3.Others (thyroid, estrogen, androgen, calcitonin,
parathyroid hormone [PTH], prostaglandins)

E.Diseases: diabetes, anemia, neuropathies,

- Diabetes, Associated with collagen defects including
decreased collagen content, defective cross-linking and
alterations in collagen sub-type ratios
F.Vitamin deficiencies: A, C, D, K
 Factors affecting fracture healing
Systemic factors
G.Drugs: nonsteroidal antiinflammatory drugs,
anticoagulants, factor XIII, calcium channel blockers
H.Other substances (nicotine, alcohol)
- Smoking inhibits osteoblasts
- Nicotine causes vasoconstriction diminishing blood
flow at fracture site
I.Systemic growth factors
J.Environmental temperature
K.Central nervous system trauma
Factors affecting fracture healing
Local factors
A.Factors independent of injury, treatment, or
complications
1.Type of bone
- flat and cancellous bones unite faster than
tubular
and cortical bones
2.Abnormal bone
a.Radiation necrosis
b.Infection
c.Tumors and other pathological conditions
 Factors affecting fracture healing
Local factors
3. Type of reduction
- good apposition of the fracture result in faster union
- atleast half the fracture surface should be in contact for
optimal union in adults
- in children , a fracture may unite even if bones are only
side-to-side in contact ( bayonet reduction)
4.Denervation

B.Factors depending on injury

1.Degree of local damage
a.Open fracture
- often go into delayed union and non-union
b.Comminution of fracture
c.Velocity of injury d.Low circulatory levels of
vitamin K1
 Factors affecting fracture healing
Local factors
2.Extent of disruption of vascular supply to bone, its
fragments, or soft tissues; severity of injury
3.Type and location of fracture (one or two bones, e.g.,
tibia and fibula or tibia alone)
- spiral fractures unite faster than oblique fractures,
which in turn unite faster than transverse fractures
4.Loss of bone
5.Soft tissue interposition
6.Local growth factors
 Complications of fracture healing
Delay union -
 When healing progresses more slowly than
average, the slow progress is referred to as
delayed union
 Union is considered delayed when healing has not
advanced at the average rate for the location and
type of fracture. (usualy 3-6 months)
 May occur from causes of delayed wound healing
in general such as, infection, inadequate blood
supply, poor nutrition, movement and old age.
 Complications of fracture healing
Nonunion -
 Failure of bone healing, or nonunion, results from

an arrest of the healing process.

 It may result if there is a soft tissue interposed

between fractured end.

 In 1986, an FDA panel defined nonunion as

‘‘established when a minimum of 9 months has

elapsed since injury and the fracture shows no visible
progressive signs of healing for 3 months.’’
 But this criterion cannot be applied to every

fracture.
 Complications of fracture healing
Nonunion -
 Two types of non-union are

recognised:
1. Hypertrophic non-union
- A large volume of callus
around the fracture site
- the fracture line is clearly
visible A‘‘Elephant foot’’ nonunion. B,
‘‘Horse hoof’’ nonunion.C,
- the gap being filled with Oligotrophic nonunion

cartilage and fibrous tissue

cell
 Complications of fracture healing
Nonunion –
2. Atrophic non-union
- Where little or no callus
forms and bone
resorption occurs at the
fracture site
- there is no evidence of
cellular activity at level
of fracture A, Torsion wedge nonunion. B,
Comminuted nonunion. C,
- bone ends are narrow , Defect nonunion. D, Atrophic nonunion
rounded and
osteoporotic, they are
frequently avascular
 Complications of fracture healing
Malunion -
 Any fracture which has unitedin less than anatomical
position.
 Where a fracture has united in a position of persistent
angulation or rotation which is of a degree that gives
the limb a displeasing appearance or affects its function.

Shortening-
 it is generally a sequel of malunion
 It occurs in transverse fractures which are off ended and
often in spiral and oblique fractures , which are
displaced
References -
 Textbook of pathology ( Harsh mohan)
 Practical fracture trauma (Ronald McRae, Max Esser)
 Campbell’s operative orthopaedics
 Essential orthopaedics ( Maheshwari & Mahaskar)
THANK YOU