FRACTURE HEALING

Introduction
Fracture is a break in the structural continuity of bone or
periosteum.

Fracture healing leads to the regeneration of of the anatomy of the

bone and complete return to function.

It starts as soon as bone breaks and is completed by 6-8 weeks

after the initial injury.
Types of Fracture (according to displacement)

Undisplaced
Displaced:
Complete
Incomplete
Types of Fracture (according to displacement)

Complete:
Complete cortical circumference is involved
Fragments are completely separated
Types of Fracture (according to displacement)

Incomplete:
Only one cortex is involved
Not fractured all the way through
Occurs due to the viscoelasticity of bone
Also known as greenstick fracture
Includes torus fracture
Types of Fracture (according to displacement)

Torus:
Bone bends and buckles
Occurs in the junction between the metaphysis (cancellous
bone--area of weakness) and diaphysis (cortical bone--area of
rigidity)
May occur with a strong cortical but weak cancellous bone
Due to longitudinal compression on the soft bone
Types of Fracture (according to open/closed)

Open:
Also known as compound fracture or open air
fracture
A fracture in which the bone penetrates the skin
There is contact with the outside environment
Some define this as a fracture with any open wound or
soft tissue laceration near the bony fracture
Types of Fracture (according to open/closed)

Closed:
Fracture with intact overlying skin
Types of Fracture (according to configuration)
Transverse:
Longitudinally across the bone
caused by tensile forces in which it arises at soft tissue
insertions to cancellous bone. There is debonding of
cement lines and pulling out of osteons.
Types of Fracture (according to configuration)
Oblique:
Angular fracture
cause be pure compression forces. Shear lines are
formed by buckling of lamellae and oblique cracking of
osteons. Which occurs first at areas of stress
concentration of the bone.
Types of Fracture (according to configuration)
Spiral:
Rotational configuration and has a transverse and oblique
segment
caused by torsional forces with two components. One spiral
fracture line around the circumference of the bone approximately
45 degrees horizontal caused by a failure in tension perpendicular
to the crack and a vertical line linking the proximal and distal ends
of the spiral due to shear fracture
Types of Fracture (according to configuration)
Comminuted:
Broken, splintered or crushed into >3 pieces
Segmental:
Bone is broken in >2 separate places and the fracture
lines of each do not connect. Four Point Bending.
Avulsion:
Specific part of the bone is fractured
Types of Fracture Healing
- Intramembranous
- Endochondral
Types of Fracture Healing
Intramembranous bone healing
- Primary bone healing
- Results when the motion between two fracture surfaces is
abolished through rigid internal fixation
- Involves direct bone formation without a cartilaginous
intermediate
- Radiographically: loss of obvious fracture line with an absence
of visible fracture callus
Intramembranous bone healing
Contact healing
- Happens when the gap between the bone ends is less than
0.01 mm and the the interfragmentary strain is less than 2%
- Cutting cones are formed at the ends of the osteons closest to
the fracture site
- These osteons later mature by direct remodelling into lamellar
bone without the formation of periosteal callus
Intramembranous bone healing
Gap healing

- Osteoblasts differentiate and deposit osteoids in the

exposed surfaces of fragment ends, which is later
converted into lamellar bone
Types of Fracture Healing
Endochondral bone healing
- Secondary bone healing
- This is associated with motion at the fracture site (e.g. cast
treatment or incomplete stability)
- Cartilaginous angle is replaced by bone as resident
chondrocytes mature and blood vessels invade the cartilage
Stages of Endochondral Fracture Repair
- Hematoma Formation
- Inflammation
- Soft Callus
- Hard Callus
- Remodeling
Stages of Endochondral Fracture Healing
HEMATOMA FORMATION
- Due to the local disruption of the bone, the associated marrow,
periosteum, surrounding muscle, and blood vessels
- Composed of debris from the above structures as well as
platelets, erythrocytes, and immune cells extravasated form
sheared blood vessels
- Site becomes swollen, painful, and inflamed.
Stages of Endochondral Fracture Healing
INFLAMMATION
- The area adjacent to the fracture site becomes hypoxic and
localized tissue necrosis occurs.
- Cellular debris initiates the inflammatory response.
- Healing process occurs by the phagocytosis of necrotic tissue
and the release of cytokines.
- Neutrophils are the first cells to arrive - 3 hours after a fracture.
Stages of Endochondral Fracture Healing
SOFT CALLUS FORMATION
- Differentiation of progenitor cells into chondrocytes and
osteoblasts
- Cartilage or osteoid becomes the predominant tissue in the
callus, replacing the fibrous tissue in hematoma
- Types I and II collagen are produced to restore stability to the
bone ends
- Radiographically: fracture site does not appear united
Stages of Endochondral Fracture Healing
HARD CALLUS FORMATION
- Formation of calcified cartilage matrix with terminal
differentiation of chondrocytes
- Dominant cells: osteoblast and osteoclast
- Radiographically: calcification and consolidation of fracture
callus
- Clinically: reduction in pain and increased sense of stability at
the fracture site
Stages of Endochondral Fracture Healing
REMODELLING
- The damaged tissue returns nearer to its pre-injured state
- Canalicular architecture of the bone is reestablished
- Haversian system within its osteocytes is restored
- Involves the functional unit in bone remodelling - the cutting
cone
- RANK, RANKL, OPG (osteoprotegerin)
Cells and Tissues in Fracture Healing
Cells and Tissues in Fracture Healing
Inflammatory Cells

Platelets Starts the cascade of mediators of the healing response

Has a role in both hemostasis and the early local fracture healing process

PMNs Perform phagocytic and degranulation functions at fracture site

+/- inhibitory

Macrophages Debrides tissue injury sites

Activates the adaptive immune system

Lymphocytes Inhibitory; Contributes by producing cytokines

Cells and Tissues in Fracture Healing
Mesenchymal Stem Cells

- Resident cells at fracture

sites
- Periosteum and endosteum
are the richest sources
- May proliferate and
differentiate in response to
the evolving cytokine milieu
- Supplies cells capable of
differentiating into
chondrocytes or osteoblasts
Cells and Tissues in Fracture Healing
Progenitor Cells

- a biological cell with a tendency to differentiate into a

more specific target cell, more specific than stem
cells
- Located at the periosteum and
endosteum and undergoes
extensive cellular proliferation

Periosteum - primary source of

chondrocytes

Endosteum - primarily gives rise to

osteoblasts
Cells and Tissues in Fracture Healing
Chondrocytes

- Produces ECM proteins, e.g.

proteoglycans and collagen
- Hypertrophies during fracture
healing and develop intracellular
calcium deposits and undergoes
apoptosis, leaving behind woven
bone
Cells and Tissues in Fracture Healing
Osteoblasts

- Form bone matrix and regulates

bone turnover by influencing
osteoclast activity
- Produce osteoid, osteocalcin, bone
sialoprotein and other matrix
proteins
- Express alkaline phosphatase
Cells and Tissues in Fracture Healing
Osteoclasts

- Responsible for bone resorption

and remodeling
- Associated with calcitonin receptor
and RANKL
Cells and Tissues in Fracture Healing
Muscle

- Leads to faster union and reduced number of secondary procedures

- Causes impaired healing when disrupted resulting to reduced
mechanical stability of the fracture callus
- Promotes revascularization
- Provides a source of osteogenic growth factors
- Potential source of stem cells
Cells and Tissues in Fracture Healing
Scaffold

- Extracellular matrix (ECM)

- Composed of 70% inorganic material and 30% organic portion
- Provides structural properties of bone and cartilage and serving cell
regulatory functions
Cells and Tissues in Fracture Healing
Blood Supply
- Most important
- initially the blood flow decreases with vascular disruption, but HIF-1 promotes VEGF production, promoting
revascularization
- after few hours to days, the blood flow increases
- this peaks at 2 weeks and normalizes at 3-5 months
Role of Bone Grafting
- Indicated for malunions, nonunions, arthrodesis and reconstructive
procedures
- Properties:

1. Osteoinductive - material contains factors that stimulate bone growth and induction of stem cells down a bone-forming
lineage

2. Osteoconductive - material acts as a structural framework for bone growth

3. Osteogenic - material directly provides cells that will produce bone including primitive mesenchymal stem cells,
osteoblasts, and osteocytes
Role of Bone Grafting
Types:

1. Autologous bone graft

- gold standard; possesses excellent osteoinductive, osteoconductive and
osteogenic potential
- Least immunogenic
- Cancellous vs cortical bone

2. Allogeneic bone graft

- Most commonly used

- Osteoconductive only
- immunogenic
Role of Bone Grafting
Types:

3. Demineralized bone matrix

- Produced by acid extraction of allograft bone

4. Bone-graft substitutes

- Calcium phosphate ceramics, hydroxyapatite, tricalcium phosphate, calcium

phosphate cements, calcium sulfate,
Role of Fracture Immobilization/Fixation
Factors affecting Bone Healing
Age and Gender

No correlation between gender and nonunion or delayed union

Faster rate of healing of fractures in children due to larger subperiosteal

haematoma and a thicker periosteum

In elderly, angiogenesis at the fracture site and the response of growth factor
to fracture in the elderly was preserved.

There is some evidence that increasing age is a factor in the inhibition of

fracture repair in the human.
Factors affecting Bone Healing
Co-morbids

Fracture callus from the diabetic animals had a 29% decrease in tensile
strength and a 50% decrease in stiffness

Reduced cellular proliferation, reduced osteoblast activity and reduced

collagen synthesis and content in diabetic animals

It is postulated that in diabetes there is reduced cell proliferation in the early

phase of fracture healing as a result of decreased expression of
platelet-derived growth factor
Factors affecting Bone Healing
Co-morbids

Levels of other growth factors (insulin-like growth factor-1 (IGF-1), vascular

endothelial growth factor (VEGF), transforming growth factor-beta (TEGF-))
have also been shown to be significantly reduced in diabetic animal

Clinical studies have demonstrated a significantly higher incidence of delayed

union, nonunion, and a doubling of the time to healing of the fracture in
diabetic patients.
Factors affecting Bone Healing
Co-morbids

Iron-deficient anaemic rats have demonstrated significant deficiencies in bone

healing, with a decrease in the rate of union and loss of strength

Attributed to a decrease in oxygen tension and a deficiency of iron, which is

required for function of the electron transport system within the cell and for
hydroxylation of proline in collagen formation

Decrease in blood volume is associated with anaemia delayed healing, but

normovolaemic anaemia had no adverse effect
Factors affecting Bone Healing
Co-morbids

Peripheral vascular disease adversely impairs delivery of oxygen,

inflammatory cells and nutrients to the fracture site.

Build up of carbon dioxide (CO2) and other metabolites rendering the local
environment acidic.

Correlation between peripheral vascular disease and nonunion has not been
directly addressed,
Factors affecting Bone Healing
Co-morbids

Hypothyroidism inhibited endochondral ossification, resulting in an

impairment of repair.

lt inhibit secondary bone healing, although primary bone healing appears

to be unaffected.
Factors affecting Bone Healing
Smoking

Adversely affect bone mineral density, lumbar disc disease, the rate of hip
fracture, and the dynamics of bone and wound healing.

Hypothesized MOA: a reduced blood supply, high levels of reactive oxygen

intermediates, low concentrations of antioxidant vitamins and the effects of
nicotine on arteriole endothelial receptors have all been postulated.
Factors affecting Bone Healing
Smoking

Alcoholics experience not only an increased incidence of fractures from falls,

but also delays in healing compared with non-alcoholics.

Alcohol-induced osteopenia results mainly from decreased bone formation

rather than increased bone resorption.

The effect of alcohol is to suppress synthesis of an ossifiable matrix, possibly

because of inhibition of cell proliferation and maldifferentiation of
mesenchymal cells in the repair tissue
Factors affecting Bone Healing
Nutrition

Vitamin B6-deficiency caused a significant delay in the maturation of callus in

rats.

An increase in the vitamin C content in the diet improved mechanical and

histological parameters of fracture repair in the rat.

In humans, an albumin level of < 3.5 gs/100 ml was predictive of increased

length of stay and in-hospital mortality following a fracture.
References
Rockwood

Ramachandran

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