Fracture Healing

By :

Monther Alkhawlany

GROUP D 2015

What TO Cover Today :

ANATOMY OF BONE

PATHOLOGY OF BONE

MECHANISM OF BONE FORMATION

INTRODUCTIONT TO FRACTURE HEALING

TYPES OF FRACTUER HEALING

STAGE OF HEALING

FACTORS INFLUENCE ON FRACTURE HEALING

REGULATION OF BONE HEALING

COMPLICATION OF FRACTURE HEALING

Types of Bone

A. Lamellar Bone

(Orderly cellular distribution)

Collagen fibers arranged in parallel layers

Normal adult bone

B. Woven Bone or immature bone (non-lamellar)

Randomly oriented collagen fibers

In adults, seen at sites of fracture healing, tendon or ligament attachment and in pathological conditions

Lamellar Bone

Cortical bone

- Comprised of osteons (Haversiansystems) runs longitudinally

Osteonscommunicate with medullary cavity by Volkmann’s canals that run horizontally

Haversian Systemosteon

Haversian

canal

osteocyte

Volkmann’s

canal

Woven Bone

Coarse with random

orientation

Weaker than

lamellar bone

Normally remodeled

to lamellar bone

Bone Composition Cells

Osteocytes

Osteoblasts

Osteoclasts

Extracellular Matrix

Organic (35%)

Collagen (type I) 90%

Osteocalcin, osteonectin, proteoglycans, glycosaminoglycans, lipids (ground substance)

Inorganic (65%)

Primarily hydroxyapatite Ca5(PO4)3(OH)2

Osteoblasts

Derived from

mesenchymal stem

cells

Line the surface of the

bone and produce

osteoid

Immediate precursor is

fibroblast-like

preosteoblasts

Osteocytes

Osteoblasts

surrounded by bone

matrix

trapped in lacunae

Function poorly

understood

regulating bone

metabolism in

response to stress

and strain

Osteocyte Network

Osteocyte lacunae are connected by canaliculi

Osteocytes are interconnected by long cell processes that project through the canaliculi

Preosteoblasts also have connections via canaliculi with the osteocytes

Network probably facilitates response of bone to mechanical and chemical factors

Osteoclasts

Derived from hematopoietic stem cells (monocyteprecursor cells)

Multinucleated cells whose function is bone resorption

Reside in bone resorption pits (Howship’s lacunae)

Parathyroid hormone stimulates receptors on osteoblasts that activate osteoclasticbone resorption

Components of BONE Formation

Cortex

Periosteum

Bone marrow

Soft tissue

Prerequisites for Bone Healing

Adequate blood supply

Adequate mechanical

stability

Mechanisms of Bone Formation

A. Cutting Cones

B. Intramembranous Bone

Formation

C. 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 .

It mainly forms cancellous bone.

Intramembranous Bone

Formation

Endochondral Bone

Formation

Mechanism by which a long bone grows in length

Osteoblasts line a cartilage precursor

The chondrocytes hypertrophy, degenerate and calcify (area of low oxygen tension)

Vascular invasion of the cartilage occurs followed by ossification (increasing oxygen tension)

Endochondral Bone

Formation

Blood Supply

Long bones have four

blood supplies

1. Nutrient artery

(intramedullary)

2. Periosteal vessels

3. Metaphyseal vessels

4. Epiphysial vesselsNutrient

artery

Metaphyseal

vessels

Periosteal

vessels

Nutrient Artery

Normally the major blood

supply for the diaphyseal

cortex (80 to 85%)

Enters the long bone via a

nutrient foramen

Forms medullary arteries up

and down the bone

Periosteal Vessels

Arise from the capillary-

rich periosteum

Supply outer 15 to 20%

of cortex normally

Capable of supplying a

much greater

proportion of the cortex

in the event of injury to

the medullary blood

supply

Metaphyseal Vessels

Arise from periarticular vessels

Penetrate the thin cortex in the

metaphyseal region and anastomose

with the medullary blood supply

Vascular Response in

Fracture Repair

Fracture stimulates the release of growth

factors that promote angiogenesis and

vasodilation

Blood flow is increased substantially to the

fracture site

Peaks at two weeks after fracture

INTRODUCTION

Fracture is a break in the structural continuity of

bone or periosteum.

The healing of fracture is in many ways similiar to

the healing in soft tissue wounds except that the

end result is mineralised mesenchymal tissue i.e.

BONE.

Fracture healing starts as soon as bone breaks

and continues modelling for many years.

The essential event in fracture healing is the

creation of a bony bridge between the two

fragments which can be readily be built upon and

modified to suit the particular functional demands .

INTRODUCTION

Fracture healing is a complex process

that requires the recruitment of

appropriate cells (fibroblasts,

macrophages, chondroblasts,

osteoblasts, osteoclasts) and the

subsequent expression of the

appropriate genes (genes that control

matrix production and organization,

growth factors, transcription factors)

at the right time and in the right anatomical location

INTRODUCTION

HISTORY

In 1975, Cruess and Dumont proposed that fracture

healing may be considered to consist of three

overlapping phases: an inflammatory phase, a

reparative phase, and a remodeling phase

In 1989, FROST proposed the stages of fracture

healing

five stages.

1- stage of haematoma

2- stage of granulation tissue

3- stage of callus

4- stage of modelling

5- stage of remodelling

Types 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

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)

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 endochondralossification

Process fairly rapid -weeks

For convenience, we describe fracture healing in terms

of the three phases recognized by Cruess and Dumont,

noting that the reparative phase combines several

processes

Inflammation

stage of haematoma formation

Repair

stage of granulation tissue

stage of callus formation

Remodelling

Stages of Fracture Healing

Duration

The inflammatory phase peaks within 48

hours and is quite diminished by 1 week

after fracture.

The reparative phase becomes activated

within the first few days after fracture and

persists for 2-3 months.

The remodelling phase lasts for many years

Inflammation

inflammatory phase is identical to the typical inflammatory response of most tissues to traumatic injury.

Vasodilation and hyperemia, presumably mediated by histamines, prostaglandins, and various cytokines, accompany invasion of the injury site by neutrophils, basophils, and phagocytes that participate in clearing away necrotic debris.

CONT…

Disruption of blood vessels in the bone, marrow, periosteum, and surrounding tissue disruption at the time of injury results in the extravasation of blood at the fracture site and the formation of a hematoma

Local vessels thrombose causing bony necrosis at the edges of the fracture

Increased capillary permeability results in a local inflammatory milieu

Osteoinductive growth factors stimulate the proliferation and differentiation of mesenchymal stem cells

Reparative phase

The reparative phase, which usually begins 4

or 5 days after injury, is characterized by the

invasion of pluripotential mesenchymal cells,

which differentiate into fibroblasts,

chondroblasts, and osteoblasts and form a soft

primary fracture callus.

Proliferation of blood vessels (angiogenesis)

within the periosteal tissues and marrow space

helps route the appropriate cells to the

fracture site and contributes to the formation

of a bed of granulation tissue.

Mesenchymal cells at the fracture site proliferate

differentiate and produce the fracture callus

Two types of callus :

1-Primary callus or Soft callus – forms in the central

region in which there is relatively low oxygen tension .

• The primary callus may consist of cartilage, fibrous tissue,

osteoid, woven bone, and vessels.

• If the primary callus is successful,

• healing progresses to the stage of bridging callus

or hard callus.

2- Hard callus – formed at the periphery of the

callus by intermembranous bone formation

CONT…

Periosteal callus forms along the periphery of the fracture site

Intramembranous ossification initiated by preosteoblasts

Intramedullary callus forms in the center of the fracture site

Endochondral ossification at the site of the fracture hematoma

Chemical and mechanical factors stimulate callus formation and mineralization

CONT…

Repair

Remodeling

The biochemical composition of the fracture callus matrix changes as repair progresses.

The cells replace the fibrin clot with a loose fibrous matrix containing glycosaminoglycans, proteoglycans, and types I and III collagen

In many regions they convert this tissue to more dense fibrocartilage or hyaline-like cartilage.

With formation of hyaline-like cartilage, type II collagen, cartilage-specific proteoglycan and link protein content increase.

Woven bone is gradually converted to lamellar bone

Medullary cavity is reconstituted

Stability of the fracture fragments progressively increases .

eventually clinical union occurs that is, the fracture site becomes stable and pain-free.

Radiographic union occurs when plain radiographs show bone trabeculae or cortical bone crossing the fracture site, and often occurs later than clinical union .

Despite successful fracture healing, the bone density of the involved limb may be decreased for years

CONT…

SUMMARY

SUMMARY

A. Age

B. Activity level including

1. immobilization

C. Nutritional status

D. Hormonal factors

1. Growth hormone

2. Corticosteroids

3. Others (thyroid, estrogen, androgen,

calcitonin, parathyroid hormone,

prostaglandins)

E. Cigarette smoking

VARIABLES THAT INFLUENCE

THE FRACTURE HEALING

I. Systemic factors or patient variables

E. Diseases: diabetes,anemia,neuropathies,

tabes dorsalis

F. Vitamin deficiencies: A, C, D, K

G. Drugs: nonsteroidal antiinflammatory drugs

(NSAIDs), anticoagulants, factor XIII,

calcium channel blockers (verapamil),

cytotoxins, diphosphonates, phenytoin

(Dilantin), sodium fluoride, tetracycline

H. Other substances (nicotine, alcohol)

I. Hyperoxia

J. Systemic growth factors

K. Environmental temperature

L. Central nervous system trauma

VARIABLES THAT INFLUENCE

THE FRACTURE HEALING

A. Factors independent of injury, treatment, or

complications

1. Type of bone

cortical or cancellous2. Abnormal bone

a. Radiation necrosisb. Infectionc. Tumors and other

pathological conditions

3. Denervation

II. Local factors or tissue variables

VARIABLES THAT INFLUENCE

THE FRACTURE HEALING

B. Factors depending on injury or injury

variables

1. Degree of local damage

a. Compound fracture

b. Comminution of fracture

c. segmental fractures

d. Velocity of injury

e. Low circulatory levels of vitamin K1

2. Extent of disruption of vascular supply to

bone, its fragments (macrovascular

osteonecrosis), or soft tissues;

VARIABLES THAT INFLUENCE

THE FRACTURE HEALING

3. Type and location of fracture (one or two bones, e.g., tibia and fibula or tibia alone

4. Loss of bone

5. Soft-tissue interposition

6. Local growth factors

7. Intraarticular fractures

VARIABLES THAT INFLUENCE

THE FRACTURE HEALING

C. Factors depending on treatment

OR treatment variables

1. Extent of surgical trauma (blood supply, heat)

2. Implant-induced altered blood flow

3. Degree and kind of rigidity of internal or

external fixation and the influence of timing

4. Degree, duration, and direction of load-

induced deformation of bone and soft tissue

VARIABLES THAT INFLUENCE

THE FRACTURE HEALING

5. Apposition of fracture fragments (gap,

displacement, overdistraction)

6. Factors stimulating posttraumatic

osteogenesis (bone grafts, bone morphogenetic protein,

electrical stimulation, surgical technique, intermittent venous

stasis ..

D- Factors associated with complications

1. Infection

2. Venous stasis

3. Metal allergy

VARIABLES THAT INFLUENCE

THE FRACTURE HEALING

REST

Regulation of Bone Healing

Growth factors

Transforming growth factor

Bone morphogenetic proteins

Fibroblast growth factors

Platelet-derived growth factors

Insulin-like growth factors

Cytokines

Interleukin-1,-4,-6,-11, macrophage and granulocyte/macrophage (GM) colony-stimulating factors(CSFs) and Tumor Necrosis Factor

Prostaglandins/Leukotrienes

Hormones

Growth factor antagonists

Transforming Growth Factor

Super-family of growth factors (~34 members)

Acts on serine/threonine kinase cell wall receptors

Promotes proliferation and differentiation of mesenchymal precursors for osteoblasts, osteoclasts and chondrocytes

Stimulates both enchondral 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

Regulate extracellular matrix production

BMP-1 is an enzyme that cleaves the carboxytermini of procollagens I, II and III

Bone Morphogenetic Proteins

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

Work through the intracellular Smad pathway

Follow a dose/response ratio

Timing and Function of Growth

Factors

Fibroblast Growth Factors

Both acidic (FGF-1) and basic (FGF-2)

forms

Increase proliferation of chondrocytes

and osteoblasts

Enhance callus formation

FGF-2 stimulates angiogenesis

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

Mitogen for cells of mesenchymal origin

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

Hormones

Estrogen

Stimulates fracture healing through receptor mediated mechanism

Modulates release of a specific inhibitor of IL-1

Thyroid hormones

Thyroxine and triiodothyronine stimulate osteoclasticbone resorption

Glucocorticoids

Inhibit calcium absorption from the gut causing increased PTH and therefore increased osteoclasticbone resorption

Hormones (cont.)

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

COMPLICATIONS OF

FRACTURE HEALING

MALUNION

DELAYED UNION

NONUNION

MALUNION

A MALUNITED Fracture is one that has

healed with the fragments in a non

anatomical position.

CAUSES1- INACCURATE REDUCTION

2- INEFFECTIVE IMMOBILIZATION

MALUNION contd…

MALUNION CAN IMPAIR FUCNTION by :

1. ABNORMAL JOINT SURFACE

2. ROTATION or ANGULATION

3. OVERRIDING

4. MOVEMENT OF NEIGHBOURING JOINT MAY BE BLOCKED

CHARACTERISTICS FOR

ACCEPTABILITY OF FRACTURE

REDUCTION

ALIGNMENT (MOST IMPORTANT)

ROTATION

RESTORATION OF NORMAL LENGTH

ACTUAL POSITION OF FRAGMENTS

(LEAST IMPORTANT)

Operative treatment for most malunited

fracture should not be considered until 6 to

12 months but in INTRA ARTICULAR fracture

early operative treatment is needed.

Surgeon should look for before surgery—

OSTEOPROSIS

SOFT TISSUE

HOW MUCH FUNCTION CAN BE GAINED

MALUNION contd…

ILIZAROV TECHNIQUE is BEST Simultaneous

restoration of :

ALIGNMENT

ROTATION

LENGTH

MALUNION contd…

Delayed Union

The exact time when a given fracture

should be united cannot be defined

Union is delayed when healing has not

advanced at the average rate for the

location and type of fracture (Btn 3-6 mths)

Treatment usually is by an efficient cast

that allows as much function as possible

can be continued for 4 to 12 additional

weeks

If still nonunited a decision should be made to treat the fracture as nonunion

External ultrasound or electrical stimulation may be considered

Surgical treatment should be carried out to remove interposed soft tissues and to oppose widely separated fragments

Iliac grafts should be used if plates and screws are placed but grafts are not usually needed when using intramedullary nailing, unless reduction is done open

Delayed Union cont…

FDA defined nonunion as “established

when a minimum of 9 months has elapsed

since fracture with no visible progressive

signs of healing for 3 months”

Every fracture has its own timetable (ie

long bone shaft fracture 6 months,

femoral neck fracture 3 months)

Delayed Union cont…

Delayed/Nonunion cont.

Systemic factors:

Metabolic

Nutritional status

General health

Activity level

Tobacco and alcohol use

Local factors

Open

Infected

Segmental (impaired blood supply)

Comminuted

Insecurely fixed

Immobilized for an insufficient time

Treated by ill-advised open reduction

Distracted by (traction/plate and screws)

Irradiated bone

Delayed weight-bearing > 6 weeks

Soft tissue injury > method of initial treatment

Delayed/Nonunion cont.

Nonunited fractures form two

types of pseudoarthrosis:

Hypervascular or hypertrophic

Avascular or atrophic

Nonunion

Hypervascular or

Hypertrophic:

1. Elephant foot

(hypertophic, rich in

callus)

2. Horse foot (mildly

hypertophic, poor in

callus)

3. Oligotrophic (not

hypertrophic, no

callus)

Nonunion

Vascular or Atrophic

Torsion wedge

(intermediate fragment)

Comminuted (necrotic

intermediate fragment)

Defect (loss of fragment

of the diathesis)

Atrophic (scar tissue with

no estrogenic potential is

replacing the missing

fragment)

Nonunion

Classification (Paley et al)

Type A<2cm of bone loss

A1 (Mobile deformity)

A2 (fixed deformity)

A2-1 stiff w/o deformity

A2-2 stiff w/ fixed deformity

Type B>2cm of bone loss

B1 with bony defect

B2 loss of bone length

B3 both

Nonunion

Treatment:1. Elecrical

2. Electromagnatic

3. Ulrasound

4. External fixation (ie deformity, infection, bone loss)

5. Surgical

Hypertrophic: stable fixation of fragments

Atrophic: decortication and bone grafting

According to classification:

type A : restoration of alignment,compression

type B : cortical osteotomy, bone transport or lengthening

Nonunion

Surgical guidelines:

Good reduction

Bone grafting

Firm stabilization

Nonunion

Reduction of the fragments:

Extensive dissection is undesirable, leaving periosteum, callus, and fibrous tissue to preserve vascularity and stability, resecting only the scar tissue and the rounded ends of the bones

External fixator, Intramedullary nailing, Ilizarov frame

Nonunion

Bone Grafting origins:

Autogenous “the golden

standard”

Allograft

Synthetic substitute

Nonunion

Bone grafting techniques:

Onlay

Dual onlay

Cancellous insert

Massive sliding graft

Whole fibular transplant

Vascularized free fibular graft

Intamedullary fibular graft

Nonunion

BONE GRAFTING

CRITERTIA FOR SUCCESSFUL BONE

GRAFT

OSTEOCONDUCTION

OSTEOGENICITY

OSTEOINDUCTION

Nonunion of

tibial shaft

treated by

dual onlay

grafts

Dual onlay

Massive sliding graft

GILL MASSIVE SLIDING GRAFT

Whole fibular transplant

Bridging of bone defect

with whole fibular

transplant. A, Defect in

radius was caused by

shotgun wound. B and

C, Ten months after defect was spanned by

whole fibular transplant,

patient had 25% range

of motion in wrist, 50%

pronation and

supination, and 80% use

of fingers.

Vascularized free fibular

graft

Posteroanterior and

lateral

roentgenograms

made 3 years after

fibular transfer,

showing excellent

remodeling with

fracture healing.

(From Duffy GP,

Wood MB, Rock MG,

Sim FH: J Bone Joint

Surg 82A:544, 2000

Intamedullary fibular graft

Anteroposterior

roentgenogram of humerus

5 months after insertion of

fibular allograft and

compression plating with a

4.5-mm dynamic

compression plate revealing

evidence of bridging callus

formation and incorporation

of the allograft. (From

Crosby LA, Norris BL, Dao KD,

McGuire MH: Am J Orthop

29:45, 2000.)

Nonunion cont..

Stabilization of bone fragments:

Internal fixation (hypertrophic #):

intamedullary, or plates and screws

External fixation(defects

associated#): ie Ilizarov

Internal fixation

Roentgenograms

of patient with

subtrochanteric

nonunion for 22

years treated with

locked second

generation

femoral nail. A,

Preoperatively. B,

Postoperatively.

Ilizarov

Bifocal osteosynthesis with Ilizarov

fixator after debridement of necrotic

segments, as recommended by

Catagni.

Monofocal osteosynthesis with

Ilizarov fixator for hypertrophic

nonunions with minimal infection, as

recommended by Catagni

Factors complicating nonunion

Infection

Poor tissue quality

Short periarticular fragments

Significant deformity

Nonunion cont..

Summary

Fracture healing is influenced by many

variables including mechanical stability,

electrical environment, biochemical factors

and blood flow

Our ability to enhance fracture healing will

increase as we better understand the

interaction between these variables

BY :

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