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GOOD MORNING

DEPARTMENT OF ORTHOPAEDICS

MODERATORS: PRESENTED BY:

DR G C BASAVARAJA DR ROHIT KUMARPROFFESOR & UNIT HEAD PG IN ORTHOPAEDICS

DR SHAKEEL KHAN DATED:19.01.11ASSOCIATE PROFESSOR

J.J.M MEDICAL COLLEGE , DAVANGERE

SEMINAR ON

ANATOMY OF FRACTURE HEALING

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Fracture is defined as a break in the

continuity of bone. Fracture results in loss of its mechanical stability and also partial destruction of blood supply.

Healing means to make whole or sound again, to cure, leaving a scar behind. But following fracture a scar is not formed, instead a bone has formed a new at the original fracture site. So rather than bone healing the appropriate nomenclature would be BONE REGENERATION

INTRODUCTION

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History of fracture and its knowledge dates back

to Egyptian mummies of 2700 B.C

In 17th century Albrecht Haller, observed invading capillary buds in fracture callus and thought that blood vessels are responsible for callus formation.

John Hunter, a pupil of Haller, described the morphologic sequence of fracture healing.

HISTORY

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In 1873, Kolliker observed the role of

multinucleated giant cells, osteoclast to be responsible for bone resorption.

In1939, Gluksman suggested pressure and shearing stresses are possible stimuli for

fracture healing.

In 1961, Tonna and Cronkie demonstrated the role of local mesenchymal cells in fracture

repair.

Contd…..

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Bone is essentially a highly vascular, living,

constantly changing mineralized connective tissue which makes up body’s skeleton.

Other functions are:- Bone provides protection for the vital organs of the body( eg: heart and brain)- The hematopoietic bone marrow is protected by the surrounding bony tissue.- Storage of calcium and phosphate.

WHAT IS BONE ?

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Living bone is white, with either dense texture like ivory or honeycombed by large cavites .

Spongy bone (cancellous) : is composed of a lattice or network of branching bone spicules or trabeculae. The spaces between the bone spicules contain bone marrow.

Compact bone (cortical / outer): appears as a mass of bony tissue lacking spaces visible to the unaided eye.

MACROSCOPY

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Woven (Immature bone): Characterized by

random arrangement of cells and collagen ,associated with periods of rapid bone formation, such as in initial stage of fracture healing.

Lamellar bone (Mature bone) : Characterized by an orderly cellular distribution and properly oriented collagen fibres . This constitutes organised bone both cortical and cancellous

MICROSCOPY

Comprises of

osteons (Haversian systems)

Osteons communicate with medullary cavity by Volkmann’s canals

CORTICAL BONE

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HAVERSIAN CANAL

Haversian canal

Cells, nerves &

vessels

Volkmann’s

canal

Connects osteons

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osteon

Haversian canal

osteocyte

Volkmann’s canal

WOVEN BONE

Coarse with random

orientation

Weaker than lamellar

bone

Normally remodeled to

lamellar bone12

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Is a membrane that lines the outer surface of all bones except at the joints of long bones.

Is made up of : Outer FIBROUS layer : made up of white

connective and elastic tissue. Inner CAMBIUM layer : which has a looser

composition, is more vascular and contains cells with osteogenic potency.

PERIOSTEUM

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1. Anchors tendons and ligaments to bone.2. Acts as a limiting membrane.3. Participates in growth (appositional) and repair

through the activities of the osteoprogenitor cells .

4. Periosteum helps in fracture healing by forming periosteal callus.

5. It also lessen the displacement of the # and helps in reduction.

6.  Allows passage of blood vessels, lymphatics and nerves into and out of the bone.

FUNCTIONS OF PERIOSTEUM:

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BLOOD SUPPLY OF BONE

Long bones have three

blood supplies

-Nutrient artery

(intramedullary) 80-85%

-Periosteal vessels

-Metaphyseal vessels

have hair pin

arrangement.

In miniature long bones, the nutrient artery breaks up into a plexus immediately upon reaching the medullary cavity.

In contrast in cancellous bone the blood supply reaches its destinations more directly without significant branching . Therefore the healing where vascular re estabilishment is necessary happens rapidly.

The nerve supply to a bone comes along with the blood supply. Nerve supply includes sensory nerve supply, vasomotor nerve supply and sympathetic nerve supply.

Accompanying the blood vessels there are

usually fine medullated /non medullated nerve fibres which extend into the haversian system and in large numbers to the periosteum.

These nerves are mainly concern with innervation of blood vessels, although periosteum and bone have been described in being sensitive to pain and vibration.

It is not clear whether bone has a direct neural input ..

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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

VASCULAR RESPONE IS FRACTURE REPAIR

BONE COMPOSITION

CELLS 1. OSTEO PROGENITOR

CELLS2. OSTEOBLASTS3. OSTEOCLASTS4. OSTEOCYTES5. BONE LINING CELLS

EXTRACELLULAR MATRIX1. ORGANIC & WATER 35%

Type Ι Collagen 90% Osteocalcin,

Osteonectin, Proteoglycans, Glycosaminoglycans, Lipids (ground substance)

2. INORGANIC 65%Primarily hydroxyapatite

Ca10(PO4)6(OH)2

1.OSTEO PROGENITOR CELLS

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Are basophilic, cuboidal to pyrimidal in shape ,

associated with bone formation, these cells are located where new bone is forming, eg: in the periosteum.

Osteoblasts often appear stratified as in an epithelium.

The nucleus is large with a single prominent nucleolus.

Osteoblasts contain the enzyme alkaline phosphatase used to calcify the osseous matrix.

2.OSTEOBLASTS

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The synthesis type 1 collagen, osteocalcin (bone Gla protein) and osteonectin

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Giant, multinuclear cells which vary greatly in

shape. They are found on the surfaces of osseous

tissue usually in shallow depressions called Howship’s lacunae.

The cytoplasm is slightly basophilic and contains lysosomal vacuoles.

Under E.M. the cell surface facing the osseous matrix shows numerous cytoplasmic projections and microvilli described as a ruffled border.

3.OSTEOCLASTS

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RUFFLED BORDER

MICROSCOPIC PICTURE ELECTRON MICROSCOPY

OSTEOCLASTS

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Basically, an osteoblast that has been enclosed within

the bony matrix in a space called the lacuna. The cytoplasm of the osteocyte is faintly basophilic

containing fat droplets and granules of glycogen with single dark stained nucleous.

In developing bone, the cytoplasmic processes from one osteocyte make contact with the processes (ie: cannaliculi) from adjoining osteocytes. In mature bone, the processes are withdrawn almost completely.

In mature bone the empty canaliculi remain as passage ways for the diffusion of nutrients and wastes between bone and blood.

4.OSTEOCYTES

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Are flattened epithelium in adult skeleton

found on resting surfaces. Plays active role in differentiation of progenitor

cells Controls osteoclasts, mineral hemostasis and

may secrete collagenase. Lines – endosteal surface of marrow cavity - periosteal surface

- vascular channels within osteons.

5.BONE LINING CELLS

HEALING AFTER FRACTURE FIXATION

DIRECT/PRIMARY:

Mechanism of bone healing seen

when there is no motion at the

fracture site (i.e. rigid internal

fixation).

Does not involve formation of

fracture callus.

Osteoblasts originate from

endothelial and perivascular

cells.

CONTD:

INDIRECT/SECONDARY:

Mechanism for healing in

fractures that are not rigidly

fixed.

Bridging periosteal (soft) callus

and medullary (hard) callus re-

establish structural continuity.

Callus subsequently undergoes

endochondral ossification.

TYPES OF BONE HEALING

PRIMARY

1. CONTACT HEALING: When there is direct

contact between the cortical bone ends,

lamellar bone forms directly across the

fracture line , parallel to long axis of the

bone, by direct extension of osteons.

2. GAP HEALING: Osteoblasts differentiate

and start depositing osteoids on the

exposed surfaces of fragment ends, mostly

without a preceding osteoclastic resorption

which is later converted into the lamellar

bone .

CONTD:

SECONDARY:

It is usual type consisting of

formation of callus either of

cartilaginous or fibrous. This

callus is later replaced by

lamellar bone. It is

comparable to healing of soft

tissue by filling of gaps with

vascular granulation tissue.

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OSTEOINDUCTION: This term mean that primitive,

undifferentiated and pleuripotent cells are somehow stimulated to develop into the bone forming cell lineage.one proposed definition is process by which osteogenesis is induced.

OSTEOCONDUCTION:A scaffold of collagenous network has developed, upon which the reparative cells produce callus and bone

OSTEOINDUCTION

CONDUCTIONINTEGRATION

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It facilitates bone deposition in an orderly fashion and helps the callus to bridge the gap between the fragments.

OSTEOINTEGRATION:The direct structural and functional connection between living bone and the surface of a load-bearing implant.

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1. Cutting Cones

2. Intramembranous Bone

Formation

3. Endochondral Bone Formation

MECHANISM OF BONE FORMATION

Primarily a

mechanism to

remodel bone.

Osteoclasts at the

front of the cutting

cone remove bone.

Trailing osteoblasts

lay down new bone.

CUTTING CONES

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Mechanism by which a long bone grows in

width.

Osteoblasts differentiate directly from pre osteoblasts and lay down seams of osteoid.

Does NOT involve cartilage anlage.

INTRAMEMBRANOUS BONE FORMATION(PERIOSTEAL)

INTRAMEMBRANOUS BONE FORMATION

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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

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There are 3 major phases with sub

divisions:

A. Reactive Phase: i. Fracture and inflammatory phase. ii. Stage of hematoma formation. iii. Granulation tissue formation.

B. Reparative Phase: iv. Cartilage Callus formation. v. Lamellar bone deposition.

C. Remodeling Phase: vi. Remodeling to original bone contour.

STAGES OF FRACTURE HEALING

A.REACTIVE PHASE

I .Fracture & inflammatory

phase :

After fracture the first change seen by light and electron

microscopy is the presence of blood cells within the tissues

which are adjacent to the injury site. Soon after

fracture, the blood vessels constrict, stopping any

further bleeding.

ii. Stage of Hematoma formation:

Within a few hours after fracture, the extravascular blood cells form a

blood clot, known as a hematoma. All of the cells within the blood clot

degenerate and die.

The fracture hematoma immobilizes

& splints the fracture.

The fracture haematoma provides a

fibrin scaffold that facilitates

migration of repair cells.

iii. Granulation Tissue Formation:

Within this same area,

the fibroblasts survive and replicate.

They form a loose aggregate of cells,

interspersed with small blood vessels,

known as granulation tissue which

grows forward, outside and inside the

bone to bridge the fracture.

They are stimulated by vasoactive

mediators like serotonin and

histamine.

B. REPARATIVE PHASE

 iv. Cartilage Callus formation :

Days after the # the periosteal cells

proximal to the fracture gap and fibroblasts

develop into chondroblasts which

form hyaline cartilage.

The periosteal cells distal to the fracture

gap develop into osteoblasts which

form woven bone. These 2 tissues unite

with their counterparts and culminate into

new mass of heterogenous tissue called

Fracture Callus restoring some of its

original strength.

v. Lamellar bone deposition:

Or consolidation ..where hyaline cartilage

and woven bone is replaced by lamellar

bone. This process is called

Endochondral ossification.

At this point, the mineralized matrix is

penetrated by channels, each containing

a microvessel and numerous osteoblasts.

 This new lamellar bone is in the form

of trabecular bone which restores bone’s

original strength.

C. REMODELLING PHASE

vi. Remodelling to original bone contour:

The remodeling process substitutes the

trabecular bone with compact bone. The

trabecular bone is first resorbed

by osteoclasts, creating a shallow

resorption pit known as a "Howship's

lacuna".

Then osteoblasts deposit compact bone

within the resorption pit.

Eventually, the fracture callus is

remodelled.

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STAGE 1- A healing bone subjected to torsion fails

through original # site with a low stiffness pattern. STAGE 2- The bone still fails through the # site ,

but the characteristic indicate high stiffness pattern(hard tissue pattern)

STAGE 3 – The bone fails partly through the original # site and partly through the previously intact bone with a high stiffness pattern .

STAGE 4 –Failure does not occur through the # site duplicates the mechanical properties of uninjured tissue.

STAGES BASED ON REACTION TO TORSIONAL TESTING

# HEALING IN CANCELLOUS BONE

1.Cancellous bone heals by -

“CREEPING SUBSTITUTION”

New blood vessels can invade

the trabecular of cancellous

bone and bone opposition may

take place directly on to the

surface of trabeculum.

2.Heals at the point of direct contact:

Cancellous bone certainly can unite

very rapidly, but it unites rapidly only

at the points of direct contact.

3.No bridging callus :

Cancellous bone unites only by

contact, not by throwing out callus

even when it is cut of due to dense

attachment of the periosteum.

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4.No death of osteocytes:

Takes place in the cut edges of divided trabeculae in cancellous bone. This must be because of the blood supply is good and large surface area of the trabecular spaces combined with relatively thin trabeculae, keep the osteocytes nourished.

5.Has tendency for late collapse :

This lack of callus production by cancellous bone explains the tendency to late collapse which have been distracted. Eg: after reduction of colle’s fracture a hallow cavity is left in the cancellous end of the radius.

FRACTURE HEALING IN CHILDREN

Compared with the relatively static mature bone of adult, the changing structure and function both physiological and biomechanical of immature bones make them susceptible to different patterns of fracture.

Fracture in children are more common and are more likely to occur after seemingly insignificant trauma. Damage involving specific growth regions such as the physis or epiphyseal ossification center may lead to acute and chronic growth disturbances.

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Higher collagen to bone ratio- this lowers the

modulus of elasticity and tensile strength of bone.

Higher cellular and porus bone –reduces tendency of # to propagate explains why children dont have communited #’s.

Bone fails in both tension and compression- explains why buckle #’s happen in children.

Bone transitions- between metaphysis and dyphysis has discontinuity, leading to certain types of #’s…

PEDIATRIC BONE ??

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FEATURES OF PEDIATRIC BONE AND THEIR MANAGEMENT EFFECTS

FEATURE:

Thick cartilage Thick periosteum More collagen More cancellous

bone Growth plate

Stronger ligaments

MANAGEMENT EFFECT:

Not imaged by x rays. Healing rapid. Fractures easily. Simple # patterns. Remodels deformity.

Bone fails first.

Growth plate:

The most obvious difference

The relative strength of plate with

the bone changes with age .eg:

physis in children is stronger than

adjacent bone so diaphyseal #’s are

more common.

HELPS # MANAGEMENT: by

remodeling..

INJURED GROWTH PLATE CAUSES

DEFORMITY due to asymmetry.

PHYSIS/GROWTH PLATE : Physis or growth plates primary function is rapid integrated longitudinal and latitudinal growth. Ischemia of physis due to fracture can lead to growth disturbances.

zones within the physis :1. The resting cartilage zone 2. The proliferating cartilage zone 3. The zone of hypertrophy and 4. The zone of calcification.

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Accounts for ¼ of childhood fractures . Physeal injuries can occur from

infection,ischemia,tumors. They are more common in boys and in upper

limb. These are of great importance as they

determine growth and remodelling potential. Fractures generally occur in zone of

provisional calcification ,sparing the germinal zone.

Most sensitive to injury is proximal tibial epiphysis.

PHYSEAL INJURIES

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BUCKLE OR TORUS #

PLASTIC BOWING OF ULNA

GREENSTICK #AVULSION # OF TIBIAL SPINE … BONE FAILS BEFORE ACL

GENU RECURVATUM DUE TO PHYSEAL GROWTH ARREST

FRACTURE REPAIR IN CHILDREN

Fracture healing in children follow same pattern of adults but with some peculiarities :

PERIOSTEUM:

In the contrast to adults the periosteum strips away easily from the underlying bone in children. Allowing fracture haematoma to dissect along the diaphysis

and metaphysis and this is evident in the subsequent amount of new bone formation along

the shaft. Dense attachment of the periosteum into the zone

of ranvier limit subperiosteal hematoma formation to the metaphysic and diaphysis.

REMODELLING IN CHILDREN

The remodelling phase is the longest phase and in children may continue until skeletal maturation. Remodelling is better in children compared to adult, This is in response to constantly changing stress Patterns in children during skeletal growth and development.

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1. LOCAL FACTORS.

2. CHEMICAL FACTORS.3. VASCULAR FACTORS.4. SYSTEMIC FACTORS.

5. ELECTROMAGNETIC FACTORS.

6. TREATMENT FACTORS.

FACTORS INFLUENCING BONE HEALING

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A.Type of bone: 

Calcellous (spongy) bone V/S cortical bone. B. Degree of Trauma:

Extensive soft tissue injury and comminuted #‘s V/S Mild contusions

C.Vascular Injury: Inadequate blood supply impairs healing. Especially

vulnerable areas are the femoral head, talus, and scaphoid bones.

D. Degree of Immobilization: Immobilized for vascular ingrowth and bone healing to occur.

1.LOCAL FACTORS

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Repeated disruptions of repair tissue, especially to areas

with marginal blood supply or heavy soft tissue damage, will impair healing.

E.Type of Fractures: Intraarticular fractures communicate with synovial fluid, which contains collagenases that retard

bone healing V/S Open fractures result in infections V/SSegmental fractures have disrupted blood supply.

F.Soft Tissue Interposition: G.others: Bone death caused by radiation, thermal or chemical burns or infection.

CONTD..

1.MESSENGER 2.GROWTH 3.PERMEABILITYSUBSTANCES FACTORS FACTORS-Serotonin -Transforming GF -Proteases-Prostaglandins -Fibroblast GF -Polypeptides-Histamines -Platelet derived GF -Amines-Thromboxane -Insulin like GF -Bone morphogenic proteins(BMP)

2.CHEMICAL FACTORS

1.MESSENGER SUBSTANCE:A.CYTOKINES- IL-1,4,6,11, macrophage and granulocyte/macrophage

(GM) (CSFs) & (TNF) stimulate bone resorption.IL-1 ,6 synthesis is decreased by estrogen

-May be mechanism for post-menopausal bone resorption & it regulates endochondral bone formation.

B. PROSTAGLANDINS of the E series--Stimulate osteoblastic bone formation and inhibit activity of isolated osteoclasts.

C.LEUKOTRINES-Stimulate osteoblastic bone formation and enhance the capacity of isolated osteoclasts to form resorption pits.

2.GROWTH FACTORS: A.Transforming growth factor(TGF):

Superfamily of growth factors (~34 members) Act on serine/threonine kinase cell wall receptors

Promotes proliferation and differentiation of osteoblasts, osteoclasts and chondrocytes

Stimulates both endochondral and intramembranous bone formation and collagen type 2 synthesis.

B.Fibroblast growth factors(FGF):Both acidic (FGF-1) and basic (FGF-2) forms

Increase proliferation of chondrocytes and osteoblastsEnhance callus formation & stimulates angiogenesis.

C.Platelet derived growth factor(PDGF):

A dimer, genes PDGF-A and PDGF-BStimulates bone cell growth

Increases type I collagen synthesis by increasing the number of osteoblasts.

PDGF-B stimulates bone resorption.

D.Insulin like growth factor(ILGF): Two types IGF1 &IGF2 out of which IGF1 is produced in liver and stimulated by growth

hormone.Stimulates bone collagen & matrix synthesis and replicates osteoblasts . It also inhibits collagen

degradation.

E.Bone Morphogenic Proteins (BMP):

BMP was discovered by Marshall Urist in 1965. They are Osteoinductive proteins initially isolated from demineralized bone matrix.

FUNCTIONS: 1. Induce cell differentiation : BMP 3(osteogenin).

2. Promote endochondral ossification: BMP 2 & 7.

3. Regulate extracellular matrix production :BMP1.

4.Increase fusion rates in Spinal fusions (anterior lumbar interbody fusion): BMP 2

5.Non unions: BMP 7 as good as bone grafting .

These are included in the TGF-β family except BMP 1. Must be applied locally because of rapid systemic clearance .

3.PERMEABILITY FACTORS:

-Protease – Plasmin , Kalikrein, Globulin permeability factor.-Polypeptides –leucotaxime, Bradykinin, Kallidin-Amines – Adrenalin, nor-adrenalin, Histamine.

These factors work in ways that : Increase capillary permeability Alteration in diffusion mechanism in intracellular

matrix Cellular migration Proliferation & differentiation New blood vessel formation Matrix synthesis Growth & development.

3.VASCULAR FACTORS

A. Metalloproteinases:

Degrade cartilage and bones to

allow invasion of vessels

B. Angiogenic factors:

Vascular-endothelial growth factors

mediate neo-angiogenesis &

endothelial-cell specific mitogens.

C. Angiopoietin (І & ІІ)

Regulate formation of larger

vessels and branches.

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A.Age: Young patients heal rapidly and have a remarkable ability to remodel V/S old .

B.Nutrition: An adequate metabolic stage with sufficient carbohydrates and protein is necessary.

C.Systemic Diseases:  and those causing an immunocompromised state will likely delay healing. Illnesses like Marfan’s syndrome and Ehlers-Danlos syndrome cause abnormal musculoskeletal healing.

4.SYSTEMIC FACTORS

D.HORMONES: Estrogen

Stimulates fracture healing through receptor mediated mechanism.

Thyroid hormonesThyroxine and triiodothyronine stimulate osteoclastic

bone resorption. Glucocorticoids Inhibit calcium absorption from the gut causing increased

PTH and therefore increased osteoclastic bone resorption. Parathyroid Hormone Growth Hormone

Mediated through IGF-1 (Somatomedin-C)Increases callus formation and fracture strength

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In vitro bone deformation produces piezoelectric

currents and streaming potentials.Electromagnetic (EM) devices are based on

Wolff’s Law that bone responds to mechanical stress: Exogenous EM fields may simulate

mechanical loading and stimulate bone growth and repair

TYPES ARE : Ultrasound. Direct electrical current. Pulsed electromagnetic fields (PEMF).

5.ELECTROMAGNETIC FACTORS

A.Ultrasound therapy:

Low-intensity ultrasound is approved

by the FDA for stimulating healing of

fresh fractures.

Modulates signal transduction,

increases gene expression (aggrecan ),

increases blood flow, enhances bone

remodeling and increases callus

torsional strength in animal models.

B.Direct Electrical

current:

Electric stimulation of bone has

been taught to be an effective

and non invasive method for

fracture healing and treating

fracture non union. Studies

shows that electric field

generated helps in proliferation

of bone cells.

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A/K CAST WITH CATHODES ELECTEOMAGNETIC FIELD

C.Pulsed electromagnetic fields (PEMF).

Approved by the FDA for

the treatment of non-unions

Efficacy of bone stimulation

appears to be frequency

dependant

are most effective (15 to

30 Hz range)

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APPOSITION OF FRACTURE FRAGMENTS.

LOADING AND MICROMOTION . FRACTURE STABILIZATION.

RIGID FIXATION.

BONE GRAFTING.

6.TREATMENT FACTORS

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OTHER RECENT ADVANCES:

GROWTH FACTOR THERAPY Due to their ability to stimulate proliferation and

differentiation of mesenchymal and osteoprogenitor cells they have shown great promise for their ability to promote fracture repair .

APPLICATION OF PLATELET RICH PLASMA Injecting platelet rich plasma at fracture site helps in

fracture healing .

TISSUE ENGINEERING, STEM CEELS AND GENE THERAPIES In past decade tissue culture and stem cells have

been implicated in enhancing fracture healing and articular cartilage regeneration.

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Fracture healing is influenced by many

variables including mechanical stability, electrical environment, biochemical factors

and blood flow etc…

Our ability to enhance fracture healing will increase as we better understand the interaction between these variables.

SUMMARY

CAMPBELL TEXTBOOK OF ORTHOPAEDICS 11TH EDITION..

TUREK ORTHOPAEDICS 4TH EDITION.

WHEELES TEXT BOOK OF ORTHOPAEDICS.

INTERNET.

FUNDAMENTAL OF PEDIATRIC ORTHOPAEDICS By Lynn T. Stahel

BIBLIOGRAPHY

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