FRACTURE HEALING IN CORTICAL AND CANCELLOUS BONE

(ADULT Vs CHILD)

MODERATERS:

Dr.G.C Basavraj M.S (Ortho)

Professor and Unit Head

Dr.Manjunath reddy M.S (ortho)

Asso.Professor

PRESENTED BY:

Dr.PRAMOD.B.M

PG IN ORTHOPAEDICS

DATE: 23/12/09

INTRODUCTION:

• 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

HISTORY : Bones have broken since the beginning of humanity and have

been recognised and treated as long as recorded history.• 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 taught that blood vessels are responsible for callus formation.

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

• In 1873, Kolliker observed the role of multinucleated giant cells, osteoclast to be responsible for bone resorption.

HISTORY contd...

• 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.

ANATOMY OF BONE:

Bone is essentially a highly vascular, living, constantly changing mineralized connective tissue. It is remarkable for its hardness, resilience and regenerative capacity, as well as its characteristic growth mechanism

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

Bone made up of two components,• Outer dense, compact / Cortical bone• Inner spongiosa /trabeacular /Cancellous bone

BONE MACROSCOPY:

HISTOLOGY OF BONE

WOVEN BONE CORTICAL BONE CANCELLOUS BONE

Microscopically: Bone is classified as• 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

HEVERSIAN SYSTEM:

PERIOSTEUM

PERIOSTEUM: The bone is surrounded by periosteum which is made up of an outer layer of white fibrous and elastic tissue and inner cambium layer which has a looser composition, is more vascular and contains cells with osteogenic potency. Another layer the endosteum, lines the surface of cancellous bone.

Functions of periosteum• The periosteum serves as a limiting membrane for bone .• The outer fibroblast layer provides fibrous attachment to

subcutaneous connective tissue, muscle, tendons and ligaments.

• Inner cambium layer contains pools of undifferentiaited cells that support bone formation during embrogenic and post natal growth.

• Periosteum helps in fracture healing by forming periosteal callus.

• Intact Periosteal hinge or sleeve may lessen the extent of displacement of fracture fragments and it also can be used to assist in the reduction

Blood supply: Bone derives its blood supply mainly from• Nutrient artey

• Epipyseal/ Metaphyseal artries

• Periosteal artries

• Muscular, ligamentous and capsular arteries

Bone cells:1.Osteoprogenitor cells: (osteogenic/ proosteoblasts) These are undifferentiated mesenchymal stem cells which under

appropriate conditions can differentiate into osteoblast, chondroblast and fibroblast. In case of fracture, they divide by mitosis once or twice and differentiate into osteoblasts.

Types:

Committed osteoprogenitor cells-committed in formation of bone tissue

Inducible osteoprogenitor cells – they differentiate depending on the inducer into osteoblast/chondroblast/fibroblast.

2.OSTEOBLASTS: They are basophilic,cuboidal,mononuclear cells about 15-

30micro meter forming the continuous monolayer over the surface of bone. They are derived from marrow stromal cells by

differentiation of pre-osteoblasts. They: 1.Synthesize major protein of bone Type 1 collagen Non collagenous protein – Osteocalcin - osteonectin 2.Control mineralization of bone by secretion of alkaline phosphatase 3.Recent evidence suggest osteoblasts control osteoclastic

function by secretion of prostaglandin , interlukin 6 and interlukin 11.

3.OSTEOCLASTS: Large, multinucleated gaint rounded cells having numerous

mitochondria and lysosomes. They help in removing of living bone know as osteoclasis. They are found where active erosions of bone and lie in direct contact with the bone surface in pits termed “Resorption bays” or “lacunae of howship”.

RESORPTION AND NEW BONE FORMATION

3.OSTEOCYTES:

Derived from osteoblasts, when they get incarcerated in the matrix which they secrete and get burried deep with in the bone. They occupy spaces in the matrix called as lacunae. Canaliculi radiate from each lacunae and permit diffusion. They secrete alkaline phosphatase to maintain calcification

The Biology of fracture fixation:Fracture in man heals or unites by two main ways:A)Primary healing / Osteonal / Direct healing : Bone formation occurs directly without any callus

formation. This occurs particularly in stable, aligned, closely apposed fractures. It is roughly comparable to healing of soft tissue by primary intention. Occurs both in Cortical and Cancellous bones. Eg:plating done in case of fracture both bone forearm

Rigid fixation “fools” the bone into “thinking”Is wasn’t broken

Types of primary healing:1.Contact healing/ Haversian remodelling : 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.

CUTTER HEAD

2.Gap healing: Osteoblats differentiate and start depositing osteods on the exposed surfaces of fragment ends, mostly without a preceding osteoclastic resorption. In large gaps of 200micro meter – 1mm, the cells fill the defect with woven bone and haversian remodelling begins to deposit the lamellar bone.

B) Secondary healing/ Indirect healing 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.

Osteoinduction and Osteoconduction

• Osteoinduction is the first step in bone healing, it causes mesenchymal cells to differentiate into various cells which then proliferate and produce messenger substances which further stimulate the messenchymal cells to differentiate. This good cycle continues till healing.

• In osteoconduction, a scaffold of collagenous network has developed, upon which the reparative cells produce callus and bone. It facilitates bone deposition in an orderly fashion and helps the callus to bridge the gap between the fragments.

• Allografts has powerful osteoinductive as well as osteoconductive properties.

The natural course of fracture healing includes :

Stabilisation of fractured bone fragments by periosteal and endosteal callus formation and by fibrocartilage differentiation.

Restoration of continuity and bone union by ossification

Substitution of avascular and necrotic areas by haversian remodelling

Malallignment can be corrected to a certain extent, by remodelling at fracture site.

Functional adaptation.

STAGES OF FRACTURE HEALING:1. STAGE OF HAEMATOMA FORMATION:

•Following fracture the local marrow, periosteum and adjacent soft tissue as well as the living bone itself get damaged.

• As a result there will be accumulation of blood within the medullary cavity, fracture ends and beneath the periosteum .

• The ring of bone immediately adjacent to each side of fracture becomes ischaemic, deprived of blood supply

•The fracture hematoma immobilizes the fracture and the swelling hydrostatically splints the fracture.

•The fracture haematoma provides a fibrin scaffold that facilitates migration of repair cells.

The hematoma provides 2 important factors:

•It provides small amount of mechanical stability of fracture site.•Hematoma brings the osteoblasts, and the chondrocytes precursors to fracture site in large numbers that being to differentiates into osteoblasts and chondrocytes to begin producing matrix.

2.Stage of granulation tissue•Granulation tissue invades and replaces the initial hematoma and then differentiates into connective tissue and fibrocartilage.

• Injured tissue and platelets releases vasoactive mediators such as serotonin and histamine cause blood vessels to dilate and exude plasma, leading to acute edema.

• Macrophages and osteoclasts come into the site to remove damaged and necrotic tissue

• The precursor cells from the deep surface of periosteum close to the fracture in the sensitized and stimulated local mediator mechanism begin to produce new cells that differentiate and organise to provide new vessels, fibroblast, intercellular matrix and supporting cells.

• Collectively they form granulation tissue which grows forward, outside and inside the bone to bridge the fracture.

3.Stage of repair/callus• The process of osteogenesis

continues and fracture callus bridges the fracture site and its subsequent transition to mature bone takes place.

• The bone can be produced through intramembranous/ endochondral ossification or both.

• Nests of cartilage cells or their precursors lay new osteoid tissue.

• The cells synthesize a matrix with high concentration of type-1 collagen fibrils, and then create condition that promote deposition of cluster of calcium hydroxyapatite crystals in collagen fibrils.

• Later osteoblasts, release “prepacked” calcium phosphates complex into the matrix. As mineralization proceeds, the bone ends gradually become enveloped in a fusiform mass of callus.

TYPES OF CALLUS:

•External bridging callus/periosteal callus

•Medullary callus

•Soft fibrous callus / Cartilagenous callus

•Hard calls

4.Stage of consolidation:

The woven bone that forms the primary callus is gradually transformed by the activity of the osteoblasts into more mature bone with a typical lamellar structure.

5. Stage of remodelling: •The process occurs along with usual deposition–resorption phenomenon.

•It is a gradual modification of the fracture region under the influence of mechanical loads until it reaches some threshold of optimal shape, which typically is similar to the shape it had before the fracture.

• Angular deformities slowly decrease/disappear as bone is laid down on the concave surface and removed from convex surface.

CHEMICAL MEDIATORS OF FRACTURE HEALING:1.Fracture haematoma contains many messenger substances:• Serotonin Histamine • PG E 2 Thrombroxane A2• Hormones Growth factors• Bone morphogenic proteins (cytokines)

2.Growth factors:• Transforming growth factor beta• Fibroblast growth factor• Platelet derived growth factor

3.Permiability factors:• Protease – Plasmin , Kalikrein, Globulin permeability factor.• Polypeptides –leucotaxime,Bradykinin,Kallidin

• Amines – Adrenalin, nor-adrenalin,Histamine All these factors influence fracture healing in various process that

involves– Increase capillary permeability– Alteration in diffusion mechanism in intracellular matrix– Cellular migration– Proliferation & differentiation– New blood vessel formation– Matrix synthesis– Growth & developmen

BONE MORPHOGENIC PROTIEN: BMP was discovered by Marshall Urist in 1969. It is a group of growth factor

proteins within the transforming growth factor-b (TGF-b) superfamily of growth factors.

More than twenty types of BMP have been recognized, but only BMP-2, 4, 6, 7, and 9 have been shown to have significant osteogenic properties.

FUNCTIONS: These molecules have osteoinductive properties which provide signal

for differenciation of mesenchymal cells into osteoblasts and chondroblasts. BMP molecules seem to induce bone formation in a stepwise fashion, with individual BMP molecules functioning at different stages of osteoblastic differentiation and osteogenesis

USES:• 1.In enhancing fracture healing: Implantation of recombinant human BMP

(rhBMP) induces bone formation by causing the differentiation of mesenchymal cells into chondroblasts and osteoblasts.

• 2.Spinal fusion: rhBMP-2 is one component in a system used during spinal fusions for the treatment of degenerative disc disease.

FRACTURE HEALING IN CANCELLOUS BONE : Cancellous bone even with an intact blood supply has in fact a very

restricted form of osteogenic activity. Healing process follows a different pattern here. Many injuries of cancellous bone are intra articular hence accurate reconstruction is essential in order to restore the congruity of the articular surface

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. In other words a cut surface of cancellous bone even with an intact blood supply does not throw out callus. Dense attachment of periosteum to cancellous bone prevents callus formation

4.No death of osteocytes : In comparing the healing of cancellous bone with cortical bone it is to be noted that cancellous bone there appears to be no death of the osteocytes in the cut edges of divided trabeculae. 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 in the healing of fractures in cancellous bone which have been distracted. Then after reduction of colle’s fracture a hallow cavity is left in the cancellous end of the radius.

FRACTURE HEALING IN CORTICAL BONE:

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.

Anatomical region of the child’s bone :

Epiphysis : Ends of long bone which ossifies from secondary center called epiphysis.

At birth each epiphysis consists of completely cartilaginous called chondroepiphysis. Cartilage gradually ossifies until the cartilagious area has been almost completely replaced by bone at skeletal maturity. External surface of an epiphysis is composed of either articular cartilage or perichondrium. Perichondrium blends into the periosteum

• Physis : Physis or growth plate present between epiphysis and metaphysic primary function of the physis is rapid integrated longitudinal and latitudinal growth. It appear radiolucent on X-ray. Ischemia of physis due to fracture can lead to growth disturbances.

Four 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.

Metaphysis :

Epiphyseal end of diaphysis is known as metaphysis Major characteristic are • Decreased thickness of cortical bone • Increased trabecular one • Shows extensive considerable bone turnover compared

with other region of the bone. • Metaphysis is the site of extensive osseous modelling

and remodelling.• A torus (Buckle) fracture is most likely to occur in a

metaphysis region with a trabecular, fenestrated compressible cortex

Diaphysis :

Shaft of long bone which ossifies from primary centre.

At birth the diaphysis is composed of laminar (fetal woven) bone. The developing diaphyseal bone is extremely vascular. Periosteum mediated, membranous bone formation leads to over all enlargement of diameter of shaft variably increased width of diaphyseal cortices and formation of marrow cavity.

Periosteum :

A child’s periosteum is thicker, more redily elevated from the diaphyseal and metaphyseal bone and exhibits greater osteogenic potential than of an adult.

Attachment : Periosteum is attached relatively loosely to the

diaphysis. It is firmly fixed to the metaphysis subsequently attaches densely into the peripheral physis, blends into the zone of ranvier as well as the epiphyseal perichondrium.

FRACTURES UNIQUE IN CHILDRENS:1.Physeal Fractures

• 18-30% of pediatric fractures

• Common in adolescence peak age 11-12 yrs

• Usually occur in the upper limb

• Physis contains the zone of provisional

calcification, which is a relatively weak area

Torus “Buckle” Fracture

• Common fracture

• Metaphyseal region secondary to a compressive loading

• Cortex “buckles” resulting

in a stable fracture

Greenstick Fracture• Most common fracture pattern in children

• Incomplete fracture at metaphyseal-diaphyseal junction

• One cortex remains intact

• Angulation and rotation common

• Often must complete the fracture to achieve union

Bowing Fracture

• Longitudinal force on the bone which stops short of fracture, but causes a persistent plastic deformity

• Little remodeling

• Functional and cosmetic deficits common

FRACTURE REPAIR IN CHILDRENFracture 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 metaphysic 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

• In children because of osteoblastic activity, the periosteum contributes significantly to new bone formation by accentuating the normal process of membranous ossification.

REMODELLING:WOLLF’s LAW Defination: The principle that every change in the form and the function

of a bone or in the function of the bone alone, leads to changes in its internal architecture and in its external form.

Bone in a healthy person will adapt to the loads it is placed under. If loading on a particular bone increases, the bone will remodel itself over time to become stronger to resist that sort of loading. The internal architecture of the trabeculae undergoes adaptive changes, followed by secondary changes to the external cortical portion of the bone

The remodelling phase is the longest phases 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.

REMODELLING:

3 yrs OLD CHILD

ACCEPTABLE ANGULATION IN PAEDIATRIC FEMORAL FRACTURES

AGE VARUS/ ANTEROIR/ ROTATION VALGUS POSTERIOR

Birth to 2yrs 30 30

2-5yrs 15 20 Not acceptable 6-10yrs 10 15 11yrs to maturity 5 10

ACCEPTABLE ANGULATION IN PAEDIATRIC

FOREARM FRACTURES

SAGITAL PLANE AGE BOYS GIRLS FRONTAL PLANE4-9 20 15 15

9-11 15 10 5

11-13 10 10 0

>13 5 0 0

VARIABLES THAT INFLUENCE FRACTURE HEALING :

I) INJURY VARIABLE : OPEN FRACTURES INTRA ARTICULAR FRACTURES

SEGMENTAL FRACTURES

SOFT TISSUE INTERPOSITION

DAMAGE TO BLOOD SUPPLY

II) PATIENT VARIABLES : AGE

NUTRITION

SYSTEMIC HORMONES NICOTINE

III) TISSUE VARIABLES : FORM OF BONE (Cancellous / cortical).

BONE NECROSIS

BONE DISEASE

INFECTION

IV) TREATMENT VARIABLES APPOSITION OF FRACTURE FRAGMENTS

LOADING AND MICROMOTION FRACTURE STABILIZATION

RIGID FIXATION

BONE GRAFTING

DEMINARALIZED BONE MARROW

RECENT ADVANCES IN FRACTURE HEALING:

• ULTRASOUND:

Low intensity pulsed ultrasound accelerates fracture healing. It increases the aggrecan gene expression as well as the concentration of intracellular calcium in fracture callus chondrocytes. Hence it provides safe, non-invasive method of facilitating healing of fractures.

• ELECTRIC STIMULATION:

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.

Types 1. Direct electrical stimulation 2. Capacity coupling 3. Inductive coupling

• GROWTH FACTOR THERAPHY Due to their ability to stimulate proliferation and differentiation

of mesenchymal and osteoprogenitor cells, growth factors such as Tumour Growth Factor, Fibroblatic Growth Factor , Bone morphogenic protein (BMP-2 and BMP-7) 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 , The platelet α granules are rich in growth factors,such as transforming growth factor-β, vascular endothelial growth factor, and platelet derived growth factor that play essential role 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.

FRACTURE HEALING IS LIKE…… MAKING LOVE

•it’s quite natural

•may take considerable time

•two components

•with good local blood supply

•in close contact

•with a little movement