BONE GRAFTING

Definition
Bone grafting is a surgical procedure that places new bone or a replacement material into spaces
between or around broken bone (fractures) or in holes in bone (defects) to aid in healing. It is a
common procedure for treatment of various delayed unions and nonunions, as well as for the
treatment of fresh fractures to help ensure union. It has been estimated that more than 200,000
bone grafts per year are used in the United States in humans.

Purpose

Bone grafting is used to repair bone fractures that are extremely complex, pose a significant risk
to the patient, or fail to heal properly. Bone grafting is also used to help fusion between
vertebrae, correct deformities, or provide structural support for fractures of the spine. In addition
to fracture repair, bone grafting is used to repair defects in bone caused by congenital disorders,
traumatic injury, or surgery for bone cancer. Bone grafts are also used for facial or cranial
reconstruction.

Demographics

Degenerative diseases of the spine increase with age. People over age 50 are more likely to need
a bone graft if their condition requires surgery. Traumatic injuries occur most often in people 18
44 years.

Description

Bone tissue is a matrix-like structure primarily composed of a protein called collagen. It is

strengthened by hydroxyapatite, deposits of calcium and phosphate salts. Four types of bone
cells are located within and around this matrix. Together, these four types of cells are responsible
for building the bone matrix, maintaining it, and remodeling the bone as needed. The four types
of bone cells are:

Osteoblasts, which produce the bone matrix.

Osteocytes, mature osteoblasts that maintain the bone.
Osteoclasts, which break down and remove bone tissue.
Bone lining cells, which cover bone surfaces.

There are three ways that a bone graft can help repair a defect.

Osteogenesis, the formation of new bone by the cells contained within the graft.
 Osteoinduction, a chemical process in which molecules contained within the graft (bone
morphogenetic proteins, abbreviated as BMP) convert the patient's cells into cells capable
of forming bone. Osteoinduction represents a process of cellular interaction in which
unspecialized mesenchymal cells may differentiate into bone. This production of bone
requires an environment that is conducive to bone formation as well as some
osteostimulating substance. These substances may be osteogenic cells or other materials
such as bone morphogenic protein. The mechanism of bone induction is presently
unknown. Creeping substitution, the process of bone remodeling by osteoclastic
resorption and creation of new vascular channels with osteoblastic bone formation
resulting in new haversian systems, is the method by which strong cortical bone is
formed from grafted material.

Osteoconduction, a physical effect whereby the graft matrix configures a scaffold on

which cells in the recipient form new bone. Osteoconduction is the process by which
capillary ingrowth into the graft occurs from the recipient bed. This may take place on a
framework or scaffold of the dead graft itself or, as in the case of a fresh autograft, may
be accomplished in concert with the viable cells that remain within the graft.

TYPES OF GRAFTS

The autograft is tissue from one person that is transferred from one portion of the body
to another.
The isograft is material that is taken from one individual and transplanted into another
genetically identical individual, such as an identical twin. In this case the donor and the
recipient must have the same genotype.
The allograft (formerly called a homograft) is tissue that is transferred from one
individual to another individual of the same species.
The xenograft (formerly known as a heterograft) is tissue that is taken from one
individual and transferred to another individual of a different species.
Bone grafts may be either cortical or cancellous in nature. Furthermore the bone that is
being transferred may be either dead or alive. Sometimes the nonviability of the
transplant is known, such as when using a frozen allograft, but at other times the viability
may be in doubt. A great deal of controversy exists regarding the transplantation of live
bone and its ability to survive.The greatest chance for the successful transplantation of
live bone is with a cancellous autograft or with the vascularized pedical cortical autograft.
Both of these grafts must be recognized by the recipient as self.

Diagnosis/Preparation

The surgeon does a clinical examination, and conducts tests to determine the necessity of a bone
graft. Diagnostic tests determine the precise location of damage. These tests include x rays,
magnetic resonance imaging (MRI), and computed tomography (CT) scan. They provide an
image of the affected area, and indicate the exact amount of damage that has occurred due to the
fracture or defect.

Orthopedic surgeries pose varying degrees of difficulty. The patient is instructed on what will
take place during the procedure, as well as risks involved. A consent form is obtained before
surgery.

The following activities will help the patient prepare for surgery.

thorough physician consult before surgery

banking some of his or her own blood in case a transfusion is needed
eating well to achieve good nutritional status before and after surgery
following a recommended exercise program before and after surgery.
maintaining a positive attitude
smoking cessation

BONE GRAFT INCORPORATION

The biology of bone graft incorporation involves many factors. To look at these factors we will
need to examine several types of grafts.

The fresh autograft is an attempt to transplant living bone that can survive and add to the
bone volume and eventually the bone strength. When fresh autograft is added to a
recipient site, the incorporation of the graft relates to the recipient site cells as well as to
the remaining viable cells within the graft itself. The cellular response seems to be
different when using a cancellous graft as opposed to using a cortical one. Cancellous
autografts as well as fresh cortical autografts begin their incorporation in much the same
way. Blood clot and hematoma provide the initial environment for the new graft. An
inflammatory response then prevails and vascular granulation tissue invades the area. By
the end of the second week, the response is that of a fibrous granulation tissue, and
cellular death occurs within the graft, which has not yet been reached by the vascular
response. At this point the differences of graft incorporation between cortical and
cancerous grafts become evident.

In cancellous autografts the vascular response is much greater than in cortical grafts. The
entire cancellous bed may be completely revascularized within approximately l to 2
weeks The cell population of this environment comprises predominantly osteoblasts. It is
not known if these cells are produced from the recipient site or if they are the descendants
of cells transplanted with the graft itself.In any case these cells line the scaffold presented
by the trabeculae of the graft and deposit a seam of osteoid that surrounds and entraps the
original dead bone. This entrapped dead bone is eventually resorbed by osteoclasts.
Radiographically the cancerous bone first becomes more ense as the new bone forms on
 the old trabeculae and then becomes less dense as the osteoclastic remodeling takes place.
However, the vascular response is less and the cells of the transplanted bone are dead
initially.

In the cortical autograft the main differences revolve around the amount of
revascularization and the completeness of the remodeling. The cortical bone may not be
revascularized as quickly as the cancellous graft. Revascularization takes about 2 months
and is caused by the structure of the cortical graft, which does not allow as large a contact
area for vascular penetration between the graft and the host. Revascularization is
accomplished through the old haversian and Volkmann canals. Following the
revascularity of the periphery of the graft, the interior follows suit quickly. Interior
revascularization of a cortical bone graft will start the process of creeping substitution,
which first resorbs bone stock before replacement with new viable bone stock. The
histologic evaluation showed that the resorption process progressed so that the peripheral
haversian systems and their adjacent interstitial lamellae were remodeled first and then
the interior haversian systems were remodeled without their corresponding interstitial
lamellae, thereby leaving areas of dead cortical bone mixed in with the newly remodeled
bone. The overall results showed that the bone at the ends of the graft was more
completely remodeled than the bone in the center of the graft.

The incorporation of cortical allografts differs slightly from that of cortical autografts. In
general the revascularization is much slower and the bone formation is less extensive.
Resorption may play a much larger part in the graft incorporation. The temporal sequence
of the cortical bone allograft shows an inflammatory response for several weeks. The
major cell type at this time is the lymphocyte. The inflammatory response lasts for
another month or two, during which time a fibrous Encapsulation of the allograft takes
place. Gradually the graft may be incorporated into the host tissue. The time period
associated with the incorporation of the allograft is one indication of the acceptance or
rejection of the graft. Callus formation is a good sign but may not be present to any great
extent if rigid internal fixation is used. The remodeling resembled that of autografts.

The mechanism of allograft rejection seems to be related most strongly to cellular rather
than humoral immunity. This cellular type of immune reaction is thought to have its
source mainly in the bone marrow.

One of the other problems of bone grafting, in addition to incorporation, is bone strength.
Fatigue fractures are a common problem when using cortical allografts in humans, and
many of the failures of bone grafts deal with mechanical problems that are related to the
biologic incorporation of the graft. Cancerous grafts initially strengthen by appositional
new-bone formation. Remodeling of this graft then yields normal strength. Cortical bone,
 however, is first resorbed, and hence weakened, before the creeping substitution can
replace the bone through the haversian remodeling process.

DONORSITES

Cancellous grafts are the most common form of autograft and can be obtained from the wing of
the ilium, the proximal tibia, and the proximal humerus. Sometimes the amount of graft that is
needed may demand that more than one site be used.

RECIPIENTSITES

In fresh fractures the recipient site is usually easily defined. The cancerous graft is placed into
and around the defect being grafted. The application of the graft may be thought of as placement
of the callus. The bone graft will form the scaffold for further bone production so that adequate
bridging of the defect will help ensure bone union.

When dealing with delayed unions or nonunions, the application site of the graft may be more
difficult to determine. The fibrous connective tissue that surrounds the old fracture site may not
allow the placement of the graft where needed. In these cases the fibrous connective tissue must
be removed so that the graft can come into contact with the bone fragments and the surrounding
vascularized tissues.

GRAFTS ASSOCIATED WITH OPEN FRACTURES AND INFECTION

In general, only cancerous bone autografts are used safely when dealing with open fractures and
certainly when dealing with infected fractures. The use of cortical bone grafts in association with
open fractures and osteomyelitis will allow the formation of infected sequestra or an involucrum.
When dealing with open fractures, grafting may have to be delayed because of inadequate
vascularity at the recipient site.

Often a bed of granulation tissue covering the lining of the wound is necessary to allow the
revascularization of the cancerous graft to occur. This may mean that bone grafting will be
delayed 10 to 14 days after the initial reduction and fixation. If a cancerous bone graft fails
because of infection, the graft undergoes coagulation necrosis and will flow from the wound,
usually without leaving an infected sequestrum. Regrafting may be tried after the infection is
under control and the vascularity of the area can support a graft.

Aftercare

Pain is normal for a few days following surgery, and medication is given regularly to alleviate
this problem. The patient will likely have a urinary catheter.
The time required for convalescence after bone grafts due to fractures or spinal fusion varies
from one to 10 days. Vigorous exercise may be limited for up to three months. Children heal
faster than adults.

If a spinal fusion was performed, the patient may be discharged from the hospital with a back
brace or cast.

Risks

The risks for any surgical procedure requiring anesthesia include reactions to the medications
and breathing problems. Bleeding and infection are also risks of surgery.

There is little risk of graft rejection for autografts, but there are drawbacks:

additional surgical and anesthesia time (typically 30 minutes per procedure) to obtain or
harvest the bone for grafting
added costs for the additional surgery
pain and infection at the site from which the graft is taken
the relatively small amount of bone available for grafting
surgical complications, such as infection and pain that sometimes last a longer period of
time than the primary surgery (up to two years)

Allografts also have drawbacks:

Bone variability because it is harvested from a variety of donors.

Grafted bone may take longer to incorporate with the host bone (than in an autograft).
Graft may be less effective than an autograft.
Possibility of transferring diseases to the patient.
Potential immune response complications (patient's immune system fighting against the
grafted bone tissue). This problem is lessened through the use of anti-rejection drugs.

Normal results

Most bone grafts are successful in helping the bone defect to heal. The extent of recovery
depends on the size of the defect and the condition of the bone surrounding the graft at the time
of surgery. Severe defects take some time to heal, and may require further attention after the
initial graft. Less severe bone defects should heal completely without serious complications.
Repeat surgery is sometimes required if the condition recurs or complications develop.

If the bone graft is done on the face or head, the surgeries usually result in a more normal
appearance.
Morbidity and mortality rates

Although bone harvested from the patient is ideal, postoperative morbidity is sometimes
associated with hip bone or fibula (part of the knee) autografts. Morbidity of allografts is usually
related to the graft incorporating more slowly, and less completely, into the body.

In one study of over 1,000 patients who received very large allografts after bone cancer surgery,
researchers found that approximately 85% were able to return to work or normal physical
activities without crutches. However, approximately 25% required a second operation because
the first graft did not heal properly.

Infections associated with bacterial contamination of allografts are rare. However, they can result
in serious illness and death.

Alternatives

Despite the increase in the number of procedures requiring bone grafts, there is no ideal bone
graft substitute. However, there are a variety of natural and synthetic replacement materials used
instead of bone, including collagen (the protein substance of the white fibers of the skin, bone,
and connective tissue); polymers, such as silicone and some acrylics; hydroxyapatite; calcium
sulfate; and ceramics. Several new products are available or in development. They function as
bone graft substitutes or extenders. Demineralized bone matrix (bone that has had its calcium
removed) possesses some of the properties that the body uses to induce bone formation. Calcium
hydroxyappetite products or coral have structures similar to bone, and act as scaffolding for new
bone.

New BMP products are expected to be strong inducers of bone growth (osteoinductive). These
new products will be relatively expensive, but will grow bone better than the patient's own bone,
eliminating the need for bone graft harvesting. Bone morphogenetic proteins have been extracted
from natural tissues and produced in the laboratory to stimulate bone production in animals and
humans. Because they do not have the same drawbacks as grafts, surgeons are hopeful that they
will soon be able to use BMP and laboratory produced BMP to aid in the generation and repair of
bone.

The INFUSE Bone Graft (rhBMP-2) has received Food and Drug Administration approval, and
has demonstrated better patient outcomes than hip autografts with regard to length of surgery,
blood loss, hospital stay, reoperation rate, median time to return to work, and fusion rates at six,
12, and 24 months following surgery.

Advances in tissue engineering have provided polymer based graft substitutes with degradable,
porous, three-dimensional structure. New bone may be grown on these products; the grafts then
slowly dissolve, leaving only the new bone behind.