Bone grafts

Autogenous bone graft
Allogeneic bone graft

Autogenous bone graft

Usually harvested from the iliac crest.

An excellent graft material, gold standard to which other graft materials measured.

The supply of autogenous bone graft is limited and enough autogenous bone graft may not be available, if there is massive segmental bone loss.

Harvesting of autogenous bone is associated with a rate of major complications of 8.6% and a rate of minor complications of 20.6%.

Properties:

Osteogenic
Osteoconductive
Osteoinductive

Available autogenous bone grafts include:

Cancellous
Vascularized cortical
Nonvascularized cortical
Autogenous bone marrow graft

Although cancellous bone is widely believed to be osteoinductive, there is no evidence to critically demonstrate that inductive proteins and cytokines are active in autogenous cancellous bone graft.
Bone formation from autogenous grafts is believed to occur in two phases.
The first phase lasts approximately four weeks, the main contribution to bone formation is from the cells of the graft.
During the second phase, cells from the host begin to contribute to the process. The endosteal lining cells and marrow stroma produce more than half of the new bone, whereas osteocytes make a small (10%) contribution.

Free haematopoietic cells of the marrow make a minimal contribution.

Autogenous cancellous bone is easily revascularized and is rapidly incorporated into the recipient site. Cancellous graft is a good space filler, but does not provide substantial structural support. Because only the osteoblasts and endosteal lining cells on the surface of the graft survive the transplant, a cancellous graft acts mainly as an osteoconductive substrate, which effectively supports the ingrowth of new blood vessels and the infiltration of new osteoblasts and osteoblast precursors. Osteoinductive factors released from the graft during the resorptive process as well as cytokines released during the Inflammatory phase may also contribute to healing of the graft, although this is only a prevailing theory.

Although cancellous graft does not provide immediate structural support, it incorporates quickly and ultimately achieves strength equivalent to that of a cortical graft after six to twelve months.

Sources of autogenous cancellous bone:

Iliac crest (Anterior or posterior iliac crest)
Greater trochanter
Gerdy's tubercle
Distal part of the radius
Distal part of the tibia

Autogenous cancellous bone graft is an excellent choice for nonunions with <5 to 6 cm of bone loss and that do not require structural integrity from the graft. It can also be used to fill bone cysts or bone voids after reduction of depressed articular surfaces such as in a tibial plateau fracture. Bone-graft substitutes may be preferable in these cases to avoid donor site morbidity. Stable internal or external fixation is also required, to provide the optimum environment for graft consolidation and successful fracture-healing.

Sources of autogenous cortical grafts:

Fibula
Ribs
Iliac crest

These grafts can be transplanted with or without their vascular pedicle.

Autogenous cortical grafts have little or no osteoinductive properties and are mostly osteoconductive, but the surviving osteoblasts do provide some osteogenic properties. Autogenous cortical grafts provide excellent structural support at the recipient site. Although nonvascularized cortical grafts provide immediate structural support, they become weaker than vascularized cortical grafts during the initial six weeks after transplantation as a result of resorption and revascularization.

By six to twelve months there is little difference in strength between vascularized and nonvascularized cortical grafts.

Vascularized cortical grafts heal rapidly at the host-graft interface, and their remodeling is similar to that of normal bone.

Unlike nonvascularized grafts, these grafts do not undergo resorption and revascularization and, therefore, they provide superior strength during the first six weeks.

Despite their initial strength, cortical grafts must still be supported by internal or external fixation to protect them from fracture while they hypertrophy in response to Wolff's law and mechanical loading.
Autogenous cortical bone grafts are good choices for segmental defects of bone of >5 to 6 cm, which require immediate structural support.

For defects of >12 cm, vascularized grafts are superior to nonvascularized grafts as indicated by failure rates of 25% and 50%, respectively.

The harvest of large cortical grafts has been associated with some problems.

Tang et al. reported that, of thirty-nine patients who had a free fibular graft harvested for treatment of avascular necrosis of the femoral head, 42% had a subjective sense of instability and 37% had a subjective sense of weakness in the lower extremity. Only mild weakness of great toe extension and flexion could be measured in 43% and 29% of these patients, respectively.

Only 2% of the patients required a reoperation for a problem at the donor site.

Bone transport may be a better option for defects of >6 cm.

The advantages of autogenous cancellous or cortical bone grafts are their excellent success rate, low risk of transmitting disease, and histocompatibility.
However, as noted above, there is a limited quantity of autogenous bone graft and there is the potential for donor site morbidity.

Bone Marrow

Contains osteoblastic stem cells found in bone marrow.
Injections of autogenous bone marrow provide a graft that is osteogenic and potentially osteoinductive through cytokines and growth factors secreted by the transplanted cells.
Bone marrow can be aspirated from the posterior iliac wing in volumes of 100 to 150 ml and can be injected into a fracture or nonunion site to stimulate healing.
When it is to be used in small bones such as the scaphoid, the bone marrow aspirate can be centrifuged to concentrate the marrow cells and to maximize osteogenic stromal colony-forming efficiency while decreasing the volume injected.
Muschler et al. showed that a 2-ml aspirate from a human anterior iliac crest has a mean of 2400 alkaline phosphatase-positive colony-forming units. The larger the volume of the aspirate, the greater the total number of alkaline phosphatase-positive colony-forming units, but they are more diluted. An increase in the volume of the aspirate from 1 to 4 ml decreases the concentration of alkaline phosphatase-positive colony-forming units by 50%.

Thus, the maximum number of alkaline phosphatase-positive colony-forming units can be delivered to the recipient site in four 1-mL aliquots as opposed to one 4-ml aliquot.

This technique has potential problems because of the tendency for the injected material to wash away from the fracture site.

Many authors have studied the effect of composite grafts formed from a combination of bone-graft substitutes and autologous bone marrow. Demineralized bone matrix is an excellent carrier because of its osteoconductive and osteoinductive properties. Connolly et al. used autogenous bone marrow mixed with 10 mg of demineralized bone matrix, which forms a sand-like material, to fill bone defects. This composite graft can be injected percutaneously as well.

Injection of autogenous bone marrow, with or without a carrier, has been used to treat nonunion and delayed union of several bones (i.e., the carpal bones, tibia, femur, humerus, etc.).

The Type-IIIB open tibial fracture may be the ideal fracture for this technique because of its high frequency of healing problems and the possible benefits of not having to expose the fracture site to deliver the graft.

Connolly reported that eighteen (90%) of twenty delayed unions of the tibia united after utilization of this technique. He recommended waiting six to twelve weeks after the acute fracture to allow the initial inflammatory reaction and osteoclastic resorption to subside before injecting the autogenous bone marrow.

Injection of autogenous bone marrow does not promote healing more rapidly or to a greater extent than do traditional bone-grafting techniques, but it has been shown to be as successful in one small series.

Advantages of autogenous bone marrow injection:

The technique is relatively simple and can be done as an outpatient procedure.
It is associated with fewer complications at the donor and recipient sites than is harvesting of autograft from the iliac crest.
Because the approach is less invasive, clinicians may be encouraged to perform early treatment of delayed unions, ultimately expediting healing and decreasing the complications of prolonged immobilization.

Allogeneic bone grafts

Allogeneic bone, with variable biologic properties, is available in many preparations:

Demineralized bone matrix
Morselized and cancellous chips
Corticocancellous and cortical grafts
Osteochondral and whole-bone segments.

Demineralized Bone Matrix

Demineralized bone matrix is osteoconductive, and possibly as an osteoinductive. It does not offer structural support, but it is well suited for filling bone defects and cavities. Demineralized bone matrix revascularizes quickly.

It is also a suitable carrier for autogenous bone marrow as discussed previously. Preparation process

Allogeneic bone is crushed or pulverized (particle size 74 to 420 µm)
Demineralized by the addition of hydrochloric acid
The residual acid is eliminated by rinsing in sterile water, ethanol, and ethyl ether.

Current methods of processing demineralized bone matrix follow the same basic steps, but refinements of the technique, many of which have been patented, have been developed by several companies and tissue banks. Process variables may include demineralization time, acid application, temperature, application of defatting agents, and use of either aseptic processing methods or irradiation or ethylene oxide sterilization of the final product.

The companies and tissue banks market these variations in processing with the claim that they provide unique advantages and superior performance over other products, although little comparative scientific data are available to support many of the claims.

The biologic activity of demineralized bone matrix is presumably attributable to proteins and various growth factors present in the extracellular matrix and made available to the host environment by the demineralization process.

The osteoinductive capacity of demineralized bone matrix can be affected by storage, processing, and sterilization methods and can vary from donor to donor.

For example, sterilization by ethylene oxide under certain conditions and 2.5 Mrad of gamma irradiation substantially reduced osteoinductivity.

Because the osteoinductive capacity differs from donor to donor and because of safety reasons, the American Association of Tissue Banks and the United States Food and Drug Administration require each batch of demineralized bone matrix to be obtained from a single human donor.

Demineralized bone matrix is available as a freeze-dried powder, as crushed granules or chips, and as a gel or paste.
Demineralized bone matrix is an excellent grafting material with which to induce bone formation within contained, stable skeletal defects such as bone cysts and cavities. Others have reported that application of demineralized bone matrix to long-bone nonunions and acute bone defects from fractures results in successful healing similar to that following autgenous bone-grafting.

The most successful grafts may be composites of demineralized bone matrix and autologous bone marrow when used with stable fixation.

A dilute mixture of demineralized bone matrix and autologous bone marrow can be injected with a syringe, and this method has been used successfully in many challenging situations.

Demineralized bone matrix can also augment and expand autogenous cancellous bone graft when the supply of autogenous bone is limited or the defect is very large.
Demineralized bone matrix is recommended for filling stable, well-contained bone defects and cysts and as a bone-graft expander when the defect is large.

No prospective, randomized controlled studies have been done to prove the efficacy of demineralized bone matrix for the treatment of nonunions, there may be some nonunion situations in which the use of demineralized bone matrix could be considered.

First, it can be used to augment autogenous cancellous or corticocancellous grafts. Demineralized bone matrix may also be an alternative for a patient who has no autogenous bone available for use as a graft or for a patient who does not wish to undergo an extensive open procedure or for whom the open procedure carries a very high risk.

In this case, a percutaneous procedure utilizing demineralized bone matrix and autogenous bone marrow could be considered.
Demineralized bone matrix as a composite graft with autogenous bone marrow has been recommended to provide an immediate supply of osteoprogenitor cells in combination with a matrix that is both conductive and inductive.

However, while some studies have shown successful outcomes with composite grafts, experience with these grafts is limited and their effectiveness is currently unproven.

Demineralized bone matrix disadvantages:

Potential to transmit human immunodeficiency virus (HIV).
The risk of transmission is very low, the decalcification process appears to inactivate and eliminate HIV. According to one manufacturer, there have been no reported cases of infectious disease transmission in 1.5 million procedures with the use of one particular preparation of demineralized bone matrix.
Similarly, one large tissue bank that processes demineralized bone matrix reported in its literature that no infectious disease transmission had occurred from more than 20,000 donors.
Different batches may have different potencies because of the wide variety of donors used to supply the graft.
Although many authors have reported healing similar to that following autogenous cancellous bone-grafting, this has not been subjected to randomized studies that would allow a true comparison of the two graft types.

Morselized and Cancellous Allografts

Morselized and cancellous allografts are osteoconductive and provide some mechanical support, mainly in compression.

They are most often preserved by freeze-drying (lyophilization) and vacuum-packing, and they undergo stages of incorporation similar to those of autogenous cancellous bone.
Morselized allograft is recommended for packing bone defects such as bone cysts after curettage or in periarticular metaphyseal locations to support elevated articular surfaces after articular depression such as occurs with tibial plateau or tibial pilon fractures.

Morselized allograft is also useful to augment autogenous cancellous bone and to fill larger defects when the supply of autologous bone is limited.
Allograft bone is associated with a very small risk of infectious disease transmission, but its use eliminates the need to harvest iliac crest bone and its associated morbidity.

Osteochondral and Cortical Allografts

Osteochondral and cortical allografts are harvested from various regions of the skeleton, such as the pelvis, ribs, femur, tibia, and fibula, for reconstruction after major bone or joint loss.

The grafts are available as whole-bone or joint segments (i.e., as the whole or part of the tibia, humerus, femur, talus, acetabulum, ilium, or hemipelvis) for limb salvage procedures or as cortical struts to buttress existing bone, to stabilize and reconstitute cortical bone after periprosthetic fractures, and to fill bone defects.

These grafts are osteoconductive and provide immediate structural support.

They are preserved by either deep-freezing or freeze-drying. Deep-frozen allografts retain their material properties and can be implanted immediately after thawing, whereas freeze-dried allografts can be friable and weak in torsion and bending, even after rehydration prior to implantation.

Again, transmission of infectious disease is a risk when osteochondral and cortical allografts are used.

However, of the three million tissue transplants performed since identification of the HIV virus, only two cases of HIV transmission have occurred and both involved transplantation of unprocessed fresh-frozen allografts.

The use of cortical allografts is recommended to fill bone voids and for reconstructive procedures requiring immediate structural support in patients who wish to avoid harvest of an autogenous fibular graft.

Fresh allografts that require no preservation are available, but they incite an intense immune reaction, making them less attractive than autografts.

These fresh allografts have limited applications and are currently being used mainly for joint resurfacing.

References

Christopher G. Finkemeier; CURRENT CONCEPTS REVIEW: Bone-Grafting and Bone-Graft Substitutes; JBJS (A), Mar 2002; 84: 454 - 464.