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Bone-Grafting and Bone-Graft Substitutes

Investigation performed at University of California Davis Medical Center, Sacramento, California

Christopher G. Finkemeier, MD
Department of Orthopaedic Surgery, University of California Davis Medical Center, 4860 Y Street, Suite 3800, Sacramento, CA 95817

The author did not receive grants or outside funding in support of his research or preparation of this manuscript. He did not receive payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, educational institution, or other charitable or nonprofit organization with which the author is affiliated or associated.

	Introduction

Top Introduction Autologous Bone Grafts Allografts Ceramics and Ceramic Composites Bioactive Glass Author’s Recommendations... References

 
The treatment of delayed unions, malunions, and nonunions requires restoration of alignment, stable fixation, and in many cases adjunctive measures such as bone-grafting or use of bone-graft substitutes.

Bone-graft materials usually have one or more components: an osteoconductive matrix, which supports the ingrowth of new bone; osteoinductive proteins, which support mitogenesis of undifferentiated cells; and osteogenic cells (osteoblasts or osteoblast precursors), which are capable of forming bone in the proper environment.

Autologous bone graft, usually harvested from the iliac crest, is an excellent graft material, but its availability may be limited and the procedure to harvest the material is associated with complications.

Bone-graft substitutes can either replace autologous bone graft or expand an existing amount of autologous bone graft.

Various forms of bone-graft substitutes are available and include allograft bone preparations such as demineralized bone matrix and calcium-based materials.

The treatment of posttraumatic skeletal conditions such as delayed unions, nonunions, malunions, and other problems of bone loss is challenging. In most cases, restoration of alignment and stable fixation of the bone is all that is necessary to achieve a successful reconstruction. However, in many cases, adjunctive measures such as bone-grafting or bone transport are required to stimulate bone-healing and fill bone defects.

When faced with a problem requiring bone replacement, the orthopaedic surgeon currently has several options: autologous or allogeneic cancellous or cortical bone, demineralized bone matrix, calcium phosphate-based bone-graft substitute, or autologous bone marrow. In the future, the options will include recombinant bone morphogenetic proteins or growth factors. The biology of each of these grafts varies and may provide one or several essential components: (1) an osteoconductive matrix, which is a scaffold or trellis that supports the ingrowth of new bone; (2) osteoinductive proteins, which stimulate and support mitogenesis of undifferentiated perivascular cells to form osteoprogenitor cells; and (3) osteogenic cells (osteoblasts or osteoblast precursors), which are capable of forming bone if placed into the proper environment. The surgeon’s choice of the proper graft must be based on what is required from the graft (structural or bone-forming function, or both), the availability of the graft, the recipient bed, and the cost. The surgeon must also remember that stable fixation is necessary for the use of any of these grafts¹. No bone graft or bone-graft substitute permits the surgeon to use less than optimum orthopaedic techniques or to deviate from proper surgical principles.

Conventional bone-grafting with autologous cortical and cancellous bone harvested from the iliac crest is the standard against which all other bone-graft substitutes are judged, but it has disadvantages. The supply of autologous bone graft is limited, and many patients with difficult problems requiring skeletal reconstruction may have undergone several previous harvests of bone grafts and thus have little or no additional useful iliac crest bone. In addition, the harvesting of autologous bone is associated with a rate of major complications of 8.6% and a rate of minor complications of 20.6%². Another problem is that enough autologous graft may not be available, especially if there is massive segmental bone loss. For these reasons, it is important to have various options available to augment, expand, or substitute for autologous bone graft.

	Autologous Bone Grafts

Top Introduction Autologous Bone Grafts Allografts Ceramics and Ceramic Composites Bioactive Glass Author’s Recommendations... References

 
Autologous bone grafts have osteogenic, osteoconductive, and osteoinductive properties. Available autologous bone grafts include cancellous, vascularized cortical, nonvascularized cortical, and autologous bone marrow grafts (Table I). Bone formation from autologous grafts is believed to occur in two phases^3,4. During the first phase, which 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 hematopoietic cells of the marrow make a minimal contribution⁵.

Autologous cancellous bone is commonly harvested from the iliac crest, which can provide a large supply of bone (especially the posterior iliac crest). Other sources are Gerdy’s tubercle, the distal part of the radius, and the distal part of the tibia. Autologous 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. However, 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 autologous cortical grafts include the fibula, ribs, and iliac crest. These grafts can be transplanted with or without their vascular pedicle. Autologous cortical grafts have little or no osteoinductive properties and are mostly osteoconductive, but the surviving osteoblasts do provide some osteogenic properties as well^12,13. Autologous cortical grafts provide excellent structural support at the recipient site as well. 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^12,14. However, by six to twelve months there is little difference in strength between vascularized and nonvascularized cortical grafts¹². 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 weeks¹². Despite their initial strength, cortical grafts still must be supported by internal or external fixation to protect them from fracture while they hypertrophy in response to Wolff’s law¹⁵ and mechanical loading. Autologous 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%, respectively¹¹. 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 extremity¹⁶. 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^17,18.

The advantages of autologous 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 autologous bone graft and there is the potential for donor site morbidity.

Bone Marrow
Another source of autologous material is the osteoblastic stem cells found in bone marrow. Injections of autologous 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 centrifuged¹⁹ 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 units²⁰. 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 aliquot²⁰.

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^21-25. Demineralized bone matrix is an excellent carrier because of its osteoconductive and osteoinductive properties. Connolly et al. used autologous bone marrow mixed with 10 mg of demineralized bone matrix, which forms a sand-like material, to fill bone defects^19,26. This composite graft can be injected percutaneously as well. Injection of autologous 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 technique¹⁹. 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 autologous bone marrow¹⁹. Injection of autologous bone marrow does not promote healing more rapidly or to a greater extent than do traditional bone-grafting techniques^27-29, but it has been shown to be as successful in one small series¹⁹. Injection of autologous bone marrow offers several advantages: (1) the technique is relatively simple and can be done as an outpatient procedure and should, therefore, be cost-effective^19,25; (2) it is associated with fewer complications at the donor and recipient sites than is harvesting of autograft from the iliac crest^19,25, although I am not aware of any direct comparison studies upon which to base a final conclusion; and (3) 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 immobilization³⁰.

Techniques for Harvesting Autologous Cortical and Cancellous Bone Graft
Bone can be harvested from either the anterior or the posterior iliac crest. Harvesting from the anterior iliac crest is usually more convenient because the patient is typically in a supine position for most operations involving the extremities. However, only a limited amount of bone can be obtained from the anterior iliac crest, and this site should not be used when >20 to 30 cc of graft is required. The posterior iliac crest, on the other hand, has an abundant supply of both cortical and cancellous bone and is an ideal location from which to harvest large amounts of bone-graft material. The general technique for harvesting bone from the ilium is similar regardless of whether the bone is taken anteriorly or posteriorly. When bone is harvested from the anterior iliac crest, I recommend that the most anterior extent be at least 2 to 3 cm posterior to the anterior superior iliac spine to avoid predisposing it to an avulsion fracture. It is important to take advantage of the relatively large amount of cancellous bone under the iliac tubercle. When bone is taken from the posterior iliac crest, I recommend that the most posterior extent be at least 4 cm from the posterior superior iliac spine to decrease the chance of violating the sacroiliac joint.

For illustrative purposes, I will describe my technique for harvesting corticocancellous bone graft from the posterior iliac wing (Fig. 1). The patient is placed in the prone position, over bolsters, and all osseous prominences are well padded. The buttock and flank ipsilateral to the operative site is prepared and draped. A vertical incision is made, centered over the proposed harvest area. Transverse incisions that parallel the posterior iliac crest should not be used routinely, as they may injure the cluneal nerves. The length of the incision is determined by the amount of bone-graft material that is needed. The deep fascia overlying the posterior iliac crest is incised over the crest down to the bone. With use of a sharp Cobb elevator and either a knife or an electrocautery, the fascia is then elevated off the iliac wing, exposing either the outer table or the inner table, depending on the surgeon’s preference. A lap sponge placed over the sharp edge of a Cobb elevator can be used to assist in clearing the periosteum. I typically expose the outer table for harvesting. I then use a 0.5-in (12.7-mm) sharp straight osteotome to cut a line into the iliac crest, starting 4 cm anterior to the posterior superior iliac spine and extending as far anteriorly as needed. From this corticotomy, I then use a straight 0.5-in osteotome to cut vertical lines toward the sciatic notch (Fig. 1, A). It is imperative to be careful not to violate the sciatic notch to avoid injury to the neurovascular pedicle, which lies adjacent to the iliac wing in the sciatic notch. Strips of graft of various widths can then be cut with the straight osteotome through the extent of the proposed harvest area. Using a gouge of the same diameter as the cortical strip, I remove corticocancellous strips with abundant cancellous bone attached to a thin layer of cortical bone from the iliac wing (Fig. 1, B). These strips are placed into a sterile basin and covered with a damp sponge or towel. The remaining portion of the cancellous bone within the iliac wing is then removed, with use of a combination of gouges or large curets (Fig. 1, C). Abundant cancellous bone is also available underneath the iliac crest itself. More cancellous graft can be removed by undermining in each direction from the harvest site.

View larger version (34K): [in this window] [in a new window]   Fig. 1: A: Posterior view of the pelvis. Strips of corticocancellous bone as well as cancellous bone can be harvested, with the most posterior extent of the harvest being no closer than 4 cm from the posterior superior iliac spine. B: Corticocancellous strips consist of cancellous bone attached to a thin layer of cortical bone. C: Cancellous bone can be removed from between the inner and outer tables of the ilium and is best stored in a container where it can be kept moist.

Other potential areas for harvesting bone include metaphyseal regions of the skeleton, such as the distal part of the radius, Gerdy’s tubercle, the tibial plafond, and the greater trochanter. The harvesting technique is similar for all of these areas, and I recommend a technique similar to that used to perform a bone biopsy. A small drill bit should be used to create perforations in an elliptical pattern. These perforations are then connected with a small osteotome or a small curet to remove the cortical roof. Beneath this roof there is a supply of cancellous bone in various quantities, depending on the anatomic region of the body from which the graft is being harvested. Once the graft is harvested, the small cortical roof can be replaced, or it can be used as part of the bone graft. Hemostasis can be obtained by packing with a sponge or with some thrombin-impregnated Gelfoam. I usually do not use suction drainage in these locations. A compression dressing works well to obtain hemostasis. Harvesting of any of the various vascularized pedicle flaps, such as the fibula or the iliac crest, requires specialized techniques and is beyond the scope of this review.

	Allografts

Top Introduction Autologous Bone Grafts Allografts Ceramics and Ceramic Composites Bioactive Glass Author’s Recommendations... References

 
Allogeneic bone, with variable biologic properties, is available in many preparations: demineralized bone matrix, morselized and cancellous chips, corticocancellous and cortical grafts, and osteochondral and whole-bone segments.

Demineralized Bone Matrix
Demineralized bone matrix acts as an osteoconductive, and possibly as an osteoinductive, material. It does not offer structural support, but it is well suited for filling bone defects and cavities. Demineralized bone matrix revascularizes quickly. It also is a suitable carrier for autologous bone marrow as discussed previously. Demineralized bone matrix is prepared by a standardized process, as originally described by Urist et al.^31,32 and modified by Reddi and Huggins³³, in which allogeneic bone is crushed or pulverized to a consistent particle size (74 to 420 m) followed by demineralization in 0.5N HCL mEq/g for three hours. 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 reduce osteoinductivity^34,35. 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 donor³⁶. Demineralized bone matrix is available as a freeze-dried powder, as crushed granules or chips, and as a gel or paste (Table II).

I recommend demineralized bone matrix for filling stable, well-contained bone defects and cysts and as a bone-graft expander when the defect is large. Although to my knowledge 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 autologous cancellous or corticocancellous grafts. Demineralized bone matrix may also be an alternative for a patient who has no autologous 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 autologous bone marrow could be considered. I recommend using demineralized bone matrix as a composite graft with autologous bone marrow to provide an immediate supply of osteoprogenitor cells in combination with a matrix that is both conductive and inductive^22,24. However, while some studies have shown successful outcomes with composite grafts^19,26,42, experience with these grafts is limited and their effectiveness is currently unproven.

Demineralized bone matrix has several potential disadvantages. Because it is an allogeneic material, there is the potential to transmit human immunodeficiency virus (HIV). However, the decalcification process appears to inactivate and eliminate HIV⁴³, so even if infected tissue got through the extensive donor screening process, the risk of transmission is very low. 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 matrix⁴⁴. 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 donors⁴⁵. Another potential limitation of demineralized bone matrix is that different batches may have different potencies because of the wide variety of donors used to supply the graft. Finally, although many authors have reported healing similar to that following autologous cancellous bone-grafting, I am not aware of any prospective, 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 autologous cancellous bone. I recommend using morselized allograft 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 will eliminate 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 allografts³⁶. I recommend the use of cortical allografts to fill bone voids and for reconstructive procedures requiring immediate structural support in patients who wish to avoid harvest of an autologous 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.

	Ceramics and Ceramic Composites

Top Introduction Autologous Bone Grafts Allografts Ceramics and Ceramic Composites Bioactive Glass Author’s Recommendations... References

 
Calcium phosphate ceramics may be used as osteoconductive matrices in orthopaedic surgical settings (Table III). Many of the current calcium phosphate biomaterials can be classified as polycrystalline ceramics. The material structure of ceramics is derived from individual crystals of a highly oxidized substance that have been fused together at the crystal grain boundaries by a high-temperature process called sintering⁴⁶. Ceramics are brittle and have poor tensile strength, making their primary clinical application one of filling contained bone defects or restoring areas of bone loss resulting from a fracture such as an articular fracture with joint depression. Calcium phosphate biomaterials should be placed in intact bone or rigidly stabilized bone in order to protect the ceramic from shear stresses, and they should be tightly packed into the adjacent host bone to maximize ingrowth⁴⁷. Calcium phosphate ceramics are available as porous or nonporous blocks of various sizes or as porous granules. Calcium phosphate ceramics do not elicit a foreign-body reaction and are well tolerated by host tissues.

Coralline hydroxyapatite is processed by a hydrothermal exchange method that converts the coral calcium phosphate to crystalline hydroxyapatite with pore diameters between 200 and 500 m and in a structure very similar to that of human trabecular bone. Bucholz et al. reported that the clinical performances of autologous cancellous bone graft and coralline hydroxyapatite are equivalent when the substances are used to fill bone voids resulting from articular surface depression in tibial plateau fractures⁴⁹. Other studies have demonstrated successful healing of cortical defects greater than one-third of the diaphyseal circumference of long-bone fractures, although the results are less predictable than those following treatment of metaphyseal fractures⁴⁷. To avoid donor site morbidity, I occasionally use coralline hydroxyapatite granules or blocks of various size, depending on the size of the defect, to fill metaphyseal defects after reduction of depressed articular segments (Figs. 2-A and 2-B). A contraindication to the use of this material is a joint surface defect that would allow the grafting material to migrate into the joint. In these cases, I prefer to use autologous or allograft cancellous bone, which is more adhesive to itself and to the surrounding metaphyseal bone.

View larger version (105K): [in this window] [in a new window]   Fig. 2-A: Preoperative anteroposterior radiograph of a depressed intra-articular tibial plateau fracture. The depressed articular surface is indicated by the arrow.

View larger version (90K): [in this window] [in a new window]   Fig. 2-B: Postoperative anteroposterior radiograph made after reduction of the articular surface and coralline hydroxyapatite grafting of the metaphyseal defect left behind after elevation of the articular surface, as indicated by the arrow.

Calcium sulfate graft material with a patented crystalline structure described as an alphahemihydrate acts primarily as an osteoconductive bone-void filler that completely resorbs as newly formed bone remodels and restores anatomic features and structural properties. Potential uses of calcium sulfate graft material include the filling of cysts, bone cavities, and segmental bone defects; expansion of grafts used for spinal fusion; and filling of bone-graft harvest sites. Currently, very limited information is available on the use of this material in humans; no published controlled studies are available, to my knowledge.

Another option available for filling bone voids after acute fractures is injectable calcium phosphate. One such material, Skeletal Repair System (SRS; Norian, Cupertino, California) is an injectable paste of inorganic calcium and phosphate that hardens within minutes, forming a carbonated apatite of low crystallinity and small grain size similar to that found in the mineral phase of bone⁵¹. After twelve hours, this material hardens to form dahlite with a compressive strength of 55 MPa, and, because of its crystalline structure, it can eventually be resorbed and replaced by host bone⁵¹. This material may be useful as a bone-graft substitute to augment cast treatment or internal fixation of impacted metaphyseal fractures. One indication for use of such a material is an impacted, extra-articular distal radial fracture that would normally require pinning after reduction to avoid dorsal settling. At least one study has demonstrated that this calcium phosphate material can be injected into the fracture site after reduction, and after a few minutes a below-the-elbow cast is applied⁵². After two weeks, the cast can be replaced by a volar wrist splint until the fracture is healed⁵². Several authors have reported promising results with this approach for distal radial fractures^52-54. However, while a multicenter study showed that patients treated with injectable calcium phosphate and cast immobilization had earlier functional return than patients treated with cast immobilization or external fixation alone, the advantage diminished by three months and no advantage was detectable after one year⁵⁵. Additional potential applications of injectable calcium phosphate materials include treatment of hip⁵⁶, spine, calcaneal, and other extra-articular metaphyseal fractures at risk for hardware failure or for redisplacement under compressive loads. Several injectable pastes are available, but little data are available to make comparisons based on clinical outcomes.

	Bioactive Glass

Top Introduction Autologous Bone Grafts Allografts Ceramics and Ceramic Composites Bioactive Glass Author’s Recommendations... References

 
Several variations of glass beads called Bioglass (USBiomaterials, Alachua, Florida) are currently being developed, and one formulation (PerioGlas) has been approved in the United States for periodontal use. The beads are composed of silica (45%), calcium oxide (24.5%), disodium oxide (24.5%), and pyrophosphate (6%). When implanted, they bind to collagen, growth factors, and fibrin to form a porous matrix to allow infiltration of osteogenic cells. The matrix provides some compressive strength, but it does not provide structural support. I have no experience with this material.

	Author’s Recommendations for Specific Problems

Top Introduction Autologous Bone Grafts Allografts Ceramics and Ceramic Composites Bioactive Glass Author’s Recommendations... References

 
The attainment of proper axial alignment and adequate stability and the preservation of vascular supply remain the most important factors for successful treatment of acute fractures as well as delayed unions and nonunions. In fractures that do not heal or that heal slowly, there is an abnormality of either the biology or the mechanical environment, or both. Therefore, unless the mechanical environment of the fracture site is optimized, usually by increasing the stability of the fracture, manipulation of the biology at the fracture site with bone graft or bone-graft substitute will have limited success. In cases of hypertrophic nonunion, successful healing can usually be accomplished simply by stabilizing the fracture. If the mechanical environment has been optimized and a nonunion still exists, the next step for the surgeon is to choose an appropriate grafting material depending on the biology of the fracture site.

The first step in matching the graft to the clinical problem is to decide whether the problem is a lack of osteoinduction and/or osteogenesis or one of structural bone loss requiring a load-bearing graft. Well-contained, stable metaphyseal defects with a good vascular supply are well suited for osteoconductive bone-graft substitutes that can resist compressive forces. Allograft chips or any of the calcium-based bone-graft substitutes would be appropriate in this setting. If a nonunion is present and a stimulus for new bone formation is needed, an autologous cancellous graft is ideal. There is no biologic rationale for using a purely osteoconductive graft in a nonunion or delayed union that requires new bone formation or when the vascularity of the grafting bed is marginal. Autologous cancellous bone or composite grafts of demineralized bone matrix and bone marrow, or demineralized bone matrix and one of the calcium-based substitutes, are appropriate in these situations.

If a diaphyseal defect is too large to heal reliably with cancellous bone-grafting, then a structural graft such as a cortical autograft or allograft may be needed. For these large defects (approximately 6 cm in my experience), vascularized cortical autografts are a better choice than nonvascularized autografts or allografts because of their more rapid and complete incorporation as well as their ability to hypertrophy. Cortical allografts are best reserved for use in areas with an excellent vascular supply (such as metaphyseal locations [Figs. 3-A, 3-B, and 3-C] or around the femur), whereas vascularized cortical autografts should be reserved for use in areas of marginal blood supply (such as the scaphoid, femoral neck, or talus) or for reconstructing diaphyseal segmental bone defects. For smaller defects (<6 cm), autologous cancellous bone used with stable internal fixation is adequate for nonunions or fresh fractures with bone loss.

View larger version (129K): [in this window] [in a new window]   Fig. 3-A: Preoperative anteroposterior radiograph of a shotgun injury to the left tibial plateau, which was previously debrided and stabilized in an external fixator.

View larger version (85K): [in this window] [in a new window]   Fig. 3-B: Anteroposterior (Fig. 3-B) and lateral (Fig. 3-C) radiographs made ten months after fibular strut allogeneic bone-grafting of the massive metaphyseal bone defect.

View larger version (91K): [in this window] [in a new window]   Fig. 3-C: Anteroposterior (Fig. 3-B) and lateral (Fig. 3-C) radiographs made ten months after fibular strut allogeneic bone-grafting of the massive metaphyseal bone defect.

	References

Top Introduction Autologous Bone Grafts Allografts Ceramics and Ceramic Composites Bioactive Glass Author’s Recommendations... References

 

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7. Burwell RG. Studies in the transplantation of bone. VII. The fresh composite homograft autograft of cancellous bone. An analysis of factors leading to osteogenesis in marrow transplants and in marrow-containing bone grafts. J Bone Joint Surg Br, 1964;46: 110-40.

8. Williams R. Comparison of living autografts and homogenous grafts of cancellous bone heterotopically placed in rabbits. Anat Rec, 1962;143: 93-105. [Medline]

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