Principles of bone grafting: non-union, delayed union

Principles of bone grafting: non-union, delayed union

GENERAL PRINCIPLES OF ORTHOPAEDIC SURGERY filler, increasing structural support where healing is proceeding satisfactorily. In non-unions or delayed ...

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GENERAL PRINCIPLES OF ORTHOPAEDIC SURGERY

filler, increasing structural support where healing is proceeding satisfactorily. In non-unions or delayed unions, grafts may be used to stimulate repair and to provide structural support to internal and external fixation devices. For example, in a deformity correction where a gap is created on the original concave site of a correction, a structural graft placed into this gap, loaded in compression by an internal or external fixation device, increases the strength of the construction. Graft and graft substitutes are almost always used in combination with mechanical devices that restore length and alignment, and provide mechanical forces at the fracture site (e.g. compression, distraction, neutralization). These devices can enhance repair by controlling motion, restoring alignment and by providing mechanical signals that stimulate repair. For instance, distraction of a malaligned hypertrophic non-union can lead to repair without grafting. Alternatively, a well-aligned hypertrophic non-union may heal from the increased stability provided by compression fixation without grafting.

Principles of bone grafting: non-union, delayed union J L Marsh

Autologous bone grafts or autografts (i.e. grafts taken from the patient’s bone) have been used to treat fracture non-unions and occasionally to treat acute fractures. Traditionally, autologous bone is harvested from the iliac crest through a generous open incision. This can result in significant pain and morbidity. Nowadays, keyhole approaches to this site are often preferred. Alternatively, allografts (grafts from another person) or synthetic bone substitutes may be used. Autologous graft remains the first-line treatment if rapid incorporation is required, and is the ‘gold standard’ in patients with: • poor vascularity • a history of infection • failed attempts at non-union repair • fracture site gaps • unfavourable mechanical circumstances. This contribution reviews the indications, contraindications and techniques of bone grafting, and briefly mentions new techniques of grafting and allografts and bone graft substitutes.

Types of autograft Cancellous autografts: the usual autografts for osteoinduction and osteoconduction are cancellous autografts. These grafts are most rapidly revascularized and incorporated, and have the greatest osteogenic potential through viable osteogenic cells and the release of bone-inducing growth factors. Good moulding characteristics have led to the frequent use of cancellous grafts as void-fillers in metaphyseal fracture defects. Rapid revascularization and incorporation make cancellous grafts ideal if infection is a risk. They must be used with internal or external fixation because they do not provide much structural support.

Mechanism of action Autologous bone grafts carry out their function in three ways: osteoinduction, osteoconduction and structural support. Some grafts or substitutes may carry out all of these functions, while others may perform one or two.

Cortico-cancellous grafts have some cortical component. They are usually harvested from the iliac crest, typically in chips or small strips. They provide more structure than pure cancellous grafts and are frequently used to bridge across a small defect using an onlay technique.

Osteoinduction: autologous bone grafts induce new bone formation, which promotes repair. They do this by providing viable osteogenic cells to the site and by releasing growth factors, which induce local repair at the recipient site by attracting new osteoprogenitor cells, stimulating osteoblastic differentiation and enhancing bone collagen synthesis.

Structural autografts harvested from the iliac crest or the fibula are used to fill discrete defects and provide immediate mechanical support and strength. Union at both ends of a defect rapidly restores mechanical integrity. Cortical graft harvest increases morbidity at the donor site. At the recipient site, cortical grafts have slower incorporation than cancellous grafts, less rapid revascularization, and provide fewer viable cells and osteogenic growth factors for osteoinduction. As the cortical graft is remodelled, it loses mechanical strength as non-viable bone is removed.

Osteoconduction: autologous bone grafts provide a scaffold or latticework onto which new bone is formed. This scaffold provides a bridge across the fracture or non-union which, when incorporated with new bone, is the mechanical link that leads to healing. Autologous bone grafts simultaneously fill the roles of osteoinduction and osteoconduction.

Free vascularized grafts are harvested on their blood supply and do not undergo cell necrosis and extensive creeping substitution. In comparison to non-vascularized cortical grafts, they have greater mechanical strength during the first six months after transplantation. These advantages make them ideal in large skeletal deficiencies and in poorly vascularized recipient sites. Free vascularized grafts have morbidity at the donor site and require a high level of technical expertise. Vascularized grafts require prolonged periods of protection to prevent late fracture at the recipient site.

Structural support to traumatic defects is provided by some autologous bone grafts. For example, grafts may augment the role of internal fixation by supporting the reduction of a metaphyseal fracture and preventing displacement of the reduced articular surface during the early phases of repair. They function as a void-

Autograft harvest • Cancellous grafts are harvested from many sites around the

J L Marsh MD is a Professor of Orthopedic Surgery at Iowa University, Iowa, USA.

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skeleton, such as the ends of most long bones and the greater trochanter, where cancellous bone is present. The anterior and posterior iliac crests are the most commonly utilized sites. The anterior crest has better accessibility, but the posterior crest has the greatest volume of graft. • Structural autografts are typically harvested from the fibula, the iliac crest or occasionally the rib. The technique involves direct harvest of graft by surgical exposure of the site, opening of the external cortex and obtaining strips or other small portions of pure cancellous bone. Cortico-cancellous strips can be harvested from the iliac crest using gouges or osteotomes. This includes some of the external cortex with the cancellous bone. Less invasive techniques have been developed where grafts can be harvested through small surgical windows or percutaneously using a trephine. The least invasive approach is to aspirate bone marrow with viable osteoprogenitor cells. Bone marrow aspirates are used to stimulate healing by direct application or injection, or in conjunction with allografts (see below) or other osteogenic scaffolds to increase their osteoinductive properties.

materials, augmenting them through their moulding and adhering characteristics. Osteogenic growth factors: investigators have previously studied potent osteoinductive protein growth factors originally derived from bone extracts. More recently, protein growth factors have been produced through recombinant gene technology. Researchers have hoped these substances can be more efficacious at inducing repair than autologous bone. Two of these bone morphogenic proteins (BMP-2 and BMP-7) have been used in large clinical trials. These clinical trials (and evidence from animal models) indicate that these substances are potent osteoinductive agents. Further data are required to determine their role in clinical practice in isolation and in conjunction with other techniques. Osteoconductive void-fillers: calcium-based osteoconductive compounds are available to fill skeletal voids and may be used to substitute for autograft. These agents work as an osteoconductive scaffold because they do not have osteoinductive properties. They have variable moulding and filling properties depending on the preparation. Some of these compounds have been mixed with autologous bone marrow to provide inductive and conductive properties. Their biggest role has been as void-fillers in acute trauma cases. They provide low-level structural support to augment internal fixation and a scaffold for eventual new repair. Most have little inherent structural strength, although calcium phosphate cement used as void-filler has been shown to increase the strength of several types of metaphyseal fracture reductions with and without internal fixation.

Alternatives to autograft Autologous bone grafting remains the ‘gold standard’ for use in a variety of skeletal deficiencies in orthopaedic trauma. Allogenic grafts in various preparations and a variety of commercially available products can substitute for autologous bone grafts, and are used with increasing frequency. These substitutes may fulfil a role identical to autografts, but some substitutes can provide structure or mechanical strength superior to traditional autografts. Allograft is used in large structural sections or in small cancellous or cortico-cancellous chips. It is osteoconductive, providing a scaffold for new repair. Allografts are also weakly osteoinductive through the release of osteogenic bone-inducing proteins. Unlike autografts, they do not provide viable osteogenic cells, and undergo slower incorporation than autografts. Hence, they are less effective at stimulating repair than equivalent quantities of autograft. Allograft also carries a higher risk of infection and a very small risk of disease transmission. An example of an allograft would be femoral heads donated after a hip replacement. Despite these disadvantages, the abundant supply (combined with the lack of morbidity at the donor site) has led to the increasing use of allograft in fracture repair and non- or delayedunion surgery. Cancellous allograft can be used as a void-filler in metaphyseal fracture reductions, limiting the need and morbidity of iliac crest graft. Allograft is also available in large structural segments which, in some locations (e. g. femoral periprosthetic fractures), are the treatment of choice. Many surgeons are wary of allograft in locations where infection is a risk (e.g. delayed healing of tibial fractures). Allograft is not as effective as autograft if optimal osteoinduction is required.

Indications for autografts and graft substitutes Structural support: autologous graft and graft substitutes provide structural support in a variety of acute and subacute repair circumstances. This function is illustrated most dramatically in the femur, where allograft struts provide sufficient structural support around periprosthetic fractures to allow patient mobilization (Figure 1). These struts neutralize bending forces at the fracture site and, in the well-vascularized femoral shaft, have a high chance of uniting to the femoral shaft. Filling a void is a different type of structural support provided by grafts or graft substitutes in acute trauma. Reducing a compression fracture in the metaphysis leaves a metaphyseal void, which presents a risk for recurrent displacement of the articular surface that may not be prevented by internal fixation (Figure 2). Filling the void with osteoconductive material adds structural support to the fixation in the lateral tibial plateau, the distal radius, the calcaneus and other metaphyseal fracture reductions. Acceleration of fracture repair: in acute fractures, grafts may accelerate fracture repair in circumstances where high mechanical demands on an implant may otherwise result in implant failure before healing. A supracondylar femur fracture with a medial gap requires rapid medial healing to protect the lateral implant. Grafts placed medially have been used to stimulate rapid repair. New techniques emphasizing indirect reduction and less harm to the soft tissues have decreased the need for grafts to provide this function.

Demineralized bone matrix: demineralized bone matrix products are widely commercially available. In these allograft-derived products, the mineral phase of bone has been extracted, leaving proteins, growth factors and collagen. They are provided as powders, pastes or putties, which permit them to be moulded into deficient areas within fracture and non-union sites. They have variable osteoinductive and conductive properties. They provide no structural support. They are often used in with other grafting

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Figure 2. A 63-year-old female has fallen and sustained a split lateral depression tibial plateau fracture. Reduction and plate fixation will lead to healing, but a large metaphyseal void must be packed with a graft or graft substitute to prevent postoperative articular displacement.

Figure 1. A 59-year-old female has fallen and sustained a periprosthetic fracture around a total hip replacement. Control of rotational and bending forces is necessary. Allograft struts provide the requisite structural support because internal fixation will be difficult.

Anticipated healing delays: grafts or substitutes in acute or subacute trauma are indicated if healing delays are anticipated. In the past, grafting was not indicated until a non-union was established after an arbitrary timeframe or a series of radiographs. Currently, surgeons frequently choose to operate earlier in the course of fracture repair when healing delays or failures are anticipated. An open tibia fracture where a large butterfly fragment has been debrided with only point-to-point contact is at high risk of developing a healing delay or non-union. A procedure to stimulate repair is indicated when the soft tissues have healed, 4–8 weeks after injury before the diagnosis of a definite non-union. Repair of non-unions or delayed unions is the classic indication for graft or graft substitutes, usually in combination with internal or external fixation. The greater the mechanical instability and the less the prior osteogenic response, the more certain it is that osteoinductive graft material will be necessary (Figure 3). Grafts are used to fill gaps, span defects or as onlays to exposed surfaces. Traditional techniques of extensive inlay or onlay grafting in association with casting are now rarely used.

Figure 3. A 76-year-old female has had a long-standing humeral nonunion with two failed attempts at surgical repair. Internal fixation will restore alignment and control motion, but rapid healing is necessary to prevent implant failure. This requires the addition of an osteoinductive agent (e.g. cancellous autograft).

Contraindications Active infection and/or inadequate soft tissue coverage is the major contraindication to bone grafting. Historically, grafting to an infected bed was possible through the Papineau technique (cancellous grafts placed in an open skeletal defect). This technique is now seldom used. Local or free-tissue transfer reconstructs soft tissue defects and is the most popular method to counteract infection. Dead space is filled with antibiotic beads. Debridement, systemic antibiotics, SURGERY 24:6

local antibiotics and soft tissue coverage aggressively treat infection. Bone grafting is done in a closed space under the soft tissue flap when the bed is likely to be sterile. Grafting into an actively infected bed is not indicated. 209

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Intramedullary nailing of comminuted femoral shaft fractures with skeletal defects has a high healing rate and acute or subacute grafting is not necessary. In plate fixation of forearm fractures, relatively small skeletal defects were traditionally grafted, but most of these fractures will heal when stabilized and grafting is typically not indicated. Established hypertrophic non-unions do not require autograft or graft substitutes to achieve union. Good vascularity, mechanical stability and callus visible on radiographs are features of a non-union that will heal with the application of distraction and compression forces. Grafting is not necessary.

to preserve rotatory movements between these bones. Grafting should be directly at the osseous site. Complications Morbidity at the donor site has been most frequently reported for the iliac crest. Paraesthesia and pain is common and occurs in 25–30% of cases. More serious complications (infection, fracture, superior gluteal artery injury, hernia) occur in up to 10% of patients. Structural grafts from the fibula (vascularized or non-vascularized) also produce morbidity at the donor site, including nerve injury, weakness in the foot and ankle and chronic pain. The frequency of complications has been the major factor stimulating clinical research in replacing autologous bone graft with substitutes that would avoid such morbidity.

Technique of graft implantation Cancellous grafts are typically packed around a recipient site by the inlay and onlay techniques. If a bone cavity is present, grafts are packed into the cavity after preparation of the bone bed, using hand or power instruments to achieve bleeding at the recipient bone surfaces. If there is bone contact without a cavity, grafts are used to bridge the site on the exterior surface of the bone. The bone surface is prepared with a burr or with an osteotome by lifting small cortical cancellous sections i.e. there is a bed of fresh injury on which to apply the grafts.

Results of bone grafting Accurate results of bone grafting procedures are difficult to determine because simultaneous treatment by a variety of techniques is common. Internal and external fixation devices are used, in tandem with direct approaches to the fracture site. Combinations of allograft, autograft and graft substitutes are often used. Physical methods (e.g. electrical stimulation, ultrasound) are also used occasionally. These combination treatments are utilized on a wide range of osseous-related healing problems, so the results of bone grafting as an isolated intervention cannot be determined. Graft and graft substitutes, when used in combination with other methods, should lead to successful repair in most cases of non-union and delayed union.

Structural grafts can be fixed directly to the skeleton to aid in restoring early mechanical integrity of the limb. Large structural grafts (e.g. fibula) benefit from direct internal fixation. In the femur, allograft struts are fixed to the femoral shaft using cables, providing immediate mechanical strength, eliminating motion and optimizing chances for union. Healing delays: variations by site The tibia most commonly experiences healing delays and requires autografting or graft substitutes. The tibia offers approaches for grafting not possible in other bones because of its paired anatomy with the fibula. The posterolateral approach to the tibia exposes the interosseous membrane between the fibula laterally and the tibia medially. Grafting along the tibia, the interosseous membrane and onto the fibula provide a broad surface to allow the graft to become incorporated and produce cross-union between the two bones.

The future Grafts of autologous bone remain the ‘gold standard’ for induction of osseous repair in a variety of difficult non-unions, delayed unions and acute fracture circumstances. Graft harvest involves morbidity, is time-consuming and, in some circumstances, autografts do not provide the optimal combination of moulding and structural characteristics. Investigators continue to search for substances that will supplant all of the functions of traditional bone grafting and provide structural support. The indications and techniques of bone grafting in non-union, delayed union and fracture surgery are in the process of evolution. The surgeon must keep abreast of this constantly changing field to provide optimal treatment. 

The femur has excellent soft tissue coverage, eliminating many of the problems present in the tibia. Delays in healing respond to a change of implants without direct grafting in many instances. Grafting is usually directly to the skeletal site. The humerus is similar to the femur in that there is a good soft tissue envelope. Delayed healing in the humerus often requires extensive approaches to the fracture site because of the local neurovascular anatomy and because of a less predictable response to intramedullary nailing. Humeral non-unions often have an atrophic appearance when viewed on radiographs, and exhibit gross motility on examination. Grafting of humerus fractures, in conjunction with internal fixation, is often required. Significant destruction of bone often leads to segmental defects if the implanted humerus fails to heal. These circumstances may require structural grafts (e.g. free fibula graft).

FURTHER READING Finkemeier C G. Bone-grafting and bone-graft substitutes. J Bone J Surg Am 2002; 84-A: 454–64. Keating J F, McQueen M M. Substitutes for autologous bone graft in orthopaedic trauma. J Bone J Surg Br 2001; 83: 3–8.

The paired radius and ulna have a functional purpose of forearm rotation. Grafting should not be to the interosseous membrane,

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