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The American Academy of Orthopaedic Surgeons

Printed with permission of the American Academy of Orthopaedic Surgeons. This article, as well as other lectures presented at the Academys Annual Meeting, will be available in March 2006 in Instructional Course Lectures, Volume 55. The complete volume can be ordered online at www.aaos.org, or by calling 800-626-6726 (8 A.M.-5 P.M., Central time).

TERR Y R. L IGHT
EDITOR, VOL. 55

C OMMITTEE TERR Y R. L IGHT

CHAIRMAN

PAUL J. D UWELIUS D AVID L. H ELFET J. L AWRENCE M ARSH VINCENT D. PELLEGRINI J R. E X -O FFICIO D EMPSEY S. S PRINGFIELD
FOR INSTRUCTIONAL

DEPUTY EDITOR OF THE JOURNAL OF BONE AND JOINT SURGERY COURSE LECTURES

J AMES D. HECKMAN
EDITOR-IN-CHIEF, THE JOURNAL OF BONE AND JOINT SURGERY

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Delayed Unions of the Tibia

BY LAURA S. PHIEFFER, MD, AND JAMES A. GOULET, MD
An Instructional Course Lecture, American Academy of Orthopaedic Surgeons

Nonunion of the tibial shaft is a common problem that can be disabling. Treatment may require multiple operative procedures, prolonged hospitalization, and years of disability before a union is obtained or an amputation is performed. Most tibial fractures heal after the initial treatment1-4, but nonunion is seen by all practitioners who treat tibial fractures. Early recognition of a potential nonunion followed by early intervention will reduce the ultimate time to union and lessen the surgeons and patients frustration. This Instructional Course Lecture provides an overview of tibial delayed unions and the treatment options available to manage this diverse group of clinical problems. We believe that most tibial nonunions can be treated by most orthopaedic surgeons without referral. A delayed union is an ununited fracture that continues to show progress toward healing or that has not been present for long enough to satisfy an arbitrary time standard for nonunion. A failure to see evidence of union on radiographs at various time-points

ranging from twenty to twenty-six weeks has been used by several authors as the criterion for defining delayed union5-9. The lack of precision in the definition diminishes its value in published reports. Delayed union might best be thought of as the point at which one should consider altering treatment to achieve union. Although the determination of a delayed union of a tibial fracture is frequently made at around twenty weeks, it may be possible to recognize delayed unions of certain fractures, especially Gustilo10 type-III open fractures, sooner. Nonunion of a fracture occurs when the normal biologic healing processes of bone cease, so that solid healing will not be achieved without further treatment. Nonunion has been defined by the United States Food and Drug Administration as a fracture that occurred a minimum of nine months previously and has not shown radiographic signs of progression toward healing for three consecutive months11. Nonunions are classified according to their radiographic appearance as hypertrophic,

Look for this and other related articles in Instructional Course Lectures, Volume 55, which will be published by the American Academy of Orthopaedic Surgeons in March 2006: Locking Plates for Proximal Tibial Fracture, by Clifford B. Jones, MD

oligotrophic, or atrophic as defined by LaVelle11. This classification helps one to understand the mechanical and biologic factors contributing to the cause of the nonunion and can be used to direct treatment. Hypertrophic nonunions have abundant callus. This indicates an adequate blood supply but a lack of sufficient mechanical stability for completion of fracture-healing. Oligotrophic nonunions have little callus but still have an adequate blood supply. These nonunions are typically due to inadequate reduction with little or no contact between the fracture surfaces. Atrophic nonunions have no or little callus and have resorption of the bone. They are thought to be due to a deficient biologic process. A malunion of a fracture is a fracture that has healed but in a nonanatomic position. Surgical intervention is indicated for a functional malposition, rather than a cosmetic deformity, that is noted early in the recovery period following the initial trauma. Close follow-up of patients with an acute tibial fracture and early intervention in cases of developing angular deformity will prevent most unacceptable malalignments associated with either early fracture-healing or delayed union. Prevalence Although reporting methods and definitions have varied from author to au-

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thor, the prevalence of nonunion and delayed union can be estimated from reports published in the literature. In twenty-two series that included a total of 5517 fractures, the combined prevalence of nonunion was 2.5% and the combined prevalence of delayed union was 4.4%1-4,8,12-28. The studies included several large series of predominantly closed tibial fractures caused by lowenergy trauma. Open fractures with gross contamination and extensive softtissue damage have a higher prevalence of nonunion and delayed union4,15,27,29. In series of open tibial fractures, Clancey et al. reported a 13% prevalence of delayed union15, Widenfalk et al. reported a 31% prevalence of delayed union4, and Edwards and Jaworski reported that 41% of grade-III fractures required bone-grafting before union was achieved30. Velazco et al. reported that the rate of nonunion for type-II and type-III open tibial fractures was 14%27. More aggressive soft-tissue management of open fractures and earlier reoperations for high-risk tibial fractures have led to a decrease in the prevalence of tibial nonunion31. Causes of Nonunion and Delayed Union Many factors have been associated with delayed union or nonunion. Most are related to the initial injury. Others are related to the patients health and behavior. Only some are within the surgeons control. Presenting factors that have been reported to contribute to nonunion or delayed union include fracture displacement, bone loss, associated fibular fracture, comminution, and infection. The prevalence of delayed union increases with the severity of an open fracture18-21,23,32-35. There is a direct correlation between the energy absorbed by the hard and soft tissues and complications related to woundhealing, including delayed union, nonunion, infection, and skin slough36,37. The nature of the injury therefore plays a large role in determining the likelihood of union. An anatomic factor that commonly determines the rate of union of tibial fractures is the degree of preserva-

tion of the tibial blood supply. The anatomy of the tibial blood supply has been described in detail38-41. The three vascular systems that supply the tibia are the nutrient vascular system, the periosteal vascular system, and the epiphyseal-metaphyseal vascular system. The nutrient and periosteal vascular systems are the most important with regard to the healing of a tibial shaft fracture. The nutrient artery system, which arises from the entrance of the posterior tibial artery into the posterior tibial cortex, distal to the soleal line, is divided at its origin into ascending and descending branches. The nutrient vessels provide the endosteal blood supply to the tibia, supplying as much as 90% of the inner cortex, as shown by Macnab38. Destruction of the endosteal blood supply is most extensive when the fracture occurs in the middle one-third of the tibia38, but the distribution of nonunions among the proximal, middle, and distal thirds of the shaft appears to be equal7. The periosteal blood supply receives segmental vascular contributions from the surrounding soft tissues, predominantly from the anterior tibial artery. While the posterior and lateral periosteum has an abundant vascular supply, the blood supply to the subcutaneous anteromedial periosteum is less abundant38. Rhinelander demonstrated that the periosteal blood supply can transiently expand to supply the entire bone if necessary40. Periosteal stripping and the resultant loss of vascular supply varies with the fracture type, and increased periosteal stripping, as seen with high-grade open fractures, contributes substantially to delayed union or nonunion42. Failure to properly manage tibial fractures has been shown to increase the prevalence of delayed union and nonunion. Distraction at the fracture site and failure to adequately immobilize the fracture are known to increase the time to union43. Brown and Urban1, Dehne et al.2, and Sarmiento44 advocated early weight-bearing with cast treatment as a means of obtaining intermittent compression at the fracture site, and they reported low rates of nonunion in their series. Adherence to the

principles of open fracture management, including aggressive multiple dbridements, administration of antibiotics, and rigid immobilization of fracture fragments, has also been shown to substantially decrease the prevalence of infection and nonunion42. Multiple patient factors have been shown to contribute to delayed union and nonunion of tibial fractures. One of them is malnutrition, which often goes unrecognized. Adequate protein is required for healing, and inadequate caloric intake has been shown to contribute to delayed union and nonunion45. Simple screening studies such as measurement of serum albumin levels and total lymphocyte counts can be performed routinely, even for patients who are not visibly malnourished. Albumin levels of <3.4 g/dL (<34 g/L) and lymphocyte counts of <1500 cells/mm3 (<1.5 109/L) are an indication of inadequate nutritional status46. Dietary protein supplementation to achieve and maintain appropriate daily requirements during fracture repair has been shown to improve fracture-healing in animal studies47,48. Cigarette smoking has been shown in numerous clinical and experimental studies to have an adverse effect on fracture-healing49-53. Although the exact mechanism remains unclear, nicotine consumption and cigarette smoking have been shown to have deleterious effects on local vascularity and cellular function at the fracture site. Patients should be made aware of the effects of smoking and be assisted with cessation efforts. Diagnosis Although establishing the diagnosis of tibial delayed union early in the course of bone and soft-tissue healing is critical in order to institute early intervention and avoid prolonged disability, it may be difficult to predict which fracture will not heal following initial treatment. The status of bone-healing of a tibial fracture is best evaluated by looking at four standard radiographic views of the tibia: two 45 oblique views centered over the fracture site and the standard anteroposterior and lateral views.

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Oblique views are especially helpful for identifying ununited fractures that are poorly visualized in the frontal or sagittal plane, and they should be made routinely for the evaluation of tibial fracture-healing. Tomography and computerized tomography are frequently useful in the evaluation of tibial union. Traditional tomography has long aided in this assessment by providing sagittal and coronal views with a limited, and therefore focused, field of view. Traditional tomography units, however, are now rarely available and, in their absence, computerized tomography has been used to evaluate tibial union. It has had mixed success, sometimes missing a critical ununited fracture plane54, although recent advances, particularly improvements in resolution and the capacity to limit metal artifact, have made computerized tomography a more useful tool for evaluating fracture-healing. As a consequence, computerized tomography with reconstructed views currently appears to be the most useful non-operator-dependent method for the evaluation of tibial delayed union available to most orthopaedic surgeons55. Ultrasound has also been used successfully in some centers to evaluate what is presumed to be callus production in the early healing period following tibial fractures that are at high risk for nonunion. Figure 1 is an ultrasound image made two months following reamed intramedullary nailing, with static locking, of a tibial shaft fracture in a patient with persistent pain over the fracture site. The image depicts a break in the cortical continuity (red arrow), which demonstrates that the fracture has not yet healed. The purpose of the ultrasound examination is to determine which patients are candidates for early surgical intervention, thereby speeding rehabilitation while limiting the need for secondary surgery. Moed et al. demonstrated that use of diagnostic ultrasound to evaluate early tibial fracturehealing had a positive predictive value of 97% with a narrow 95% confidence interval (0.9 to 1.0)56. The tibia seems particularly well suited for ultrasound

study because of its thin overlying soft tissue, and the presence of an intramedullary nail facilitates evaluation of the intervening tissue by serving as an easily identifiable marker. When performed by an experienced technician, ultrasound appears to be a very helpful prognostic aid in the evaluation of early tibial fracture-healing following intramedullary nailing. The greatest limitation of this technique may be the expertise and experience of the technician performing the study. Whether the tissue seen on ultrasound examination is bona fide fracture callus is an important consideration. With limited data to support this contention, the validity of an ultrasound determination of fracture-healing could be questioned despite the apparent clinical success of the technique. However, an animal study performed by Moed et al. indicated that there is a direct correlation between tissue that is presumed to be callus on ultrasound scans and actual fracture callus as determined with histologic examination57.

Treatment Considerations Optimal treatment of a tibial delayed union begins with a critical assessment of both biologic and mechanical factors. The location and configuration of the fracture, the classification of the open fracture, and any previous infection or surgical interventions are essential elements of the history. Physical examination determines the status of the soft tissue, the presence or absence of a draining sinus, and the neurovascular status of the foot. Initial and current fracture alignment should be assessed clinically and with radiographs. Bone loss should be determined, as an osseous defect limits the choices for management. Infection, soft-tissue defects, and malalignment substantially alter the options for treatment of tibial delayed unions. Both the biologic and mechanical problems must be addressed. A closed, uninfected delayed union with acceptable alignment requires intervention only to achieve union; posterolat-

Fig. 1

Ultrasound image made two months after treatment of a tibial shaft fracture with reamed intramedullary nailing and static locking. The patient had persistent pain over the fracture site, and the image depicts a break in the cortical continuity (red arrow), which indicates that the fracture has not yet healed.

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eral bone-grafting, closed reamed intramedullary nailing, and application of a compression plate with or without bone graft are all acceptable solutions to the problem. Acceptable approaches to infection associated with delayed union include thorough dbridement and soft-tissue coverage in addition to bone stabilization and bone-grafting. Stabilization
Intramedullary Nailing

Intramedullary nailing is the most common form of stabilization currently used in the management of unstable acute tibial fractures. Consequently, a majority of the tibiae with a delayed union that are encountered in current practice already have a tibial nail inserted, and considerations regarding further treatment must take this into account. Reamed intramedullary nailing has broad applications in the treatment of uninfected tibial delayed unions that have previously been managed without operative intervention. Treating an infected or previously infected tibial delayed union with reamed tibial nailing is associated with a high risk of infection58,59. Reports on the use of reamed intramedullary nailing in the setting of previous infection have documented a reinfection rate of 22% to 38% even when union is achieved60,61. When reamed nailing is performed in an uninfected tibia with a delayed union, the autogenous graft that is created by the reamer seems to stimulate the fracture site and the procedure provides greater stabilization than does nailing without reaming. Union rates of 95% to 100% have been reported in association with reamed nailing for tibial nonunions and delayed unions with no history of infection15,62,63. Use of locked intramedullary nails has had the same success64,65. The mean healing time following reamed nailing in this setting has ranged from five to nine months15,63. Unlike compression plate fixation, reamed intramedullary nailing offers the advantage of early full function, including weight-bearing and motion of the adjacent joints. Fragments created by the intraoperative reaming should be sent for standard cultures to rule out

the possibility of subclinical infection. Intramedullary nailing may be an option for an uninfected tibial fracture for which previous surgical treatment has failed. A previously placed nail (inserted without reaming) or plate that has maintained the alignment of the canal facilitates reamed nailing. Laboratory and clinical studies have validated this approach and have proved that, after application of a plate, vascularity can be sufficiently reestablished to allow later intramedullary reaming66-68. It is best to avoid soft-tissue damage when the plate is being removed. Removing a subcutaneous plate and screws through multiple small incisions may be preferable to operating through a larger incision, especially if skin quality is poor. Reamed intramedullary nailing has also been proposed as a method of stabilizing open fractures after application of an external fixator69, with its advocates pointing out the advantages of intramedullary nail fixation compared with external fixation. However, the prevalence of infection associated with this procedure was reported to be as high as 66% in one series, even with a minimum delay of three months between fixator removal and reamed nailing70. The risk of infection associated with reamed intramedullary nailing following prolonged external fixation seems to be too high to warrant its use. Most commonly in current practice, delayed unions and nonunions of tibial shafts are associated with a previously inserted intramedullary nail. Just as continued weight-bearing in an appropriate brace or cast will often lead to union of a tibial fracture that is being treated nonoperatively, the same treatment may be appropriate for fractures that had been initially fixed with an intramedullary nail. However, if union does not occur relatively early and it is not certain that it will occur if the patient is managed with observation alone, the implants may fail and become more difficult to extract. Moreover, if failure of fracture-healing is accompanied by disability, pain, or malalignment, continued watchful waiting is no longer warranted.

If the fracture is stable, removal of locking screws from one end of an intramedullary nail (known as dynamization) might be considered. Dynamization can be performed as an outpatient procedure, with local anesthesia, which lends it popularity. The procedure is viewed favorably by many orthopaedic surgeons, but the value of dynamization in the treatment of delayed union of the tibia has been poorly documented. Success rates have been thought, principally on the basis of anecdotal reports, to approach 50% for well-chosen patients. In contrast, Court-Brown et al. reported that dynamization appears to have little effect on the speed of fracture union71. Wu et al. demonstrated a 54% rate of union of tibial and femoral fractures after dynamization72. Although there is little objective evidence to support routine dynamization of tibial nails, the risks and costs of the procedure seem relatively minor compared with those of more invasive operative alternatives. As a result, dynamization remains a reasonable treatment option for patients with a tibial fracture that is well aligned and not associated with substantial bone loss. Exchange nailing is performed by removing an existing intramedullary nail from the tibia, reaming the medullary canal, and inserting a larger-diameter nail. If reamed nailing has already been performed in the medullary canal, the canal should be reamed to accommodate a nail that is at least 1 mm larger than the existing nail. If the medullary canal is large or if the existing intramedullary nail is particularly small, then an even larger nail may be needed, and reaming should proceed until bone is clearly seen on the reamers. Exchange nailing has been reasonably well evaluated, with consistent findings in the published series. Templeman et al. treated twenty-eight delayed unions or nonunions with exchange nailing, and they achieved a 93% success rate following the first procedure and a 100% rate of union following a second exchange nailing in those patients in whom the initial ex-

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change nailing had failed73. They reported three malunions. Court-Brown et al. evaluated the results of exchange nailing for thirty-three tibial nonunions and found that twenty-nine (88%) united after one exchange nailing procedure and the remaining four united after a single repeat exchange nailing procedure. Both Templeman et al. and Court-Brown et al.74 reported an unexpectedly high rate of infection. Templeman et al. reported three infections (11%), and Court-Brown et al. found a 12% prevalence of wound sepsis, with one deep infection. Other series have demonstrated similar findings75-76. On the basis of the findings in these studies, we currently recommend that the tibial nail be removed and the intramedullary reaming be performed before the initiation of perioperative antibiotics. We routinely send material produced by the intramedullary reaming to the microbiology laboratory for culture and sensitivity testing, and we continue to administer antibiotics for a prolonged period (usually six weeks) after surgery if bacteria are found in the medullary space. Figures 2-A, 2-B, and 2-C are a series of radiographs of a fifty-twoyear-old man in whom a closed comminuted fracture of the tibial shaft with an associated compartment syndrome was initially treated with four compartment fasciotomies and reamed intramedullary nailing. Five months postoperatively, the patient had persistent pain over the fracture site and radiographic findings consistent with a delayed union. He showed no clinical signs of infection, and the preoperative laboratory values were unremarkable. He was treated with exchange reamed intramedullary nailing. Methicillinresistant Staphylococcus aureus grew on culture of material produce by the medullary reaming. The patient was treated with intravenous antibiotics for six weeks, and clinical and radiographic healing was seen two months after the procedure. Exchange nailing poses fewer technical challenges than primary nailing, but several procedural issues bear mention. First, unless a fibular malunion prevents the achievement of

acceptable tibial alignment, there seems to be little need to perform a fibular osteotomy in conjunction with the reamed exchange nailing. Second, interlocking screws rarely seem to be necessary, and their use may be counterproductive in the treatment of middiaphyseal fractures that have been present for more than three months and have been stabilized by a fibrous union. However, because Templeman et al.73 reported three relatively minor distal tibial malunions following reamed exchange tibial nailing done without distal interlocking screws, we have a low threshold for insertion of interlocking screws for fractures near the metaphyseal-diaphyseal junction.

External Fixation

External fixation is the preferred method of stabilization for patients with a delayed union of a tibial fracture and a previous infection. External fixation may also be considered for definitive fixation of grade-II and III open fractures that had not been managed early with intramedullary fixation and for patients with compromised soft tissue77. Experimental and clinical studies have shown a single-frame anterior fixator with use of 4.5-mm or 5.0-mm half-pins to be an adequate device78-80. This form of external fixation provides free wound access, allows stabilization of bone fragments at a distance from the lesion, permits motion of adjacent

Fig. 2-A

Figs. 2-A, 2-B, and 2-C A closed comminuted fracture of the tibial shaft with associated compartment syndrome was treated with fasciotomies and reamed intramedullary nailing in a fifty-two-year-old man. Fig. 2-A Initial postoperative anteroposterior and lateral radiographs.

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Fig. 2-B

Fig. 2-C

Fig. 2-B Anteroposterior and lateral radiographs made five months postoperatively demonstrate a delayed union of the tibia. Fig. 2-C Anteroposterior and lateral radiographs made two months after exchange reamed intramedullary nailing demonstrate fracture union.

joints, and encourages patient mobility. Pin-track drainage, reported to occur in association with 5% to 10% of all pins and to be responsible for removal or alteration of one of thirty frames, may be minimized with fastidious local care81,82. There has been some controversy concerning the role of internal fixation following previous external fixation. Because of the risk of infection, we do not recommend insertion of plates or performance of reamed tibial nailing following prolonged external fixation (for longer than ten to fourteen days), regardless of the condition of the soft tissue. After short periods (shorter than ten to fourteen days) of external fixation with dry pin sites, reamed nailing may be performed, but it must be clearly understood that the risk of infection is increased even in the absence of previous pin track infection. We avoid

performing reamed intramedullary nailing whenever an external fixator has been in place for more than two weeks.
Compression Plates

Use of compression plates for the treatment of closed tibial nonunions has been advocated by Muller and Thomas83,84, Rosen85, and Weber and Brunner86. Success rates with compression plates alone have been reported to be high in the treatment of hypertrophic nonunions, but supplementary bone-grafting is required for atrophic nonunions. Weber and Brunner reported union of 126 of 127 uninfected tibial nonunions treated with compression plates. Like most other forms of internal and external fixation discussed in this lecture, compression plates allow motion of adjacent joints and prevent fracture disease. Although proven

successful for the treatment of uninfected tibial nonunions, compression plates are load-bearing devices and do not tolerate weight-bearing until healing has occurred. The risk of infection associated with compression plates is slightly higher than that following simple cancellous bone-grafting for the treatment of uninfected tibial nonunions and is unacceptably high for the treatment of previously infected tibial nonunions87. We therefore prefer reamed intramedullary nailing or posterolateral bone-grafting to compression plates for the treatment of tibial nonunions that are in acceptable alignment, but we recognize that use of plates with or without grafting is an acceptable alternative to bone-grafting. The greatest application of compression plates is in the treatment of uninfected angulated delayed unions of

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the tibia. The plate may be used to realign the fracture if it is positioned on the tension side of the nonunion, placed under additional tension with an independently placed distractor, and then used as a template for fracture realignment.
Ilizarov Technique

The Ilizarov technique has been used for the treatment of angulated malunions and failures of union associated with malalignment. There is considerable enthusiasm for this approach, although the need for frequent postoperative visits as well as a relatively high rate of pin track problems may temper enthusiasm for the technique for less complicated cases. Because of its versatility, however, this method may be the salvage procedure of choice for difficult tibial delayed unions that would oth erwise not be amenable to functional limb salvage. The technique may be especially useful when shortening or compromised soft tissues complicate the more readily approachable simple angulated delayed union. Considerable preoperative planning is recommended when the Ilizarov technique is used. Patients requiring the Ilizarov technique should be treated by a surgeon who is experienced with the method. Bone-Grafting Bone-grafting techniques deal with the biologic issues of delayed union after mechanical stability has been addressed. Bone formation is a process consisting of osteogenesis, osteoinduction, and osteoconduction. Graft osteogenesis refers to the synthesis of new bone at the recipient site by the cellular elements within a donor graft that survive transplantation. Graft osteoinduction is the process by which host mesenchymal stem cells from the surrounding tissue differentiate into bone-forming osteoblasts as a result of the presence of proteins or chemotactic factors within the graft that attract vascular ingrowth and healing. Graft osteoconduction is the process by which the graft provides a scaffold on which new bone growth can occur. Autogenous bone graft, typically from the iliac

crest, remains the gold standard with which all other grafts and graft substitutes must be compared. It incorporates all of the above-mentioned properties with no associated risk of viral transmission, but there are problems with donor-site morbidity88. Many methods of bone-grafting for tibial defects have been described. These include multiple forms of sliding onlay grafts89-92, inlay grafts93, nonvascularized fibular transplants94,95, free vascularized fibular grafts96, and other techniques for creating a tibiofibular synostosis97,98. Cortical bone grafts have demonstrated weakness due to the development of internal porosity. They incorporate within six weeks after grafting but remain weak for at least six months99. In comparative series, cortical grafts have required a longer time to achieve union and have been associated with more complications than cancellous grafts91,100. Proposed alternatives to cancellous bone-grafting include the use of percutaneous marrow injections101, human bone morphogenetic protein102, platelet concentrates103, and synthetic bone-graft substitutes104. Although promising, the precise role of each of these alternatives in a general orthopaedic practice has yet to be defined. Anterolateral grafting of the tibia has been used in the past, but the proximity to traumatic anterior wounds increases the rate of wound complications; also, only limited amounts of bone graft can be inserted because of the risk of the development of a compartment syndrome. Posterolateral grafting is the preferred technique in the middle and distal thirds of the tibia105,106, whereas posteromedial bonegrafting is preferable in the proximal third of the tibia because of the proximity to the neurovascular structures with the posterolateral approach107. Several large series in which cancellous bone-grafting had been used for tibial nonunions have demonstrated union rates of 87% to 100%5,19,108-114. Similar rates of success might be anticipated for the treatment of delayed unions, but the results for delayed unions have not been as extensively documented.

Complications of posterolateral bonegrafting, which are uncommon, include stiffness, deformity, and loss of ankle motion. These complications have been ascribed to the initial injury, but they may be aggravated by the additional, prolonged immobilization associated with bone-grafting. Paresthesias on the sole of the foot and delayed vascular impairment have also been reported but seem to be rare5,111. Formation of a synostosis has been associated with, but is not clearly the cause of, ankle pain9. Because these complications are uncommon and the union rate after posterolateral bonegrafting is high, the procedure is used in conjunction with other procedures to treat angulated or infected delayed unions.
Posterolateral Bone-Grafting

The posterolateral approach to the tibia can be performed with the patient in the lateral or prone position. Either position allows a two-team approach; one surgeon can begin harvesting the bone graft from the iliac crest while the other begins the approach to the tibia. This two-team approach decreases the operating time and provides maximum exposure of the posterior iliac crest and posterior part of the tibia. A generous skin incision is made 10 cm proximal to and 10 cm distal to the level of the nonunion. The dissection proceeds longitudinally, medial to the palpable border of the fibula, between the gastrocnemius-soleus and flexor hallucis longus and the peroneal muscles. After the fascia of the soleus has been entered, a fixed palpable fascia on the anteromedial border of the fibula provides a landmark for the next level of dissection. Lateral stripping of the peroneal muscles from the fibula should be avoided as this unnecessarily compromises the regional blood supply. The soleus and flexor hallucis longus muscles are reflected with use of a periosteal elevator. The posterior compartment is elevated free from the fibula with care taken to avoid inadvertent entry into the posterior tibial compartment, which could injure the posterior tibial neurovascular bundle. Once the

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appropriate plane has been entered, the dissection extends to the nonunion site, which frequently is encased in scar tissue. At this point, the posterior tibial compartment is lifted off of the interosseous membrane with a periosteal elevator, exposing the nonunion site. After the nonunion has been identified, the tibia is assessed proximally and distally to ensure that there is viable bleeding cortical bone. Tissue from the nonunion site should be sent for culture before systemic antibiotics are initiated. Once all nonviable tissue has been dbrided, the proximal and distal cortical bone can be shingled with an osteotome to aid in revascularization, and the harvested bone graft is packed into the nonunion site. After the bone graft is in place, a suction drain is placed, the soleus fascia is loosely closed to the peroneal fascia to hold the bone graft in position, and the skin is closed. Delayed Union Associated with Bone Defects Large segmental defects of the tibia are usually the result of severe open tibial fractures, the treatment of which is often associated with severe contamination, neurologic and vascular injury, and polytrauma. One approach to these large segmental defects includes initial surgical dbridement, stable external fixation, and soft-tissue coverage with late massive posterolateral cancellous bone-grafting. With this approach, a synostosis can be created proximally and distally with internal fixation of the fibula to provide a strut for bonegrafting procedures. It may take two years and multiple bone-grafting procedures to achieve a stable functional union. Intramedullary nailing and tibial plate fixation are associated with a higher risk of infection and are therefore not used in this setting. Although treatment is prolonged and multiple hospitalizations and bone-grafting procedures are required, massive posterolateral bone-grafting continues to be a viable alternative for the treatment of some patients with severe segmental bone loss. It is the only technique with an acceptable rate of success that can be

used without specialized instrumentation and training.

Ilizarov Technique

Recently, segmental defects have been treated most effectively with the Ilizarov technique of corticotomy and bone transport. Available reports of the results of this technique have been enthusiastic and promising115-117. There have been several reports on relatively small series with sufficient follow-up for a critical evaluation of the outcomes and complication rate associated with this technique115,118-121. Because the Ilizarov technique is substantially different from other available methods for treating segmental bone loss, a steep learning curve must be expected. It is recommended that a surgeon receive formal training in the technique before proceeding with any Ilizarov procedure. A relatively high rate of pin-track problems and other, potentially more serious complications should be anticipated, and a good ancillary medical support network is highly recommended. Adjuncts to Enhance Bone-Healing of Tibial Delayed Unions
Electrical Stimulation

Electrical stimulation has been proposed as a nonoperative alternative for established nonunions122,123. There is considerable laboratory and clinical evidence suggesting that electrical stimulation enhances fracture-healing. Three forms of electrical stimulation have been used clinically. The method in which the stimulation device is totally implanted, championed by Paterson123, is the only form that permits weightbearing. Two surgical procedures, one for implantation and a second for removal, are required, and the union rate has been reported to be 75% to 89% of all nonunions, including those of the tibia. Complications have included delayed wound-healing, infection, broken wires, soft-tissue reaction around the generator, and protrusion of the cathode wire through the skin122,123. The percutaneous, or semiinvasive, method developed by Brighton et al.122,124,125 involves percutaneous

insertion of the cathode directly into the nonunion site, which requires drilling across one bone cortex or fragment. Weight-bearing is prohibited during the first twelve weeks of treatment123. Complications in Brightons series included pin-track infection (13.8%), broken wires (13%), recurrent osteomyelitis (4.2%), cathode dislodgement (3.6%), and failure of the battery pack124. The corrected union rate (excluding patients for whom the electricity was suboptimal or in whom the nonunion gap was greater than half the bone diameter) was reported to be 80% for tibial nonunions124. Bassett et al. developed a noninvasive system for application of pulsing electromagnetic fields126-128. The method requires non-weight-bearing and is contraindicated for patients with a nonunion gap of >1 cm126. The tibial union rate was reported to be 82% to 87% after the use of this technique. No complications other than those associated with prolonged non-weight-bearing and immobility were recorded. To our knowledge, only one prospective double-blind study of electrical stimulation has been published129,130. Although there is some evidence that delayed unions show earlier radiographic evidence of union when an electrical stimulator is applied, it has been difficult to demonstrate the clinical benefit of a functioning electrical stimulator over a nonfunctioning stimulator129,130. The invasive approach, the only one that allows weight-bearing, requires a minimum of two operative interventions and its success rate is lower than that associated with use of a single posterolateral bone graft. Pending proof of the clinical effectiveness of electrical stimulation in a prospective double-blind study, we cannot recommend electrical stimulation for treatment of tibial delayed unions.
Ultrasound

Ultrasound has been proven to enhance the healing of fresh closed tibial fractures131,132, and it may be effective for the treatment of some tibial delayed unions. Because ultrasound has not been proven to be effective for fractures

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stabilized with an intramedullary nail, however, it may have a diminished role in the treatment of tibial delayed unions.
Biologic Adjuncts

In comparison with other currently available adjuncts, bone morphogenetic protein (BMP) may have a more substantial role to play in the treatment of tibial nonunions and, perhaps, of delayed unions as well. Recombinant human bone morphogenetic protein-7 (rhBMP-7) was shown to promote union in a prospective, randomized, controlled study of 122 patients with a total of 124 tibial nonunions133. All of the nonunions were at least nine months old and had shown no progress toward healing for three months. Each patient had been treated with an intramedullary nail as well as with rhBMP-7 in a type-1 collagen carrier or with autogenous bone graft. At nine months postoperatively, 81% of the patients treated with rhBMP-7 and 85% of those treated with autogenous bone graft were judged to have bone-healing according to clinical criteria and 75% and 85%, respectively, were judged to have radiographic evidence of healing. These results suggest that BMP is as effective as autogenous bone graft in the treatment of tibial nonunion and that it could be similarly effective in the treat-

ment of tibial delayed union. Another recent, Level-I study demonstrated evidence that BMP could be effective earlier in the treatment of tibial fractures that have a relatively high risk of nonunion. A series of 450 patients with an open tibial shaft fracture were treated with recombinant rhBMP-2 (0.75 mg/kg or 1.50 mg/kg on an absorbable collagen sponge) as well as a locked intramedullary nail at the time of wound closure and or were treated with a locked intramedullary nail alone (control group)134. At twelve months, the group treated with the higher rhBMP dose (1.50 mg/kg) had a higher rate of fracture-healing, a 44% reduction in the risk of secondary interventions, fewer hardware failures, fewer infections, and faster woundhealing compared with the control group. BMP has clearly shown promise with regard to early enhancement of healing of problem tibial fractures. Better identification of patients who are likely to benefit from the application of BMP in the course of fracture-healing seems likely. Overview Delayed union of the tibia represents a diverse group of clinical problems that can at times be challenging even in the most experienced hands. Early recognition and treatment can save patients from prolonged periods of pain and References

disability. Although multiple treatment options are available, most delayed unions can be managed by nonspecialist orthopaedic surgeons using simple methods. Treatment must take into account the biologic and mechanical factors contributing to the delay in fracture union.
Laura S. Phieffer, MD Department of Orthopaedic Surgery, The Ohio State University, N1037 Doan Hall, 410 West 10th Avenue, Columbus, OH 43210 James A. Goulet, MD Department of Orthopaedic Surgery, University of Michigan Medical School, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0328 The authors did not receive grants or outside funding in support of their research for or preparation of this manuscript. They 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 authors are affiliated or associated. Printed with permission of the American Academy of Orthopaedic Surgeons. This article, as well as other lectures presented at the Academys Annual Meeting, will be available in March 2006 in Instructional Course Lectures, Volume 55. The complete volume can be ordered online at www.aaos.org, or by calling 800-626-6726 (8 A.M.-5 P.M., Central time).

1. Brown PW, Urban JG. Early weight-bearing treatment of open fractures of the tibia. An end-result study of sixty-three cases. J Bone Joint Surg Am. 1969;51:59-75. 2. Dehne E, Metz CW, Deffer PA, Hall RM. Nonoperative treatment of the fractured tibia by immediate weight bearing. J Trauma. 1961;1:514-35. 3. Sarmiento A, Sobol PA, Sew Hoy AL, Ross SD, Racette WL, Tarr RR. Prefabricated functional braces for the treatment of fractures of the tibial diaphysis. J Bone Joint Surg Am. 1984;66:1328-39. 4. Widenfalk B, Ponten B, Karlstrom G. Open fractures of the shaft of the tibia: analysis of wound and fracture treatment. Injury. 1979;11:136-43. 5. Jones KG. Treatment of infected nonunion of the tibia through the posterolateral approach. Clin Orthop Relat Res. 1965;43:103-9. 6. Mller ME, Allgwer M, Schneider R, Willenegger H. Manual of internal fixation: techniques recommended by the AO-Group. 2nd ed. New York: Springer; 1979.

7. Nicoll EA. Fractures of the tibial shaft. A survey of 705 cases. J Bone Joint Surg Br. 1964;46:373-87. 8. Rosenthal RE, MacPhail JA, Ortiz JE. Non-union in open tibial fractures. J Bone Joint Surg Am. 1977;59:244-8. 9. Skelley JW, Hardy AE. Results of bone grafts in the treatment of tibial fractures. Clin Orthop Relat Res. 1981;158:108-10. 10. Gustilo RB, Mendoza RM, Williams DN. Problems in the management of type III (severe) open fractures: a new classification of type III open fracturs. J Trauma. 1984;24:742-6. 11. LaVelle DG. Delayed union and nonunion of fractures. In: Canale TS editor. Campbells operative orthopaedics. 9th ed. St. Louis: Mosby;1998. p 2579-629. 12. Anderson LD, Hutchins WC, Wright PE, Disney JM. Fractures of the tibia and fibula treated by casts and transfixing pins. Clin Orthop Relat Res. 1974;105:179-91. 13. DAubigne RM, Maurer P Zucman J, Masse Y. ,

Blind intramedullary nailing for tibial fractures. Clin Orthop Relat Res. 1974;105:267-75. 14. Christensen NO. Kuntscher intramedullary reaming and nail fixation for non-union of fracture of the femur and the tibia. J Bone Joint Surg Br. 1973;55:312-8. 15. Clancey GJ, Winquist RA, Hansen ST Jr. Nonunion of the tibia treated with Kuntscher intramedullary nailing. Clin Orthop Relat Res. 1982; 167:191-6. 16. Donald G, Seligson D. Treatment of tibial shaft fractures by percutaneous Kuntscher nailing. Technical difficulties and a review of 50 consecutive cases. Clin Orthop Relat Res. 1983;178:64-73. 17. Gershuni DH, Halma G. The A-O external skeletal fixator in the treatment of severe tibia fractures. J Trauma. 1983;23:986-90. 18. Karlstrom G, Olerud S. Fractures of the tibial shaft: a critical evaluation of treatment alternatives. Clin Orthop Relat Res. 1974;105:82-115. 19. Lamb RH. Posterolateral bone graft for nonunion

215
THE JOUR NAL OF BONE & JOINT SURGER Y JBJS.ORG VO L U M E 88-A N U M B E R 1 J A N U A R Y 2006 D E L AYE D U N I O N S OF THE TI BI A

of the tibia. Clin Orthop Relat Res. 1969;64: 114-20. 20. Mayer L, Werbie T, Schwab JP Johnson RP The , . use of Ender nails in fractures of the tibial shaft. J Bone Joint Surg Am. 1985;67:446-55. 21. Nicoll EA. Closed and open management of tibial fractures. Clin Orthop Relat Res. 1974;105: 144-53. 22. Pankovich AM, Tarabishy IE, Yelda S. Flexible intramedullary nailing of tibial-shaft fractures. Clin Orthop Relat Res. 1981;160:185-95. 23. Sakellarides HT, Freeman PA, Grant BD. Delayed union and non-union of tibial-shaft fractures. A review of 100 cases. J Bone Joint Surg Am. 1964;46:557-69. 24. Sedlin ED, Zitner DT. The Lottes nail in the closed treatment of tibia fractures. Clin Orthop Relat Res. 1985;192:185-92. 25. Taylor GI, Miller GD, Ham FJ. The free vascularized bone graft. A clinical extension of microvascular techniques. Plast Reconstr Surg. 1975;55:533-44. 26. Velazco A, Fleming LL. Open fractures of the tibia treated by the Hoffmann external fixator. Clin Orthop Relat Res. 1983;180:125-32. 27. Velazco A, Whitesides TE Jr, Fleming LL. Open fractures of the tibia treated with the Lottes nail. J Bone Joint Surg Am. 1983;65:879-85. 28. Witschi TH, Omer GE Jr. The treatment of open tibial shaft fractures from Vietnam War. J Trauma. 1970;10:105-11. 29. Clancey GJ, Hansen ST Jr. Open fractures of the tibia: a review of one hundred and two cases. J Bone Joint Surg Am. 1978;60:118-22. 30. Edwards CC, Jaworski MF. Hoffman external fixation in open tibial fractures with tissue loss. Orthop Trans. 1979;3:261-2. 31. Cierny G 3rd, Byrd HS, Jones RE. Primary versus delayed soft tissue coverage for severe open tibial fractures. A comparison of results. Clin Orthop Relat Res. 1983;178:54-63. 32. Boyd HB, Lipinski SW. Causes and treatment of nonunion of the shafts of the long bones, with a review of 741 patients. Instr Course Lect. 1960;17:165-83. 33. Ellis H. A study of some factors affecting prognosis following tibial shaft fractures [Thesis]. Oxford: Bodleian Library; 1956. 34. Urist MR, Mazet R Jr, McLean FC. The pathogenesis and treatment of delayed union and non-union; a survey of eighty-five ununited fractures of the shaft of the tibia and one hundred control cases with similar injuries. J Bone Joint Surg Am. 1954;36:931-80. 35. Watson-Jones R, Coltart WD. Slow union of fractures. With a study of 804 fractures of the shafts of the tibia and femur. Br J Surg. 1942;30:260-75. 36. Cierny G 3rd, Byrd HS, Jones RE. Primary versus delayed soft tissue coverage for severe open tibial fractures. A comparison of results. Clin Orthop Relat Res. 1983;178:54-63. 37. Hoaglund FT, States JD. Factors influencing the rate of healing in tibial shaft fractures. Surg Gynecol Obstet. 1967;124:71-6. 38. Macnab I. Blood supply of the tibia [abstract]. In: Proceedings and Reports of Councils and Associations. J Bone Joint Surg Br. 1957;39:799. 39. Nelson GE Jr, Kelly PJ, Peterson LF, Janes JM. Blood supply of the human tibia. J Bone Joint Surg Am. 1960;42:625-36.

40. Rhinelander FW. Tibial blood supply in relation to fracture healing. Clin Orthop Relat Res. 1974;105:34-81. 41. Trueta J. Blood supply and the rate of healing of tibial fractures. Clin Orthop Relat Res. 1974;105:11-26. 42. Sanders R, Swiontkowski M, Nunley J, Spiegel P The management of fractures with soft-tissue . disruptions. J Bone Joint Surg Am. 1993;75: 778-89. 43. Connolly JF. Common avoidable problems in nonunions. Clin Orthop Relat Res. 1985;194: 226-35. 44. Sarmiento A. Functional bracing of tibial fractures. Clin Orthop Relat Res. 1974;105:202-19. 45. Smith TK. Prevention of complications in orthopedic surgery secondary to nutritional depletion. Clin Orthop Relat Res. 1987;222:91-7. 46. Jensen JE, Jensen TG, Smith TK, Johnston DA, Dudrick SJ. Nutrition in orthopaedic surgery. J Bone Joint Surg Am. 1982;64:1263-72. 47. Day SM, DeHeer DH. Reversal of the detrimental effects of chronic protein malnutrition on long bone fracture healing. J Orthop Trauma. 2001;15:47-53. 48. Einhorn TA, Bonnarens F, Burstein AH. The contributions of dietary protein and mineral to the healing of experimental fractures. A biomechanical study. J Bone Joint Surg Am. 1986;68:1389-95. 49. Fang MA, Frost PJ, Iida-Klein A, Hahn TJ. Effects of nicotine on cellular function in UMR 106-01 osteoblast-like cells. Bone. 1991;12:283-6. 50. Daftari TK, Whitesides TE Jr, Heller JG, Goodrich AC, McCarey BE, Hutton WC. Nicotine on the revascularization of bone graft. An experimental study in rabbits. Spine. 1994;19:904-11. 51. Schmitz MA, Finnegan M, Natarajan R, Champine J. Effect of smoking on tibial shaft fracture healing. Clin Orthop Relat Res. 1999;365:184-200. 52. Harvey EJ, Agel J, Selznick HS, Chapman JR, Henley MB. Deleterious effect of smoking on healing of open tibia-shaft fractures. Am J Orthop. 2002; 31:518-21. 53. Castillo RC, Bosse MJ, MacKenzie EJ, Patterson BM; LEAP Study Group. Impact of smoking on fracture healing and risk of complications in limbthreatening open tibia fractures. J Orthop Trauma. 2005;19:151-7. 54. Bain GI. Clinical utilisation of computed tomography of the scaphoid. Hand Surg. 1999;4:3-9. 55. Kuhlman JE, Fishman EK, Magid D, Scott WW Jr, Brooker AF, Siegelman SS. Fracture nonunion: CT assessment with multiplanar reconstruction. Radiology. 1988;167:483-8. 56. Moed BR, Subramanian S, van Holsbeeck M, Watson JT, Cramer KE, Karges DE, Craig JG, Bouffard JA. Ultrasound for the early diagnosis of tibial fracture healing after static interlocked nailing without reaming: clinical results. J Orthop Trauma. 1998;12:206-13. 57. Moed BR, Kim EC, van Holsbeeck M, Schaffler MB, Subramanian S, Bouffard JA, Craig JG. Ultrasound for the early diagnosis of tibial fracture healing after static interlocked nailing without reaming: histologic correlation using a canine model. J Orthop Trauma. 1998;12:200-5. 58. Laurent LE, Langenskiold A. Osteosynthesis with a thick medullary nail in non-union of long bones. Acta Orthop Scand. 1967;38:341-58. 59. Lidgren L, Onnerfalt R. Infected non-union of the

tibial shaft treated by Kuntscher intramedullary reaming and nail fixation. A report of four cases. Acta Orthop Scand. 1982;53:669-74. 60. Miller ME, Ada JR, Webb LX. Treatment of infected nonunion and delayed union of tibia fractures with locking intramedullary nails. Clin Orthop Relat Res. 1989;245:233-8. 61. Sledge SL, Johnson KD, Henley MB, Watson JT. Intramedullary nailing with reaming to treat nonunion of the tibia. J Bone Joint Surg Am. 1989;71: 1004-19. 62. Bohler J. Treatment of nonunion of the tibia with closed and semiclosed intramedullary nailing. Clin Orthop Relat Res. 1965;43:93-101. 63. Bone LB, Johnson KD. Treatment of tibial fractures by reaming and intramedullary nailing. J Bone Joint Surg Am. 1986;68:877-87. 64. Kempf I, Grosse A, Abalo C. Locked intramedullary nailing. Its application to femoral and tibial axial, rotational, lengthening, and shortening osteotomies. Clin Orthop Relat Res. 1986; 212:165-73. 65. Kempf I, Grosse A, Rigaut P The treatment of . noninfected pseudarthrosis of the femur and tibia with locked intramedullary nailing. Clin Orthop Relat Res. 1986;212:142-54. 66. Galpin RD, Veith RG, Hansen ST. Treatment of failures after plating of tibial fractures. J Bone Joint Surg Am. 1986;68:1231-6. 67. Karlstrom G, Olerud S. Secondary internal fixation. Experimental studies on revascularization and healing in osteotomized rabbit tibias. Acta Orthop Scand Suppl. 1979;175:3-39. 68. Olerud S, Karlstrom G. Secondary intramedullary nailing of tibial fractures. J Bone Joint Surg Am. 1972;54:1419-28. 69. Puno RM, Teynor JT, Nagano J, Gustilo RB. Critical analysis of results of treatment of 201 tibial shaft fractures. Clin Orthop Relat Res. 1986;212: 113-21. 70. Tornqvist H. Tibia nonunions treated by interlocked nailing: increased risk of infection after previous external fixation. J Orthop Trauma. 1990;4: 109-14. 71. Court-Brown CM, Christie J, McQueen MM. Closed intramedullary tibial nailing. Its use in closed and type I open fractures. J Bone Joint Surg Br. 1990;72:605-11. 72. Wu CC, Shih CH, Chen WJ, Tai CL. High success rate with exchange nailing to treat a tibial shaft aseptic nonunion. J Orthop Trauma. 1999;13:33-8. 73. Templeman D, Thomas M, Varecka T, Kyle R. Exchange reamed intramedullary nailing for delayed union and nonunion of the tibia. Clin Orthop Relat Res. 1995;315:169-75. 74. Court-Brown CM, Keating JF, Christie J, McQueen MM. Exchange intramedullary nailing. Its use in aseptic tibial nonunion. J Bone Joint Surg Br. 1995;77:407-11. 75. Court-Brown CM, McQueen MM. High success rate with exchange nailing to treat tibial shaft aseptic nonunion. J Orthop Trauma. 1999;13:274. 76. Levin PE. Exchange reamed intramedullary nailing for delayed union and nonunion of the tibia. Clin Orthop Relat Res. 1996;332:304-5. 77. Green SA, Garland DE, Moore TJ, Barad SJ. External fixation for the uninfected angulated nonunion of the tibia. Clin Orthop Relat Res. 1984; 190:204-11. 78. Behrens F. Basic concepts and applications in

216
THE JOUR NAL OF BONE & JOINT SURGER Y JBJS.ORG VO L U M E 88-A N U M B E R 1 J A N U A R Y 2006 D E L AYE D U N I O N S OF THE TI BI A

open tibial fractures. Instr Course Lect. 1984;33:124-30. 79. Behrens F, Johnson WD, Koch TW, Kovacevic N. Bending stiffness of unilateral and bilateral fixator frames. Clin Orthop Relat Res. 1983;178: 103-10. 80. Wu JJ, Shyr HS, Chao EY, Kelly PJ. Comparison of osteotomy healing under external fixation devices with different stiffness characteristics. J Bone Joint Surg Am. 1984;66:1258-64. 81. Behrens F, Jones RE 3rd, Fischer DA, Mears DC. External skeletal fixation. Instr Course Lect. 1981;30:112-82. 82. Green SA. Complications of external skeletal fixation. Clin Orthop Relat Res. 1983;180:109-16. 83. Muller ME. Treatment of nonunions by compression. Clin Orthop Relat Res. 1965;43:83-92. 84. Muller ME, Thomas RJ. Treatment of non-union in fractures of long bones. Clin Orthop Relat Res. 1979;138:141-53. 85. Rosen H. Compression treatment of long bone pseudarthroses. Clin Orthop Relat Res. 1979;138:154-66. 86. Weber BG, Brunner C. The treatment of nonunions without electrical stimulation. Clin Orthop Relat Res. 1981;161:24-32. 87. Smith JE. Results of early and delayed internal fixation for tibial shaft fractures. A review of 470 fractures. J Bone Joint Surg Br. 1974;56:469-77. 88. Goulet JA, Senunas LE, DeSilva GL, Greenfield ML. Autogenous iliac crest bone graft. Complications and functional assessment. Clin Orthop Relat Res. 1997;339:76-81. 89. Boyd HB. The treatment of difficult and unusual non-unions. With special reference to the bridging of defects. J Bone Joint Surg. 1943;25:535-52. 90. Flanagan JJ, Burem HS. Reconstruction of defects of the tibia and femur with apposing massive grafts from the affected bone. J Bone Joint Surg. 1947;29:587-97. 91. Holden CE. Bone-grafts in the treatment of delayed union of tibial shaft fractures. Injury. 1972;4:175-9. 92. Milch H. Tibiofibular synostosis for non-union of the tibia. Surgery. 1950;27:770-9. 93. Wagner JH. Anterolateral approach in bone grafting for ununited fractures of tibia. Am J Surg. 1947;73:282-99. 94. Carnesale PL, Guerrieri AG. Fibular transplant for loss of substance of tibia: report of a case. J Bone Joint Surg Am. 1955;37:204-6. 95. Davis AG. Fibular substitution for tibial defects. J Bone Joint Surg. 1944;26:229-37. 96. Ito T, Kohno T, Kojima T. Free vascularized fibular graft. J Trauma. 1984;24:756-60. 97. Campanacci M, Zanoli S. Double tibiofibular synostosis (fibula pro tibia) for non-union and delayed union of the tibia. End-result review of one hundred seventy-one cases. J Bone Joint Surg Am. 1966;48:44-56. 98. Hand FM. Crisscross tibiofibular graft for nonunion of the tibia. Clin Orthop Relat Res. 1953; 1:154-60. 99. Enneking WF, Morris JL. Human autologous cortical bone transplants. Clin Orthop Relat Res. 1972;87:28-35. 100. Holderman WD. Results following conserva-

tive treatment of fractures of the tibial shaft. Am J Surg. 1959;98:593-7. 101. Connolly JF, Guse R, Tiedeman J, Dehne R. Autologous marrow injection for delayed unions of the tibia: a preliminary report. J Orthop Trauma. 1989;3:276-82. 102. Johnson EE, Urist MR, Finerman GA. Distal metaphyseal tibial nonunion. Deformity and bone loss treated by open reduction, internal fixation, and human bone morphogenetic protein (hBMP). Clin Orthop Relat Res. 1990;250:234-40. 103. Slater M, Patava J, Kingham K, Mason RS. Involvement of platelets in stimulating osteogenic activity. J Orthop Res. 1995;13:655-63. 104. McAndrew MP Gorman PW, Lange TA. Trical, cium phosphate as a bone graft substitute in trauma: preliminary report. J Orthop Trauma. 1988;2:333-9. 105. Simpson JM, Ebraheim NA, An HS, Jackson WT. Posterolateral bone graft of the tibia. Clin Orthop Relat Res. 1990;251:200-6. 106. Harmon PH. A simplified surgical approach to the posterior tibia for bone-grafting and fibular transference. J Bone Joint Surg Am. 1945;27:496-8. 107. Behrens F. Bone grafting: general principles and use in open fractures. Instr Course Lect. 1981;30:152-5. 108. Freeland AE, Mutz SB. Posterior bone-grafting for infected ununited fracture of the tibia. J Bone Joint Surg Am. 1976;58:653-7. 109. Hanson LW, Eppright RH. Posterior bone-grafting of the tibia for non-union. A review of twenty-four cases. J Bone Joint Surg Am. 1966;48:27-43. 110. Harkins HW, Phemister DB. Simplified technic of onlay grafts for all ununited fractures in acceptable position. JAMA. 1937;109:1501-6. 111. Jones KG, Barnett HC. Cancellous-bone grafting for non-union of the tibia through the posterolateral approach. J Bone Joint Surg Am. 1955; 37:1250-60. 112. McCarroll HR. The surgical management of ununited fractures of the tibia. JAMA. 1961;175: 578-83. 113. Simon JP Hoogmartens M. The value of poster, olateral bone-grafting for non-union of the tibia. Acta Orthop Belg. 1984;50:557-64. 114. Souter WA. Autogenous cancellous strip grafts in the treatment of delayed union of long bone fractures. J Bone Joint Surg Br. 1969;51:63-75. 115. Paley D. Treatment of tibial nonunion and bone loss with the Ilizarov technique. Instr Course Lect. 1990;39:185-97. 116. Marsh JL, Prokuski L, Biermann JS. Chronic infected tibial nonunions with bone loss. Conventional techniques versus bone transport. Clin Orthop Relat Res. 1994;301:139-46. 117. Cierny G 3rd, Zorn KE. Segmental tibial defects. Comparing conventional and Ilizarov methodologies. Clin Orthop Relat Res. 1994;301:118-23. 118. Laursen MB, Lass P Christensen KS. Ilizarov , treatment of tibial nonunions results in 16 cases. Acta Orthop Belg. 2000;66:279-85. 119. Marsh DR, Shah S, Elliott J, Kurdy N. The Ilizarov method in nonunion, malunion and infection fractures. J Bone Joint Surg Br. 1997;79:273-9. 120. Murray JH, Fitch RD. Distraction histiogenesis: principles and indications. J Am Acad Orthop Surg. 1996;4:317-27.

121. Saleh M, Royston S. Management of nonunion of fractures by distraction with correction of angulation and shortening. J Bone Joint Surg Br. 1996;78:105-9. 122. Brighton CT. Use of constant direct current in the treatment of nonunion. Instr Course Lect. 1982;31:94-103. 123. Paterson D. Treatment of nonunion with a constant direct current: a totally implantable system. Orthop Clin North Am. 1984;15:47-59. 124. Brighton CT. The semi-invasive method of treating nonunion with direct current. Orthop Clin North Am. 1984;15:33-45. 125. Brighton CT, Friedenberg ZB, Zemsky LM, Pollis PR. Direct-current stimulation of non-union and congenital pseudarthrosis. Exploration of its clinical application. J Bone Joint Surg Am. 1975;57: 368-77. 126. Bassett CA. The development and application of pulsed electromagnetic fields (PEMFs) for ununited fractures and arthrodeses. Orthop Clin North Am. 1984;15:61-87. 127. Bassett CA, Mitchell SN, Gaston SR. Pulsing electromagnetic field treatment in ununited fractures and failed arthrodeses. JAMA. 1982;2 47:623-8. 128. Bassett CA, Mitchell SN, Gaston SR. Treatment of ununited tibial diaphyseal fractures with pulsing electromagnetic fields. J Bone Joint Surg Am. 1981;63:511-23. 129. Barker AT, Dixon RA, Sharrard WJ, Sutcliffe ML. Pulsed magnetic field therapy for tibial non-union. Interim results of a double-blind trial. Lancet. 1984;1:994-6. 130. Sharrard WJ. A double-blind trial of pulsed electromagnetic fields for delayed union of tibial fractures. J Bone Joint Surg Br. 1990;72:347-55. 131. Heckman JD, Ryaby JP McCabe J, Frey JJ, Kil, coyne RF. Acceleration of tibial fracture-healing by non-invasive, low-intensity pulsed ultrasound. J Bone Joint Surg Am. 1994;76:26-34. 132. Guerkov HH, Lohmann CH, Liu Y, Dean DD, Simon BJ, Heckman JD, Schwartz Z, Boyan BD. Pulsed electromagnetic fields increase growth factor release by nonunion cells. Clin Orthop Relat Res. 2001;384:265-79. 133. Friedlaender GE, Perry CR, Cole JD, Cook SD, Cierny G, Muschler GF, Zych GA, Calhoun JH, LaForte AJ, Yin S. Osteogenic protein-1 (bone morphogenetic protein-7) in the treatment of tibial nonunions. J Bone Joint Surg Am. 2001;83 Suppl 1(Pt 2):S151-8. 134. Govender S, Csimma C, Genant HK, ValentinOpran A, Amit Y, Arbel R, Aro H, Atar D, Bishay M, Borner MG, Chiron P Choong P Cinats J, Courtenay , , B, Feibel R, Geulette B, Gravel C, Haas N, Raschke M, Hammacher E, van der Velde D, Hardy P Holt M, , Josten C, Ketterl RL, Lindeque B, Lob G, Mathevon H, McCoy G, Marsh D, Miller R, Munting E, Oevre S, Nordsletten L, Patel A, Pohl A, Rennie W, Reynders P , Rommens PM, Rondia J, Rossouw WC, Daneel PJ, Ruff S, Ruter A, Santavirta S, Schildhauer TA, Gekle C, Schnettler R, Segal D, Seiler H, Snowdowne RB, Stapert J, Taglang G, Verdonk R, Vogels L, Weckbach A, Wentzensen A, Wisniewski T; BMP-2 Evaluation in Surgery for Tibial Trauma (BESTT) Study Group. Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients. J Bone Joint Surg Am. 2002;84:2123-34.