Chapter 27: Principles of Nonunion Treatment

William M. Ricci, Brett Bolhofner

Chapter Outline

Introduction to the Principles of Nonunion Treatment and Definitions

Bone healing is an elegant but complex biologic phenomenon. Most other tissues in the human body can only manage to heal with scar, but bone heals by forming new bone. Although fracture healing usually occurs unencumbered, it may be adversely affected or interrupted in many ways. The associated treatments, functional disability, prolonged pain, and lost wages can lead to substantial psychosocial impairment, economic burden to the patient, and stress on the health care system.72 
Nonunion occurs when a fracture has failed to heal in the expected time and is not likely to heal without new intervention.35,37,197 Delayed union occurs when a fracture has not completely healed in the time expected, but still has the potential to heal without further intervention. While these descriptions may seem simply put, defining the expected time for healing and identifying when healing has finally occurred can be elusive. Establishment of a nonunion can also be defined based on a lack of complete bone healing in a specified time frame, commonly 6 to 8 months, but this is arbitrary.134 
In delayed union, clinical and radiographic evidence of healing lags behind what would ordinarily be present in a similar fracture in the same bone. This, of course, depends on the particular bone involved, the anatomic region of that bone, the fracture pattern, the energy of the original injury, the associated soft tissue damage, and the method of treatment. Comparison with healing times reported in the literature for similar fractures along with clinical experience is necessary to identify delayed union. The potential inaccuracies in this analysis are confounded by the fact that attempts to define a cellular process by reviewing radiographic data are inherently flawed. It has been suggested that cessation of the periosteal and not the endosteal healing response prior to fracture bridging may define delayed union at the cellular level.199 
Nonunion, while often obvious in retrospect, is often difficult to define and diagnose in real time. For example, in the tibia the time for a metaphyseal fracture to be considered ununited will be different than for a fracture in the diaphysis. Both clinical and radiographic findings are necessary for the diagnosis of nonunion. However, such signs may be elusive as primary and secondary healing may be occurring simultaneously. On a cellular level, nonunion occurs when there is cessation of a reparative process antecedent to bony union.115,318 Prior operative fracture treatment may alter the definition of nonunion and may also further complicate the ability to diagnose nonunion. While hardware failure may make the diagnosis obvious, with newer implants and techniques (locked nails and plates), a paucity of clinical symptoms and radiographic findings may persist long after progress in healing has ceased. This chapter will review the important aspects of nonunion pathophysiology including risk factors for the development of a nonunion, discuss the current methods for evaluating and diagnosing nonunions, present the common nonoperative and operative methods for treating nonunions including adjuncts to surgical treatments and their outcomes, and present and discuss the author’s preferred treatments for nonunions. 

Pathophysiology and Etiology of Nonunion

Failure of an acute fracture to progress to timely union may be caused by a myriad of factors. Impaired fracture healing, delayed union and nonunion, is estimated with a combined prevalence of 6.9%.248 A host of factors have been identified that may affect bone healing including patient age, gender, nutritional status, bone quality, endocrine disorders (most notably diabetes), smoking, fracture energy, location and pattern, associated injuries, exposure to radiation, and exposure to medications (most notably steroids, chemotherapy, and nonsteroidal anti-inflammatory drugs [NSAIDs]).20,46 Some of these factors are and some are not within the surgeon’s control. 
The risk for nonunion increases with greater injury energy. Higher energy of injury is associated with greater damage to the bone and greater damage to the surrounding soft tissues. The damaged bone has a reduced inherent capacity to form new bone and the damaged soft tissues have a reduced ability to stimulate the reparative process. The incidence of nonunion in the presence of an open fracture and extensive soft tissue injury, not surprisingly, approaches 20%.297 The characteristics of the original injury, the patient’s ability (or inability) to generate a normal healing response to the particular injury, the mechanical and biologic environment created by the chosen treatment method, and the presence or absence of associated infection are among the factors that can influence the rate and the likelihood of uncomplicated and timely fracture healing. 

Fracture-specific Factors Related to Nonunion

The involved bone and the specific location of the fracture within any given bone influence the innate ability for fracture healing. This is related, in large part, to the associated vascular supply to the fractured region. The talar neck, the proximal metaphyseal–diaphyseal junction of the fifth metatarsal, the femoral neck, and the waist of the scaphoid are examples of anatomic sites that have relatively limited or watershed vascular supplies that are potentially disrupted by fracture. Hence, fractures in these sites have a propensity for healing complications or the development of osteonecrosis. On the other hand, the metaphyseal regions of most other long bones as well as the pelvic bones and scapula have a robust vascular supply, and in the absence of other complicating factors, heal reliably. The diaphyseal regions of long bones, especially the tibia, fall between these extremes. The diaphyseal region of long bones has a relatively limited blood supply and therefore diaphyseal fractures usually require longer periods of time to achieve union than metaphyseal fractures and are more likely to proceed to nonunion. 
Independent of the anatomic location of the fracture, the degree of bone and surrounding soft tissue injury influences the healing potential. The degree of soft tissue injury was recently identified in a survey of surgeons as one of the most important factors that contribute to the development of a nonunion.22 High-energy fractures cause devascularization of the fractured bone in the form of periosteal stripping or disruption of the endosteal blood supply or both. This is clearly evident with open fractures (Fig. 27-1), but internal soft tissue stripping can occur equally in closed fractures. In addition, severe high-energy injuries can render the bone ends nonviable either from immediate cell death or via the process of apoptosis.34 Bone loss, either traumatically associated with open fracture or the result of surgical debridement, is a potential precursor of nonunion. Nonunion is also closely related to the degree of open fracture by virtue of its providing a source of bacterial contamination and creating the potential for infection. 
Figure 27-1
AP radiograph (A) of an open tibial shaft fracture with associated periosteal stripping seen in the clinical photograph (B).
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Host Factors Related to Nonunion

Host factors clearly play a major role in the potential for alterations in fracture healing. Specific conditions that are most notably considered to affect fracture healing are smoking, diabetes, and vascular disease.22,109,208 Smoking was considered to be a major factor in the development of nonunion by 81% of polled orthopedic trauma surgeons, diabetes by 59%, and vasculopathy by 53%.22 Other factors such as exposure to certain medications, the presence of osteoporosis, advanced age, and immunosuppression have also been implicated, with varying degrees of supportive data, as risk factors for nonunion. 

Diabetes

Laboratory evidence demonstrates that most phases of fracture healing are affected by diabetes mellitus. Decreased cellular proliferation is seen in the early phases of fracture healing194 and decreased callus strength at the later phases.14,107 The ultimate clinical effect of long-standing and especially uncontrolled diabetes is to increase the risk for delayed union and nonunion. It is postulated that the microvascular disease, and perhaps the reduced immunocompetence and the neuropathy associated with diabetes, leads to alterations in bone metabolism leading to delayed fracture healing.249 Diabetes also poses greater risks for soft tissue healing complications as well as increased risk for infection after surgical fracture management.158 The association of hyperglycemia with complications related to orthopedic surgery has been established.122,263,301 However, it is unclear which, if any, diabetic-related comorbidities might also affect bone healing. A recent study suggested that peripheral neuropathy and hemoglobin A1c levels >7% were significantly associated with bone-healing complications in the foot and ankle.301 

Smoking

Cigarette smoking is commonly identified by orthopedic trauma surgeons as one of the factors to cause delayed union and nonunion.22 This perception is grounded by sound evidence linking smoking to delayed acute fracture healing,49,148,193 and failure of nonunion treatment,208 as well as failure of bone healing associated with spinal fusion and osteotomies.177 Even a history of prior smoking and exposure to second-hand smoke has been shown to delay bone healing.49,177 Not only does smoking affect bone healing, it also increases the risk of other complications such as acute infection and osteomyelitis.208 
Animal studies suggest that the vasoconstrictive properties of nicotine inhibit tissue differentiation and the normal angiogenic responses in the early stages of fracture healing, and that nicotine directly interferes with osteoblast function.71,323,360 Recent human data, where samples of fractured and nonfractured bones from smokers and nonsmokers were assayed for BMP-2, -6, -4, and -7 using polymerase chain reaction, indicate that smoking reduces periosteal bone morphogenetic protein (BMP) gene expression.53 
Smokers with open tibia fractures treated with intramedullary (IM) nails were found, in a prospective study by Castillo et al.,49 to be 37% less likely to achieve union and 3.7 times more likely to develop osteomyelitis than nonsmokers. Smoking was also found to delay healing in a dose-dependent manner after closed management of tibial shaft fractures.180,287 In the setting of Ilizarov limb reconstruction, McKee et al.208 demonstrated that smoking was associated with multiple complications. The overall complication rate was over three times higher in the smokers compared with nonsmokers including higher rates of persistent infection, nonunion, and amputation. 
Despite being one of the few risk factors that is potentially modifiable, smoking cessation in the face of the stresses associated with acute fracture is exceedingly difficult. Despite these challenges, it is prudent to advocate and support smoking cessation in all patients with fractures at risk for nonunion and in those facing nonunion repair. Given the direct adverse effects of nicotine on bone healing, nicotine supplementation (e.g., nicotine patch) as part of a smoking cessation program should be avoided. This concept is supported by animal data linking transdermal nicotine to nonunion and decreased mechanical strength of healing fractures.84 

Nonsteroidal Anti-inflammatory Drugs

Nonsteroidal anti-inflammatory medications, once used ubiquitously to control postfracture pain, have been implicated in inducing fracture nonunion.215 These medications are now used much more sparingly in the setting of acute fracture or nonunion repair, especially in the initial weeks after injury, a time corresponding to the inflammatory phase of fracture healing. The initial biologic healing response to fracture is an inflammatory process. Therefore, it is logical that NSAIDs may be inhibitors of this process. Prostaglandins are inflammatory mediators present during the initial phases of fracture healing. Their synthesis from arachidonic acid is catalyzed by the cyclooxygenase (COX) enzymes. Both traditional NSAIDs and selective COX-2 inhibitors have been found to interfere with COX-2 up-regulation and therefore prostaglandin synthesis, including such synthesis in healing bone.116,258 
Results of clinical studies on the effect of NSAIDs on fracture healing have yielded conflicting recommendations.15,60,114,175,255,295 Adding to the controversy is alleged fraudulent research activity in this area that led to retraction of at least 20 articles and has cast doubt on some results.83,341 A number of important clinical factors related to NSAID use in the face of fracture healing were investigated in a recent meta-analysis of over 10,000 patients.83 Exposure was found to increase the risk of nonunion (odds ratio 3); however, lower study quality was found to be a confounding variable. Lower study quality was associated with higher risk of nonunion. Lower quality studies affected the association of NSAID use with spinal union rate, but not with long-bone fracture healing. When only moderate quality long-bone fracture studies were considered in isolation, NSAID exposure still was associated with an increased risk of nonunion (odds ratio 4.4). No association of factors, including dose or route (parenteral or oral) of administration or duration of treatment, was found to affect the risk of nonunion. Although these data provide no clear contraindication to NSAIDs in patients with healing bone, it appears reasonable to use alternative medications when possible. 

Other Medications and Systemic Conditions

Other chronic health conditions, although not directly shown to negatively impact fracture healing, empirically can lead to altered healing responses. Any state leading to malnutrition or immunosuppression, including steroid use, rheumatoid disease, and malignancy, can negatively impact the body’s healing response including fracture healing. Previously irradiated bone or bone actively infiltrated with tumor also are at high risk for delayed union or nonunion.47 Although children clearly have higher healing potential than adults, whether advanced age, once physeal closure has occurred, is an independent risk factor for nonunion is unclear.132 Advanced age was found to be an independent risk factor for nonunion in patients with an acute clavicle fracture,269 but other prognostic studies have failed to identify age as a risk factor for nonunion in other anatomic locations.25,61 Although osteoporosis is clearly a risk factor for acute fracture, once fracture has occurred, osteoporosis does not appear to be a risk factor for the subsequent occurrence of nonunion.329 
Bisphosphonates are a class of drugs that prevent bone loss by decreasing osteoclastic mediated bone turnover and have been used successfully in the treatment of osteoporosis, most commonly in the form of the drug alendronate. Recently, long-term use of bisphosphonates have been implicated in the development of atypical stress fractures,124,186,220,298 and with impaired healing of these fractures. According to the task force of the American Society for Bone and Mineral Research, the major criteria for atypical femur fractures are location between the lesser trochanter and the supracondylar flare, association with minimal trauma, transverse or short oblique configuration, lack of comminution, and a medial spike in complete fractures.298 The atypical fractures have characteristic radiographic findings including a simple transverse fracture, cortical thickening, and medial beaking at the fracture site. Additional minor features include prodromal symptoms, the use of bisphosphonates, and delayed healing. Cessation of bisphosphonates has been suggested to help promote union in the face of an atypical fracture.76,227 However, given the long half-life of the drug and that physiologic effects are thought to continue for at least 5 years after discontinued use, it is unclear if cessation is of any clinical utility. 

Treatment Factors Related to Nonunion

Appropriate mechanical stability is required to create an environment conducive to fracture healing. Unfortunately, appropriate stability is very difficult to define and even more difficult to quantify. In fact, the desired degree of stability depends, to a great extent, on the chosen method of stabilization. The natural process of bone healing, commonly referred to as secondary bone healing, through the formation of callus relies on micromotion at the fracture site. In nature, fractures can heal without stabilization, but stabilization can reduce the risk of nonunion. The use of external immobilization such as with a splint, as a method to effect fracture healing, evolved from an effort to control pain. Medical practice has similarly evolved to understand that fractures heal more reliably when immobilized. Indeed, most fractures heal with the relatively limited stability provided by splint or cast immobilization. Rigid internal fixation, as provided by the compression plating technique, represents the opposite end of the stability spectrum associated with fracture care. Rigidly stabilized fractures heal without callus via primary bone healing, a relatively unnatural, yet successful, strategy. 
Regardless of whether the chosen treatment method relies on primary or secondary bone healing, improper technique can lead to an increased risk of nonunion. A poorly applied cast or one applied to a severely lipomatous extremity, for instance, may provide inadequate stability resulting in excessive fracture site motion and the development of nonunion. It is often difficult to predict the fracture healing response to excessive motion, as either abundant callus or a paucity of callus may result (Fig. 27-2). Relatively rigid internal fixation techniques that fail to accomplish bone-to-bone contact and compression (i.e., ones with gaps at the fracture site) do not support the primary bone healing process, which relies upon direct remodeling of bone via cutting cones that traverse the fracture, and can also lead to nonunion (Fig. 27-3). Whereas modern surgical techniques emphasize biologically friendly tissue handling, older techniques that included anatomic reduction of individual fracture fragments were at the expense of soft tissue stripping from the fracture fragments and led to a suboptimal environment for fracture healing. Whether fracture reduction is direct or indirect, or the fixation construct is relatively stable or rigid, minimizing soft tissue disruption is paramount to maximizing the healing potential and minimizing other complications that relate to devitalization of bone, namely infection. 
Figure 27-2
Three humeral shaft fractures treated nonoperatively developed different types of nonunions: hypertrophic (A), oligotrophic (B), and atrophic (C).
 
Final radiographs after management of the nonunions with plate fixation alone for the hypertrophic (D) and oligotrophic (E) nonunions and plate fixation supplemented with bone graft for the atrophic nonunion (F).
Final radiographs after management of the nonunions with plate fixation alone for the hypertrophic (D) and oligotrophic (E) nonunions and plate fixation supplemented with bone graft for the atrophic nonunion (F).
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Figure 27-2
Three humeral shaft fractures treated nonoperatively developed different types of nonunions: hypertrophic (A), oligotrophic (B), and atrophic (C).
Final radiographs after management of the nonunions with plate fixation alone for the hypertrophic (D) and oligotrophic (E) nonunions and plate fixation supplemented with bone graft for the atrophic nonunion (F).
Final radiographs after management of the nonunions with plate fixation alone for the hypertrophic (D) and oligotrophic (E) nonunions and plate fixation supplemented with bone graft for the atrophic nonunion (F).
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Figure 27-3
Postoperative radiograph showing fibular fracture gap (A).
 
At 3 months postoperatively, the gap persists (B). Nonunion repair with bone grafting yields union (C).
At 3 months postoperatively, the gap persists (B). Nonunion repair with bone grafting yields union (C).
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Figure 27-3
Postoperative radiograph showing fibular fracture gap (A).
At 3 months postoperatively, the gap persists (B). Nonunion repair with bone grafting yields union (C).
At 3 months postoperatively, the gap persists (B). Nonunion repair with bone grafting yields union (C).
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Infection as a Factor Related to Development of Nonunion

Fractures can heal in the face of infection; however, even a suppressed infection may substantially alter the healing process, and uncontrolled osteomyelitis can inhibit normal fracture healing altogether (Fig. 27-4). The inflammatory process in response to infection may inhibit fracture healing by causing excessive remodeling and osteolysis.105 Tissue necrosis may be accelerated by infection, but histologic evidence indicates that soft tissue disruption caused by the initial trauma and surgical insult are the primary events leading to bone necrosis in cases of osteomyelitis associated with fracture.226 Loose nonvital bone fragments and bone pieces demarcated by osteoclastic activity are eventually transformed into sequestra (Fig. 27-5).226 Infection not only predisposes to nonunion, but makes nonunion repair substantially more complex, often requiring multistaged treatment protocols that are discussed later in this chapter. 
Figure 27-4
AP radiograph of an infected nonunion of the femur after IM nailing.
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Figure 27-5
Lateral radiograph (A) and sagittal CT scan (B) showing a sequestrum.
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Classification of Nonunion

Nonunions may be classified based on the presence or absence of infection and the relative biologic activity of the fracture site. Septic nonunion implies that there is an infectious process at the site while aseptic nonunion is the absence of infection. Further classification of nonunion is an attempt at describing the biologic occurrences or lack thereof at the fracture site. Atrophic, oligotrophic, and hypertrophic nonunions represent increasing biologic potential for fracture healing. Radiographic analysis is the most common method used to distinguish among these classification types. Any inherent interpretation inaccuracies are confounded by attempting to identify a biologic phenomenon by radiographic analysis. 

Atrophic Nonunion

Atrophic nonunion, also referred to as avascular, nonviable, or avital nonunion indicates poor healing response with little or no bone-forming cells active at the fracture site.205,210 The blood supply to an atrophic nonunion is typically poor. This is typically manifested radiographically by the absence of any bone reaction (Figs. 27-2C and 27-3). This lack of healing response may be because of the injury (e.g., open fracture) or subsequent surgical treatment (e.g., surgical stripping of soft tissues about the fracture site) or because of host issues (e.g., diabetes or smoking).285 Strategies for the treatment of atrophic nonunions generally include a method to provide a biologic stimulus to the fracture site, most commonly with autogenous bone graft or BMP. Debridement or excision of nonvital bone ends is another principle for the management of atrophic nonunion. The degree of bone resection can vary greatly depending upon the mode of treatment to be utilized and the presence or absence of infection. An aseptic atrophic nonunion treated with compression plating will require little bone resection, whereas a septic atrophic nonunion treated with Ilizarov methods including bone transport may benefit from a relatively large area of bone resection. 

Hypertrophic Nonunion

At the other end of the spectrum from atrophic nonunion is hypertrophic nonunion, also referred to as hypervascular, viable, or vital nonunion. Associated is an adequate healing response with satisfactory vascularity.206,211 These fractures lack adequate stability to progress to union. The viable healing fibrocartilage cannot mineralize because of unfavorable mechanical factors at the fracture site.285 This is manifested radiographically by callus formation, usually abundant, with an interceding area of fibrocartilage-lacking mineral, and so appearing dark on standard radiographs. Hypertrophic nonunions can occur after initial nonoperative management (Fig. 27-2A) or after attempts at operative stabilization (Fig. 27-6A,B). Successful treatment of hypertrophic nonunions utilizes methods to provide the stability required to allow the adequate biologic response to complete (Figs. 27-2D and 27-6C–F). Rigid stabilization allows chondrocyte-mediated mineralization of the fibrocartilage at the hypertrophic nonunion site, usually by 8 weeks. Resection or debridement of the aseptic hypertrophic nonunion is neither required nor desired. Unlike atrophic nonunions, biologic stimulus, such as bone grafting, is not a treatment necessity for hypertrophic nonunions. 
Figure 27-6
Hypertophic nonunion resulting after IM nailing of a distal tibial shaft fracture (A, B) treated with plate and screw fixation (C, D) heals without adjuvant bone graft (E, F).
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Oligotrophic Nonunion

Oligotrophic nonunions probably represent a condition somewhere between atrophic and hypertrophic nonunions. They are viable, but usually manifest minimal radiographic healing reaction (callus), often because of inadequate approximation of the fracture surfaces (Figs. 27-2B and 27-7). A bone scan may be necessary to distinguish this type of nonunion from a frankly atrophic one. The oligotrophic situation will be manifested by increased uptake where the atrophic situation would be relative cold on bone scan.306 Management of oligotrophic nonunions usually involves addressing deficiencies in bone contact either by mechanical compression or bone grafting of associated defects or a combination of biologic and mechanical methods (Fig. 27-7B and C). 
Figure 27-7
An oligotrophic femoral shaft nonunion after initial IM nailing (A) treated with exchange nailing (B) heals uneventfully (C) probably as the result of bone graft generated by reaming and improved stability.
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Pseudoarthrosis

Pseudoarthrosis, a subclassification of nonunion, has properties of hypertrophic nonunion, but because of excessive and chronic motion, an actual synovial pseudocapsule is formed, containing fluid much like an actual synovial joint (Fig. 27-8). The medullary ends are usually sealed and an interceding cold cleft is noted on bone scan. Management of these nonunions usually requires debridement of the pseudoarthrosis, opening of the medullary canal, and enhancement of stability, typically with compression at the nonunion site. Although these nonunions are technically vital, biologic stimulation can be helpful to promote more rapid and reliable healing. 
Figure 27-8
Pseudoarthrosis 20 years after shotgun injury and nonoperative treatment.
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Evaluation and Diagnosis of Nonunion

The diagnosis of nonunion is an inexact science even when ignoring the temporal issues of defining when a fracture should or should not yet be considered a nonunion. At any given time point, determining if a fracture is united or not, is more straightforward than diagnosing a nonunion, but this is not a simple task either. Bone healing is a progressive process where the strength of the reparative process, under usual circumstances, gradually increases over a period of time. Clinical attempts to define union are hampered by utilizing indirect means to evaluate the strength of the healing process. Further, even if the strength of the healing bone could be accurately evaluated, neither the baseline strength of the uninjured bone nor the fraction of that value required to achieve union is known. However, technologic advances in microelectronics have made measurement of mechanical properties of healing bone possible. A recent preliminary report evaluated a telemetric system to measure bending load in a titanium internal fixator to determine if clinically relevant information could be drawn from its application.294 Well before radiographic signs of healing could be detected, a substantial decrease in elasticity of the fixator was recorded. This and similar technologies have the potential to revolutionize the evaluation of fracture healing and also to change the management of healing fractures. It will be possible to identify progression towards union or nonunion and to accurately define a healed fracture without the use of ionizing radiation. Accelerated weight bearing could be allowed or reduction in activity recommended based on automated systems that evaluate real time data. Prior to the maturation of this exciting new technology, clinicians must continue to rely on indirect means in the evaluation of fracture healing and in determining if union has occurred. 
Depending on the modality being used, the diagnosis of a nonunion may be one of inclusion or exclusion. That is, when evidence of union exists, then nonunion is ruled out. Some diagnostic modalities such as a bone scan may directly identify nonunion by a positive test result. In usual clinical practice, the information gathered from many modalities, such as history, physical examination, radiographs, and other special tests is used in concert to determine the presence or absence of fracture union. Since the majority of these evaluation tools are subjective, each clinician can interpret results differently and assign different relative importance to various measures. This leads to inherent difficulty in establishing uniform and agreed-upon definitions of delayed union and nonunion.22,24,67,199 A recent survey of 335 orthopaedic trauma surgeons endorsed that currently there exists a lack of standardization in the definitions of delayed union and nonunion.22 These surgeons did agree that these definitions should account for both radiographic and clinical criteria. 

History and Physical Examination Related to Nonunion

History and physical examination are critically important to both the initial evaluation of the patient being scrutinized to determine the presence or absence of fracture union after acute fracture, as well as the patient suspected of having an established nonunion. The history of the events surrounding the index injury provides insight into any deviations from the normal course of fracture healing for the particular fracture being evaluated. This information may heighten the index of suspicion for not only nonunion but also for associated problems such as infection. The mechanism of injury, and perhaps more importantly, the energy associated with injury, have implications regarding fracture healing. Higher energy injuries, by virtue of the greater damage done to the bone and surrounding soft tissues, have a higher risk for healing complications. Similarly, the nature of the associated soft tissue injury may be prognostic for delayed bone healing. If the fracture was open, delayed fracture healing is expected and infection becomes more common. 
The details of prior treatments and subsequent recovery complete the history of the problem at hand. It is important to uncover the type and timing of the initial treatments and any subsequent interventions. The indication for the specific details of, and the result of any additional procedures should be identified. Specifically, it is critical to distinguish if secondary debridement procedures were done as planned prophylactic procedures or for the treatment of a documented infection. Causative organisms, antibiotic susceptibilities, and details of antibiotic treatments should be elucidated. The clinical response to such treatments can provide valuable insight into future responses to similar treatment. The nature of prior surgical procedures aimed at augmenting fracture healing provides useful information regarding the diagnosis and helps direct future treatments. It is important to distinguish prior implant removal performed for pain from similar procedures done to promote fracture healing such as nail dynamization. With a history of prior bone grafting, it should be clarified if the graft was autologous or otherwise. If autologous, the prior harvest site is confirmed with physical examination such that if future graft harvest is contemplated a unique site can be prepared for. If there was treatment with bone growth stimulators, such devices may be incorporated in future treatments with little or no additional patient expense. 
The typical signs and symptoms of nonunion are a combination of pain, tenderness, and detectible motion at the site of fracture. It should be noted that symptoms of nonunion can be masked in patients with relatively stable or rigid fixation such as is seen with locked plate constructs. It is not uncommon for such patients to present with the acute or subacute onset of pain and disability associated with implant fracture subsequent to a period of full weight bearing with no or a relative paucity of symptoms (Fig. 27-9). In these circumstances, the loss of stability accompanying implant failure incites the onset of symptoms. In a recent opinion poll of orthopedic trauma surgeons, the lack of ability to bear weight was felt to be the most important clinical factor in diagnosing a lower extremity nonunion followed by fracture pain, weight-bearing status, and tenderness on palpation.22 
Figure 27-9
At 4 months after distal tibia nonunion repair, radiographs (A, B) and painless weight bearing suggest union.
 
Two weeks later, the patient presents with increasing pain with weight bearing. Radiographs (C, D) show plate failure indicating a persistent nonunion.
Two weeks later, the patient presents with increasing pain with weight bearing. Radiographs (C, D) show plate failure indicating a persistent nonunion.
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Figure 27-9
At 4 months after distal tibia nonunion repair, radiographs (A, B) and painless weight bearing suggest union.
Two weeks later, the patient presents with increasing pain with weight bearing. Radiographs (C, D) show plate failure indicating a persistent nonunion.
Two weeks later, the patient presents with increasing pain with weight bearing. Radiographs (C, D) show plate failure indicating a persistent nonunion.
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Radiographic Assessment of Nonunion

Plain Radiographs

Plain radiographs are used ubiquitously in the evaluation of fractures as they provide timely, accurate, and inexpensive means to diagnose an acute fracture. The utility of plain radiographs in evaluating fracture union is less clear. As the process of fracture healing is slow and progressive, when “union” occurs is often difficult to determine. Plain radiographs often help with the diagnosis of nonunion by excluding union. 
The diagnosis of fracture union by plain radiographs is typically defined by the presence of bridging callus across the fracture. Whether circumferential bridging, as evidenced by bridging across four cortices on orthogonal x-rays, is required to accurately diagnose union is without consensus. The orthopedic literature is conflicted with regard to this requirement as different studies can define union as healing across only two or three, rather than four, cortices on orthogonal views.22 Although identifying the number of healed cortices may seem straightforward, in practice this is a very subjective and imprecise exercise especially in the presence of implants that obscure visualization. Furthermore, it is often difficult to know if the radiograph and fracture are coplanar. When not, fracture gaps may be disguised by overlying bone. Minor variances in the angle of the x-ray beam can completely disguise a nonunion (Fig. 27-10). Scoring systems have been proposed to better quantify information gathered from plain radiographs to help predict healing, most notably the Radiographic Union Score for Tibia Fractures (RUST), but they have not yet gained widespread clinical use.340 
Figure 27-10
A lateral radiograph (A) fails to clearly identify a nonunion 8 months after ORIF of a distal humeral shaft fracture, whereas a slight oblique from the lateral projection (B) clearly shows the nonunion.
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The location and type of fracture and the relative stability of the fixation method creates great variations in the expected biologic healing response, and therefore, variations in the expected radiographic appearance of union. Simple diaphyseal fractures fixed anatomically with rigid compression plate techniques that promote primary bone healing without fracture callus may look nearly identical at healing as they did immediately after fixation (Fig. 27-11). Abundant fracture callus would be unexpected. Under these circumstances, accurate diagnosis of union may be difficult, but lack of union may be directly or indirectly evident. Direct evidence is a fracture gap seen on a radiograph taken coplanar with the fracture (Fig. 27-10B). In the absence of direct evidence of nonunion, plain radiographs should be carefully scrutinized for indirect evidence for incomplete healing. Progressively loosened or broken implants indicate persistent motion at the fracture. More subtle findings are motion artifacts seen in bone at or around the margin of seemingly stable implants or fractured screws without complete loss of fixation (Fig. 27-12). Judicious utilization of other imaging methods helps to confirm the diagnosis of nonunions when only indirect evidence is present using plain radiographs. It should be noted that fracture healing can continue and sometimes is augmented by implant fracture. An example is “auto-dynamization” of an IM nail where interlocking screws fracture allowing dynamic compression at the fracture site. This phenomenon can also occur after plate fixation (Fig. 27-13), but is often associated with progressive malalignment which may or may not be problematic. 
Figure 27-11
A distal humerus fracture.
 
A: treated with rigid fixation. B: yields fracture healing without callus.
A: treated with rigid fixation. B: yields fracture healing without callus.
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Figure 27-11
A distal humerus fracture.
A: treated with rigid fixation. B: yields fracture healing without callus.
A: treated with rigid fixation. B: yields fracture healing without callus.
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Figure 27-12
Radiographs showing a healing tibia fracture after IM nailing (A, B).
 
One month later a fractured distal interlock confirms fracture nonunion (C, D).
One month later a fractured distal interlock confirms fracture nonunion (C, D).
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Figure 27-12
Radiographs showing a healing tibia fracture after IM nailing (A, B).
One month later a fractured distal interlock confirms fracture nonunion (C, D).
One month later a fractured distal interlock confirms fracture nonunion (C, D).
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Figure 27-13
A patient with an open distal humeral shaft fracture (A) was treated with irrigation and debridement and plate fixation (B).
 
Despite having a nonunion at 6 months, she was functioning well and without pain because of the stability provided by the plate. An acute increase in pain resulted from failure of the plate (C). The fracture then healed in slight varus without further surgery (D).
Despite having a nonunion at 6 months, she was functioning well and without pain because of the stability provided by the plate. An acute increase in pain resulted from failure of the plate (C). The fracture then healed in slight varus without further surgery (D).
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Figure 27-13
A patient with an open distal humeral shaft fracture (A) was treated with irrigation and debridement and plate fixation (B).
Despite having a nonunion at 6 months, she was functioning well and without pain because of the stability provided by the plate. An acute increase in pain resulted from failure of the plate (C). The fracture then healed in slight varus without further surgery (D).
Despite having a nonunion at 6 months, she was functioning well and without pain because of the stability provided by the plate. An acute increase in pain resulted from failure of the plate (C). The fracture then healed in slight varus without further surgery (D).
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Computed Tomography

Computed tomography (CT) offers an opportunity to more accurately delineate bony anatomy at the site of a suspected nonunion than does plain radiography. Modern CT scans can be reformatted in high quality in any plane. This allows image orientation precisely optimized to evaluate potential absence of bridging bone, eliminating the major shortcoming of plain radiography. CT scans have been shown to be highly sensitive (100%) for detecting tibial nonunion.26 The limitation of CT, however, is a relative lack of specificity (62%) that can lead to surgery in patients who have healed fractures (Fig. 27-14).26 
Figure 27-14
Lack of specificity of CT in the diagnosis of nonunion.
 
AP and lateral radiographs (A, B) 6 months after repair of a distal humeral nonunion show equivocal healing. Coronal CT (C) demonstrates a lucent line consistent with nonunion prompting revision nonunion repair where solid healing, rather than nonunion, was encountered. Further scrutiny of the CT reveals healing of the posterior cortices of the medial (D) and lateral (E) columns.
AP and lateral radiographs (A, B) 6 months after repair of a distal humeral nonunion show equivocal healing. Coronal CT (C) demonstrates a lucent line consistent with nonunion prompting revision nonunion repair where solid healing, rather than nonunion, was encountered. Further scrutiny of the CT reveals healing of the posterior cortices of the medial (D) and lateral (E) columns.
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Figure 27-14
Lack of specificity of CT in the diagnosis of nonunion.
AP and lateral radiographs (A, B) 6 months after repair of a distal humeral nonunion show equivocal healing. Coronal CT (C) demonstrates a lucent line consistent with nonunion prompting revision nonunion repair where solid healing, rather than nonunion, was encountered. Further scrutiny of the CT reveals healing of the posterior cortices of the medial (D) and lateral (E) columns.
AP and lateral radiographs (A, B) 6 months after repair of a distal humeral nonunion show equivocal healing. Coronal CT (C) demonstrates a lucent line consistent with nonunion prompting revision nonunion repair where solid healing, rather than nonunion, was encountered. Further scrutiny of the CT reveals healing of the posterior cortices of the medial (D) and lateral (E) columns.
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In the future, CT may prove to provide a quantitative evaluation of not just union, but fracture stability. In one study, patients with less than 25% bridging of the circumference of bone were found to be at high risk (37.5%) for clinical failure of fracture union, whereas those with greater than 25% bridging had only a 9.7% failure rate.68 Finally, an added benefit of CT is the ability to evaluate rotational deformities associated with nonunion. 

Nuclear Imaging

The use of bone scintigraphy dates back to the 1920s. A multitude of radioactive materials have been applied to the diagnosis of musculoskeletal pathologies including Technetium-99m (99mTc), Indium-111 (111In), Galliumcitrate-67 (67Ga), and Fluorine-18 (18F).219,292 Technetium-99m methylene diphosphonate (Tc-99m) bone scintigraphy can be used to help diagnose nonunion. The major limitation of this technique is that a positive result can be relatively nonspecific. The vast majority of nonunions show an intense tracer uptake at the fracture site, as do fractures undergoing normal healing.284 Various other types of scans used individually or in combination have been used in attempts to differentiate simple nonunion from those that are complicated by infection. Increased blood flow and blood pool as demonstrated during the first and second phases of a three-phase bone scan are consistent with the inflammatory reaction seen with infection, but are not pathognomonic for infection. Combined use of a Tc-99m and a Gallium-67 scan has produced inconsistent results for accurately detecting infection at the site of nonunion.92,284 In contrast to other forms of nonunion, a synovial pseudoarthrosis correlates with the presence of a cold cleft between two intense areas of uptake on scintigraphy.93 Newer technologies such as single-photon emission computed tomography (SPECT) have been investigated for use in differentiating infected from noninfected and vital from nonvital nonunions.189 The technology appears to have high specificity but low sensitivity to confirm nonviability at a nonunion site. 

Laboratory Studies for the Diagnosis of Nonunion

Given that clinical and radiographic evidence is unreliable for the early detection and prediction of eventual nonunion, repeated efforts have been made to identify reliable laboratory tests to evaluate bone healing. If reliable, early prediction of eventual nonunion would provide an opportunity for early intervention to prevent subsequent nonunion and thereby reduce associated time, pain, costs, and disability. Markers of bone metabolism are natural targets for such investigation but have not yet been proven to be clinically reliable.69 The main application of laboratory tests in the setting of a nonunion is to help diagnose associated infection. This topic is discussed briefly in the later section of this chapter related to infected nonunions and in detail in the chapter dedicated to orthopedic infections and osteomyelitis, Chapter 26

Nonunion Treatment

Objectives and General Principles of Nonunion Treatment

Regardless of the chosen method for operative nonunion repair, there are common principles that can be applied. As with most medical conditions, accurately identifying the diagnosis is a critical first step to designing a rational treatment plan. This is especially important when dealing with nonunions. Classifying the nonunion as either hypertrophic, oligotrophic, atrophic, or pseudoarthrosis, identifying whether it is septic or aseptic, and recognizing associated deformity are each critical to the formulation of a complete diagnosis and then the preferred treatment plan. The classification of the nonunion dictates whether a direct exposure and debridement is required and if adjuvant bone grafting is indicated. Hypertrophic nonunions, by definition, have inherent biologic capacity but lack sufficient mechanical stability required for completion of union. Treatment for this diagnosis is therefore focused upon increasing, and often maximizing, mechanical stability. More rigid forms of fixation such as plate fixation or a snug fitting nail in a diaphyseal region are generally preferred to less rigid means such as bridge plating techniques or loose fitting nails in metaphyseal regions. Because hypertrophic nonunions have the biologic potential to heal, debridement of the nonunion site and bone grafting is not an absolute requirement to accomplish union (Figs. 27-2A and 27-2D).155 
Atrophic nonunions and pseudoarthroses have in common the need for debridement of the nonunion site despite atrophic nonunions being considered avital whereas pseudoarthroses are vital. Principles of atrophic nonunion management call for debridement of the nonviable bone ends back to healthy bleeding bone. Both of these classes of nonunions also typically require bone grafting. The relative paucity of healing potential of an atrophic nonunion calls for a graft with osteoinductive or osteogenic properties. A pseudoarthrosis, once debrided, has viable vascular ends, and technically speaking, may therefore not require a bone graft. However, in the absence of bone transport or purposeful shortening, graft material is usually used to fill the gap that is invariably left by debriding the synovial tissue central to the pseudoarthrosis. Oligotrophic nonunions are intermediate in their biologic capacity. Whether failure to unite was related to a primary problem of biology or a problem related to mechanics or a combination of both can be difficult to establish. It is therefore prudent to aim treatment of oligotrophic nonunions at improving both the biologic and mechanical environment. 
Control, and preferably eradication, of any associated infection is another general principle of nonunion treatment. Even complex nonunions can be successfully treated in the absence of infection while simple nonunions can be recalcitrant in the presence of infection. If infection is diagnosed before initiating nonunion treatment, then treatment of the infection becomes a priority over treatment of the nonunion. Occasionally, infection and nonunion can be treated simultaneously with success. However, in most circumstances, it is prudent to optimize infection treatment first followed by optimal nonunion treatment. This strategy of serial, rather than parallel, treatments for infection and nonunion is at the expense of additional treatment duration. Optimal management of infection associated with nonunion begins with removal of associated implants. Serial debridement of necrotic soft tissues and bone follows until a stable healthy environment is accomplished. Skeletal stabilization by means that are conducive to eradication of infection calls for sparing the zone of infection from implants, typically with external fixation devices. Internal fixation is generally avoided with the notable exception of antibiotic-coated IM nails that have recently been shown to be successful in this scenario.229,257,319 Also, certain anatomic areas, most notably the proximal femur, are not well suited for external fixation or antibiotic nails. In these circumstances, clinical judgment dictates whether plate/screw constructs or no internal fixation should be pursued. Infection treatment continues with organism-specific antibiotics, usually delivered parentally for 6 weeks. Once clinical and laboratory data indicate infection control, definitive treatment of the nonunion ensues. If conversion of external to internal fixation is planned, then a staged protocol consisting of removal of the external fixators and cast application (when it is reasonably appropriate) allows pin site healing prior to definitive nonunion surgery. On occasion, union can be accomplished concurrent with the antibiotic phase of nonunion treatment, but infection treatment should not be compromised toward this goal. 
In the presence of a malaligned nonunion, correction of any associated deformity is paramount to a successful outcome. Correction of alignment not only restores normal anatomy and improves the potential for functional recovery, but it is also critical to establishing appropriate mechanics at the site of nonunion to maximally promote healing. 
Finally, of critical importance to the choices made for treatment of a nonunion are the patient’s individual response to prior treatment, their current level of disability, time constraints for future weight-bearing restrictions, and their occupational needs. With all other factors being equal, the patient with a progressive increase in pain and disability from an ununited fracture is more likely to benefit from surgical intervention than a patient with minimal or improving symptoms. Conversely, the patient with clear radiographic signs of nonunion but with limited pain and marginal functional disability may be more suited for less invasive treatment means such as external bone growth stimulation, especially if comorbid conditions made surgery risky or if restrictions after operative management would result in untimely loss of employment. 

Soft Tissue Management Associated with Nonunion

In many cases, the soft tissues about nonunions are compromised by the original injury or subsequent surgeries. In situations where operative treatment is planned, it may be necessary to acquire soft tissue coverage with local, rotational, or free tissue flaps prior to successful nonunion repair. This is especially true if plate fixation is contemplated for stabilization of the nonunion. This requires forethought as a perfect osseous procedure may be planned and carried out only to have insufficient tissue for a tension-free closure to occur at the conclusion of the case. Preoperative consultation with a soft tissue reconstructive team to allow planning of any needed coverage and to coordinate logistic issues related to their availability is prudent. In the setting of an infected nonunion there is often the need for soft tissue reconstruction. This is usually performed after one or more debridements once control of infection has been obtained. 
Of the myriad of flaps available, only tissue transfer brings something new to the local environment by way of vascularity and oxygen.52,97,97,202 Particular attention should be paid to the soft tissue on the concave side of any associated deformity when angular correction of a malaligned nonunion is planned. When soft tissue coverage is lacking and flap coverage is not practical, deficient soft tissues can be dealt with using an external fixation technique or primary shortening by other means. Purposeful shortening and bone deformation to allow soft tissue closure without tension followed by gradual correction of alignment and distraction osteogenesis has been described utilizing the Taylor Spatial Frame device.222 Another successful strategy is primary shortening during nonunion repair, followed by secondary lengthening after union has occurred.196,235 

Indications and Contraindications for Nonoperative and Operative Treatment

Given the inherent inability to accurately evaluate the biologic potential of ununited fractures, nonoperative means can be considered for most. Additional time for the completion of fracture healing, without any other intervention, may be all that is required. When serial examinations show little or no progress to healing and the diagnosis of nonunion, defined as a fracture that is unlikely to heal without further intervention, is established, treatment interventions are indicated. On the surface there may appear to be little downside to nonoperative treatment other than the time required for successful treatment with nonoperative methods. These issues, however, should not be discounted. The socioeconomic and psychological aspects of prolonged periods of pain, functional loss, disability, and economic hardship can be profound. Also, there are some inherent associated risks with prolonged nonoperative management. Progressive fracture malalignment can occur, especially when implants fail. This represents one relative contraindication to nonoperative management of nonunions. Persistent and excessive motion at a nonunion site also can cause bone resorption, especially when an indolent infection is present. Known infection at the site of nonunion is another relative contraindication to nonoperative management. Therefore, the ideal situation for nonoperative management of a nonunion is when the limb has acceptable alignment and this method is thought to have a reasonable potential for success and the time anticipated for healing is associated with little morbidity. Most nonunions do not meet these criteria; therefore, most nonunions are best suited for operative management. 

Nonoperative Treatment of Nonunion

Nonoperative interventions for bone healing problems can accelerate the existing healing process or promote additional healing that would otherwise not have taken place. Such strategies may be most successful for promoting a delayed union to proceed to union, but healing of established nonunion can also be accomplished. The attractiveness of nonoperative treatment is the avoidance of surgical complications. 
Nonoperative treatment can be divided into direct and indirect interventions. Direct intervention implies application of treatment directly to the ununited bone. Examples include electrical stimulation and ultrasound. Indirect intervention implies institution of treatment directed more toward the patient as a whole. Examples of indirect intervention would include nutritional augmentation or vitamin supplementation, alteration of certain medications, and smoking cessation (Table 27-1). 
 
Table 27-1
Nonoperative Treatment of Nonunions
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Table 27-1
Nonoperative Treatment of Nonunions
Indirect Intervention
  •  
    Smoking cessation
  •  
    Optimizing nutrition
  •  
    Correction of endocrine and metabolic disorders
  •  
    Elimination or reduction of certain medications
Direct Intervention
  •  
    Weight bearing
  •  
    External immobilization or support (e.g., cast or orthosis)
  •  
    Electromagnetic stimulation
  •  
    Ultrasound stimulation
  •  
    Parathyroid hormone
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Indirect Nonoperative Treatment Interventions

Adequate nutrition is probably the most obvious and necessary ingredient for healing of all tissues including bone. Adequate caloric intake, vitamins, and protein are necessary to optimize the healing process.133,135,307 Patient nutrition can be indirectly investigated by assessing total albumin levels. If low, nutritional supplementation and nutrition counseling can be helpful. 
Smoking is probably the most commonly studied patient comorbidity that affects bone healing. Higher rates of delayed union and nonunion have been reported in smokers and the effect is probably proportional to the number of cigarettes smoked.180,287 The mechanism, although not completely understood, likely relates to diminished osteoblast function and decreased local vascularity.71,96 Therefore, cessation of smoking would logically be very important for any patient with a fracture or nonunion regardless of the treatment method. However, smoking cessation in the face of the stresses associated with an acute fracture is exceedingly difficult. Referral to a physician with expertise in smoking cessation or to a smoking cessation program can provide the support necessary for success. Given the direct adverse effects of nicotine on bone healing, nicotine supplementation (e.g., nicotine patch) as part of a smoking cessation program should be avoided. This concept is supported by animal data linking transdermal nicotine to nonunion and decreased mechanical strength of healing fractures.84 
Medical conditions such as diabetes also affect bone healing and increase the risk of nonunion. Diabetic patients with one or more comorbidities are at increased risk for the development of nonunion.165 Diet modification and maintenance of well controlled blood sugar levels should be encouraged as they may minimize the negative effect of hyperglycemia on fracture and wound healing.14 
Other metabolic and endocrine abnormalities may also play a role in nonunion in some patients. Conditions like calcium imbalance, hypogonadism, and thyroid and parathyroid disorders should be addressed medically by the appropriate specialist.39 Patients with an established nonunion have a very high likelihood of having some endocrine dysfunction. The precise screening tests that should be obtained are not clearly defined. Serum vitamin D levels, at a minimum, are commonly obtained during the evaluation of the patient with a nonunion. This is an easy test to perform (as it is a relatively routine serologic test), is relatively inexpensive, may elucidate a potential confounding factor in fracture healing, and is relatively easily treated.57 Nonunion repair surgery, if contemplated, is deferred until vitamin D levels are restored to normal whenever possible. Patients with low vitamin D levels are treated with 50,000 IU of vitamin D weekly in single doses for 4 to 6 weeks. If levels remain low, this regimen is repeated. Patients with low vitamin D levels, recalcitrant to such treatment, deserve a thorough evaluation by an endocrine or metabolic bone disease specialist.39 
In addition to nicotine, other drugs and medications including steroids, dilantin, chemotherapeutic agents, NSAIDs, and some antibiotics (fluroquinolones) negatively affect bone healing.40,120,244 Any adverse effects associated with cessation of such drugs must be balanced with benefits associated with nonunion treatment. 
Adequate medical treatment of systemic infections, including HIV, is desirable in the face of fracture, and probably necessary in the treatment of an established nonunion, especially when CD4 counts are low.143 
There appears to be no clinical evidence at this time to support the use of hyperbaric oxygen for the treatment of nonunion.17 

Weight Bearing and External Stabilization

Probably the simplest and most long-standing direct intervention for a nonunion would be application of weight bearing in a functional brace. This, however, is only reasonably practical for the tibia. The mechanism for the success of this treatment is said to be stimulation of osteoblastic activity by mechanical loading.252,282 The improved stability of a cast or brace can be most effective in the treatment of hypertrophic nonunions. Sarmiento et al.282 managed 16 delayed unions and 57 nonunions of the tibia with below-the-knee functional braces. In 48 cases, a fibular osteotomy was performed to allow compression at the nonunion site with weight bearing and 10 patients had adjuvant bone grafting. Healing occurred in 91.3% of the patients at a median of 4 months with an average of 5 mm of shortening for the nonunions. External supportive devices have little role in the management of atrophic nonunions, pseudoarthrosis, malaligned nonunions, and infected nonunions. These methods are generally considered to be less effective that modern operative means for almost all nonunions are associated with the potential for progressive deformity, and can result in skin breakdown. 

Electrical Stimulation

Four forms of electrical stimulation including direct current (DC), capacitive coupling (CC), pulsed electromagnetic field stimulation (PEMF), and combined magnetic fields (CMFs) are currently used for the treatment of delayed unions and nonunions. It is estimated that more than 400,000 fracture nonunions and delayed unions have been treated with these physical forces.218 DC electrical stimulation is unique in that it involves surgical implantation and potentially surgical removal of the stimulation device. The other methods are noninvasive and involve daily external application for various durations. PEMF is typically recommended for approximately 8 to 12 hours per day; CC must be worn for 24 hours a day; and CMFs are applied for 30 minutes a day. The substantial daily time requirements for PEMF and CC provide limitations with regard to patient compliance. 
The mechanism of action with all of these devices is thought to be alteration of electrical potentials at the fracture site.102,245,291 Electromagnetic fields have shown, in animal studies, to reduce osteoclastic-related bone resorption, increase osteoid formation, and stimulate angiogenesis.232 
Although PEMF has been reported to be equally effective as compared to operative treatment of nonunions,127 some degree of skepticism for these methods still exists because of the lack of well designed clinical trials of this technology. The only prospective double blind trial of CC, published in 1994, showed a 0% healing rate in the placebo group with no treatment, compared with 60% healing in the treated group. The series, however, was small with only 21 patients enrolled.291 Four meta-analyses of electrical stimulation have recently been compared.125 The most rigorous of these reported that the evidence available is insufficient to conclude a benefit of electromagnetic stimulation in improving fracture union rates or preventing nonunions.212 
With regard to prevention of nonunion, Adie et al. reported on a large multicenter, prospective, randomized double-blind trial.1 Two hundred and eighteen patients with acute tibial shaft fractures completed the 12-month trial. There was no difference in the need for secondary surgical intervention because of delayed union or nonunion in the group with active PEMF devices and the group with inactive devices (risk ratio 1.02). Because of moderate compliance with the recommended treatment protocol of 10 hours per day for 12 weeks (average daily use was 6.2 hours), a subanalysis between compliant patients with active units and patients with inactive units combined with noncompliant patients with active units also failed to demonstrate any benefit of pulsed electromagnetic field devices (risk ratio 0.97). 
Requisite conditions for the successful application of electrical stimulation to nonunions include acceptable limb alignment, bone edge proximity, and the absence of pseudoarthrosis. Risk factors and relative contraindications for electrical stimulation are considered to be prolonged nonunion, prior bone graft surgery, prior electrical stimulation which failed, open fractures, active osteomyelitis, extensive comminution, and atrophic nonunion.36 Electrical stimulation at this time can probably be considered to be a reasonable, acceptable nonoperative form of treatment for nonunion. Additional large double-blind trials offering level I evidence can probably not be expected because of the necessity of the control group having no treatment for nonunion for a prolonged time period. 

Ultrasound Stimulation

Low-intensity pulsed ultrasound (LIPUS) is one of various noninvasive biophysical methods used to promote fracture and nonunion healing. LIPUS signals have a frequency of 1.5 MHz, a signal burst width of 200 μs, a repetition frequency of 1 kHz, an intensity of 300 mW/cm37 (Fig. 27-15), and an administration time of approximately 20 minutes per day.335 The LIPUS signal is of low energy, similar to that used for diagnostic ultrasound of vital organs and fetuses (10 to 50 mW/cm2). Its side effect profile is therefore negligible as compared to high-energy shock wave therapy. 
Figure 27-15
A schematic diagram depicting characteristics of the low-intensity pulsed ultrasound signal.
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The mechanism is believed to be in part related to the actual mechanical phenomenon created by the ultrasound. LIPUS is a form of low mechanical energy which may be simulative to ossification.344 It has been theorized that the acoustic waves of LIPUS can provide a surrogate for the forces involved in Wolff’s law.126 In addition, other investigations indicate that LIPUS affects cellular interactions, gene expression, signal transduction, and cellular level calcium regulation.7,136,240,271,273,274 As a result of these complex cellular effects, multiple phases of fracture healing including inflammation, repair and remodeling, as well as angiogenesis, chondrogenesis and osteoblastic activity, are each thought to be influenced by LIPUS.7,259,273,354 
LIPUS has been shown to accelerate fracture healing in both animal models85,334,354,355 and in clinical trials.145,178,187 Clinically, LIPUS has a role to speed fracture healing, to reduce healing complications in the high-risk population (diabetics, smokers, etc.), and to treat existing delayed unions and nonunions. In a study of closed or Gustilo type I open tibial shaft fractures treated with cast immobilization, significant improvements in time to healing were demonstrated for LIPUS with the proportion of fractures healed at 120 days being 88% in the LIPUS group and 44% in the controls.145 The benefit of LIPUS appears to be greater for patients with risk factors for delayed healing such as smoking.65,146 Laboratory data also indicates that LIPUS can increase the usually blunted fracture response associated with diabetes to nearly normal levels.66 
High-quality, double-blind placebo-controlled clinical trials for the use of ultrasound in the treatment of nonunions does not exist and will probably not be done. Once again, there is an ethical consideration as the control group as a necessity would essentially need to have no treatment for their nonunions for a long period of time. There are, however, studies supporting its use (primarily self-pared controls for nonunion cases) with healing rates approaching 90% and healing times ranging from approximately 100 to 180 days.101,113,204,224,271,335 The success rate for deeper bones seems to be lower than for subcutaneous bones.335 Again, acceptable limb alignment, bone edge proximity, and the absence of a pseudoarthrosis are requisite conditions for ultrasound treatment. 

Extracorporal Shock Wave Therapy

Extracorporal shock wave therapy (ESWT) is a higher energy treatment modality than LIPUS. It has been applied in the treatment of many musculoskeletal disorders including tendinopathy of the rotator cuff, lateral epicondylitis, and chronic plantar fasciopathy. Unlike LIPUS, which is patient self-administered on a daily basis, high-energy shock wave therapy typically requires general or regional anesthesia and investment in capital equipment by the treating institution. Studies have shown that the shock waves generated can elicit augmented osteogenic differentiation of mesenchymal stem cells, and can enhance biomechanical properties of bone and angiogenesis.90 These properties make this technology potentially applicable to the treatment of nonunion. Early experiences have demonstrated a favorable response and side effect profile.27,90,283,328,332 Side effects have included swelling, hematoma formation, and petechial hemorrhages. In a report of 115 patients with established nonunions or delayed unions treated with high-energy shock waves, 75.7% healed after one treatment283 and in a follow-up report from the same group 80.2% healed after one to three treatments at an average of 4.8 ± 4 months.90 A recent review of ESWT identified 10 studies (all level IV evidence) that included 924 patients.358 The overall union rate was 76% and was significantly higher in hypertrophic nonunions. The majority of these studies were confounded by associated treatment with cast or external fixator immobilization, and, in the absence of a control group without shock wave treatment, it remains unproven how much effect this therapy has on nonunion healing. 

Parathyroid Hormone

Parathyroid hormone (PTH) is a regulator of calcium metabolism and also assists in the regulation of bone turnover. Animal research has established PTH as having an important role during fracture healing. PTH binds to osteoblasts stimulating release of mediators that in turn stimulate osteoclasts to resorb bone.79 This oversimplification of the action of PTH in the complex interplay of osteoclasts and osteoblasts suggests a potential role for PTH in fracture healing. The utility of PTH to augment acute fracture healing and stimulate healing of nonunions has been the subject of several recent reports. Teriparatide is a synthetic hormone, containing the 1–34 amino acid fragment of recombinant human PTH, that has been used in such human investigations. Case reports have demonstrated healing of nonunions and atypical fractures related to bisphosphonate therapy after administration of teriparatide.54,117,230 Whether bone healing would have occurred without the drug administration casts some doubt on the efficacy of PTH in these settings. Controlled clinical studies evaluating the effectiveness of PTH for the treatment of nonunions are anxiously awaited.250 

Gene Therapy

A growing body of research indicates that gene therapies have the potential to augment fracture healing and to treat nonunions. Answers to critical questions such as what gene to transfer, where to transfer them, how to transfer them, does transfer work, and is transfer safe are beginning to unfold.94 Genetically engineered stem cells have been successfully utilized in segmental defect and nonunion models.73,214,230,247,299 Another approach that does not require stem cell isolation utilizes direct introduction of an osteogenic gene into a target tissue, some with viral vectors21,108,188 and others without.173,300 These direct methods rely on transient expression of the delivered gene. Such transient expression of members of the BMP family (BMP-2, -4, -6, and -9) has been shown to be sufficient for bone formation.300 These targeted gene therapy techniques are promising in that they rely on relatively small quantities of inexpensive plasmid DNA in contrast to the mega doses of expensive recombinant proteins (e.g., rhBMP) used currently in clinical practice. Although the proof of concept has been demonstrated in small animal models, a few large animal studies have yielded encouraging results.94 Progress toward developing clinically relevant gene therapies to augment bone healing is limited by substantial financial constraints and the ever changing regulatory environment.217 

Operative Treatment of Nonunion

Although a common goal of surgical nonunion treatment is bone healing, there is large variation in the methods available for achieving this. Whereas a single treatment option is often clearly superior for an acute fracture such as IM nailing for a closed mid-diaphyseal tibia fracture, several options may be equally suited for the treatment of a nonunion of the same injury (e.g., exchange nailing, nail dynamization, plate osteosynthesis, circular external fixation, and external bone stimulation for a mid-diaphyseal tibial nonunion). The vast array of options can usually be refined with consideration of the integrity of the soft tissue envelope, the degree of bone loss, and coexisting conditions. For instance, nonunion in the face of associated infection makes repair with plates less, and external fixation more attractive. Malaligned nonunions are not well suited for interventions that do not address the deformity such as external stimulation or nail dynamization. Further refinement of the most desired treatment method considers surgeon experience and skill with, the relative risks and benefits of, as well as patient tolerance for, the remaining treatment methods. 

Timing of Operative Intervention

Difficulty in establishing the optimal time to intervene surgically in the treatment of a nonunion parallels the difficulty in the diagnosis of a nonunion. Once the diagnosis of a nonunion is firmly established, operative intervention can reasonably be recommended at any time thereafter. However, if a future nonunion can be accurately predicted at an early stage, before meeting the criteria for the establishment of a nonunion, early operative intervention may be beneficial. This strategy could save patients from the prolonged adverse effect of living with an ununited facture and all the incumbent physical and psychological morbidities and socioeconomic hardships. However, if the prediction for eventual nonunion was inaccurate, patients could be subjected to unnecessary operations. Several recent studies have addressed these issues. A multicenter prospective study to evaluate reamed and unreamed IM nailing of tibia fractures suggested that delaying any surgical intervention for at least 6 months postoperatively may decrease the need for reoperation.23 Other investigators suggest that nonunion repair be performed as early as 3 months.38,51,98 In a survey of orthopedic trauma surgeons, >55% of them felt more confident about predicting nonunions at and past the 14th week after fracture for tibial and femoral shaft fractures and by the 12th week after humeral shaft, pubic rami, and scaphoid fractures.22 The overall diagnostic accuracy of early (12 weeks) prediction of eventual nonunion was recently reported to be 74% with a sensitivity of 62% and specificity of 77%.352 The diagnostic accuracy was higher in patients with less callus formation, high energy mechanisms, closed injuries, and diabetes. These authors concluded that a standardized protocol of waiting for 6 months before reoperation in all patients with nailed tibia fractures may subject a large proportion of the patients to unnecessary, prolonged disability and discomfort. 

Plate and Screw Fixation for Nonunion Repair

Nonunion repair with plate and screw constructs is applicable to most anatomic locations (Fig. 27-16), and plates are applicable to repair of diaphyseal as well as end segment nonunions. Whereas IM nailing is almost universally considered the treatment of choice for acute mid-diaphyseal fractures of the femur and tibia, and by some the humerus, plate fixation is applicable and may be preferred for repair of ununited fractures in these locations. Additional relative advantages of plate and screw fixation of nonunions are the ability to address angular, rotational, and translational deformities, and with minor technical modifications the ability to manage periprosthetic nonunions. In the absence of soft tissue concerns, where the local soft tissues can accommodate the bulk of the implant and the dissection required for insertion, nonunion repair with plate constructs is a very powerful method that can be used successfully for any class of nonunion (i.e., atrophic or hypertrophic) by providing the stability, alignment control, and (when appropriate) the compression required for successful nonunion treatment. 
Figure 27-16
Plates can be used to treat nonunions at almost any part of any long bone.
 
A proximal femur nonunion was repaired with a proximal femoral locking plate with adjuvant ICBG and an intramedullary fibular strut (A). Nonunions of the midshaft (B) and distal (C) portions of the femur were repaired with distal femoral locking plates.
A proximal femur nonunion was repaired with a proximal femoral locking plate with adjuvant ICBG and an intramedullary fibular strut (A). Nonunions of the midshaft (B) and distal (C) portions of the femur were repaired with distal femoral locking plates.
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Figure 27-16
Plates can be used to treat nonunions at almost any part of any long bone.
A proximal femur nonunion was repaired with a proximal femoral locking plate with adjuvant ICBG and an intramedullary fibular strut (A). Nonunions of the midshaft (B) and distal (C) portions of the femur were repaired with distal femoral locking plates.
A proximal femur nonunion was repaired with a proximal femoral locking plate with adjuvant ICBG and an intramedullary fibular strut (A). Nonunions of the midshaft (B) and distal (C) portions of the femur were repaired with distal femoral locking plates.
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Whether the tibia, femur, or humerus is involved, a pre-existing IM nail is, in most circumstances, removed at the time of nonunion repair with plates. However, successful locked and compression plate fixation of nonunions without nail removal has been reported.216,356 Eccentric plate positioning allows bicortical screw fixation around the nail to augment unicortical locked screws.216 
There are some inherent limitations of plate and screw techniques in the management of nonunions. Nonunion repair with plates is limited most by its relative invasiveness, most notably with regard to the potential compromise of any already marginal soft tissue envelope that is often encountered when dealing with nonunions. These constructs are generally load bearing and therefore, early postrepair weight bearing typically must be limited. The extreme stresses on plates spanning long segmental defects, because of their eccentric extramedullary location, may lead to premature implant failure (Fig. 27-17). Plate and screw constructs are also limited by an inability to correct limb shortening from bone loss. 
Figure 27-17
An open distal femur fracture treated with debridement and lateral plating resulted in a large segmental defect (A).
 
High varus stresses on the eccentrically placed plate (B) resulted in plate fracture prior to union despite bone grafting (C). Nonunion repair with revision plating and additional autologous bone graft led to fracture union (D).
High varus stresses on the eccentrically placed plate (B) resulted in plate fracture prior to union despite bone grafting (C). Nonunion repair with revision plating and additional autologous bone graft led to fracture union (D).
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Figure 27-17
An open distal femur fracture treated with debridement and lateral plating resulted in a large segmental defect (A).
High varus stresses on the eccentrically placed plate (B) resulted in plate fracture prior to union despite bone grafting (C). Nonunion repair with revision plating and additional autologous bone graft led to fracture union (D).
High varus stresses on the eccentrically placed plate (B) resulted in plate fracture prior to union despite bone grafting (C). Nonunion repair with revision plating and additional autologous bone graft led to fracture union (D).
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Aftercare specific to plate-repaired nonunions must consider the soft tissue envelope. These procedures are often extensive and postoperative swelling can be substantial and lead to blistering, unforeseen wound issues, and even compartment syndrome. Therefore, efforts to minimize limb swelling are paramount. A well padded splint, one without proximal occlusiveness, is often used, even if not required, to protect the mechanical integrity of the repair. Elevation of the limb above the heart level and cold therapy are mainstays of the initial postoperative regimen. Careful and timely observation of wounds is a practice that can identify and potentially help avoid impending problems. The results of nonunion repair with plate and screw constructs will be presented in each chapter that is specific to an anatomic location. 

IM Nailing of Nonunions

IM nailing of nonunions and delayed unions can take three forms: primary nailing of a nonunion in the absence of a pre-existing nail, exchange nailing, and dynamization. Regardless of which situation is present, nail treatment is most applicable to diaphyseal nonunions. Nailing metaphyseal nonunions has been associated with mixed results and is dependent upon the specific region being treated with success most notably being reported for the distal femur and the distal tibia.265,349 
Primary and Exchange Nailing.
Primary IM nailing of a nonunion is less common than exchange nailing. This is because nonunions that are amenable to nailing would most likely have had IM nailing as an attractive initial method of treatment. Therefore primary nailing of mid-diaphyseal nonunions usually occurs after primary nonoperative management of tibia and humeral shaft fractures. Well aligned end segment nonunions initially treated with plate fixation are also potential candidates for primary nailing. 
Exchange nailing, the practice of removing a pre-existing nail in favor of a new nail, is most applicable to situations where deficiencies of the pre-existing nail can be overcome with a new, larger reamed nail. Such deficiencies can include a lack of rotational control by absence or fracture of interlocking screws and lack of adequate stability caused by an undersized nail. Even when there are no obvious mechanical deficiencies of the pre-existing nail, the reaming associated with an exchange nailing procedure can deposit small amounts of local bone graft and can stimulate an inflammatory response sufficient to promote healing.62 It should be noted, however, that the local graft deposition provided by exchange nailing cannot be expected to fill defects of any substantial size. Therefore, exchange nailing is most applicable to situations without bone loss, unless adjuvant open bone grafting accompanies the procedure. Also, exchange nailing is best considered when angular alignment is satisfactory. The new nail will tend to follow the pre-existing IM path of the prior nail, and therefore, angular malalignments tend to persist after exchange nailing without specific efforts being taken to correct them (Fig. 27-18). 
Figure 27-18
Exchange nailing of a malaligned tibia nonunion.
 
An undersized nail was used to treat an open tibial shaft fracture leading to an atrophic nonunion in slight valgus alignment (A). Exchange nailing was performed without specific consideration of the malalignment resulting in an almost identical amount of valgus (B). A persistent nonunion, although now oligotrophic, with fractured interlocking screws has resulted (C).
An undersized nail was used to treat an open tibial shaft fracture leading to an atrophic nonunion in slight valgus alignment (A). Exchange nailing was performed without specific consideration of the malalignment resulting in an almost identical amount of valgus (B). A persistent nonunion, although now oligotrophic, with fractured interlocking screws has resulted (C).
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Figure 27-18
Exchange nailing of a malaligned tibia nonunion.
An undersized nail was used to treat an open tibial shaft fracture leading to an atrophic nonunion in slight valgus alignment (A). Exchange nailing was performed without specific consideration of the malalignment resulting in an almost identical amount of valgus (B). A persistent nonunion, although now oligotrophic, with fractured interlocking screws has resulted (C).
An undersized nail was used to treat an open tibial shaft fracture leading to an atrophic nonunion in slight valgus alignment (A). Exchange nailing was performed without specific consideration of the malalignment resulting in an almost identical amount of valgus (B). A persistent nonunion, although now oligotrophic, with fractured interlocking screws has resulted (C).
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The technique for IM nailing of nonunions is generally similar to the technique used for nailing of acute fractures. The degree of overreaming required for effective application of exchange nailing is somewhat controversial. Newer evidence suggests that 1 mm of overreaming is sufficient rather than the historical recommendations for at least 2 mm of overreaming.348 It should be clear that a minimum requirement for exchange nailing is the ability to insert a large enough nail to provide mechanical strength to the repair. When considering exchange nailing for the tibia, an associated fibular osteotomy to allow fracture compression during repair has been considered an integral part of the procedure, but recent evidence suggests this is not always essential.154 
Alterations of angular alignment can be made during exchange nailing, but this adds substantial technical challenges to the procedure with any correction of malalignment needing to be made before reaming. This requires mobility of the nonunion, either at baseline or created by surgical means such as debridement of the nonunion and, for the tibia, osteotomy of the fibula. Externally applied devices, such as a femoral distractor, are invaluable tools to help obtain and maintain alignment during the procedure. When multiplanar deformities are present, simultaneous use of two distractors can be helpful, one in the sagittal plane and one in the coronal plane. Obviously, all distractor pins should be placed in locations that will not interfere with nailing. 
Union rates for exchange nailing of femoral and tibial diaphyseal nonunions have ranged substantially, from less than 50% to over 90%.38,139,228,338,346,348 With regard to the major long bones, success is most often reported for the tibia and femur, with exchange nailing of humeral nonunions being less consistent unless supplemental bone graft is utilized.38,139,176,331,348 Results for exchange nailing of the femur were found to be better for isthmal fractures (87% union) compared with results for nonisthmal fractures (50% union).353 
Dynamization.
Dynamization, the practice of removing interlocking screws at one end of a nail to allow axial shortening with weight bearing, is a method advocated to promote healing of delayed unions or nonunions when small gaps are present at the fracture site. Such gaps may be present because of bone loss, osteoclastic bone resorption, or prior static nailing with distraction at the fracture site. Dynamization with modern nails that provide a dynamic interlocking slot can take two forms. Removal of static screws with retention or addition of a dynamic screw has the advantage of maintaining rotational control, but limits the amount of shortening to the amount of excursion of the dynamic screw within the oval dynamic slot in the nail, usually just a few millimeters with most nail designs. This limit may on one hand be advantageous to avoid excessive shortening or, on the other hand, it may be detrimental by preventing sufficient compression at the fracture to accomplish union. The other form of dynamization is removal of all interlocking screws from one end of the nail. This allows more freedom for shortening at the expense of a lack of any axial or rotational control inherent in the nail construct, and therefore, creating the potential for complications of excessive shortening and malrotation.41 The ideal situation for this form of dynamization is when the fracture pattern itself will result in limited shortening and when the existing healing response is thought to provide some inherent rotational stability. The compression allowed by dynamization will also provide increasing rotational stability. Several considerations should go into the decision regarding which end of a nail should be dynamized. Stability is maximized if screws near the fracture are retained and those on the opposite side of the isthmus relative to the nonunion site are removed. Another consideration relates to which end should be allowed to telescope over the nail. As the bone shortens, the nail will become more prominent on the end of the nail with removed screws. Therefore, screws should not be removed if this result (such as protrusion of the nail into the adjacent joint) is undesirable. One must also realize that predicting the degree of shortening can be imprecise. Removal of distal screws, those near the knee, in the case of a retrograde femoral nail is a notable example. In this scenario, the driving end of the nail, if devoid of interlocking screws, can theoretically back into the knee joint and potentially cause devastating damage to the patellar articulate cartilage.261 
The practice of dynamization, given its relatively simplicity and minimal patient morbidity, was at one time commonplace, and even became a routine planned staged procedure after femoral nailing in some cases. This practice was utilized despite a lack of clinical evidence to support its use. Good results after routine dynamization of acute femur fractures was a justification for the practice.170,171,320 Later evidence revealed that high union rates could be expected with static femoral nailing without secondary dynamization.42 In the case of an established femoral delayed union or nonunion, dynamization has been shown to be successful in promoting union in only approximately 50% of cases.239,251,345,347,351 Despite the marginal results of dynamization, it has a role in the management of femoral and tibial nonunions and should be considered in cases where shortening is unlikely. Its advantages are minimal morbidity and the potential for immediate full weight bearing. 

External Fixation for Nonunion Treatment

Of the many different types of external fixation frames and techniques used to treat fractures, circular ring fixators utilizing thin wires and the concepts of Ilizarov are the mainstays for treatment of nonunions by external fixation. The general principles of these techniques are presented in Chapter 8 (Principles of External Fixation). The applicability of thin wire fixators in the treatment of nonunions extends to almost any location within any long bone as well as to the hand, foot, and even to the clavicle.4,45,50,157,168,174,182,277,321 These techniques can even be applied in the setting of failed plate fixation.13 Other advantages of Ilizarov techniques are the relative paucity of soft tissue trauma imparted by this nonunion repair method and the ability to slowly correct the associated deformities. The latter advantage also protects the soft tissues from the stretching that can accompany acute deformity correction with other methods. Other advantages of circular external fixation include the ability to fine tune correction and the potential for early weight bearing. 
Computer-guided treatment with the Taylor Spatial Frame is a recent advance that has considerably simplified Ilizarov type correction of any malalignment, even complex multiplanar deformities.89,270 The Taylor Spatial Frame differs from traditional Ilizarov fixators by utilizing adjustable struts that are oriented in a hexapod configuration. In conjunction with special web-based software programs, six axes of deformity can simultaneously and accurately be corrected (Fig. 27-19). 
Figure 27-19
 
A malaligned tibial nonunion (A, B) is treated with a Taylor Spatial Frame (TSF) (C, D) which allows gradual correction of alignment (E, F). The frame was removed after the correction and union was achieved with IM nailing (G, H).
A malaligned tibial nonunion (A, B) is treated with a Taylor Spatial Frame (TSF) (C, D) which allows gradual correction of alignment (E, F). The frame was removed after the correction and union was achieved with IM nailing (G, H).
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Figure 27-19
A malaligned tibial nonunion (A, B) is treated with a Taylor Spatial Frame (TSF) (C, D) which allows gradual correction of alignment (E, F). The frame was removed after the correction and union was achieved with IM nailing (G, H).
A malaligned tibial nonunion (A, B) is treated with a Taylor Spatial Frame (TSF) (C, D) which allows gradual correction of alignment (E, F). The frame was removed after the correction and union was achieved with IM nailing (G, H).
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Decision making for nonunion treatment with ring fixators must consider if adjuvant open bone grafting is prudent either at the initial nonunion procedure or later in a staged manner. The nonunion characteristics dictate this aspect of the treatment strategy, with stiff nonunions being differentiated from mobile nonunions. Stiff nonunions rarely require bone grafting, whereas mobile nonunions often will benefit from the osteogenic stimulus of a graft. Radiographic evaluation of the stiff nonunion usually reveals hypertrophic callus formation and upon physical examination stress on the nonunion site is accompanied by pain with resistance to deformation. In contrast, mobile nonunions are characterized by either atrophic features on radiographic examination or by features of a synovial pseudoarthrosis. The mobile nonunion moves easily with stress, often without substantial pain. Stiff nonunions have inherent biologic activity and therefore usually do not require a bone graft and respond favorably to closed external fixation methods that utilize compression, distraction, or a combination of both.50,157,168,174 According to the principles of distraction osteogenesis, gradual distraction of the hypertrophic nonunion can stimulate new bone formation and eventual union. Hypertrophic nonunions act similarly to the regenerate seen with limb lengthening or bone transport procedures. Modest lengthening, of up to approximately 1.5 cm, can typically be accomplished through a hypertrophic nonunion. If more length is required, lengthening can be performed separately through a distant osteotomy. Before distraction, a short period of compression, typically 7 to 14 days, may be helpful to “prime” the site for the osteogenic process. In certain circumstances, when there exists a transverse nonunion site where external compression will result in compression of the fracture fragments, union can be accomplished with pure compression. Clearly, an advantage of the gradual treatment afforded by thin wire external fixation, especially when associated with deformity correction, is the preservation of the often compromised soft tissue envelope. 
Treatment of mobile nonunions with ring fixators usually requires opening the nonunion site to surgically convert the nonviable atrophic nonunion to fresh viable bone ends, or in the case of a pseudoarthrosis, to resect the synovium, pseudocapsule, and the fibrocartilage covering the bone ends. In either case, the medullary canal is opened and the site is typically bone grafted. Pure adherents to the Ilizarov techniques may, instead of bone grafting, perform a corticotomy of the involved bone at a site surrounded by healthy soft tissues followed by transport of the intercalary segment to eventually achieve healing by compression at the nonunion and regenerate formation at the corticotomy site, respectively. This technique is technically much more demanding, potentially more time consuming, relies on healing at two sites rather than one, and has the potential complications inherent with bone transport. But, despite this, it is a powerful strategy in experienced hands especially when lengthening of more than 2 cm is required. 
Aftercare specific to nonunion treatment with circular frames obviously requires management of the pin sites. Pin site infection near a joint has the potential for joint sepsis, and in these cases careful pin site care and close observation can avoid disastrous consequences. The accepted strategies for pin site care are many, but at least one should be chosen and clearly outlined to the patient and caregivers. Signs and symptoms of infection should prompt more aggressive treatment such as initiation of antibiotic therapy or wire exchange. The potential for safe and early weight bearing is an advantage of nonunion treatment with ring fixators. Once any associated deformities are corrected and any soft tissue deficiencies are healed, some degree of weight bearing in the frame is generally permitted in all but the most extreme cases. 
Ring fixators have limitations for the treatment of end segment nonunions related to the proximity of thin wires to the involved joint.313 Wires that puncture joint capsule pose a risk for the development of joint sepsis if pin site infection develops. 

Arthroplasty for Nonunion Treatment

There are limited circumstances that make total joint arthroplasty or hemiarthroplasty a viable option for the treatment of nonunion. However, when circumstances are appropriate, arthroplasty can result in rapid and profound symptomatic and functional improvement. Several factors determine the appropriateness for arthroplasty. A minimum requirement is nonunion in a periarticular location that has an associated arthroplasty option that can accommodate the bone resection required to eliminate the nonunion. Depending upon other factors, arthroplasty for nonunion can either be an excellent first choice, an option of last resort, or contraindicated. In the elderly, especially with associated joint arthrosis, which may be in the form of pre-existing arthritis, post-traumatic arthritis, joint destruction from prior implants, or osteonecrosis, arthroplasty is preferred to other methods of nonunion treatment. In contrast to the distal metaphyseal ends of the femur and humerus, metaphyseal nonunions of the proximal ends of these bones are somewhat less ideal for arthroplasty. The common reason is related to the tendon insertions onto the greater trochanter of the femur and the greater and lesser tuberosities of the humerus, respectively. These tendon attachments must be preserved to maintain normal function, and therefore, proximal replacing arthroplasty in these regions should only be considered in extreme circumstances where other options are of equal or greater disfavor.262 When arthroplasty is selected it usually offers the advantages of immediate weight bearing and concomitant treatment of the associated arthrosis, two things that are not accomplished with nonunion repair. 
In physiologically younger patients, arthroplasty becomes less advantageous because of limited longevity of the implants. In the absence of substantial and debilitating arthrosis in this patient population, periarticular nonunions are usually best treated with repair. Regardless of the patient’s age, active infection at the site of nonunion is a contraindication to arthroplasty. Strategies for arthroplasty after eradication of infection, often accompanied with antibiotic spacer placement, are not unreasonable, but are associated with substantial risk of recurrent infection. Arthroplasty can be considered after aggressive treatment of an infected nonunion. This typically involves relatively radical debridement of involved bone, internal implantation of antibiotic-impregnated cement spacers, and prolonged administration of organism-specific parental antibiotics. Whether an infection-free period of time off antibiotics prior to arthroplasty, aimed to prove eradication of the infection, or whether arthroplasty should be accompanied by long-term oral suppression, are both unresolved issues and these decisions are typically individualized and made in concert with consultant infectious disease specialists. A more distant history of infection presents a similar quandary. Biopsy or joint aspiration prior to arthroplasty can be a useful guide to decision making. 
One of the most suitable metaphyseal nonunion locations that is amenable to arthroplasty is the distal femur. Here, a knee arthroplasty that includes distal femoral replacement is relatively mainstream, technically of moderate, but not extreme, complexity, and, because of a lack of critical soft tissue attachments on the distal femur, is generally associated with good functional outcomes.5,30,77,138,225,327 However, good results with this method are certainly not universal and complication rates, especially for infection, are potentially high.142,153 Noninfectious complications occurred in 6 of 15 cases in one series153 and a revision rate of 13% after a follow-up period of 24 months has been reported in another.18 In the absence of complications, and even in some patients with treated complications, distal femoral replacement offers the potential for substantial improvement in function.153,327 
Standard hip arthroplasty, either partial or total as dictated by other factors such as the condition of the hip joint and patient demand, are options for nonunions of the femoral neck and intertrochanteric region.78,137,359 
Arthroplasty for nonunion of the proximal tibia, although reported,153 is typically avoided in favor of staged knee arthroplasty after nonunion repair even in the presence of knee arthrosis because of the critical importance of the tibial tubercle for extensor function. In addition, infection was reported in 50% of proximal tibia replacements in one recent small series.153 
Critical soft tissue attachments do not limit the applicability of total ankle replacement for nonunion of the distal tibia, but the lack of prostheses that can accommodate bone loss in this location does. 
Nonunions of the distal humerus can often be treated with standard total elbow replacements rather than requiring distal humeral replacement.8,213,281 This is because of a combination of the high frequency of fractures occurring within the articular block of the distal humerus, the potential problems with fixation of very distal fractures in this region, and the common association of osteoporosis with these factors. When nonunions are more proximal, a distal humeral replacing total elbow prosthesis can be used.59 

Amputation for Nonunion Treatment

Amputation as definitive treatment for nonunions is often dictated by associated comorbid conditions and by patient preference rather than a technical inability to eventually achieve union.195,231 Psychological and psychosocial factors specific to each individual patient are important to recognize, discuss, and consider before pursuing shared decision making for amputation in the setting of nonunion. The time and effort invested in prior treatments makes some patients reluctant to consider amputation and eager for fresh ideas and strategies for repair, whereas the same investments in prior failures may leave other patients frustrated, worn out, and ready to proceed with a definitive procedure such as amputation. Candid assessments for potential success with additional attempts at nonunion repair, the required investment of time and energy of the patient, and the relative functional, cosmetic, and neurologic (i.e., pain, neuralgia) outcomes of success versus failure of nonunion repair should be discussed and used to guide treatment decisions. Chronic pain from nonunion that will dissipate with bone healing needs to be differentiated from neurogenic pain which is likely to linger. If such neurogenic pain is chronically disabling, then efforts at nonunion repair may be misguided and amputation deserves serious consideration. Also, a contingency plan for what follows if a future nonunion repair fails is useful. A plan for amputation if failure occurs with the next intervention may make it much easier for some patients to reconcile amputation. 

Arthrodesis for Nonunion Treatment

Arthrodesis is sometimes indicated for the management of periarticular nonunions.12,44 The choice of arthrodesis is typically one of last resort when repair with standard techniques or arthroplasty is either contraindicated, unavailable, or not desired. Nonreconstructable periarticular nonunions without good arthroplasty options that can accommodate bone defects (e.g., ankle), nonreconstructable periarticular nonunions with good arthroplasty options, but in young patients who are likely to have poor long term success with arthroplasty, and infected periarticular nonunions, are typical indications for arthrodesis. Often, especially when dealing with infected nonunions of the lower extremity in a compromised host, the choice is between arthrodesis and amputation. It is useful to expose patients trying to make such a decision to other patients who have undergone either arthrodesis or amputation. 

Fragment Excision and Resection Arthroplasty for Nonunion Treatment

Nonunions can be treated directly or indirectly with excision. Direct excision of one or more nonunited bone fragments is most applicable when the excision is designed to eliminate pain-associated contact of the fracture fragments with each other and when the excision minimally disrupts function. Ununited avulsion fracture fragments, where a portion of the ligamentous attachment to the intact bone remains in continuity, are prime candidates for excision. Anatomic examples include avulsion fractures of the base of the fifth metatarsal,268 fractures of the medial malleolus, the inferior pole of the patella, the greater trochanter of the femur,48 the ulnar styloid,144 the olecranon,238 and the greater tuberosity of the humerus. Although avulsed fragments represent a large category of ununited bone fragments amenable to excision, any ununited fragment is a potential candidate for excision. Excisions of an ununited radial head fragment,86 the proximal pole of the scaphoid,44,272 and the anterior process of the calcaneus192 have been reported. 
The utility of this method of nonunion treatment has recently been reported for excision of proximal fifth metatarsal avulsion fractures in six elite athletes.268 All patients experienced relief of activity-related pain and all returned to competitive play at a mean of 11.7 weeks after surgery. The majority of the peroneus brevis tendon attachment to the fifth metatarsal was found to be preserved in all except one case. In the case with more than 50% of the tendon attached to the excised fragment, the tendon was repaired to the remaining fifth metatarsal base. 
Nonunions may be treated indirectly with partial excision of an intact adjacent bone to facilitate healing of the ununited bone. A prime example is excision of a segment of fibula to allow compression of the tibia. As osteotomy and excision serve the same purpose; this type of excision will be discussed further in the next section on osteotomy. 

Osteotomy for Nonunion Treatment

Osteotomy related to the treatment of nonunions usually serves the purpose to realign the nonunion directly or to allow secondary axial shortening of an adjacent bone (e.g., fibular osteotomy for tibial nonunion). In either case, the ultimate goal of osteotomy is to allow compression at the nonunion site to promote healing. The prototypical realignment osteotomy is the Pauwels osteotomy for a femoral neck nonunion described in 1935 and still used today.9,200,242,309 In this case, a closing wedge osteotomy distal to a femoral neck nonunion serves to reorient a vertical nonunion to a more horizontal plane. Fixation across both the osteotomy and the femoral neck nonunion, typically with a blade plate, provides direct compression at the osteotomy and allows secondary dynamic compression across the nonunion (Fig. 27-20). This procedure has reported success rates of up to 90%.200,309 
Figure 27-20
 
A femoral neck nonunion (A) is treated with a valgus producing osteotomy (B) and blade plate fixation. The obliquity of the osteotomy allows compression at the osteotomy site with tightening of the distal screws (C, D), and the orientation of the nonunion relative to the blade plate allows compression of the nonunion with weight bearing. Union is achieved at both the nonunion and osteotomy sites (E).
A femoral neck nonunion (A) is treated with a valgus producing osteotomy (B) and blade plate fixation. The obliquity of the osteotomy allows compression at the osteotomy site with tightening of the distal screws (C, D), and the orientation of the nonunion relative to the blade plate allows compression of the nonunion with weight bearing. Union is achieved at both the nonunion and osteotomy sites (E).
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Figure 27-20
A femoral neck nonunion (A) is treated with a valgus producing osteotomy (B) and blade plate fixation. The obliquity of the osteotomy allows compression at the osteotomy site with tightening of the distal screws (C, D), and the orientation of the nonunion relative to the blade plate allows compression of the nonunion with weight bearing. Union is achieved at both the nonunion and osteotomy sites (E).
A femoral neck nonunion (A) is treated with a valgus producing osteotomy (B) and blade plate fixation. The obliquity of the osteotomy allows compression at the osteotomy site with tightening of the distal screws (C, D), and the orientation of the nonunion relative to the blade plate allows compression of the nonunion with weight bearing. Union is achieved at both the nonunion and osteotomy sites (E).
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When manipulation of tibial length, either compression or distraction (associated with bifocal Ilizarov methods), is required during nonunion treatment and the fibula is intact, a fibular osteotomy or partial excision is performed. Osteotomy without excision allows compression for a relatively short period of time, until healing of the osteotomy occurs. When more time is needed to accomplish the desired compression of the tibia, an excision of a fibular segment large enough that healing is unlikely to occur is preferred over a simple osteotomy. The level of fibular excision has been suggested to be at a site other than that of the nonunion to avoid destabilization.63 However, this recommendation is most applicable to nonunion treatment with cast immobilization without other fixation.282 The level of fibular excision in the setting of adequate internal or external fixation is likely to be of less importance. 

Synostosis for Nonunion Treatment

The lower leg and the forearm, by virtue of having paired bones, are amenable to synostosis techniques for treatment of nonunions of one of the bones. These techniques are most applicable to tibial nonunions as synostosis between fibula and tibia is of little functional consequence.181,305 This is in contrast to the forearm, where synostosis of the radius and ulna eliminates supination and pronation. Forearm synostosis may, however, be a reasonable option in situations where loss of forearm rotation is already a forgone conclusion, such as in the late management of a mangled extremity. Synostosis of the fibula and tibia may be identified by a number of terms: fibula transfer; fibula-pro-tibia; fibular transposition; fibulization; fibular medialization; posterolateral bone grafting, tibialization of the fibula, transtibio-fibular grafting; and synostosis. Synostosis techniques generally attempt to create continuity between the paired bones above and below the nonunion. Weight-bearing forces are transmitted, via the synostosis, around the nonunion through the adjacent bone. Healing of the nonunion is not a requisite for success of the synostosis procedure. 

Adjuncts to Operative Nonunion Repair

Approximately 500,000 bone graft procedures are performed annually in the United States.129 Autologous bone grafts are the gold standard for use in fracture nonunions, but allografts and other bone graft substitutes are each part of the armamentarium for those treating nonunions. The optimal choice of graft material is determined by factors such as the required properties (e.g., osteogenic, osteoinductive, or osteoconductive), the required volume, the accessibility of the material, the cost, and known efficacy. 

Autogenous Bone Graft

Autogenous bone graft remains the standard graft substance used in the repair of atrophic nonunions, some oligotrophic nonunions, and some pseudoarthroses. It has the best and longest documentation and experience and does not confer the risk of spreading infectious diseases. For instance, autograft from the iliac crest used in the treatment of tibial and femoral nonunion typically results in union rates exceeding 90%.275 Cancellous autogenous bone graft supplies osteogenic and osteoconductive materials. Osteogenic cells, including stroma cells, are present in the graft material. It provides an excellent osteoconductive scaffold by way of cancellous bone spicules. It is estimated that 15% of the osteocytes and osteoblasts can survive the bone graft procedure.88 Recent data also indicate that various growth factors and BMPs are present in autologous bone graft and that these levels seem to be independent of harvest site.286,317 
The disadvantages of autogenous bone grafting relate to limited quantities that can be harvested, variable quality, and donor site morbidity. The volume required to fill a cylindrical defect in the femoral or tibial diaphysis has been estimated to be 11.3 cm3/cm and 7.1 cm3/cm, respectively.311 Defects of several centimeters or more in length may therefore exceed the volume of autogenous graft that is available. It has been estimated that the limit of defect length that can be filled using iliac crest bone graft (ICBG) is 5 to 7 cm.169 The quality of the autogenous graft is dependent on host health in general and perhaps to some degree on bone health, such as osteoporosis, as well. Donor site morbidity includes the potential for infection, pain (acute and chronic), neurovascular injury, secondary fracture, and hematoma.6,316 Iliac crest is the most commonly used site for large volume grafts, but other sites such as the greater trochanter and the femoral and tibial condyles can be used for small amounts. 

Iliac Crest Bone Graft (ICBG)

The anterior iliac crest is the most common site of autologous bone graft harvest for the treatment of nonunions. It is a relatively accessible location in all but the most obese patient, and it can provide relatively large quantities of graft, which can be either cancellous, cortical, or a combination of both. Furthermore, the efficacy of this graft is proven. The posterior iliac crest is a nearly identical alternative except for the obvious implications for patient positioning and surgical approach. 
The disadvantages of using the anterior iliac crest are those described for autologous bone graft harvest in general.2,11,80,303,316,339 The reported rates have varied from 2% to 26% for pain,2,80,190,303,316,339 from 0% to 7.5% for infection,2,16,80,339 and from 0% to 16% for persistent lateral femoral cutaneous nerve symptoms.2,11,179,190,303,316 Less common, but severe complications related to ICBG harvest include arterial injury,91 abdominal herniation,260 pelvic instability,70 and secondary fracture through the harvest site.2,6,253 A recent prospective study of 92 patients who underwent anterior iliac crest bone grafting for delayed union or nonunion indicated that this was a well-tolerated procedure. Only two patients (2%) reported a pain value of >3 at 1 or more years postoperatively, there was no functional impairment compared to controls without ICBGs, there were no sensory deficits related to the lateral femoral cutaneous nerve, and deep infection was minimal (3%). These data are in contrast to those of one of the most cited articles in the history of the Journal of Orthopaedic Trauma185 where an 8.6% major and a 20.6% minor complication rate were reported after autogenous bone grafting.357 This report included harvest from different donor sites, a heterogeneous patient population, and multiple surgeons. 
A number of techniques are available for harvesting anterior iliac crest graft. It can be harvested via a trap door in the crest, from the inner table, or from the outer table. Structural graft is available in the form of a tricortical wedge from the crest.32 Cancellous graft may be harvested in isolation via the trap door approach or in combination with the thin cortical bone of the inner or outer table. Curettes, osteotomes, and gouges are useful tools for harvest. Alternatively, acetabular reamers can be used to shave the table and the underlying cancellous bone providing a homogeneous combination of cortical and cancellous bone (Fig. 27-21).339 
Figure 27-21
Acetabular reamers (A) can be used to harvest bone graft from the iliac crest (B).
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Alternative Sites for Autologous Bone Graft Harvest

Although the iliac crest, anterior and posterior, are the most common sites for autologous bone graft harvest, other anatomic regions can provide cancellous graft for use in nonunion surgery, especially when small volumes of graft are required. The distal femur and proximal tibia can provide a modest volume of graft material as can the distal tibia, proximal humerus, and olecranon. Concerns regarding the efficacy of graft obtained from these alternative harvest sites have been one factor limiting their use. Recent data, however, suggests that sites other than the iliac crest have similar levels of endogenous BMP as crest graft317 and grafts from such sites are associated with good clinical results.184,233 However, another recent study suggested that the iliac crest may have a superior content of hematopoietic and osteogenic progenitor cells based on histologic differences.55 

Reamer–Irrigator–Aspirator

Autogenous graft can also be harvested using the reamer–irrigator–aspirator (RIA) (Synthes, Paoli, PA) (Fig. 27-22).221 This device was originally designed as a one-pass reamer for IM nailing to minimize embolic phenomenon.74,75,162,163,290,315 Using this device, reamings are evacuated via suction and collected to be used as bone graft. In the relatively limited experiences reported so far, minimal complications have occurred, but potential certainly exists for mechanical malfunction, femur fracture, embolism, and excessive blood loss.221,310 Reamings in general have been shown in in vitro analysis to contain pleuripotential stem cells with the possibility of dedifferentiation into osteoblasts.337 Specifically quantitative assessment has demonstrated the presence of significant growth factors using the RIA technique106,152,254,286,337 and also that the complement of osteogenic elements in the aspirate may be superior to those in ICBG.342 In addition, an animal study has suggested that a superior quality of callus may result from implantation of graft material harvested in this way.140 
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Figure 27-22
The reamer–irrigator–aspirator (RIA).
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Clinical results of RIA graft used for segmental defects and nonunions are generally favorable. Stafford and Norris311 reported a 70% union rate at 6 months and 90% union rate after 12 months in 27 segmental long bone defect nonunions (average defect 5.8 cm, range 1 to 25 cm) managed with a femoral RIA bone graft. McCall et al.205 reported on a similar group of 21 patients with defects averaging 6.6 cm. Seventeen of the twenty-one healed at 11 months; however, only ten of the twenty-one healed without a secondary intervention. The combined use of RIA graft plus rhBMP-2 in recalcitrant tibial nonunions resulted in union in a small case series of nine patients reported by Desai et al.81 
Trials comparing RIA harvest with other standard methods of reaming and graft harvest are emerging. Streubel et al.314 retrospectively compared conventional reaming with RIA during IM nailing of femoral shaft fractures. They found no benefit to RIA with regard to reducing pulmonary complications and found a trend toward increased healing complications in the RIA group. Belthur et al.16 found the pain associated with graft harvest with RIA to be less than the pain after traditional ICBG. 
Complications associated with RIA bone graft harvest have most notably included fracture and excessive blood loss. Lowe et al.191 reported five postoperative fractures after RIA bone graft harvest and suggested that harvest in osteoporotic or osteopenic patients be avoided and that the degree of cortical reaming be carefully monitored. 
A reamer is selected that is 1 to 4 mm greater than the narrowest part of the femoral canal as measured on preoperative or intraoperative images. The starting point is the same as for IM nailing and may be a piriformis or trochanteric entry site. Using standard IM nailing technique, a guidewire is inserted into the canal of the femur with image control and a one-time pass reamer is gently used to ream the femoral canal with an in and out motion so as not to advance too aggressively. A trap is used to collect the reamings. Typically 60 to 80 cm35 of graft can be harvested with experience without critically weakening the donor bone.99,256 

Vascularized Grafts

Vascularized grafts are most commonly used to treat segmental defects and nonunions of the femoral neck.167 They are advantageous in this situation as they provide a live bone graft that also has structural properties. These are properties not provided by standard iliac crest cancellous autograft. The fibula is the most commonly harvested bone although other sites such as the iliac crest279 and rib336 have been used. Vascularized grafts typically must undergo some degree of hypertrophy for ultimate success in addition to healing to the host tissue at each end.156 Double vascularized grafts (fibula) combined with cancellous grafts have been proposed to gain additional and more rapid stability.10 This is, however, a technically demanding procedure requiring mircovascular anastomosis. Complications include recurrent graft fractures and donor site morbidity.141 

Bone Graft Substitutes and Other Modifiers of Bone Healing

Autologous bone graft has recently been challenged as the gold standard bone graft substance for nonunions.297 Alternatives to autologous bone graft including demineralized bone matrix (DBM), bone marrow aspirate, platelet-rich plasma (PRP), allograft, and ceramics have been developed and utilized for nonunion treatment with varying degrees of success. New advances in bioengineering based on enhanced understanding of the cellular and molecular aspects of fracture healing have led to the development and clinical use of growth factors, such as BMPs, that are used to augment fracture healing. The details of the basic science and mechanism of action of these alternatives are presented in Chapter 5. The advantages of these substitutes, relative to autologous bone graft, in the treatment of nonunion include reduced or eliminated patient morbidity and increased or unlimited supply. 
The ideal graft substitute for nonunion treatment would be inexpensive, of unlimited supply, easy to prepare and handle, easy to implant, without adverse reactions, and 100% efficacious. Each of the above mentioned graft substitutes has some of these ideal graft attributes but none have all. Effectiveness in the treatment of nonunion has been reported for each of these substitutes but there is little in the way of direct comparison to autologous bone grafting.28,64,119,123,151,172,198,304 The utility of BMPs to enhance the effects of autogenous bone graft is controversial.118 It seems logical that adding a bone growth stimulator such as BMP to autogenous bone graft would augment healing capacity. In a noninstrumented spinal fusion model, the combination of osteogenic protein-1 (OP-1) with autograft yielded a 55% fusion rate that was similar to historical controls.325 In the setting of fracture nonunion, a similar lack of efficacy has been demonstrated recently.264 

Recombinant Proteins

BMPs have been increasingly studied as potential substitutes for autologous bone graft.288 Their production from recombinant gene technology makes them available in unlimited quantities. Furthermore, BMPs are available in exact concentrations therefore allowing accurate therapeutic dosing. Their major drawback nevertheless remains the high cost at which they are available. Recombinant human osteogenic protein-1 (rhOP-1), also known as BMP-7, has been studied in the setting of upper and lower extremity nonunions showing high healing rates when used either alone or in combination with autologous or allogeneic bone graft.31,82,280,361 When used only in combination with a type I collagen carrier, BMP-7 has been shown to achieve healing rates similar to iliac crest autograft in tibial nonunions without the associated donor site morbidity.103,104 BMP-7 has however only been approved in the United States under a humanitarian device exemption stipulating that its use is limited to situations where autologous graft is not available, thereby limiting its clinical applicability.112 BMP-2 has been shown to improve healing rates and reduce the risk for infection and secondary procedures after IM nailing of acute open tibia fractures.128 Similar healing rates to autologous ICBG have been reported for the combination of BMP-2 and freeze dried cancellous allograft in the management of diaphyseal tibial shaft fractures with segmental defects.164 While approved by the US FDA only for the treatment of acute open tibia fractures, spinal fusions and oral facial bone augmentation, BMP-2 has been used off-label for the management of established nonunions alone or in combination with ICBG.159,160,161,280,312,322,326 
rhOP-1 was directly compared to autograft in the treatment of 124 tibial nonunions in a prospective randomized study.104 At 9 months after repair using an IM nail, 81% of the rhOP-1 and 85% of the autograft-treated nonunions had healed clinically. Radiographic healing in the rhOP-1 group was 75%, whereas it remained essentially unchanged from clinical healing in the autologous group (84%). The main advantage of rhOP-1 was elimination of the donor site pain which was present in 20% of the patients receiving autograft. Noncomparative data has shown good healing rates, 89% to 92%, with rhBMP-7 (rhOP-1) in the treatment of various upper and lower extremity nonunions.82,206 One randomized controlled study exists comparing rhBMP-2 and allograft to autogenous bone graft for reconstruction of diaphyseal tibial fractures with cortical defects.164 Thirteen patients in the rhBMP-2 group had comparable results to 10 patients in the autograft group. These fractures were not nonunions, but with an average 4-cm defect, they were certainly unlikely to heal without intervention. A recent retrospective comparison of BMP-2 plus cancellous allograft to autologous ICBG for the treatment of long bone nonunion revealed a moderate but not statistically significant difference in healing rates between the two groups of 68.4% and 85.1%, respectively.322 The authors concluded that BMP-2 might provide a suitable alternative to ICBG, but acknowledged the potential for a β-error in their study. Although a disadvantage of recombinant BMPs is their cost, recent data suggests their use could actually reduce costs when treating complex or recalcitrant nonunions by reducing the number of procedures and the number of hospital days.72 

Demineralized Bone Matrix

DBM is produced by extraction of proteins from allograft bone.324 DBM contains type I collagen and noncollagenous proteins including osteoinductive growth factors. There is a requirement from the American Association of Tissue Banks and the US FDA that each batch of DBM be from a single donor. This requirement produces the potential for substantial differences in biologic activity between batches. Further heterogeneity between different formulations of DBM exists because of different manufacturing processes and different carriers used by various commercial producers.246 
A number of studies report good results after nonunion treatment using DBM either alone or in combination with other graft materials.266,343,362,363 These studies suffer from a lack of controls leaving definitive conclusions regarding the efficacy of DMB uncertain. DBM used as an adjunct to locked compression plating of osteoporotic humeral shaft nonunions resulted in union in 11 out of 13 patients.366 Both failures united after secondary iliac crest bone grafting. By comparison in the same study, all 12 nonunions in patients treated with autograft healed without further intervention. 

Bone Marrow Aspirate

Bone marrow aspirate, primarily from the iliac crest, has been shown to contain osteoprogenitor cells and has osteogenic and osteoinductive properties.19 The generally low concentration of such cells (612/cm3) and the variability between patients (12 to 1,224/cm3) has led to the development of improved aspiration techniques with specialized aspiration needles and cell concentration systems aimed at increasing both the number and density of the progenitor cells.149 Without concentration, the evidence suggests that the number of cells in a marrow aspirate is suboptimal for nonunion treatment.150 Furthermore, some controversy exists as to whether concentrated cells should be injected directly and percutaneously into nonunion sites or if applications with an osteoconductive carrier after open debridement of the nonunion are required for optimal results.297 The actual efficiency of direct marrow injection is difficult to interpret in the face of associated interventions including cast immobilization and IM nailing that have accompanied the injection in series reporting union rates ranging from 75% to 90%.64,111,123 

Platelet-rich Plasma

PRP is harvested as the thin layer between clear plasma and red blood cells in centrifuged peripheral blood. This fluid contains concentrated platelets (300% to 600%) which are believed to promote osteoblast proliferation and differentiation.330 However, to date no clinical evidence exists to support PRP in the treatment of nonunions. 

Allograft and Ceramics

Other graft substitute materials such as ceramics (calcium sulfate, calcium phosphates, beta tricalcium phosphate, and hydroxyapatite) and allograft lack osteoinductive or osteogenic properties and have little role in promoting bone healing in the setting of nonunion. These ceramic materials are primarily osteoconductive and function best as graft extenders or carriers for other osteoinductive compounds.33 The structural properties of allograft struts have been exploited most commonly for periprosthetic nonunions with bone loss241 and in the management of proximal humeral nonunions.110 

Graft Site Preparation

Successful application of a bone graft or a bone graft substitute requires preparation of the local recipient site. 
The general principles are to expose healthy bone by removing local scar or other intervening materials, to increase surface area for graft adherence, and to stimulate blood flow to the affected area. These principles can be extended to the situation of a nonunion being repaired primarily with compression without the use of adjuvant graft. Debridement of a nonunion site is tedious and time consuming, but it is perhaps one of the most critical steps in nonunion management. Thorough debridement is at times at odds with preservation of local soft tissue attachments. Debridement of the space directly between the bone ends can be accomplished with exposure from one direction and therefore with limited circumferential soft tissue stripping. However, application, adherence, and consolidation of graft to the periphery of a long bone nonunion are biomechanically advantageous. Graft material placed at a further radius from the center axis provides substantially more strength than centrally placed material. This is based on calculations of cylinder strength: Torsional strength is proportional to the third power of the radius and bending strength is proportional to the fourth power of the radius. Therefore it is advantageous to circumferentially prepare either side of a diaphyseal nonunion while at the same time minimizing soft tissue stripping. 
The technique of Judet and Patel,166 which dates back over 40 years, remains a standard method to prepare the bone for grafting. This technique involves raising osteoperiosteal fragments from the periphery of the nonunion, either through cortex or callus. An osteotome is used to create small, 2- to 3-mm, fragments of cortex, each with an attached soft tissue sleeve. An area 3 to 4 centimeters in length on each side of the nonunion and covering approximately two-thirds of its circumference is so treated. This method increases surface area for bone graft healing and may stimulate the healing process. Various modifications have been proposed,203,223 yet the original Judet principles remain steadfastly utilized. Petaling or fish scaling represents a less elegant and technically easier modification. An osteotome or a small gauge is used to simply raise flakes of bone that resemble flower petals or fish scales. This increases surface area and can promote bleeding into the area, but may have more limited biologic effects than the true Judet technique. These techniques should be applied with caution in osteoporotic bone, as iatrogenic fractures and weakening of the bone may hamper fixation. 

Special Circumstances in the Treatment of Nonunions

Managing Articular Nonunion

Articular nonunions are relatively uncommon. A potential causative factor is inadequate compression of the articular fracture gap leading to prolonged exposure of the fracture surfaces to synovial fluid. These nonunions are therefore commonly oligotrophic and amenable to compression techniques.293 Evaluation of and operative planning for articular nonunions should consider, in addition to standard factors evaluated for nonarticular nonunions, articular congruity, associated arthrosis, stability, and stiffness of the affected joint. The ideal situation for repair of an articular nonunion is one without associated joint arthrosis, without joint instability, and with minimal stiffness. Repair will not address or improve arthrosis and joint stability is often difficult to accomplish with nonunion repair alone. A stiff joint will put the nonunion repair under greater stress during postoperative rehabilitation than is seen with the repair of a nonunion involving a supple joint. Therefore, either the joint contracture should be released during nonunion repair or postoperative range of motion exercises should be modified to minimize the risk of implant failure before union can occur. As with any articular fracture, the goals of articular nonunion treatment include restoration of articular congruity, recreation of proper limb alignment, maximization of joint function, and minimization of pain. When these goals cannot be accomplished with nonunion repair, joint arthroplasty becomes a relatively attractive option.18,30,78 Arthroplasty is particularly beneficial when patient age is advanced or baseline function is low. In the presence of active infection total joint arthroplasty is contraindicated and resection arthroplasty or arthrodesis become considerations. Both arthroplasty and arthrodesis as treatments for nonunion are discussed in further detail in prior sections of this chapter. 

Managing Segmental Bone Loss

Segmental defects related to trauma may result from acute bone loss or be related to established nonunions. Regardless of the etiology, these are very challenging problems for the patient and the surgeon alike. Management of the chronic skeletal defect may be only part of the challenge, as infection and soft tissue compromise are often associated. Several surgical options are available to manage segmental defects including autogenous bone grafting, free vascularized fibular bone grafts, and bone transport. The relative rarity of these problems and the substantial variability between cases means that high-level evidence to guide treatment is difficult to come by. Therefore, treatment decisions are based on knowledge of the available low-level evidence, but more importantly, knowledge of contemporary principles of nonunion management, and consideration of personal experience and skill with the various methods. 
A critical-sized defect is generally regarded as one that requires an intervention, most commonly some type of grafting or transport procedure, in addition to bony stabilization to achieve union. What constitutes a critical-sized defect varies based on a number of factors including the particular bone involved, the relative location within the bone, the state of the surrounding soft tissues, and the expected biologic response of the host (acute fracture vs. established nonunion, healthy patient vs. diabetic smoker, etc). 

Autogenous Bone Grafting Using the Masquelet Technique

For segmental loss, the technique of Masquelet or primary shortening followed by lengthening is favored. In the technique of Masquelet, the area of segmental loss is filled with a PMMA cement. At 4 to 6 weeks, when an osteogenic membrane has been formed around the cement, the membrane is surgically reopened, the cement is removed, and generous cancellous grafting is carried out (Fig. 27-23). Recorticalization generally occurs slowly but usually by 3 to 6 months. This, of course, is done in conjunction with internal stabilization most frequently using a locked IM rod for diaphyseal defects or locked plates for metaphyseal defects.201 The initial role of the spacer is to maintain the space for future grafting by avoidance of fibrous ingrowth. The secondary role of the spacer is the induction of membrane formation. This membrane is synovial-like with few inflammatory cells.243 The membrane itself serves to contain the graft, prevent fibrous ingrowth, and provide growth factors.3 Immunochemistry has shown that the membrane produces growth factors and inductive factors including BMP-2 which are probably maximal around 4 weeks.243 In his original article, Masquelet reported successful use of this two-stage technique in 35 cases with defects ranging from 4 to 25 cm in length.201 Other authors have had similar success with this staged membrane-induced technique.267,289 The underlying mechanism of the membrane formation is not well understood but cases when the membrane itself has generated enough bone so that secondary grafting is not necessary have been observed in our practices. It is unclear whether this membrane can form with substances other than methyl methacrylate and this technique requires an excellent soft tissue envelope.201 
Figure 27-23
 
An infected nonunion of the distal femur (A) is treated with removal of failed implants, debridement, and implantation of an antibiotic-impregnated cement spacer according to the Masquelet technique (B). Healing is accomplished after appropriate antibiotic therapy followed by nonunion repair with removal of the cement spacer, iliac crest bone grafting of the defect, and plate stabilization (C).
An infected nonunion of the distal femur (A) is treated with removal of failed implants, debridement, and implantation of an antibiotic-impregnated cement spacer according to the Masquelet technique (B). Healing is accomplished after appropriate antibiotic therapy followed by nonunion repair with removal of the cement spacer, iliac crest bone grafting of the defect, and plate stabilization (C).
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Figure 27-23
An infected nonunion of the distal femur (A) is treated with removal of failed implants, debridement, and implantation of an antibiotic-impregnated cement spacer according to the Masquelet technique (B). Healing is accomplished after appropriate antibiotic therapy followed by nonunion repair with removal of the cement spacer, iliac crest bone grafting of the defect, and plate stabilization (C).
An infected nonunion of the distal femur (A) is treated with removal of failed implants, debridement, and implantation of an antibiotic-impregnated cement spacer according to the Masquelet technique (B). Healing is accomplished after appropriate antibiotic therapy followed by nonunion repair with removal of the cement spacer, iliac crest bone grafting of the defect, and plate stabilization (C).
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Ilizarov Techniques for Bone Defects

Using Ilizarov techniques to treat nonunions without associated bone defects typically involves simple compression or distraction or some combination of compression and distraction at the nonunion site. This is considered a monofocal Ilizarov technique (Fig. 27-24). When bone defects are present, corticotomy at an adjacent site followed by distraction osteogenesis through the corticotomy (bone transport) and eventual compression at the nonunion site is a bifocal (distraction-compression) Ilizarov method for management of bone defects (Fig. 27-25). Two-level lengthening with compression at the nonunion site is considered trifocal bone transport. These methods have been applied with success for more than the last two decades in the management of tibial defects.58,234,237,308 
Figure 27-24
Schematic diagram of monofocal Ilizarov lengthening technique.
 
Increased length (L2–L1) is accomplished by increasing distance at one location (D2–D1).
Increased length (L2–L1) is accomplished by increasing distance at one location (D2–D1).
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Figure 27-24
Schematic diagram of monofocal Ilizarov lengthening technique.
Increased length (L2–L1) is accomplished by increasing distance at one location (D2–D1).
Increased length (L2–L1) is accomplished by increasing distance at one location (D2–D1).
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Figure 27-25
Schematic diagram of bifocal Ilizarov technique.
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Blum et al.,29 in a retrospective series of 50 consecutive patients treated with distraction osteogenesis for an infected femoral nonunion, evaluated the associated complications. The infected nonunion sites were widely debrided creating segmental defects. In this exceedingly difficult group of patients who had an average of 3.8 prior surgical procedures, it is not unexpected that treatment was protracted, and a majority of patients experienced some complication. The duration of the distraction osteogenesis was 24.5 months; all patients sustained pin tract infections; knee range of motion was consistently reduced; 26% had persistent pain; and the residual leg length discrepancy was 1.9 cm on average. However, union was achieved in all but one patient. 
The relative ease of use and the ability for simultaneous deformity correction have made the use of the Taylor Spatial Frame an attractive option for these cases.270,278 Good results in a small (n = 12) retrospective series were recently reported by Sala et al.278 for the management of postinfectious atrophic tibial nonunions using techniques of bifocal and trifocal bone transport. All patients were treated using Ilizarov principles but with the Taylor Spatial Frame apparatus. All patients achieved union and eradication of the infection. 

Management of Infected Nonunions

The diagnosis of an infected nonunion can be obvious or very subtle. The diagnostic gold standard is a positive deep tissue or bone culture. However, the morbidity and expense of a separate surgical procedure to obtain deep cultures from a nonunion site is not warranted unless there is a sufficient index of suspicion. Establishing the correct threshold for what constitutes a “sufficient” index of suspicion is more art than science. An astute history and physical examination are of critical importance. A history of a previous open fracture or open fracture management raises the suspicion more than a prior closed fracture treated nonoperatively. Any history of a confirmed prior infection or of persistently draining traumatic or surgical wounds also substantially raises suspicion for infection. Pain at a nonunion site that is constant rather than activity-related may be another clue to an underlying infection. Any physical examination finding consistent with acute or chronic inflammation should also be considered a sign of potential deep infection in the setting of nonunion. Laboratory evaluation for the diagnosis of infection associated with nonunion typically includes a complete blood count (CBC), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) level. The utility of these and other tests to diagnose bone infection are discussed further in Chapter 26
After gathering diagnostic information regarding the potential for an infected nonunion, the clinician is often left contemplating the relative risk of infection and the appropriate course of action. It is useful to stratify risk as low, moderate or high. Again, as stated above, such stratification is largely based on experience rather than established guidelines. In a low risk setting, nonunion repair may proceed with the assumption that infection does not exist. Intra-operative cultures prior to the administration of antibiotics is a consideration but not mandatory in such cases. Surprise positive cultures in this scenario, when pre-operative clinical or laboratory evidence of infection was minimal or absent, are occasionally encountered. Internal fixation and bone grafts used in such a clinically non-infected but culture positive nonunion site can be successfully left in-situ with continuation of antibiotic therapy until union is achieved.87 
When there is a moderate suspicion for infection it is prudent to plan for deep intraoperative cultures, intraoperative frozen section of the associated soft tissue (as frozen section of bone is usually not possible), careful inspection of the local environment for signs of infection, and a potentially staged treatment strategy. Patients should be advised of this possibility preoperatively. When intraoperative findings are benign, nonunion repair at this operative setting is reasonable. Suspicious findings usually trigger a staged protocol directed at infection control and eradication while awaiting definitive culture results. If final cultures are negative, nonunion repair can then commence. 
When the suspicion for infection is high but not yet established, the initial management plan usually proceeds with the assumption that infection is present. The initial operative setting is therefore dedicated to confirming the diagnosis and preparing the nonunion for eventual repair as discussed in the following paragraphs. In the setting of an established infected nonunion, control, and when possible eradication, of infection normally takes precedence over efforts to achieve union. In the absence of infection, achieving union, even in the setting of a segmental defect, is usually achievable in all but the most challenging host. However, each case must be individualized and at times a reasonable strategy can be formulated to manage infection simultaneously with efforts to achieve bone healing or even to prioritize bone healing. 
One consideration in the management of infected nonunions is whether to remove or retain existing implants. When evidence suggests that existing implants are providing no or marginal stability, removal is the usual course because retention provides little or no benefit. In the circumstance when the existing implants are providing sufficient stability and appear that they will continue to provide sufficient stability during the course of management of the infected nonunion, the decision to remove or retain implants is more controversial.87,183 This decision represents a conundrum. Internal implants may increase the risk for persistent infection and impair the host’s ability to eradicate it, yet the stability imparted by the implants may benefit the treatment of infection and may provide patient comfort and retained function. Situations most amenable to implant retention are those where union can be expected without the need for grafting procedures. The strategy relies on suppression of infection while allowing the existing biologic process, with the existing implants, to progress toward union. Once union occurs, implant removal becomes part of the strategy to eradicate infection. The alternative strategy, removal of implants, is most applicable when control of infection is particularly problematic or when bone grafting is thought to be required. Metal implants are known to promote both adherence of microbes and biofilm formation and adversely affect phagocytosis, thereby making control of infection more difficult, especially in a compromised host.130,131 Bone graft, whether autograft or allograft, is generally considered avascular upon initial implantation and therefore can provide fertile ground for infection. In the situation when removal of internal implants leaves the nonunion unstable, external fixation with pins and wires placed outside the zone of infection, is normally selected. In the long bones, a reinforced antibiotic bone cement rod can serve to simultaneously provide local antibiotic administration and stability (Fig. 27-26).229,236,296,319 This technique is relatively simple and well tolerated. The cement nail is fashioned using an appropriately sized chest tube as a mold. Chest tube sizing units, French (Fr), represent the outer circumference. The inner diameter depends on the wall thickness of the chest tube, a parameter that varies based on the manufacturer. The approximate outer and inner diameters of various-sized chest tubes is presented in Table 27-2. Cement in a semi-liquid state is injected into a chest tube of appropriate inner diameter, usually about 1.5 mm smaller than the reamed canal to avoid excessive stress on the nail during insertion. Length is based upon intraoperative measurements. A thin rod, such as a guidewire used for IM reaming, is inserted as a reinforcing metal core before curing of the cement. A hook can be fashioned at the driving end of the nail to facilitate removal. Once the cement has hardened and cooled down, the chest tube is cut off. The cement nail is then inserted through the same portal as used for prior IM nailing, is easily removed, and allows easy subsequent exchange nailing. When additional strength is required, such as a very unstable femoral nonunion in a large patient, cement can be manually placed around a standard small-diameter nail. One retrospective analysis revealed success in 14 of 16 patients with infected nonunions of long bones treated with a protocol of culture-specific IV and oral antibiotics, surgical debridement, and stabilization with an antibiotic-impregnated bone cement rod.296 
Figure 27-26
 
An infected tibial nonunion (A) is managed initially with removal of implants, debridement, and local antibiotic delivery (in addition to IV antibiotics) (B), then repeat debridement and placement of an antibiotic impregnated IM “nail” (C).
An infected tibial nonunion (A) is managed initially with removal of implants, debridement, and local antibiotic delivery (in addition to IV antibiotics) (B), then repeat debridement and placement of an antibiotic impregnated IM “nail” (C).
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Figure 27-26
An infected tibial nonunion (A) is managed initially with removal of implants, debridement, and local antibiotic delivery (in addition to IV antibiotics) (B), then repeat debridement and placement of an antibiotic impregnated IM “nail” (C).
An infected tibial nonunion (A) is managed initially with removal of implants, debridement, and local antibiotic delivery (in addition to IV antibiotics) (B), then repeat debridement and placement of an antibiotic impregnated IM “nail” (C).
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Table 27-2
Inner and Outer Diameters of Chest Tubes
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Table 27-2
Inner and Outer Diameters of Chest Tubes
Chest Tube Size Outer Diameter Approximate Inner Diameter
38 Fr 12.1 mm 9.4 mm
40 Fr 12.7 mm 10 mm
42 Fr 13.3 mm 10.5 mm
44 Fr 14 mm 11.3 mm
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Management of the infectious process in the setting of an infected nonunion follows the general principles for the treatment of osteomyelitis as presented in Chapter 26. Surgical debridement of the infected nonviable bone and surrounding nonviable soft tissues, culture-specific parenteral antibiotics, and bone stabilization are the primary goals. Local antibiotic delivery is often included, especially when a dead space results from debridement, in the form of an antibiotic-impregnated synthetic material. Polymethylmethacrylate (PMMA) as cement beads or as a cement spacer is the most common vehicle used for antibiotic delivery in this setting.43,56,95 Beads have greater surface area than a spacer and therefore may provide higher initial antibiotic concentrations, but the effective duration for antibiotic elution may be shorter.302 Creation of a bead pouch is an excellent method for local antibiotic delivery between serial debridement procedures. With regard to longer term implantation, beads can be substantially more difficult to remove after more than 4 weeks than a block of cement because of the ingrowth of scar tissue. Also, an antibiotic cement spacer prepares the defect for bone grafting according to the Masquelet technique previously described. An obvious shortfall of a nonabsorbable delivery system such as PMMA is the typical need for removal. Bioabsorbable bone substitutes that can be impregnated with antibiotics are osteoconductive, may promote bone healing, and do not necessarily require a second stage procedure for removal. Numerous animal, and more recently human, clinical trials support this approach.121,210 McKee et al.209 have recently reported promising results in a prospective randomized trial comparing an antibiotic-impregnated calcium sulfate bone substitute to standard antibiotic-impregnated PMMA beads in the treatment of chronic osteomyelitis and infected nonunion. Infection was eradicated in 86% of the patients from both groups; seven of the eight patients achieved healing of their nonunion in the bioabsorbable group compared to six of the eight in the PMMA group, and there were more operations in the PMMA group. 
Infected nonunions are generally treated in a staged manner. However, Wu350 reported success with one-stage surgical treatment of infected nonunion of the distal tibia. Twenty-two consecutive patients were successfully managed to union with a protocol of implant removal, intra- and extramedullary debridement, cancellous autograft with antibiotics (vancomycin and gentamycin), and stabilization with an Ilizarov fixator. 

Management of Soft Tissue Compromise Associated with Nonunion

When soft tissues are poor or deficient and free tissue transfer is not possible, primary shortening with an IM rod followed by full weight bearing and an elevated shoe is preferred. Once healing has occurred, the limb can be relengthened if the patient desires with either an internal skeletal distraction nail (ISKD Orthofix Inc, McKinney, Texas) (Fig. 27-27) or the Ilizarov technique.222,276,333 In some cases with less than 3 or 4 cm of shortening, patients are often satisfied with the result and do not desire secondary lengthening. The internal skeletal distraction nail seems to be better tolerated than the skinny wire external fixator techniques. It is, however, no faster. Complications similar to those with other distraction or transport techniques still exist including too fast or too slow distraction, failure or delay of regenerate bone formation, adjacent joint problems, a need for exchange nailing, and failure of the distraction device itself. 
Figure 27-27
A 40-year-old female with a grade IIIB open tibia.
 
The central fragment was completely stripped of soft tissue. She was not a candidate for free tissue transfer. (B) After resection of the devitalized bone, the leg was shortened and treated with a locked rod. The fracture healed with full weight-bearing ambulation in a built-up shoe. Note the overlapping fibula. Only local soft tissues, which were adequate in volume after shortening, were used for coverage. (C) Subsequent lengthening withthe internal skeletal distraction nail. (D) After exchange nailing the regenerate was mature at about 6 months. (Case courtesy of Dr. Timothy Weber Orthoindy Indianapolis, IN.)
The central fragment was completely stripped of soft tissue. She was not a candidate for free tissue transfer. (B) After resection of the devitalized bone, the leg was shortened and treated with a locked rod. The fracture healed with full weight-bearing ambulation in a built-up shoe. Note the overlapping fibula. Only local soft tissues, which were adequate in volume after shortening, were used for coverage. (C) Subsequent lengthening withthe internal skeletal distraction nail. (D) After exchange nailing the regenerate was mature at about 6 months. (Case courtesy of Dr. Timothy Weber Orthoindy Indianapolis, IN.)
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Figure 27-27
A 40-year-old female with a grade IIIB open tibia.
The central fragment was completely stripped of soft tissue. She was not a candidate for free tissue transfer. (B) After resection of the devitalized bone, the leg was shortened and treated with a locked rod. The fracture healed with full weight-bearing ambulation in a built-up shoe. Note the overlapping fibula. Only local soft tissues, which were adequate in volume after shortening, were used for coverage. (C) Subsequent lengthening withthe internal skeletal distraction nail. (D) After exchange nailing the regenerate was mature at about 6 months. (Case courtesy of Dr. Timothy Weber Orthoindy Indianapolis, IN.)
The central fragment was completely stripped of soft tissue. She was not a candidate for free tissue transfer. (B) After resection of the devitalized bone, the leg was shortened and treated with a locked rod. The fracture healed with full weight-bearing ambulation in a built-up shoe. Note the overlapping fibula. Only local soft tissues, which were adequate in volume after shortening, were used for coverage. (C) Subsequent lengthening withthe internal skeletal distraction nail. (D) After exchange nailing the regenerate was mature at about 6 months. (Case courtesy of Dr. Timothy Weber Orthoindy Indianapolis, IN.)
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Author’s Preferences in the Treatment of Nonunions

 
 
Nonoperative Nonunion Treatment
 

External stimulation alone, typically ultrasound, is reserved for patients who are minimally symptomatic from their nonunion and who are not candidates for surgery or additional procedures (Fig. 27-28). Ultrasound stimulation is sometimes used in conjunction with operative treatment in high-risk patients such as smokers and diabetics.

 
Figure 27-28
 
AP radiograph (A) showing a nonunion in a 27-year-old man 6 months after intramedullary nailing of a mid-diaphyseal femur fracture. At this point, the patient was fully weight bearing with minimal pain and an ultrasound external bone stimulator was applied 20 minutes daily. Six months later and without further surgical intervention the nonunion is healed (B).
AP radiograph (A) showing a nonunion in a 27-year-old man 6 months after intramedullary nailing of a mid-diaphyseal femur fracture. At this point, the patient was fully weight bearing with minimal pain and an ultrasound external bone stimulator was applied 20 minutes daily. Six months later and without further surgical intervention the nonunion is healed (B).
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Figure 27-28
AP radiograph (A) showing a nonunion in a 27-year-old man 6 months after intramedullary nailing of a mid-diaphyseal femur fracture. At this point, the patient was fully weight bearing with minimal pain and an ultrasound external bone stimulator was applied 20 minutes daily. Six months later and without further surgical intervention the nonunion is healed (B).
AP radiograph (A) showing a nonunion in a 27-year-old man 6 months after intramedullary nailing of a mid-diaphyseal femur fracture. At this point, the patient was fully weight bearing with minimal pain and an ultrasound external bone stimulator was applied 20 minutes daily. Six months later and without further surgical intervention the nonunion is healed (B).
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Operative Treatment of Nonunion
 
Preferred Treatment of Septic Nonunions
 

Septic nonunions are one of the most challenging reconstructive procedures facing the orthopaedic traumatologist. These patients deserve the expertise of a team fluent in their management. Often, infected nonunions are limb-threatening conditions. Given the seriousness of this condition, our approach is to maximize the treatment decisions toward eradicating infection. Therefore, hardware removal, wide debridement, soft tissue coverage as needed, culture-specific local and IV antibiotics, and bony stabilization are utilized in the initial phase of a multistage management protocol. Local antibiotic delivery is typically with antibiotic beads between serial debridements and with antibiotic PMMA spacers or antibiotic rods after definitive closure. Stabilization is with an antibiotic rod when applicable (e.g., diaphyseal tibia nonunion), otherwise with external fixation.

 

The second phase of management is dedicated to treatment with IV antibiotics and monitoring. We rely on an infectious disease team experienced in the management of osteomyelitis to direct the selection and duration of antibiotic therapy and manage any encountered side effects. The second phase ends when clinical, laboratory, and radiographic signs of infection are absent, usually after 6 weeks of therapy.

 

The third phase in the management of infected nonunions typically mimics the management of atrophic aseptic nonunions as discussed in the following section. One important decision at this juncture is whether to discontinue antibiotic therapy prior to nonunion repair or to continue therapy through and after nonunion repair. We generally lean toward continuation of oral therapy until union has occurred whenever there is any doubt regarding the success in eradication of infection.

 
Preferred Treatment of Aseptic Nonunions
 
Preferred Treatment of Atrophic and Oligotrophic Nonunions
 

The first consideration when dealing with nonviable or marginally vital nonunions is whether direct compression of the bone ends is possible without unacceptable shortening. When the answer is yes, then compression with a nail or plate is desired unless the soft tissues dictate the need for thin wire external fixation. If the nonunion is well aligned, then the choice of IM nailing or plating is largely based on the location of the nonunion. Well aligned nondiasphyseal nonunions, in the absence of bone loss, are preferably managed with compression plating. Diaphyseal nonunions without bone defects are preferably managed with primary IM nailing or exchange nailing (if a nail was previously used) if well aligned. If the nonunion is malaligned, compression plating is preferred regardless of location. When direct compression of atrophic nonunions can be accomplished without any remaining defects, we find it unnecessary to add bone graft. This is an unusual circumstance most commonly encountered when dealing with humeral and clavicle nonunions. When direct compression still leaves some bony defect, autologous cancellous bone is our primary choice of graft material. Cancellous allograft combined with BMP is a reasonable alternative. We find no utility in grafting atrophic nonunions with allograft alone.

 

When bone defects are present we prefer to fill the defect with autologous bone graft when available in sufficient quantities. Graft from the iliac crest harvested with an acetabular reamer and graft harvested from the femur using the RIA system have been found to be equally effective in our experience. When the volume of autologous graft is insufficient to fill the defect, we preferentially use cancellous allograft to expand the volume. As a rule of thumb, a ratio of autograft to allograft of up to 1:2 is acceptable. When greater relative quantities of allograft are expected to be required, bone transport methods rather than direct void filling is generally utilized. We prefer to think of the autologous and allograft mixture as being one of three grades. Grade A graft is pure autograft. This has the greatest potential for healing and is used in the most important regions of the nonunion, typically at the periphery. Grade B graft is a mixture of autograft and allograft. This has intermediate biologic potential for healing and is used centrally to fill the medullary canal of long bone nonunions. Grade C graft is pure allograft. It has the least potential for healing of the three grades and it is used sparingly and in locations that are the least important for rapid healing. Fixation in the presence of a filled defect is either with an IM nail or a bridge plate.

 
Preferred Treatment of Hypertrophic Nonunions
 

Hypertrophic nonunions are simply realigned if necessary, then stabilized and when possible, compressed (Fig. 27-2A and 27-2D). The choice of implant depends upon the location of the nonunion and limb alignment. Well aligned hypertrophic nonunions at the end segment of long bones or of flat bones are preferably managed with plating. Hypertrophic diaphyseal nonunions are preferably managed with primary IM nailing or exchange nailing (if a nail was previously used) when well aligned. If the nonunion is malaligned, plating is preferred regardless of location (Fig. 27-29).

 
Figure 27-29
Author’s preferred treatment algorithm for nonunions.
 
When soft tissues are compromised IM nailing is favored over plate fixation unless tissue transfer precedes nonunion treatment. For diaphyseal nonunions, IM nailing is preferred over plating and for metaphyseal or articular nonunions, plating is preferred over IM nailing (TSF = Taylor Spatial Frame).
When soft tissues are compromised IM nailing is favored over plate fixation unless tissue transfer precedes nonunion treatment. For diaphyseal nonunions, IM nailing is preferred over plating and for metaphyseal or articular nonunions, plating is preferred over IM nailing (TSF = Taylor Spatial Frame).
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Figure 27-29
Author’s preferred treatment algorithm for nonunions.
When soft tissues are compromised IM nailing is favored over plate fixation unless tissue transfer precedes nonunion treatment. For diaphyseal nonunions, IM nailing is preferred over plating and for metaphyseal or articular nonunions, plating is preferred over IM nailing (TSF = Taylor Spatial Frame).
When soft tissues are compromised IM nailing is favored over plate fixation unless tissue transfer precedes nonunion treatment. For diaphyseal nonunions, IM nailing is preferred over plating and for metaphyseal or articular nonunions, plating is preferred over IM nailing (TSF = Taylor Spatial Frame).
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