Managing Bone Loss in Open Fractures.12-2
Managing Bone Loss in Open Fractures.12-2
OPEN
Abstract
Segmental bone loss continues to pose substantial clinical and technical challenges to orthopaedic surgeons. While several surgical options
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exist for the treatment of these complex patients, there is not a clear consensus or specific guidelines on the optimal management of these
injuries as a whole. Many factors must be taken into consideration when planning surgery for these individuals. In order for these techniques
to yield optimal results, each injury must be approached in a step-wise and multidisciplinary fashion to ensure that care is taken in bone and
wound bed preparation, that soft tissues are healthy and free of contaminants, and that the patient’s medical condition has been optimized.
Through this article, we will answer relevant questions and discuss common obstacles and challenges encountered with these complex
injuries. We will also review the many treatment options available or in development to address this problem.
Keywords: bone loss, lower extremity fracture, open fracture
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amputation for most patients in the Lower Extremity Assessment factors to be considered and will be covered elsewhere in this
Project trial.[10] current symposium.
Early initiation of intravenous antibiotics is crucial.[11,12] When addressing the traumatic or iatrogenic bone void caused
First-generation cephalosporins should be administered prompt- by radical bony debridement prior to closure, antibiotic
ly for Gustillo-Anderson Grade I and II open fractures. Most impregnated polymethylmethacrylate (PMMA) spacers have
authors recommend additional gram-negative coverage in the provided an excellent option. They not only provide a local
form of an aminoglycoside for grade III injuries.[2,13] In the high concentration of antibiotic elution, but increase fracture
setting of fecal contamination or possible clostridial contamina- stability, maintain adequate soft tissue tension, and prevent
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tion, penicillin is also recommended.[14] Prophylactic antibiotics fibrous ingrowth. This technique is not only used in the case of
should not be continued longer than 24-hours after each surgical staged induced membrane (Masquelet) technique, but also in
debridement since longer courses have not yielded a reduction in cases of delayed closure where the goal is to decrease the local
infection rates and could lead to greater rates of antibiotic bio-burden prior to proceeding with primary closure or soft tissue
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fracture site, extending the wound proximally and distally and or iatrogenically during debridement of an open fracture when
completing an excisional debridement of all nonviable skin, devitalized bone is removed. Although classification systems exist
subcutaneous tissue, muscle, periosteum, and bone with the goal for the description of open fractures, their ability to describe the
of achieving a healthy and clean surgical wound. The “tug test” extent of bone loss is lacking.[2,3] Describing bone loss should
can be used to assess the viability of cortical fragments within the begin with a description by anatomical bone location: diaphyseal,
wound[20] and consists of removing fragments that are easily metaphyseal, or articular. The extent of the defect is then
removed using a pair of forceps or 2 fingers. These fragments are described by stating its length and whether the segment presents
assumed to have insufficient viability for survival and are partial or complete circumferential bone loss. When Orthopaedic
therefore discarded. This concept holds true primarily for cortical Trauma Association members were surveyed with regards to the
fragments of the diaphysis considering its poor surrounding soft definition of a “critical-sized” segmental bone defect, a precise
tissue environment and blood supply. Metaphyseal fragments are size and volume of bone fitting this criteria was not defined.[29]
much less commonly loose or free given the rich periosteum and Some authors have suggested that this usually occurs when the
musculotendinous attachments. Additionally, metaphyseal frag- length of the defect is 2 to 2.5 times the diameter of the bone
ments may contain articular cartilage and/or critical ligamentous involved.[30] Others have described this entity as a defect length
attachments which warrant consideration for retention. All greater than 1 cm and greater than 50% loss of the circumference
viable fragments and reconstructible osteochondral or articular of the bone.[1,31] In general, a “critical” defect is regarded as one
fragments should be preserved.[20–22] that will not heal spontaneously despite surgical stabilization and
In contradiction to the above, a specific scenario relevant to requires further surgical intervention, such as bone grafting.[1,32]
the concept of “critical” sized defect is the very large segmental The SPRINT study remains one of the largest randomized
fragment devoid of soft tissue attachment that, if removed, control trials in surgical history, yet despite including over 1000
significantly worsens the reconstruction challenge. The decision tibia fractures, bone loss was relatively uncommon. In this study
to keep or remove this fragment requires weighing the value of of 1125 patients with tibia fractures, only 37 (3%) had a
the fragment and the risk-benefit ratio of both scenarios. For “critical” bone defect defined as greater than 1 cm in length and >
example, the comparison between a “low value” fragment such 50% of the cortical diameter. Of these 37 patients, 47% achieved
as a moderate sized cortical piece of diaphyseal bone, which can union without additional treatment, suggesting that although
be managed with contemporary techniques and the “high worrisome, this “critical” size defect may not be truly
value” fragment such as the large osteoarticular segment or “critical.”[31] A study conducted by Haines et al may offer the
whole extruded bone that may not be replaceable.[23] Methods most detailed assessment of fracture gap size. In their study, the
on how to treat and reimplant large extruded segments of bone average radiographic apparent bone gap (RABG) measures bone
in an acute and delayed fashion in the open fracture setting have loss on all 4 cortices (Fig. 1). A RABG of < 25 mm had a union
been described in the literature and have demonstrated good rate of 54% and a RABG >25 mm had a union rate of 0%.[33]
results despite going against popular belief; however, this It is important to understand the complex nature of bone
evidence is largely low-level, based on case reports and case healing. The definition of “critical sized” defect is likely
series.[24–27] oversimplified and therefore, bone gap size should not be used
No matter the debridement technique chosen, once thorough in isolation to make clinical decisions. Rather, multiple factors
debridement has been performed, the wound should be from an anatomical, biomechanical, and biological perspective
thoroughly irrigated in the operating room.[28] Issues such as all play a role in predicting nonunion. Anatomical location of the
timing of surgery, amount and type of fluid to be used, primary vs defect has a significant impact on healing potential. For example,
delayed closure, and timing of flap coverage are all important segmental defects of the femur often present favorable soft tissue
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Figure 1. Defining the lower limit of a “Critical Bone Defect” in open diaphyseal tibial fractures. (Taken from Haines NM, Lack WD, Seymour RB, and Bosse MJ.
Defining the lower limit of a “Critical bone defect” in open diaphyseal tibial fractures. J Orthop Trauma 30, e158–e163 (2016).)
environment with spontaneous healing reported in segmental corrected, spontaneous healing of the nonunion without
defects measuring as much as 6 to 15 cm in length.[34] In contrast additional surgical intervention occurred in >25% of patients.[37]
to the femur, the tibia has relatively poor outcomes with lack of Other patient factors such as diabetes, radiation therapy, and
spontaneous healing in segments of bone loss as low as 1 cm with alcohol abuse have also been associated with nonunion.[38]
greater than 50% cortical circumference.[35,36] In the setting of Finally, poor vascular supply to the affected extremity is
nonunion, the biological environment is often the rate-limiting invariably associated with failure of bony and soft tissue
factor, with impaired cellular and molecular signaling, regardless reconstruction. Consultation with a vascular surgeon is recom-
of biomechanical stability. [1,29,31] mended for patients with compromised perfusion, as revascular-
ization may be indicated. The treatment and optimization of these
patients is necessarily multidisciplinary and the source of
5. Surgical management of bone defects in open motivation for many centers to create limb salvage teams which
fracture are better equipped to help treat these modifiable risk factors and
improve the rate of successful outcomes.
5.1. Patient optimization
Patient optimization is a crucial step that cannot be overlooked.
5.2. Induced membrane technique (Masquelet)
Bone healing is predicated on both mechanical stability and a
favorable biological environment; therefore, ignoring this step Although autologous bone grafting has been successful for bone
may be detrimental to overall outcomes. Tobacco cessation, defects < 5 cm in size, defects beyond this size have been
glycemic control, nutritional optimization, and management of associated with a high failure rate due to secondary graft
metabolic and endocrine abnormalities are interventions that resorption and consolidation failure.[7] To address this, Mas-
should be optimized. In a study of 37 nonunions, patients who quelet and Begue described an alternative induced membrane
were referred for metabolic and endocrine testing, abnormalities technique with 3 main benefits.[7] The first benefit is that the
such as vitamin D deficiency, thyroid, and parathyroid disorders PMMA spacer maintains the defect space, preventing surround-
and hypogonadism were found in > 80% of cases with otherwise ing tissue contracture. Second, the membrane created is rich in
unexplained nonunions.[37] With these metabolic abnormalities growth factors including vascular endothelial growth factor,
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transforming growth factor-ß1, BMP-2 and core binding factor phase can often last twice as long as the transport phase.[47] The
alpha-1, that improve graft consolidation by stimulating cell main advantages of using distraction osteogenesis for the
proliferation and differentiation into the osteoblastic lineage.[39] management of segmental bone defects are reliability, ability to
Finally, the membrane creates a separate compartment, protect- bear weight during reconstruction, and, most importantly, the
ing autograft from resorption. absence of limits with regards to size of the defect that can be
The Masquelet technique occurs in 2 stages. The first stage reconstructed. The disadvantages, however, are the length of time
consists of radical bony debridement followed by the placement required to achieve consolidation (an average of 10–12 months for
of a PMMA cement spacer. The bone defect is then stabilized with a defect of 10 cm in size) and the resultant physical and
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external fixation (as originally described), internal fixation, or an psychological burden on the patient with prolonged transports.
intramedullary rod. To allow enough time for the membrane Another method of distraction osteogenesis that has minimized
maturation, the second stage is delayed to allow ideal biologic transport time has been that of bifocal distraction osteogenesis,
and wound bed conditions. The ideal biologic timing is 4 weeks; which involves performing a metaphyseal corticotomy at both
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however, the soft tissues may not be mature enough at this time ends of the defect. This has been demonstrated to reduce
and this often delays surgeon intervention this early. Typically, transport time by 2.5 times as well as that of consolidation by
the second stage is completed 6 to 12 weeks following spacer between 1.3 and 1.9 times. However, this technique also
placement. At this time the membrane is carefully incised and demonstrated slower maturation of regenerated bone. Further-
preserved while the spacer is removed. The void is then filled with more, this technique requires complex frame construct and
autologous bone graft, with or without allograft or other bone meticulous frame management by both surgeon and patient.[47]
substitutes as needed as graft extender. A graft extender should In a recent long-term study looking at the Ilizarov technique,
not exceed a 3:1 ratio of autograft to allograft.[7,40] although all patients eventually achieved union, the rate of union
The time required prior to initiation of full weight bearing is was 91.2% with a 29% reoperation rate.[48] Other studies have
fracture and fixation dependent. By definition, fixation of any reported union rates between 92% and 94%,[46,49] with 1 study
segmental defect requires a load-bearing fixation construct, since requiring secondary bone grafting in 36% of patients to achieve
no initial bone-to-bone contact exists at the outset to share load union.[46] Neurovascular complications and amputation rates
have been reported at 2.2% and 2.9% respectively.[49]
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with the implant. Also, the time required for the bone graft to
incorporate and corticate to a degree that it can bear load is often Hybrid techniques in bone transport have demonstrated a
much longer than in typical fracture healing. As a result, the decrease in time required for external fixation by stabilizing the
fixation construct must be able to withstand both high peak loads bone with internal fixation during the consolidation phase.
and many cycles of submaximal loads without failure. With Kocaoglu et al[50] transported bone over an IM nail with an
multiplanar external fixators coupled with hydroxyapatite average defect size of 10 cm (femur) and 7 cm (tibia). The external
coated external fixation pins, locked IM nails, locking plate fixator index (EFI), which is calculated by dividing the number of
technology, and allograft cortical substitution, very stable and days in the external fixation by the total length of the defect, was
rigid fixation constructs can be created and immediate full weight 13.5 d/cm.[50] Once the transported segment reaches the docking
bearing may be permitted. However, the optimal mechanical site and the frame is removed, the segment is secured using
environment for graft healing remains unknown, though locking screws through the nail. Oh et al,[51] using a similar
Masquelet has empirically recommended high initial fixation technique, demonstrated 100% union with no malunion and an
rigidity to promote incorporation followed by more flexible EFI of 13.4 days. This hybrid technique has led to increased
fixation to promote remodeling and cortication.[40] patient comfort, decreased complications with more convenient
Masquelet and Begue’s initial series of 35 patients with defects and rapid recovery. However, these devices are significantly more
ranging from 5 to 24 cm in length demonstrated graft incorpo- costly and present an increased risk for subsequent deep infection
ration and defect healing in 89% of patients.[7] This has since due to the use of an internal fixation device.[39]
been replicated in other studies with success rates of 85% to 92%
reported;[41] however, multiple interventions may be required to
5.4. Acute limb shortening and lengthening
achieve union with this technique.[42–44] In summary, the
Masquelet technique is reliable and allows for reconstruction Although uncommon, if faced with segmental bone loss in the
of large segmental bone defects. Its advantage over distraction upper extremity, limb shortening is a viable option as function is
osteogenesis is that time to union is not dependent on the size of not dependent on limb length symmetry.[39] This technique can
the bone defect, whereas its main disadvantage is the need for also be utilized in the lower extremity, but less commonly. It is the
sufficient volumes of autologous bone graft to be successful. simplest and presumably fastest treatment option for segmental
bone loss. It allows for early primary closure without soft tissue
tension, which can allow for delayed lengthening via distraction
5.3. Distraction osteogenesis
osteogenesis once the soft tissue envelope has healed.[52] However,
Management of segmental bone loss with distraction osteogenesis a major known complication of acute shortening is kinking of the
involves the transportation of a segment of bone in a controlled arterial system and is most commonly seen with shortening of more
fashion, typically via the use of an external fixator or an IM device. than 3 to 5 cm5; therefore, thorough monitoring of pulses during
This was initially described by Ilizarov while treating nonunions and after surgery is paramount to prevent this complication. Also,
with fine wire circular frames.[45] With the advent of the spatial and acute limb shortening can impair muscle contractile function if the
monolateral frames, this technique has gained further populari- muscle length-tension relationship is excessively altered.
ty.[39] In brief, once the frame has been applied with fine wire or half
pins, a metaphyseal corticotomy is performed and the transport
phase begins. This may occur at a rate of up to 1 mm per day.[46] 5.5. Vascularized fibular allograft
Once the transported segment reaches the docking site, it is The vascularized fibular graft was developed in the 1970s as the
compressed for weeks until healing occurs. The consolidation microvascular field evolved. It had been the preferred choice for
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defects > 10 cm; however, it has lost some of its popularity with in-vitro and in-vivo animal models, if proven to be fruitful for the
the dawn of the improved induced membrane techniques and treatment of “critical” bone defects, it may be able to solve the
distraction osteogenesis. The main drawbacks of this technique problem of donor site morbidity in the case of autograft harvest
are the associated donor side morbidity and the need for a as well as disease transmission, lack of osteogenicity, cost, and an
microvascular trained surgeon to perform the procedure. In a already limited supply of allograft bone. To do so, 3D bioprinting
study looking at its use in the treatment of type III tibia fractures, combines a biocompatible scaffold that recapitulates the natural
a donor site morbidity of 30% was reported.[53] Furthermore, bone extracellular matrix niche, inclusion of osteogenic cells to
restricted weight bearing is required to prevent fractures during secrete the necessary extracellular matrix, and morphogenic
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fibular hypertrophy, which can take up to 2 years. Despite signals that spatiotemporally biodirect the cells to the phenotypi-
prolonged protected weight-bearing, approximately 20% frac- cally desirable type and sufficient vascularization to meet the
ture during the first year.[54] When resecting the fibula in this growing tissue nutrient supply and metabolic needs.[66] Bio-
technique, bone can be taken as close as 4 cm to the fibular head printing also provides a much better compressive modulus, one
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without compromising the proximal tibiofibular joint and up to 6 that can exceed 500 kPa, approximating human tissue compres-
cm proximal to the ankle joint without causing ankle instabili- sive moduli,[67] where conventional bone grafts possess poor
ty.[54] Despite its significant donor site morbidity and fracture compressive modulus.[68] These prints would not only be patient
risk, union typically occurs within 6 to 9 months, which is specific from a geometric standpoint but also the level of tissue
substantially shorter than other reconstruction techniques with insufficiency and the anatomy of the composite tissue as well as
union rates reported as high as 97%.[53,55] vascular network. As this technology evolves, this additive
manufacturing technique may be used to reconstruct bone as well
as articular cartilage in areas where our current available clinical
6. Modern techniques in the management of bone
technologies and tissue manufacturing strategies fail.
defects
Current treatment modalities pose a significant burden to the
7. Conclusion
patients both physically and psychologically as these treatments
“Critical” bone loss associated with open fractures is a relatively
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are lengthy and cumbersome for the patient to live with on a daily
basis. To address these issues, both technique and technology uncommon but very challenging problem. The tibia and the
must evolve in order to better treat this problem and allow femur are the most commonly involved sites, and bone loss in the
patients to achieve a better quality of life during treatment. upper extremities and articular surfaces is rare. Bone defects can
vary dramatically in size and selecting the most appropriate
treatment plan to address a given defect, must be carefully
6.1. Plate-assisted bone segment transport (PABST)
thought out on a case-by-case basis. Detailed discussion and
Although only a case report, Barinaga et al[56] were recently able shared decision making with the patient is critical since these are
to treat a 51-year-old male presenting with a type IIIB tibia often life-changing injuries and surgical procedures that have
fracture with segmental bone loss with an all inside technique, lasting impacts on quality of life.
involving a combination of internal fixation for bony stability There are many techniques available to treat these complex
and the PRECISE 2 IM Limb Lengthening System (Nuvasive), injuries and determining the best approach for each scenario remains
which they used for all inside distraction osteogenesis. Although controversial. In order for these techniques to yield optimal results,
this novel IM system cannot be used for all sizes of defect, it does each injury must be approached in a step-wise and multidisciplinary
allow for up to 80 mm of lengthening. This system may also fashion to ensure that care is taken in bone and wound bed
provide more precise distraction as it is capable of bidirectional preparation, that soft tissues are healthy and free of contaminants,
control, which allows for both distraction and compression (i.e., and that the patient’s medical condition has been optimized. With
the accordion technique).[57–60] To their knowledge, this group is the advances in all inside distraction osteogenesis techniques as well
the first to describe the use of this IM system to correct a “critical” as 3D bioprinting with enhanced biologics, restoring satisfactory
bone defect via segmental bone transport without shortening or limb function may not pose as much of a burden physically,
concurrent use of an external fixation device and have coined psychologically, and economically as it continues to today.
the technique as plate-assisted bone segment transport. The
advantages of this technique are that it reduces joint stiffness and
7.1. Case 1
muscle contracture associated with shortening and secondary
lengthening,[61–63] it eliminates the need of an external fixation Eighty-seven-year-old female was involved in a motor vehicle
device which is uncomfortable for the patient and associated with accident in July of 2017. On initial assessment, she presents an
several postoperative complications; and lastly, the magnetic open distal femur fracture with segmental bone loss, ipsilateral
device removes the need for subcutaneous receiver antenna;[64,65] intertrochanteric hip fracture (initial x-rays not available), right
therefore, potentially removing a source of failure. Although closed wrist fracture, left bimalleolar ankle fracture, intracranial
further work remains to be done regarding this technique, it does hemorrhage, flail chest injury, and multiple spinal fractures.
look promising for the future. Prior to arriving at our center, she is treated at an outside
Level 1 Trauma Centre for her above-mentioned injuries.
Primary treatment of her open femur fracture with associated
6.2. Three-dimensional bioprinting
14 cm segmental bone defect involved irrigation and debride-
Three-dimensional (3D) bioprinting is a tissue engineering ment, open reduction and internal fixation with distal femoral
fabrication method that uses spatial patterning of living cells locking plate and placement of PMMA spacer in 1st stage
and other biological materials assembling them in a layer-by- Masquelet technique, as well as supplementary ipsilateral short
layer deposition approach for the construction of living tissue and InterTAN femur nail for treatment of her basicervical femoral
organ analogs.[66] Although most of this work has been mainly in neck fracture (Fig. 2).
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Figure 2. (A) AP, (B) lateral left femur (C) AP pelvis, and (D) Iateral left hip 3 weeks postop from irrigation and debridement, with open reduction internal fixation of
distal femur, short InterTan and first stage Masquelet technique at an outside tertiary care center.
Figure 3. (A) AP, (B) lateral left femur, and (C) AP left hip postoperative day 1 from second stage masquelet technique with fibullar strut allograft.
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Figure 4. (A) AP and (B) lateral left femur 6 months postop, demonstrating maintenance of internal fixation stability, and good consolidation.
Figure 5. (A) AP and (B) lateral left femur 1 year postop, demonstrating maintenance of hardware fixation, and complete graft consolidation.
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