Keywords
induced membrane technique - bone defect - infected non-union
Introduction
The bone is one of the few organs that, even in adults, retains its regenerative potential.
It preserves its original pre-fracture properties before fracture and can consolidate
primarily or secondarily. In secondary consolidation, intramembranous and endochondral
ossification forms a bone callus due to osteoprogenitor periosteal cells and undifferentiated
mesenchymal cells stimulation. This stimulation activates a cascade of cell proliferation
and differentiation that, with adequate vasculature, culminates in bone callus formation.[1] Bone defect management is complex in traumatology. It has been reported that significant
bone loss occurs in 0.4% of fractures, and this percentage is higher in open fractures.
Even with adequate fixation, defects larger than 2 centimeters are unlikely to heal
spontaneously. In selected cases, debridement to remove necrotic or infected edges
increases the initial defect, creating a more difficult scenario for the reconstruction
of the affected bone.[2]
Bone defect repair techniques include the distraction osteosynthesis (DO) and the
induced membrane technique (IMT) described by Masquelet.[1]
DO consists of bone formation between two vascularized fragments separated by slow,
gradual traction. Under the right conditions, bone neoformation occurs through intramembranous
ossification.[3]
Another alternative for bone defect reconstruction, particularly larger ones, is the
membrane ossification technique or MOT. In their original work, Masquelet et al. reported
100% union in segmental bone defects ranging from 4 to 25 cm. This technique combines
the formation of a biological membrane with characteristics similar to the periosteum
and an avascular bone graft.[4] The Masquelet technique consists of two stages. The first stage is the debridement
of the infected, necrotic, or tumorous bone tissue, followed by the implantation of
a cemented polymethylmethacrylate (PMMA) spacer, which may or may not be soaked in
antibiotics, and bone defect fixation using internal or external immobilizers. The
second stage consists of spacer removal, preserving the formed membrane, bone edge
debridement, and placement of a bone graft in the defect.[5]
This paper reviews two cases of gunshot open fractures progressing with infected non-unions
and bone defects and the subsequent bone reconstruction with IMT.
Case 1
A 43-year-old female patient suffered an open fracture of the distal femur due to
a gunshot. The radiograph showed a comminuted fracture of the left distal femur ([Figure 1]), and a computed tomography (CT) scan ruled out vascular damage. The patient was
admitted and received an external fixation. She was admitted again four days later
for definitive surgical management, i.e., placement of a retrograde intramedullary
nail (rIMN) in the femur. Serial imaging follow-up occurred while the patient underwent
motor kinesitherapy with progressive loading starting six weeks after definitive surgery
with rIMN. However, in the outpatient follow-up 8 months after surgery, she reported
pain with a visual analog scale of 5/10 at rest and 7/10 under load. Physical examination
revealed surgical wounds with no signs of infection but a slight increase in volume.
Inflammatory parameters were within the normal range. A CT scan of the left femur
([Figure 2]) showed atrophic non-union of the distal femur.
Figure 1 Comminuted fracture in the left distal femur.
Figure 2 Computed tomography scan 8 months after surgery. Note the atrophic non-union (orange
arrow) with no bone callus but presenting edge resorption.
The patient was admitted again due to a suspected atrophic non-union with abundant
necrotic tissue. We performed aggressive debridement of all devitalized tissue, leaving
a bone defect measuring 4 × 4 × 3 cm. We decided on IMT and collected culture and
biopsy samples. Subsequently, we filled the defect with bone cement with 1 g of vancomycin
surrounding the previously placed nail ([Figure 3]). As cultures revealed Staphylococcus epidermidis, we evaluated the patient after surgery for infectious disease to define antibiotic
therapy. Antibiotic therapy continued for 8 weeks, before the second stage of the
Masquelet technique. Upon completing the antibiotic therapy and evaluating the inflammatory
parameters, we decided to perform the second stage. In this surgery, we removed the
cemented spacer, replaced the rIMN, and filled the defect with a mixture of femoral
head autograft and allograft ([Figures 4] and [5]), preserving the Masquelet membrane. Postoperative follow-ups revealed a good clinical
evolution, with clinical and radiographic bone consolidation at 6 months ([Figure 6]). At the 27-month follow-up, the patient had bone remodeling and excellent clinical
outcomes, with normal gait and full range of motion.
Figure 3 Intraoperative image from the first stage of the Masquelet technique. A) Bone defect
after necrotic, devitalized tissue debridement of an infected non-union 8 months after
the initial surgery. Stabilization with an intramedullary nail. B) Bone defect filling
with cement (polymethylmethacrylate) and vancomycin (arrow) covering the whole defect.
Figure 4 Anteroposterior and lateral radiographs after necrotic, devitalized tissue debridement.
Note the polymethylmethacrylate cement (orange arrow) with vancomycin around the intramedullary
nail covering the 4 x 4 x 3 cm bone defect.
Figure 5 Intraoperative view of the femur at the second stage of the Masquelet technique.
A) Note the femoral bone defect with intramedullary nail in situ and preserved membrane
(arrow). B) Filled bone defect using autograft and allograft, achieving full coverage.
C) Postoperative anteroposterior radiograph showing the complete bone defect coverage
with the graft.
Figure 6 Anteroposterior, lateral, and oblique 9 months after surgery. Note the radiographic
bone consolidation in at least three cortices.
Case 2
A 21-year-old male patient went to the emergency room due to an open distal femur
fracture caused by a gunshot ([Figure 7]). After admission, the patient underwent surgical cleansing and received an external
device.
Figure 7 Anteroposterior radiograph of the left distal femur. Displaced comminuted fracture
at the left distal femur.
The placement of a retrograde femur nail occurred 3 weeks later. The patient was discharged
the next day ([Figure 8]).
Figure 8 Anteroposterior radiograph of the left distal femur after intramedullary nail placement.
Two weeks after discharge, he returned to the emergency room due to persistent bleeding
from the surgical wound and a 10-point drop in the packed cell volume. As an angioCT
revealed femoral artery pseudoaneurysm, the patient was hospitalized for aneurysm
repair. During this procedure, we noted a purulent secretion from the wound next to
the fracture focus. We collected culture samples from the surgical bed, which were
positive for multidrug-resistant, carbapenem-sensitive Serratia marcenscens. After
the osteomyelitis diagnosis, antibiotic therapy started.
Since then, the patient underwent multiple surgical cleanings, with pre-cleaning cultures
positive for the same infectious agent with equal sensitivity. At one cleansing, a
bone tissue culture was positive for Enterococcus faecalis, so we adjusted the antibiotic therapy. We removed the intramedullary nail and placed
external devices ([Figure 9]). In the last cleaning, 3 months after readmission, we performed bone sequestration
resection, leaving a 4 cm defect. We filled this defect with tobramycin and cement,
maintaining fixation with external devices ([Figure 10]). Six weeks later, we proceeded to the second IMT stage, removed the external devices,
and placed an intramedullary nail and an iliac crest autograft ([Figure 11]). Serial radiographs during hospitalization showed bone callus formation and fracture
consolidation ([Figures 12]).
Figure 9 Anteroposterior and lateral radiograph of the left femur after intramedullary nail
removal and external device placement.
Figure 10 Anteroposterior radiograph of the distal femur. Note the bone defect filled with
cement (polymethylmethacrylate) and tobramycin (orange arrow).
Figure 11 Anteroposterior radiograph of the distal femur after external device and cement spacer
removal and intramedullary nail and cement placement at the bone defect with iliac
crest autograft (orange arrow).
Figure 12 Anteroposterior radiographs of the distal femur. Note the bone callus formation and
fracture consolidation 2 (left) and 6 months (right) after the second stage of the
Masquelet technique, respectively.
Discussion
IMT was a successful salvage surgery for two patients with medium-sized bone defects
after a femur non-union caused by a gunshot wound. The outcomes were satisfactory,
with bone defect repair, adequate infection control, and subsequent good functionality.
IMT is an attractive alternative for managing infected non-unions and bone defects,
particularly those ≥ 4 cm.
Treating long bone defects in the lower extremities remains complex, with no consensus
on its management, which is frequently salvaged, particularly in infectious non-unions
or tumor lesions. Treatment of small defects, up to 2 cm in length, may use an autologous
cancellous bone graft,[6] while larger segmental bone defects, especially those exceeding 4 to 5 cm, typically
require bone transport by DO or bone graft through the induced membrane.[7]
[8] The Masquelet technique is an attractive alternative for treating these defects.
This technique has been proven effective in treating bone defects caused by trauma
or surgical debridement due to infections and non-unions.[5] Since its publication in 2003, IMT has been widely accepted, with a percentage of
67 to 100% union in well-indicated surgeries and a success rate higher than 90%.[9] In infected post-traumatic segmental bone defects in the tibia and femur, the Masquelet
technique has also achieved a consolidation rate of over 95%.[10] In addition, it is widely used and the preferred technique for traumatic bone defects
and those caused by gunshots in the military.[11]
The main alternative to the Masquelet technique is DO, which induces bone formation
between two vascularized bone fragments that slowly and gradually separate, forming
new bone through intramembranous ossification.[12]
[13]
Few studies have compared DO and IMT. Animal studies have suggested their therapeutic
effects on segmental bone defects depend on the lesion size. Zhen et al. studied bone
repair in mice using radiographic, CT, histological, and immunohistochemical follow-up
for bone defects of different sizes treated with IMT or DO. For small segmental bone
defects, DO proved to be more appropriate and efficient than IMT, while the opposite
occurred in larger defects, with a clear advantage of IMT over DO.[14] To our knowledge, no studies to date directly compared the Masquelet technique with
DO. Multiple guidelines showed both techniques are effective but recommend the IMT
or DO for large bone defects, particularly those over 15 cm.[15]
[16]
[17] DO provides a 95% success rate, early loading (when performed with an external Ilizarov
device), angiogenesis stimulation, and production of good quality bone.[15] Important disadvantages include the technical difficulty in its implementation,
the need for considerable and prolonged patient compliance, long treatment times,
the need for unloading during treatment (with exceptions, such as Ilizarov external
fixation), risk of nail and path infection, non-union, chronic pain, and joint contractures.[15] For DO, the elongation rate ranges from 0.5 to 1 mm per day, which is a significant
issue when dealing with large bone defects, sometimes requiring 18 months or more
for correct treatment.[3]
[14] In contrast, IMT offers a clear advantage in medium and large bone defects (≥ 4 cm)
since the repair usually does not depend on the defect size, and most defects heal
in 8 to 12 months. The complete consolidation of a 25-cm bone defect occurred in 12
months.[16]
[17]
[18]
[19] Moreover, it uses standard surgical techniques and implants as a less technically
demanding surgery; it allows early loading with intramedullary nails, and the need
for high patient compliance and frequent clinical follow-up is lower, especially with
internal fixation.[16] A significant part of these advantages comes from the membrane, which is essential
to provide vascularization and growth factors to the bone autograft filling the defect,
ensuring that this graft acts as a guide for bone callus formation and defect repair.
Reviewing IMT, Taylor et al. reported that the membrane is well vascularized and consists
of type I collagen with fibroblasts, an inner layer of epithelial cells, and high
vascular endothelial growth factor (VEGF), runt-related transcription factor 2 (RUNX2,
also known as core-binding factor subunit alpha-1 [CBFA1]), transforming growth factor
(TGF)-ß1, and bone morphogenetic protein 2 (BMP2) levels. These authors also noted
a second internal membrane around the nail, potentially increasing local vascularization
and osteoinductive factor levels.[15]
[20] There were two cases of infected non-union with post-surgical cleaning defects of
at least 4 cm treated with the Masquelet technique. Both cases achieved excellent
outcomes, with infection management, clinical and radiological consolidation, and
favorable functional results.
Today, there is no evidence comparing IMT and DO, and no solid literature supports
one technique over the other. In our experience, for bone defects greater than 4 cm,
particularly in infectious non-unions, the Masquelet technique offers clear advantages
compared to DO, leading to good outcomes when used correctly.
Conclusion
Based on our experience with these cases and the literature analyzed, we consider
IMT a good alternative in patients with bone defects greater than 4 cm, particularly
in infected non-unions, with excellent outcomes. The advantage offered by IMT regarding
infection management and bone defect repair makes it a highly attractive alternative
for these cases. This technique allows limb salvage, is less dependent on the patient's
compliance, and allows consolidation in limited times.
