The Ilizarov technique has been used successfully for many years to treat bone defects [5, 7–10, 19, 20], and bone transport can be recently accomplished with many devices, such as circular fixator, unilateral fixator, or intramedullary nail systems. Each device has its advantages and disadvantages [2, 21]. However, to our knowledge, few studies focus on the TGBD after removal of the external fixator in the finished lower limb's bone transport. In this study, complete electronic medical records and at least 20 postoperative months of follow-up data of 178 patients who were managed the bone transport surgery using a unilateral external fixator for bone defects were collected and analyzed to figure out the incidence and associated risk factors of TGBD. Briefly, the occurrence of TGBD was in forty-two (12.3%) of 178 patients. Furthermore, defect of tibia, BMI > 25kg/m2, duration of bone infection > 24 months, age > 45years, and diabetes were the top five risk factors. The incidence of developing TGBD among patients having three or more risk factors is 22–42%.
Via published research [1, 2, 5], a satisfactory bone union index with the Ilizarov technique using an external fixator than internal fixation has been noticed. Compared with the Masquelet technique, autologous bone graft and other options, the external fixator is capable to adjust the direction and angle of bone transport under direct vision, which gives the ability to lengthen or shorten the length of the bone and correct the angular deformity. The case series published by Li et al. illustrated that the unilateral external fixators possessed the advantages of lightweight, simple operation and better patient acceptance. However, in the comparison of the circular external fixator, the stability of the whole frame is poor, and the force line distribution is not uniform enough since the two-dimensional spatial configuration. So the transport of bone segments at multiple angles during bone transport or lengthening cannot be adjusted. If not intervened, the fresh bone in the transport area may be affected and contribute to the occurrence of TGBD. Moreover, the published study also pointed out that fresh bone formation tissue with differentiation ability indeed lived in the transport gap and changed the growth direction easily under the mechanical stimulation by external force [22, 23]. TGBD, bone shortening, and even failure of bone transport were at a high rate of occurrence if bone healing in the transport gap was not assessed accurately according to ASAMI criteria. Therefore, one of the challenges faced by orthopaedic surgeons using the bone transport technique for bone defects was to grasp the standard of transport gap bone consolidation and construct stable external fixation frames for bone transport to avoid TGBD after the external frame is removed. Certainly, the equally important was to identify the potential risk factors that patients may have and keep them away from these promptly before such a dreadful outcome occurred.
TGBD may be attributed to many factors, such as the patient's physical function, the status of the bone, the mechanism and location of the bone defect, and additional violence [3, 24–28]. Our results showed that patients older than 45 years (OR0.88, CI0.82-0.94) were more likely to acquire the TGBD. Via published studies [29–32], ageing is often considered to be accompanied by the loss of bone calcium, resulting in osteoporosis, which greatly increases the duration of the consolidation stage, the EFT as well as EFI. Another conjecture is that lower extremity bones in the elder are less able to cope with deformity caused by additional forces than young bones, such as bending and rotation. For instance, the extraosseous morphology of the bone in the elder, the internal trabecular structure, and the connective tissue filled around the trabeculae are degraded in quantity and biological activity [33–35]. These reasons have become the culprit of TGBD in elderly patients gradually. Hence, prophylactic administration of calcium supplementation is recommended when bone transport is managed for patients > 45 years.
Obesity (OR2.42, CI1.01-5.79) and osteoporosis (OR0.40, CI0.18-0.81) are two common diseases with increasing incidence. Fat and bone are connected by many pathways that ultimately serve to provide a skeleton suitable for the quality of the adipose tissue they carry . Leptin, adiponectin, and insulin/amylin are all associated with this connection . However, excessive body fat, especially abdominal fat, produces inflammatory cytokines, which stimulate bone resorption and reduce bone strength, as has been pointed out by recent studies [18, 36–39]. Despite some studies have shown conflicting results that the resistance of lower limb bones to deformity can be enhanced by obesity, more evidence holds that obesity may be involved in an increased risk of skeletal disorders, as well as the skeletal structure deformity after reconstruction. Similarly, obese patients were nearly 2.7 times more likely to have TGBD than normal-weight in this study. This phenomenon can be explained exactly by the high weight load on the lower limb bones, and abnormal bone metabolism caused by the inflammatory factor pathway of obesity. Then, it is meant to emphasize weight control through a healthy diet and exercise for preventing TGBD when the external fixator was removed.
TGBD occurred in more femoral bone transport (OR2.51, CI1.16-5.42) than the tibial in our cohort, after the removal of the external fixator. With the view of anatomy, there is better soft tissue coverage in the femur than in the tibia, which means a richer blood supply. With this, nutritional elements required for new bone formation can be accumulated in the femur in a shorter time, which makes the bone union time, EFT, and EFI lower in the treatment of bone defects. However, the greater forces biased toward the alignment force line of the femur than the tibia are also brought by such abundant muscle (i.e., quadriceps, anterolateral thigh muscle, etc.) attachments, which requires the surgeon to design a more stable external frame structure. Our experience is to increase the length of the external fixator railway to obtain a moment. When the length between the proximal or distal clamp and the transport segment clamp is greater than the 1.5 times length of one normal clamp, the stability of the external frame can be increased by adding a new clamp in between these according to the location of the bone defect. Besides, the stronger holding force may be received by inserting three Schanz screws on each of the clamps in the proximal and distal metaphysis, the hydroxyapatite-coated screws are also recommended for utilization. However, for the clamps in the middle part of the bone, including the transport segment clamp, we believe that it is practical to insert the screws in the 1st and 4th position of the clamp. As for the tibia, there is no such physiological structural advantage in tibial defects, especially in the lower third of the tibia, which is the location of structural changes. A higher rate of nonunion and skeletal structure deformity has been observed here by previous studies [16, 40] since the less blood supply and poor soft tissue coverage. However, whether there is an association between the occurrence of TGBD and the delayed union is unknown. We consider that the occurrence of the delayed union can be reduced by the early reasonable walking exercise of the lower limb, under stable external fixation. Non-weight-bearing walking exercise with the crutches for 2–4 weeks after removal of the external fixator, which is a feasible way to prevent bone shortening or TGBD caused by self-gravity compression. Gradual resumption of weight-bearing walking is recommended when the radiographs showed that the screw holes were filled with new bone.
At the same time, some causal relations were noticed in our cohort between TGBD and some comorbidities, such as diabetes (OR0.46, CI0.19-0.80). While microvascular and peripheral nerve degeneration is the most common complication of diabetes, the risk of osteoporosis and pathological skeletal structure deformity must also be considered when treating bone defects in diabetic patients [41–44]. The newly generated bone was affected by the unique interactions, given the causes which lead to different types of diabetes . Controversy exists regarding the exact mechanism of bone loss in the diabetic environment, but there is a shred of important evidence to support that high concentrations of glucose are toxic to osteoblasts , which are implicated in the formation of bone. Serum osteocalcin levels in diabetic patients also appear to be suppressed by hyperglycemia. High glucose concentrations impair the ability of osteoblasts to synthesize osteopontin for bone formation . Simultaneously, the risk of TGBD caused by falls is also increased by common complications in diabetic patients, such as poor visual acuity, peripheral neuropathy, and reduced balance [41, 44]. As detailed above, there is strong evidence that bone loss and increased risk of pathological skeletal structure deformity can be caused by diabetes and its associated complications, regardless of type. In this study, there were 11 diabetic patients associated with osteoporosis at the same time. And TGBD was observed in all of these patients since their fragile new bone. Therefore, postoperative management is of great importance for diabetic patients to avoid TGBD, including personalized diabetes plans to achieve glycemic control safely, calcium supplementation, and antiresorptive agents.
Radical debridement is a key step in the control of bony infection, especially post-traumatic osteomyelitis [2, 15, 45]. Subsequently, the problem of bone loss after radical debridement has been solved by the bone transport techniques, which are based on the principle of distraction osteogenesis. Gradually, these two procedures constitute a systematic protocol for the treatment of infected bone defects [2, 5, 9, 15]. Although the definition of radical debridement has been illustrated, the occult nature of bone infection makes its long disease period without typical symptoms, which may not be easy for normal surgical procedures or antibiotics to control, which brings out insidious bone destruction. In this study, unfortunately, each patient in our cohort had a duration of bony infection of at least 16 months. The average duration of bone infection (OR1.07, CI0.99-1.15) was up to 25 months in patients who experienced TGBD. The microarchitecture of the bone (periosteal and trabecular) and the surrounding blood vessels were destroyed by such a prolonged duration of bacterial infection undoubtedly [17, 46]. Bone mineral density was then reduced, resulting in poor bone healing quality and bone degeneration was even aggravated. Simultaneously, immobilization osteoporosis may be caused by less mobility since the discomfort and pain of the affected limb, which increased the difficulty of bone transport and reconstruction surgery. Besides, EFT (OR0.10, CI0.03-0.33) and EFI (OR0.06, CI0.01-0.27) were also risk factors for TGBD during bone transport. One of our conjectures is that the immobilization osteoporosis of the reconstructed bone was brought about by the longer EFT and higher EFI when treating patients with a long period of bone infection, especially in the treatment of critical size bone defects (> 4.5cm). The larger bone defect requires more adjustment for the clamp procedure and the angle of transport bone segment, which was also a great challenge for orthopaedic surgeons and patients. Hence, radical debridement is recommended in the event of bone nonunion caused by infection. Double-level bone transport is a practical option for the reconstruction of critical bone defects. The immobilization of osteoporosis may also be avoided effectively by early walking exercise after bone transport surgery. For example, non-weight-bearing walking with crutches was recommended to start on the second postoperative day and gradual normal walking was managed in the second week.
In our study, TGBD was recorded in 42 cases, and the more risk factors patients had, the higher incidence of TGBD they got (Table 4). There are still ways to cope with this complication, including the open reduction and internal fixation (intramedullary nail and internal plate), external fixator after close reduction (unilateral fixator or external locking compression plate) and plaster or splint fixation after manual reduction. Fortunately, bone unions were received by patients with TGBD, through treatment with the above methods. Additionally, a satisfactory recovery that the excellent and good rate of the bone result was 81.5%, and the excellent and good rate of function outcome was 92.3% were obtained in our cohort. Amputation surgery was performed on no patient and none of the infection recurrences occurred.
Last but not least, there are some advantages in this study, including a large number of patients, standard techniques, and multi-level data comparison. However, it also has several drawbacks. First of all, this was a retrospective study of a patient with two different bone locations for the osteomyelitis caused by an infection in a single medical institution, the results should be considered carefully. Secondly, only one technique was applied to treat infectious bone defects, the ability was then lacked to compare with other techniques. This indicates that (multi-centre) collaboration is essential to pool treatment results from individual hospitals into (prospective) clinical studies and subsequently into meaningful analysis.