4. Discussion
Building upon our previous study “Predictive Factors for docking site procedure in bone transport for large lower extremity segmental defects,” we have now examined 93 patients with various types of segmental transport for bone defects of the lower extremities and comorbidities with respect to predictive factors for the necessity of a docking site procedure [
1]. In addition to these factors, Risk Zones for the necessity of a docking site operation were created based on our data. The most reliable predictors were transport duration with a valid cut-off value above 290.5 days and transport speed with a cut-off value of 0.1340 mm/day.
The four-quadrant representation in
Figure 5, formed by the identified cut-off values for transport speed (horizontal: 0.35–0.4 mm/day threshold zone) and transport duration (vertical: 290.5 days), demonstrates a potential prognostic stratification approach based on our empirical findings. The lower right quadrant (speed < 0.35 mm/day, duration > 290.5 days) constitutes a high-risk zone where all 7 patients (100%) required a docking site procedure, yielding a positive predictive value (PPV) of 100% for this zone. The upper left quadrant (speed > 0.4 mm/day, duration < 290.5 days) represents a low-risk zone containing 12 of 14 patients (85.7%) who did not require docking site procedures and none of the 25 patients who required procedures, corresponding to a negative predictive value (NPV) of 100% within this zone. The overall model sensitivity for identifying patients requiring docking site procedures was 72.0% (18/25 patients correctly identified by the duration threshold > 290.5 days), while the specificity was 85.7% (12/14 patients correctly classified as not requiring intervention). It should be noted that the intermediate zone (speed 0.35–0.4 mm/day) contains patients from both outcome groups, highlighting the need for close clinical monitoring in this range. These predictive values should be interpreted cautiously, given the small sample sizes in individual quadrants, and require prospective validation.
This risk stratification model represents a methodologically innovative approach to assessing docking site procedure likelihood by integrating two readily obtainable clinical parameters. Despite the significant correlations observed, our findings are constrained by the limited sample size (n = 39 segmental transport patients, of which n = 25 required docking site procedures). The model could potentially serve as a foundation for future refined frameworks that incorporate additional parameters such as vascularity, soft tissue coverage, and specific defect locations—factors identified as potentially significant in both our analysis and existing literature [
2]. Such developments could contribute substantially to standardizing assessment and treatment protocols for docking site complications in segmental transport cases, though prospective validation in larger cohorts remains essential before clinical implementation can be recommended.
Our results differ from our previous findings, “Predictive factors for docking site procedure in bone transport for large lower extremity segmental defects”. While a cut-off value of 188 days for transport duration was identified there (sensitivity 72%, specificity 67%, AUC 0.78), the updated data with 93 patients show a cut-off value at 290.5 days (sensitivity 72%, specificity 85.7%, AUC 0.911) [
1]. This discrepancy in cut-off values likely reflects fundamental differences in cohort composition. The pilot study (n = 27) exclusively included patients who underwent segmental bone transport, whereas the current analysis encompasses a broader institutional cohort of 93 patients with various treatment outcomes, of which only 39 (41.9%) received segmental transport. Additionally, as a tertiary referral center, our expanded cohort may include proportionally more complex cases with longer treatment durations, potentially explaining the shift toward higher cut-off thresholds. The improved diagnostic accuracy (AUC 0.911 vs. 0.78) in the current study may reflect the larger sample size, providing more stable estimates.
Particularly striking is the difference in transport speed as a predictor. While a cut-off at 0.32 mm/day with moderate predictive power (sensitivity 78%, specificity 44%, AUC 0.48) was found in our previous study, the results of this study show a significantly lower cut-off of 0.1340 mm/day with better diagnostic accuracy (sensitivity 72%, specificity 100%, AUC 0.931). This discrepancy could be due to the different transport methods [
1].
Our study included 93 patients, predominantly male (78.5%), with a higher prevalence of tibial defects (73.1%) compared to femoral defects (26.9%). The main causes of the defects were fractures (55.9%), osteomyelitis (38.7%), and tumors (5.4%), with a remarkably high rate of open fractures (86.2% of documented cases). Despite the obvious gender imbalance in our cohort, gender did not prove to be a significant predictor (p = 0.217) for complications or the necessity of intervention, in contrast to some studies suggesting gender-specific differences in bone healing and complication rates.
Regarding treatment approaches, amputation was the most commonly applied treatment in our cohort (45.2%), followed by segmental transport (41.9%) and the Masquelet technique (12.9%). Among the 39 patients who received segmental transport, 53.8% used the piston technique, which we included in our previous study, resembling a combination of a classic external segmental transport by the LRS monorail system and the first step of the Masquelet technique, which the literature recently reported as the piston technique. Retrospectively, the reasons for amputation could not be reconstructed, for example, using the Mangled Extremity Severity Score (MESS). Beyond amputations, transport methods showed variations between Monorail (52.6%), Ring fixator (31.6%), and intramedullary nail transport (15.8%). The relatively low use of nail transport (15.8%) is consistent with observations that bone transport with magnetic nails is a relatively new technique with limited evidence, mainly from case series and case reports [
3,
10].
Docking site procedures were required in 64.1% of segmental transport cases. Our results are consistent with a systematic analysis by Liodakis et al., which showed that planned docking site interventions significantly improved union rates [
4]. In their pooled analysis of 1153 patients from 23 studies, 90% of docking sites with planned interventions achieved union without further intervention, compared to only 66% in pure observation groups (
p < 0.0001) [
4].
Our data analysis showed high rates of pseudarthrosis (54.3%) and impaired wound healing (37.0%), highlighting the complexity in treating bone defects. Microbial pathogens were detected in 83.7% of patients, emphasizing the infectious component in many cases.
Surprisingly, comorbidities such as diabetes mellitus (15.1%,
p = 0.377), nicotine abuse (19.4%,
p = 0.735), and alcohol abuse (5.4%,
p = 0.377) did not prove to be significant predictors for pseudarthrosis or the need for additional interventions despite their prevalence in our cohort [
4]. Upon closer examination of our Forest Plot (
Figure 4), some comorbidities show point estimates below 1 (e.g., diabetes mellitus or nicotine abuse OR of 0.47,
p = 0.377 and OR 1.25,
p = 0.735). However, these findings should not be interpreted as protective effects. The wide 95% confidence intervals for all these factors cross the neutral line at OR = 1, indicating that the observed point estimates are statistically indistinguishable from no effect. The apparent direction of these non-significant associations likely reflects random variation in our limited sample rather than true biological relationships. These unexpected results contradict conventional clinical expectations that these comorbidities would significantly influence healing outcomes [
4]. Similar results were reported by Liodakis et al. in their systematic review, in which patient-specific factors showed inconsistent associations with docking site union rates [
4]. Given our limited sample size (n = 93), however, caution is advised in interpreting these negative results, as the study may lack the statistical power to detect smaller effect sizes associated with these comorbidities.
The high prevalence of pseudarthrosis in our cohort (54.3%) significantly exceeds the rates reported in some studies, such as by Feng et al., who found pseudarthrosis at the docking site in only 3.9% of cases among 103 patients with tibial defects treated with bone transport [
2]. This significant discrepancy could be explained by the particularly complex nature of our cases, including the high rate of open fractures (86.2% of available cases) and confirmed infections (83.7%). Additionally, methodological differences in the definition and diagnosis of pseudarthrosis may contribute to this variance [
2]. These divergent results underscore the need for standardized reporting of complications in the literature on bone transport.
Our results suggest that anatomical and mechanical factors may be more predictive than patient-specific comorbidities, providing a differentiated perspective that contributes to the existing evidence base [
1,
2,
5]. Feng et al. conducted a more comprehensive analysis of risk factors in 103 patients with tibial defects and found that “the blood supply status is related to the quality of osteotylus formation at the docking site,” specifically identifying the distal third location (OR: 11.379) and soft tissue defects as independent risk factors for delayed healing. Their multivariate analysis showed that bone defect length was also a significant predictor, with an OR of 1.976, suggesting that each additional centimeter of the defect nearly doubled the risk of delayed healing [
2]. Similarly, they found that the external fixation time (EFT) had an OR of 1.017, indicating a cumulative risk with longer fixation [
2].
The high rate of tibial injuries (73.1%) in our cohort could partially explain the frequency of pseudarthrosis, as the limited vascularity of the distal tibia presents challenges for bone healing [
2,
5]. This anatomical consideration is consistent with the findings of Feng et al. that “bone defects in the distal third and soft tissue defects are independent risk factors for delayed healing” due to the fewer arteries supplying nutrients in this region [
2]. Our data on the frequency of vascular injuries (27.5%) and wound healing disorders (37.0%) provide additional context for understanding the vascular challenges in these cases. In comparison, Zhong Wan Run reported a pseudarthrosis rate of 28.6% at the docking site in patients with soft tissue defects, which is closely aligned with our results, despite our smaller sample size [
2]. This convergence of results across different studies strengthens the evidence for soft tissue status as a predictive factor, despite the limitations of our study.
In our logistic regression analysis, we identified significant predictors for docking site procedures, including age (
p = 0.024), vascular injury (
p = 0.009), transport duration in days (
p = 0.001), and transport speed (
p < 0.001) (see
Table 2). The ROC analysis showed that transport speed has a high diagnostic accuracy (AUC = 0.931) for predicting docking site procedures, while transport duration also showed high predictive power (AUC = 0.911). These findings provide valuable insights for clinical decision-making regarding the planning of docking site interventions.
Interestingly, our MANOVA and post hoc tests showed no significant differences in transport duration between different transport methods (Monorail, Ring fixator, PRECICE nail) (p = 0.329), with mean transport durations of 292.85 days for Monorail, 403.58 days for Ring fixator, and 362.17 days for PRECICE nail systems. This finding suggests that, although the technologies differ, the overall treatment duration remains similar across different methods. From a clinical perspective, our findings suggest several practical applications pending prospective validation. First, transport speed can be monitored during treatment; patients demonstrating speeds below 0.35 mm/day may benefit from early counseling regarding the high likelihood of requiring docking site procedures and potentially from proactive surgical planning. Second, the risk stratification matrix could facilitate shared decision-making by providing patients with individualized risk estimates based on readily measurable parameters. Third, for patients falling within the high-risk zone, clinicians might consider earlier planned docking site interventions rather than awaiting docking site failure, potentially reducing overall treatment duration and external fixation time. However, we emphasize that these clinical applications require prospective validation before implementation. It should be noted that transport duration and external fixation time (EFT) are inherently correlated parameters, as reported by Feng et al., who identified EFT as an independent risk factor (OR 1.017 per day). Our finding that longer transport duration predicts docking site procedure necessity may partially reflect the cumulative biological effects of prolonged external fixation, including pin-site colonization, soft tissue tethering, and bone quality deterioration. Future studies should attempt to disentangle these interrelated temporal factors.
Antibiotics were administered to 93.5% of patients, reflecting the high prevalence of infections in our cohort. Fung et al. identified tibial defects and larger defect sizes as significant risk factors for postoperative infections [
6]. Hsu et al. found that initially infected pseudarthrosis and defect lengths over seven centimeters were risk factors for post-infections when using the induced membrane procedure [
7].
Patients in our study underwent an average of 8.37 ± 6.08 operations (range: 1–33) and 4.59 ± 4.50 revisions (range: 0–26), with external interventions performed in 39.8% of patients. This quantifies the considerable surgical burden these patients experience and underscores the importance of developing effective prediction models to minimize unnecessary interventions while ensuring optimal outcomes [
7,
8,
9,
11]. Comparable studies on the frequency of external and subsequent in-house revisions are not known to us to date.
Our sample size (n = 93, with only 39 patients who received segmental transport) limits the statistical power for identifying predictive factors. A particular statistical consideration is the risk of overfitting in our multivariate logistic regression model [
12,
13]. With 25 events (docking site procedures) and four significant predictors identified, our events-per-variable ratio of approximately 6:1 falls below the commonly recommended threshold of 10:1 to 15:1 for stable regression estimates [
12,
13]. This limitation is reflected in the wide confidence intervals observed, particularly for transport speed (OR 14.29, 95% CI: 2.80–71.43), indicating estimation instability due to limited sample size. The precision of our odds ratio estimates should therefore be interpreted with appropriate caution. While the identified predictors demonstrate statistically significant associations, the exact magnitude of effect sizes may vary in larger validation cohorts. External validation in independent, adequately powered datasets is essential before these findings can be reliably implemented in clinical decision-making algorithms [
12,
13]. For comparison, Feng et al. included 103 patients specifically with tibial defects, while Liodakis et al. meta-analyzed 1153 patients [
11,
14]. This smaller sample increases the risk of both Type I and Type II errors in the analysis of predictive factors.
The retrospective design of our study also leads to inherent biases in data collection and analysis, potentially affecting the reliability of certain results. Heterogeneity among patients represents another limitation. Our cohort included various defect etiologies (fractures, osteomyelitis, tumors), different anatomical locations (although predominantly tibia), and a wide range of defect sizes (12.1 mm to 225.1 mm). This heterogeneity, while reflecting real-life clinical practice, could obscure findings that would be apparent in more homogeneous populations.
The lack of standardized definitions for key parameters such as pseudarthrosis and wound healing complications in the literature makes direct comparison with other studies challenging. Our remarkably high pseudarthrosis rate (54.3%) compared to other published series (e.g., 3.9% reported by Feng et al.) highlights this definitional inconsistency in the field [
15].
Furthermore, our study did not include patient-reported outcome measures or quality of life assessments, which would provide valuable insights into the functional and psychological impacts of these complex procedures, the duration of therapy, and their complications. Such data would help contextualize the clinical significance of docking site procedures beyond purely surgical endpoints.
Finally, although we have identified significant predictors for the necessity of a docking site procedure, our model does not account for surgeon-specific decision-making factors that might influence the threshold for intervention. The decision to perform a docking site procedure involves clinical judgment that may vary between surgeons and institutions, potentially biasing our outcome measure.
5. Limitations
Our study has several important limitations that should be considered when interpreting the results. The retrospective design introduces inherent biases in data collection and analysis, potentially affecting the reliability of certain findings.
The sample size, particularly within the segmental transport subgroup (n = 39), limits statistical power for identifying predictive factors, especially when compared to larger studies in the literature. This relatively small sample increases the risk of both Type I errors and Type II errors when analyzing potential predictors. The reduced power is particularly relevant for detecting more subtle associations, potentially explaining why established risk factors like diabetes and smoking did not emerge as significant predictors in our analysis. Furthermore, with four predictors and only 25 events, our multivariate model carries substantial overfitting risk, as evidenced by the wide confidence intervals (e.g., transport speed OR 14.29, 95% CI: 2.80–71.43). These estimates should be considered exploratory pending external validation.
Patient heterogeneity represents another limitation. Our cohort included various defect etiologies (fractures, osteomyelitis, tumors), different anatomical locations (though predominantly tibia), and a wide range of defect sizes (12.1 mm to 225.1 mm). This heterogeneity, while reflective of real-world clinical practice, may obscure findings that would be apparent in more homogeneous populations. The inclusion of different transport methods (Monorail, ring fixator, intramedullary nail) further compounds this variability, although our analysis found no significant differences between these approaches.
The lack of standardized definitions for key parameters such as pseudarthrosis and wound healing complications across the literature makes direct comparison with other studies challenging. Our notably high pseudarthrosis rate (54.3%) compared to other published series (e.g., 3.9% reported by Feng et al.) highlights this definitional inconsistency in the field (10).
Additionally, our study did not include patient-reported outcome measures or quality-of-life assessments, which would provide valuable insights into the functional and psychological impact of these complex procedures and their complications. Such data would help contextualize the clinical significance of docking site procedures beyond mere surgical endpoints.
Finally, while we identified significant predictors for docking site procedure necessity, our model does not account for surgeon-specific decision-making factors that might influence the threshold for intervention. The decision to perform a docking site procedure involves clinical judgment that may vary between surgeons and institutions, potentially introducing bias in our outcome measure. Additionally, the retrospective nature of our study precluded blinded outcome assessment, potentially introducing observer bias in the determination of pseudarthrosis and the decision to perform docking site procedures. Surgeon-dependent variability in intervention thresholds represents another limitation; some surgeons may have lower thresholds for performing docking site procedures, which could influence our outcome rates. Furthermore, we did not systematically record soft tissue quality using standardized classifications such as the Gustilo-Anderson grading system for open fractures. Given the established importance of soft tissue status in bone transport outcomes, the absence of this parameter limits our ability to fully characterize wound-related risk factors and may represent an important unmeasured confounder.
These limitations highlight the need for larger, prospective multicenter studies with standardized definitions, assessment protocols, and outcome measures to further validate our findings and develop more robust predictive models for optimizing treatment approaches in this challenging patient population.