Origin and factors for overgrowth in pediatric fractures of the femoral shaft after flexible intramedullary nail fixation

Introduction

Fracture of the femoral shaft in children is common. Various methods of treatment can be used successfully, depending on the patient’s age and the specific fracture characteristics. For children below four years old, the standard approach involves immediate utilization of a spica cast or initial traction followed by casting (1,2). In adolescents with mature skeletal structures, the preferred intervention typically involves flexible intramedullary nail (FIN) fixation (3).

In 1988, Ligier first reported the successful use of FIN in the fracture of the femoral shaft in children. Since then, FIN has gained increasing popularity mainly in children aged 4–12 years, due to its characteristics of easy operation and reliable stability (4-6). Even though, according to reports, the incidence of complications with FIN is approximately 17%, which typically include soft-tissue irritation by the extra-osseous portion of the nail at the site of insertion, rotational or angular deformity of the femur, leg-length discrepancy (LLD), delayed or nonunion of the fracture (7).The overgrowing of the affected limb is the most common factor leading to postoperative leg length discrepancy following femoral fractures in childhood and has been much discussed (8-10). However, the exact reasons for the postoperative excessive growth following femoral shaft fracture remain unclear. This phenomenon is often attributed to hyperplasia at the fracture site, though this is purely speculative (10). While in other studies, LLD has been attributed to factors of physis stimulation, as in surgical procedure, stimulation of physis may be due to insertion of nails and screw (11-13).

To the best of our knowledge, there is no dedicated research analyzing the cause of overgrowth in pediatric femoral shaft fractures after treatment with FIN. The objective of this study is to precisely measure various radiological parameters of the femur, thereby indirectly inferring the origins of excessive elongation of the femur. In the following sections, we will proceed to address this intriguing question in a highly interesting manner. We present this article in accordance with the STROBE reporting checklist (available at https://tp.amegroups.com/article/view/10.21037/tp-24-171/rc).

Methods

The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). Ethics approval for this study was approved by the Human Research Ethics Committee of Children’s Hospital of Fudan University (No. 2022528) and written informed consent was obtained from guardians of all children. The pre-operative anteroposterior and lateral radiographs of the injured femur were reviewed and different types of fractures were described as Transverse, Oblique fractures, Spiral fracture and Comminuted fractures. Careful closed reduction under general anesthesia with optimal relaxation and fluoroscopic control was conducted by senior surgeons. If closed reduction failed or in the case of an open fracture, an open reduction was performed. Two titanium elastic nails were retrograde inserted from the medial and lateral distal femoral metaphyseal flares. The selection of intramedullary nails strived to meet the criterion: the diameter of the nail should be approximately 35% of that of the narrowest point of the femoral canal. Patients were placed in one-and-a-half spica cast until bony union became evident during radiological follow-up (11).

The location of the fracture was recorded as the ratio of the distance from the midpoint of the fracture line to the distal articular surface of the femur and the total length of the femur (c/b). (Figure 1). A c/b value greater than 50% is considered a proximal femur fracture (upper side), while a c/b value less than 50% is considered as a distal femur fracture (lower side). Distance from the end of the medial or lateral nails to the distal epiphysis were calculated. We preferentially selected the more convenient side based on imaging findings. By measuring the difference in distance between the intramedullary nail tip and the physis on two time points, namely immediately postoperative (recorded as “a”) and prior to removal of the intramedullary nail (recorded as “A”), we estimate the increased length of the distal femur (recorded as “A − a”). Similarly, the immediate postoperative total length of the femur is recorded as ‘b’, and the distance of the femur before nail removal is recorded as ‘B’. By dividing the increased length of the distal femur (A − a) by the total increase in femoral length (“B − b”), we can obtain the distal physis growth proportion (DPGP) (Figure 1). DPGP is a highly intriguing parameter that we have introduced for the first time, which enables us to subtly deduce the sources of femoral lengthening. An early study conducted by Westh found that the distal and proximal physis of the femur contributed 70% and 30% of total femur length growth respectively (14). Based on this theory, we assume that during the fracture healing process, the growth rate of the distal and proximal physis of the femur remains constant. Therefore, when DPGP exceeds 70%, it suggests either excessive growth stimulation in the distal femoral physis or fracture side overlap, malalignment with angulation leading to relative shortening of the femur. Conversely, when DPGP is less than 70%, it is highly likely that there has been an overgrowth at the fracture site. Despite being a highly idealized calculation model, this theory does indeed offer a high level of feasibility. In order to assess the stability of internal fixation, we measured the intramedullary NCD (15), which is the sum of the diameters of the two intramedullary nails divided by the width of the femoral canal at its narrowest segment (Figure 2).

Figure 1 The location of the fracture was recorded as the ratio of the distance from the midpoint of the fracture line to the distal articular surface of the femur and the total length of the femur c/b (left); DPGP was calculated by dividing the increased length of the distal femur (A − a) by the total increase in femoral length (B − b) (right). DPGP, distal physis growth proportion.

Figure 2 NCD is defined as the sum of the diameters of the two intramedullary nails divided by the width of the femoral canal at its narrowest segment. NCD, nail-canal diameter ratio.

We excluded the following patients: (I) pathological fractures caused by simple bone cysts, fibrous dysplasia, aneurysmal bone cyst, eosinophilic granulomafibrous dysplasia, and other tumor lesions; (II) systemic or metabolic disorders (e.g., osteogenesis imperfecta, cerebral palsy) associated with high fracture risk; (III) femoral metaphysic fracture fixed with Kirschner wires; simple cast fixation for young children; plate fixation; single intramedullary nail fixation; antegrade intramedullary nail fixation; (IV) lost follow-up; (V) incomplete imaging data or image failed meeting measurement standards; (VI) shortening of the effected femur.

Statistical analysis

General statistical analysis was performed using software RStudio version 2023.06.2+561. Continuous variables were presented as mean ± standard deviation if normally distributed. Categorical variables were presented as frequencies or percentages. Statistical significance was calculated using Welch two-sample t-test, one-sample t-test or Wilcoxon signed rank test according to the distribution of the variables. Welch two-sample t-tests (two-sided) were performed between subgroups to see if subgroups with different classifications were interfering with the results. The sample was divided into seven subgroups according to (I) gender, (II) fracture side, (III) fracture type, (IV) mode of reduction, (V) associated craniocerebral injury, (VI) fracture site, (VII) NCD with the threshold of 60%. One-sample t-test (one-sided) and one-sample rank sum test (one-sided) were used in test for significant differences between the sample and the population, each subgroup and the population. The value of DPGP for children’s growth in normal conditions was identified as 70%, here the mean of population was taken as 70%. A P value of <0.05 was considered statistically significant.

Results

Detailed characteristics of the patients

From June 2012 and December 2022, a total of 724 cases of pediatric and adolescent femoral fractures were treated at our hospital.

Based on our inclusion and exclusion criteria (Figure 3), 138 participants (mean age: 5.38±0.18 years, boys/girls: 93/45) were finally enrolled in this study. Overall, all the patients had fractures with 54.3% occurring on the left side and 45.7% occurring on the right side. The fracture type observed in this study included comminuted fractures (8.7%, n=12), transverse fractures (52.9%, n=73), oblique fractures (37.7%, n=52), and spiral fracture (0.7%, n=1). The patient with a spiral fracture was excluded from the subsequent analysis in examining the effect of fracture type. Among the patients, closed reduction was performed on 77.5% (n=107) and open reduction on 22.5% (n=31). Notably, 90.6% (n=125) of the patients were disassociated with craniocerebral injuries, while 9.4% (n=13) sustained associated craniocerebral injuries. The fracture occurred in the upper side of the femoral shaft in 98 cases (71%), and the lower side in 40 cases (29%). Despite setting corresponding criteria for intramedullary nail diameter selection prior to surgery, there were only 11% of the patients meeting the criterion of having an NCD value greater than 70%. Hence, we chose 60% as the grouping criterion for NCD. In 37 cases (26.8%), the NCD value exceeded 60%, while in 101 cases (73.2%), the NCD value was less than 60% (Table 1).

Figure 3 Screening flow chart.

Test for significant differences between the sample and the population

The distribution of samples and subgroups of DPGP is represented by bar graphs (Figure 4). The mean DPGP value of 138 samples was 50.9%, of which 24 (17.4%) were greater than 70% and 114 (82.6%) were less than 70%. Results show that except for the subgroup with associated craniocerebral injury [P value (t) =0.01, P value (Wilcox) =0.01], the P value (t) and P value (Wilcox) for the whole population and all other subgroups were less than 0.01 (Table 2).

Figure 4 The distribution of samples and subgroups of DPGP is represented by bar graphs. DPGP, distal physis growth proportion.

Tests of significance between subgroups

Comparing the DPGP values among the various subgroups, it was observed that the P values were consistently greater than 0.05 within the six subgroups of gender, fracture side, fracture type, mode of reduction, associated craniocerebral injury and the fracture location, indicating that there was no significant difference between these subgroups. It should be noted that DPGP was significantly different in the subgroups according to NCD value (P=0.03) (Table 3). In the group with NCD values ≥60%, the proportion of patients with DPGP values exceeding 70% is significantly higher compared to the group with NCD values <60%.

Complications

There were 23 complications during the post-operative follow-up in 138 fractures including: inflammatory reaction due to nails (N=4), angulation exceeding the guidelines at the final follow-up (N=6), LLD exceeding 2 cm by radiologic assessment (N=11) (16), limitation of knee movement (worse than 10˚ to 110˚) (N=1).

Discussion

Although satisfactory results have been reported, the FIN technique may not consistently deliver the desired level of stability (17). Numerous studies have documented a high risk of LLD after FIN fixation of femoral shaft fracture compared to non-surgical treatment (18). LLD is mainly induced by an increase in the length of the affected limb due to excessive growth attributed to physis stimulation or fracture ends irritation (11,12). However, due to a lack of clinical or experimental data support, so far, no study has been able to confirm the exact source of the lengthening of the femur, whether it originates from the fracture ends or the stimulation of the physis.

Colton did a radiographic study of a consecutive series of 50 children who had undergone conservative treatment following a closed femur fracture. In his study, the primary factor influencing the extent of excessive growth in the fractured femurs was the sex of the patient. Interestingly, factors such as patient age, injury type, fracture location and type, degree of fragment overlap, as well as patient handedness, did not seem to impact the occurrence of overgrowth. The growth plates in children exhibit sensitivity to hormonal fluctuations. It may be that before puberty there is greater activity in the growth plate of the normal female than that in the normal male. Colton suggested that increased blood flow, or hyperemia, might lead to growth stimulation, particularly affecting the comparatively less active growth plates in male children (19). According to Colton’s theory, we can deduce that the growth in physis constitutes a significant proportion of the total length of the femur. In alignment with the findings of Colton’s research, Flinck also found that children with a fracture before age 9 years had a longer limb on the fractured side, while among older children and adolescents, both shortening and lengthening were seen (20). In addition, Flinck has found that the degree of fracture stability or callus formation at the time of fracture did not significantly affect leg length discrepancy (20). This result implies that the repair of fracture ends is likely to have no impact on the excessive growth of the femur.

Our research findings are in direct contrast to the conclusions of the two scholars mentioned above. We found that the proportion of the lengthening of the distal femur relative to the total femoral length was lower than the expected 70%, and it was not influenced by gender, fracture side, fracture type, mode of reduction, associated craniocerebral injury nor the distance from fracture site to epiphyseal plate/femur. This also implies that the repair and healing of the fracture ends not only restores the continuity of the bone but also plays a role in promoting femoral lengthening. The conclusions of both Colton and Flinck are based on their assumptions, whereas our results are founded on empirical scientific data; perhaps our findings better represent the true answer to this issue.

Park et al. reported increased femoral growth in children treated with FIN if the NCD was low. Instability during fracture healing may generate indirect bone healing with extensive callus formation, prolonged healing and the remodeling process which may lead to excessive growth at the fracture site (10). We also observed that as the NCD value decreased, the DPGP value decreased, and the proportion contributed by the fracture ends increased. It is well known that the NCD value is closely related to the stability of fractures, with smaller values indicating relatively poor fracture stability. Reduced stability leads to more pronounced micro-motion and stimulation at the fracture ends, thereby promoting bone growth. Our results indirectly support the hypothesis that fracture ends stimulation may be a significant factor in driving femoral lengthening.

The discrepancy in the relationship between NCD and DPGP that we observed compared to Flinck who found that NCD did not influence femur length may be attributed to the influence of the timing of cast removal. Inadequate time in plaster cast fixation is most common cause of femoral shortening. Bony union of femur is evident at a mean of 3 months postoperatively (21). During partial weight-bearing after earlier cast removal, the initial fracture reduction is prone to collapse, especially in initial comminuted fractures. In this scenario, the true relationship between NCD and DPGP will be affected. When NCD remains constant, the DPGP value will definitely increase due to bone collapse thereby offsetting the influence of NCD on DPGP. In our study, all patients were managed with a minimum cast immobilization duration of at least 4 months, effectively minimizing the occurrence of bone collapse. So, we contend that a reduced NCD ratio signifies an unstable configuration in FIN and have established a correlation between a decreased NCD ratio and the development of femoral overgrowth, which may in turn lead to LLD.

Limitation

First, though 249 cases were excluded due to inadequate image quality, there were still be some inaccurate measurements for the included images, which may lead to a certain degree of bias. Second, the follow-up time was short and further investigation is warranted to determine whether the long-term effects of fracture ends stimulation will diminish and whether the trend of LLD will increase or decrease before skeletal maturity (20). Third, we did not measure the changes in the length of the uninjured femur at the time of injury and at the latest follow-up. This was due to some ethical problem in our patients. We only took bilateral full-length lower limb X-rays at the last follow-up when there was a clear clinical manifestation of unequal leg length, in order to understand the discrepancy in length between the affected and unaffected limbs. So we cannot utilize the changes in the length of the contralateral healthy limb as a reference. The last is the nature of retrospective study design and lack of control group of this study.

Conclusions

Directly measuring the site of femoral overlengthening is challenging; however, the DPGP parameter allows us to indirectly estimate the possible origin. In children with femoral shaft fractures treated with FIN, a DPGP value below 70% indicates the significant role of fracture end stimulation in femoral lengthening.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://tp.amegroups.com/article/view/10.21037/tp-24-171/rc

Data Sharing Statement: Available at https://tp.amegroups.com/article/view/10.21037/tp-24-171/dss

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-24-171/prf

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-24-171/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by the Human Research Ethics Committee of Children’s Hospital of Fudan University (No. 2022528) and written informed consent was obtained from guardians of all children.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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