Hemiepiphysiodesis for Treating Lower Limb Deformities in Children with Hypophosphatemic Rickets: Can Diaphyseal Angular Deformities Be Corrected Concurrently?

doi:10.21203/rs.3.rs-4439259/v1

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Hemiepiphysiodesis for Treating Lower Limb Deformities in Children with Hypophosphatemic Rickets: Can Diaphyseal Angular Deformities Be Corrected Concurrently?

https://doi.org/10.21203/rs.3.rs-4439259/v1

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Aims: This study was conducted to explore the ability of hemiepiphysiodesis to correct mechanical axis deformities of the long bones and concurrently improve diaphyseal angular deformities, and further analyze the correlation between corrections of mechanical and diaphyseal anatomical axis angular deformities.

Methods: A retrospective analysis was conducted on 11 pediatric patients with hypophosphatemic rickets who underwent hemiepiphysiodesis at our hospital from July 2017 to July 2022. General clinical data were collected, and parameters of radiographs were measured and statistically analyzed.

Results: At the last follow-up, the correction of TMag1 was statistically significant (P=0.002) compared to preoperative values, while corrections of FMag1, FMag2, and TMag2 were not statistically significant (P>0.05). There was a positive correlation between FMag2 and mLPFA (0.43). FMag1 showed a weak correlation with mLDFA (0.38) and mMPTA (0.35). For each degree correction in mLPFA, FMag2 corrected by an average of 1.2°. For each degree correction in mLDFA, FMag1 corrected by an average of 0.6°. For each degree correction in mMPTA, FMag1 corrected by an average of 1.2°.

Conclusion: Hemiepiphysiodesis in children with hypophosphatemic rickets can correct mechanical axis deformities of the lower limbs and partially improve diaphyseal anatomical axis angular deformities.

Level of Evidence:Retrospective comparative study, III

Health sciences/Anatomy/Musculoskeletal system

Health sciences/Medical research

Hemiepiphysiodesis

Eight-plate

Hypophosphatemic rickets

Deformities of the lower extremities

Hypophosphatemic rickets (HR) in children is a group of hereditary or acquired diseases, with an incidence rate of approximately 1/20,000 to 1/60,000.¹ The clinical characteristics of HR usually manifest after the onset of walking, including short stature, slow growth rate, and progressive skeletal deformities (such as varus or valgus deformities of the knees and coxa vara),² severely affecting the quality of life of the affected children and increasing the medical burden on families.³ Currently, significant progress has been made in the pharmacological treatment of HR, which can control mild skeletal deformities to a certain extent.⁴ However, about two-thirds of patients do not respond well to medication, ultimately requiring surgical correction of lower limb deformities.^5,6

In recent years, hemiepiphysiodesis using eight-plates has emerged as the most common minimally invasive treatment for lower limb deformities caused by HR in children.^7–9 Hemiepiphysiodesis shows good results in correcting mechanical axis deformities of the lower limbs. However, besides mechanical axis deformities, children with HR often exhibit bowing of the diaphyses resulting in anatomic axis angular deformities. Currently, only a few studies have reported on the efficacy of hemiepiphysiodesis using eight-plates to treat lower limb deformities caused by HR in children, and these studies have been limited to the correction of mechanical axis deformities. No studies have yet reported on whether it can also simultaneously improve diaphyseal anatomical axis angular deformities.

Therefore, this study aims to perform a retrospective analysis on children with HR who underwent hemiepiphysiodesis using eight-plates, to investigate whether the use of hemiepiphysiodesis can improve diaphyseal anatomical axis angular deformities while correcting mechanical axis deformities of the lower limbs.

A total of 11 children with HR were included in the study (involving 22 knee joints). The average age at the time of surgery was 7.64 ± 2.45 years, with 5 males and 6 females. All children presented with full-length lower extremity standing anteroposterior radiograph, with 18.1% (4/22) of the knee joints exhibiting valgus and 81.8% (18/22) exhibiting varus deformities. There were 44 lower limb segments, of which 42 exhibited deformities (20 tibia, 22 femur); two tibia had no deformities, while the rest exhibited multi-apex deformities of the diaphysis. All children underwent hemiepiphysiodesis using eight-plates. The average surgical duration was 74.09 ± 27.82 minutes, with intraoperative blood loss less than 5 ml, average correction time of 16.72 ± 8.10 months, and average follow-up period of 21.91 ± 7.27 months (Table 1).

At the last follow-up, the lower limb mechanical axis parameters of eight patients were compared with pre-operative values, with an average correction of 24.95 ± 18.95mm for MAD, 12.00 ± 6.91 degrees for mLDFA, 5.50 ± 4.83 degrees for mMPTA, 4.91 ± 4.24 degrees for mLDTA, and 5.45 ± 3.95 degrees for mLPFA. Among these, significant improvements were observed in MAD (P = 0.000), mLDFA (P = 0.035), mMPTA (P = 0.011), and mLPFA (P = 0.032), all showing statistical significance. mLDTA (P > 0.05) also improved, however, the pre- and post-operative comparison did not show a statistical difference. Comparing pre-operative deformity angles of the lower limb diaphysis, the average correction degrees were 6.73 ± 6.08° for FMag1, 1.55 ± 4.03° for FMag2, 4.50 ± 5.42° for TMag1, and 2.59 ± 4.77° for TMag2. Among these, TMag1 (P = 0.002) showed significance, while corrections for FMag1, FMag2, and TMag2 did not show statistical significance (P > 0.05).

At the last follow-up, for each millimeter correction in MAD, there was an average correction of 0.2° in TMag1, 0.1° in TMag2, 0.3° in FMag1, and 0.1° in FMag2. For each degree correction in mLDFA, there was an average correction of 0.4° in TMag1, 0.2° in TMag2, 0.6° in FMag1, and 0.1° in FMag2. For each degree correction in mMPTA, there was an average correction of 0.8° in TMag1, 0.5° in TMag2, 1.2° in FMag1, and 0.3° in FMag2. For each degree correction in mLDTA, there was an average correction of 0.9° in TMag1, 0.5° in TMag2, 1.4° in FMag1, and 0.3° in FMag2. For each degree correction in mLPFA, there was an average correction of 0.8° in TMag1, 0.5° in TMag2, 1.2° in FMag1, and 0.3° in FMag2. Spearman correlation analysis showed a strong positive correlation between MAD and mLDFA (0.76), and a strong positive correlation with mMPTA (0.6). mLDTA and mMPTA showed a positive correlation (0.56). FMag2 and mLPFA showed a positive correlation, but it was weaker (0.43). FMag1 had a weaker correlation with mLDFA (0.38) and mMPTA (0.35), while TMag1 and TMag2 did not show significant correlations with other variables (Fig. 3).

Table 1

General data of patients
Characteristic	Value
Age, years	7.64 ± 2.45
Sex, n (%)
Male	5(45.45)
Female	6(54.55)
Initial deformity, n (%)
Valgus	4(18.18)
Varus	18(81.82)
Deformed diaphysis, n (%)
Femur	44(100.00)
Tibia	42(95.45)
Follow-up, months	21.91 ± 7.27

For skeletally immature patients, hemiepiphysiodesis is commonly employed in clinical practice. This study retrospectively analyzes data from children with lower limb deformities due to HR who were treated with hemiepiphysiodesis using eight-plates, thereby investigating the corrective effect of hemiepiphysiodesis on diaphyseal anatomical axis angular deformities while correcting mechanical axis deformities of the lower limbs.

This study analyzed the correction of diaphyseal deformities. According to Paley's principles for measuring lower limb deformities,¹⁰ diaphyseal deformities can be classified into single apex deformities and multi-apex deformities, with different measurement methods for different deformity categories. This distinction is crucial for accurately assessing the degree of deformity correction. In this study, all cases included exhibited multi-apex deformities of the lower limb diaphyses, resulting in two deformity apexes, Mag1 and Mag2, by the final follow-up. TMag1 showed significant improvement with statistical significance, while FMag1, FMag2, and TMag2 showed relative improvements but were not statistically significant. The research by Horn et al.⁷ found that growth modulation surgery also partially improved the bending of the tibial and femoral diaphyses. However, their method of measuring diaphyseal deformities differed from ours, considering it as a single deformity apex. All cases included in this study were children with multi-apex diaphyseal deformities. By comparing radiographic parameters of multi-apex deformities, significant improvements were observed in the diaphyseal deformity levels among the eight patients with ideal correction outcomes. However, the final results did not show significant differences, which might be influenced by the three patients who had suboptimal correction outcomes at the last follow-up.

Furthermore, previous studies did not explore the correlation between improvement in the lower limb mechanical axis and correction of diaphyseal deformities. Our study found that when the lower limb mechanical axis was improved, the angles of multi-apex deformities in the lower limb diaphysis also proportionally improved. Spearman correlation analysis revealed a positive correlation between FMag2 and mLPFA, indicating that improvements in the mechanical axis parameters around the hip joint also lead to simultaneous correction of distal femoral deformities. Additionally, FMag1 showed a positive correlation with mLDFA and mMPTA, suggesting that improvements in the mechanical axis parameters around the knee joint lead to simultaneous correction of proximal femoral deformities. Children with HR exhibit weakened growth plates due to impaired temporary calcification of hypertrophic cartilage, resulting in widened, cup-shaped growth plates prone to deformities under compressive and shear loads. These deformities often first affect the distal femur and proximal tibia physis and gradually extend to the epiphyseal ends and diaphysis with growth, causing severe malalignment of the lower limb mechanical axis.¹¹ Long-term misalignment of the lower limb force line and gait abnormalities may damage knee joint growth through the Heuter-Volkmann effect and eventually have adverse effects on the growth of the hip and ankle joints. According to the Heuter-Volkmann principle, normalization of physeal load eliminates ongoing imbalances in relative growth, further causing gradual correction of diaphyseal deformities.¹² Thus, improvements in the mechanical axis parameters around the knee and hip joints lead to normalization of physeal load, guiding gradual correction of femoral diaphyseal deformities, as evidenced by improvements in FMag2 and FMag1 deformity parameters. Combining the results of the correlation analysis, we can infer that improvements in the lower limb mechanical axis parameters significantly affect the correction of the anatomical axis of the femoral diaphysis. However,Correlation analysis showed no significant association between the correction of TMag1 and TMag2 and the correction of the lower limb mechanical axis. This may be due to two reasons: the small sample size and the presence of patients with suboptimal correction outcomes, which could affect the results of the correlation analysis. Secondly, the different growth rates of the femur and tibia, with studies by Gigante et al.¹³ indicating that the femur corrects faster than the tibia, may result in less apparent correlation between tibial diaphyseal deformity correction and lower limb axis correction compared to femoral diaphyseal deformity correction. At the final follow-up in this study, significant improvements were observed in MAD, mLDFA, mMPTA, and mLPFA with statistical significance, while mLDTA correction showed no statistical difference, suggesting that hemiepiphyseal stapling has a corrective effect on the lower limb mechanical axis but not a significant effect on the correction of ankle joint walking direction angles. Studies by Kumar and Sonanis¹⁴ also confirmed that improvements in the mechanical axis parameters around the knee joint positively affect the hip joint but did not find correction for the ankle joint deformities. Considering the faster correction rate of the femur compared to the tibia,¹³ the difference in correction rates may result in the non-significant correction of ankle deformities during the follow-up period of this study, suggesting a longer follow-up period may be necessary to observe effects on the ankle joint.

This study is a single-center study, and the obtained samples may not fully represent a broader population, which could limit the generalizability and extrapolation of the study results. In the future, we consider conducting multi-center studies to increase the diversity and representativeness of the samples, thereby enhancing the universality and reliability of the research findings. Besides, the sample size of this study is relatively small, which might affect the extrapolability and overall credibility of the results. In the future, we plan to include more cases that meet the criteria to maximize the study's effectiveness and reliability. Finally, there is a lack of three-dimensional assessment of deformities. Our study only evaluated the correction of deformities in the coronal plane. however, research by Bonnet-Lebrun et al.¹⁵ has shown that sagittal plane measurements have significance in monitoring and assessing deformities. Future studies could further collect and analyze data from three-dimensional CT scans. Overall, future studies could involve multicenter research, collect ample samples from various sources, and perform multiplanar analysis of deformities, aiming to better assess the efficacy of hemiepiphyseal stapling in correcting lower limb deformities caused by HR.

Hemiepiphysiodesis in children with HR can correct mechanical axis deformities of the lower limbs and partially improve diaphyseal anatomical axis angular deformities.

This retrospective study was approved by the ethics review committee of hospital institutions (approval number:202404001-1), and informed consent was obtained from all the childrens' parents or legal guardian(s).

The inclusion criteria were as follows:

1. Patients with documented HR and with an open physis at the area of planned surgery confrmed by radiographs; (2) No concurrent musculoskeletal system diseases; (3) Patients must have adhered to at least 12 months of standard medical treatment before surgery, and continue to receive medical treatment postoperatively; (4) No prior surgical treatment for lower limb deformities before the current procedure; (5) Absence of other diseases affecting the development of the musculoskeletal system; (6) Postoperative regular follow-ups with complete radiographs, and the follow-up period is more than 9 months.

The exclusion criteria were as follows:

Incomplete radiographic data or loss to follow-up; (2) History of orthopedic surgery for other lower limb deformities or history of lower limb trauma surgery; (3) Presence of other metabolic bone diseases; (4) Mental developmental disorders; (5) Failure to adhere to standard medical treatment postoperatively.

Subjects included children with HR

Children with HR who underwent hemiepiphysiodesis using eight-plates at our institution from July 2017 to July 2022 (Fig. 1).

Data Collection and Parameter Measurement

The medical records were obtained, including the age, gender, and type of surgery at the first operation. Before surgery, 12 months post-surgery, at the time of eight-plate removal, and during the final follow-up visit, full-length lower extremity standing anteroposterior radiographs were obtained using long-distance X-ray imaging (SIEMENS, Munich, Germany) with the knee joint as the center for a single exposure. The full-length images of the lower extremities are measured using PACS software (Neusoft, Shenyang, China), recording the following parameters to assess the mechanical axis deformity of the lower limbs: Mechanical Axis Deviation (MAD); proximal femoral mechanical lateral angle (mLPFA); distal femoral mechanical lateral angle (mLDFA); proximal tibial mechanical medial angle (mMPTA); and distal tibial mechanical lateral angle (mLDTA). In order to quantify the diaphyseal deformity in the coronal plane, the centre of rotation of angulation (CORA) was deternubed, and then measured the magnitude of angulation (Mag). Mag1 and Mag2 were the angles at each CORA with 2 CORAs in each long bone diaphysis due to multi-apical deformitie.(Fig. 2).

Statistical analysis

All statistical analyses were performed using the SPSS 24.0 software package (IBM, Armonk, New York, USA) and graphs were drawn using Python. Quantitative data were described using mean ± standard deviation, while qualitative data were described using frequency counts. Categorical variables were expressed as frequencies (percentages), and continuous variables were expressed as means (range). For quantitative data, the Kolmogorov-Smirnov test was first used to check the normality of continuous variables. Based on this, within-group paired t-tests or analysis of variance (for normally distributed data) or Mann-Whitney tests (for non-normally distributed data) were conducted. For qualitative data, chi-square tests or Fisher's exact tests were used for analysis. P < 0.05 was considered statistically significant. Upon verification of normality, Pearson (for normally distributed data) or Spearman (for non-normally distributed data) correlation analyses were conducted.

Acknowledgements

No.

Author Contributions

Pengfei Zheng contributed to the study conception and design. Material preparation, data collection and analysis were performed by Qiangli and Yulong Ben. The first draft of the manuscript was written by Hanjie Zhuang, Ruoyi Guo and Danfeng Zheng. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Data availability statement

The data that support the findings of this study are available on request from the corresponding author.

Competing interests

The author(s) declare no competing interests.

Ethics approval

This is an observational study. The Children's Hospital of Nanjing Medical University Research Ethics Committee has confirmed that no ethical approval is required.

Consent to participate

Informed consent was obtained from all individual participants included in the study.

Consent to publish

All authors listed have approved this manuscript. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee.

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No competing interests reported.

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Hemiepiphysiodesis for Treating Lower Limb Deformities in Children with Hypophosphatemic Rickets: Can Diaphyseal Angular Deformities Be Corrected Concurrently?

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Version 1

Abstract

Figures

Introduction

Results

Discussion

Conclusion

Methods

The inclusion criteria were as follows:

The exclusion criteria were as follows:

Subjects included children with HR

Data Collection and Parameter Measurement

Statistical analysis

Declarations

References

Additional Declarations

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