The Fourth Cervical Vertebra Anterior and Posterior Body Height Projections (Vba) for the Assessment of Pubertal Growth Spurt

Round 1

Reviewer 1 Report

This paper studies the fourth cervical vertebra anterior and posterior body height as a potential parameter to project pubertal growth spurt. I appreciate the authors’ works, which will help further (pre)clinical practice. However, to grow into a publication, I think there are some issues the authors need to address.

1.     The authors did not clearly define β (coefficients) in the methods section

2.     I recommend the authors to put OR values in Figure 3 and the figure legends. It will help readers quickly get the point.

3.     I recommend the authors to increase the sample size for forecast. 20 subjects may not be big enough for the 

4.     The samples are all from Croatia. The authors should discuss this point as the conclusion may not applied to other countries/race of people/etc.

5.     The language needs improvement. 

In summary, I feel the study is solid. However, improvement is needed. I hope the author(s) could find some of the above discussions helpful for improving the paper. 

Author Response

Response to Reviewer 1 Comments

Point 1: The authors did not clearly define β (coefficients) in the methods section

Response 1: We added few lines in the text to better explain the meaning of the betas.

Point 2: I recommend the authors to put OR values in Figure 3 and the figure legends. It will help readers quickly get the point.

Response 2: We know OR, that means Odds Ratio, but, if this is so, OR has nothing to do with regressive models. Which legend do we report in Fig 3? We don’t know what else can do.

Point 3: I recommend the authors to increase the sample size for forecast. 20 subjects may not be big enough for the

Response 3: The forecast sample was extended from 20 to 50 subjects

Point 4: The samples are all from Croatia. The authors should discuss this point as the conclusion may not applied to other countries/race of people/etc.

Response 4: The need for validation and verification of the presented method is stated in the conclusion

Point 5: The language needs improvement.

Response 5: The language was improved by the English language editor.

Author Response File: Author Response.pdf

Reviewer 2 Report

This study analyzed the ratio of the anterior height projection to the posterior of the C4 vertebral body or Vba during childhood, where preadolescence and adolescence occurred and proved the applicability of Vba for estimating the beginning and end of the pubertal growth spurt and their distributions. The paper can be accepted after a minor revision.

1. What does it add to the subject area compared with other published 

material?

2. More recent references should be cited in the text.

3. Are any reports in recent years also related on a statistical model based on segmented regression to calculate the residual proportion of the skeletal maturation? Please undated related references.

Author Response

Response to Reviewer 2 Comments

Point 1: What does it add to the subject area compared with other published

Response 1: Standard clinical practice used to assess the onset of pubertal growth spurt by comparing the patient's cephalogram or hand-wrist with images from certain stages of development. This work wanted to check whether the value of one variable, the ratio of the anterior height projection to the posterior of the C4 vertebral body or Vba, can be used for the pubertal growth spurt, given that the assessment of the stage depends on the subjective assessment of the observer, while the values of the anterior height projection to the posterior of the C4 vertebral body exact.

Point 2: More recent references should be cited in the text.

Response 2: Appropriate references were added

Point 3: Are any reports in recent years also related on a statistical model based on segmented regression to calculate the residual proportion of the skeletal maturation? Please undated related references

Response 3: We searched the literature extensively, including recent databases, including Scopus and Pubmed, and did not find a relevant reference related to a statistical model based on segmented regression to calculate the residual proportion of the skeletal maturation. We reported the seminal paper of Muggeo et. Al. which remains a fundamental paper in the regression models with segmented approach. Many other papers devoted to segmented regression, also with Bayesian methods, have been published subsequently but are not related to the topic of this manuscript. We found only the following reference in pubmed related to the topic of the paper and it can be added to the reference: Yuan JT, Furdock RJ, Benedick A, Liu RW. Estimating Skeletal Maturity by Segmented Linear Modeling of Key AP Knee Radiographic Parameters. J Pediatr Orthop. 2022 Mar 1;42(3):169-173. doi: 10.1097/BPO.0000000000001988. PMID: 35138299.

Author Response File: Author Response.pdf

Reviewer 3 Report

The manuscript entitled “The fourth cervical vertebra anterior and posterior body height projections (Vba) for the assessment of pubertal growth spurt”, is concentrated on proposing a statistical model evaluating pubertal growth spurt using the ratio of the anterior height projection to the posterior (Vba) of the fourth cervical vertebra body (C4) on cephalograms and for a given Vba to calculate the residual proportion of skeletal maturation and the time for the pubertal growth spurt to end. Authors used a cross-sectional sample of 538 cephalograms from healthy living children aged between 5 and 15 years. They also utilized a segmented regression model to explain the different Vba stages relative to the pubertal growth spurt. Moreover, the time to achieve skeletal maturation was evaluated for a given Vba between the beginning (Vba1) and the end (Vba2) of the pubertal growth spurt. Authors studied a longitudinal sample of ten males and ten females to validate the proposed method. They declared that results showed the model did not produce any incorrect forecasts. Finally, authors claimed that the proposed method estimates the beginning and the end of the pubertal growth spurt together with the residual proportion of Vba.

The subject is interesting and useful for beneficiaries. The manuscript could be improved by addressing the comments raised here.

1-      Authors need to highlight the novelties of this work in the manuscript, especially with respect the previously published works.

2-      The number of samples for study seems small. It is recommended to increase the number of samples.

3-      More statistical parameters and used methods should be reported within the manuscript.

4-      Authors are strongly recommended to use response surface methodology (RSM) or Taguchi for regression and modeling by using these references [10.1016/j.supflu.2016.04.006, /doi.org/10.1016/j.supflu.2011.02.002 ]. You also may discuss and compare the used method in the present work with the above mentioned methods (introduced references) in the main manuscript.

5-      The literature review, results and discussion must be strengthening by new references, (especially years 2019 to now)

6-      Have authors verified the proposed model by experimental data?

7-      Conclusion must be improved.

Author Response

Response to Reviewer 3 Comments

Point 1: Authors need to highlight the novelties of this work in the manuscript, especially with respect the previously published works

Response 1: This is the first study that validates the possibility of estimating the beginning of the pubertal growth spurt using the ratio of the anterior height projection to the posterior (Vba) of the fourth cervical vertebra body (C4) on cephalograms and calculating the residual proportion of skeletal maturation and the time for the pubertal growth spurt to end for a given Vba.

Point 2: The number of samples for study seems small. It is recommended to increase the number of samples.

Response 2: The forecast sample was extended from 20 to 50 subjects

Point 3: More statistical parameters and used methods should be reported within the manuscript.

Response 3: Statistical parameters are further explained in the Material and Methods section.

Point 4: Authors are strongly recommended to use response surface methodology (RSM) or Taguchi for regression and modeling by using these references [10.1016/j.supflu.2016.04.006, /doi.org/10.1016/j.supflu.2011.02.002 ]. You also may discuss and compare the used method in the present work with the above mentioned methods (introduced references) in the main manuscript.

Response 4: The authors carefully read the proposed references:

1. Optimization of Ferulago Angulata oil extraction with supercritical carbon dioxide and
2. Application of supercritical carbon dioxide to extract essential oilfrom Cleome coluteoides Boiss: Experimental, response surface and grey wolf optimization methodology,

and we could not compare the segmented regression model with the response surface methodology with certainty. We searched the literature extensively, including recent databases, including Scopus and Pubmed, and did not find a relevant reference related to a statistical model based on response surface methodology to calculate the residual proportion of the skeletal maturation. We reported the seminal paper of Muggeo et. Al. which remains a fundamental paper in the regression models with a segmented approach. Many other papers devoted to segmented regression, also with Bayesian methods, have been published subsequently but are not related to the topic of this manuscript. We found only the following reference in PubMed related to the topic of the paper, and they can be added to the reference: Yuan JT, Furdock RJ, Benedick A, Liu RW. Estimating Skeletal Maturity by Segmented Linear Modeling of Key AP Knee Radiographic Parameters. J Pediatr Orthop. 2022 Mar 1;42(3):169-173. doi: 10.1097/BPO.0000000000001988. PMID: 35138299.

Point 5: The literature review, results and discussion must be strengthening by new references, (especially years 2019 to now)

Response 5: References were thoroughly reviewed, and relevant references were added, primarily published after 2020.

Point 6: Have authors verified the proposed model by experimental data?

Response 6: The obtained results were verified by analyzing 50 patients whose cephalograms were recorded during their growing up with reference data, whether it was pre-puberty, puberty or post-puberty, available from the Michigan Growth Center supported by the American Association of Orthodontists Foundation (AAOF).

Point 7: Conclusion must be improved.

Response 7: The conclusion has been significantly improved, and recommendations for future research have been added.

Author Response File: Author Response.pdf

Round 2

Reviewer 3 Report

Authors have tried to respond the reviewers comment. However, the manuscript still needs a required revision. Two main concerns should be addressed. Comments are pointed out again as below:

1- Regarding comment #2, authors must justify what are the criteria for the selection of 50 samples. Meanwhile, if the data were available, why authors have not used it at previously stage.

2- Regarding comment #4, it is necessary to include explanations raised there in the manuscript. Accordingly, authors should mention and discuss this in the manuscript as "there are methods such response surface methodology with statistical potentials in other topics  (authors should add here the suggested references,[10.1016/j.supflu.2016.04.006, /doi.org/10.1016/j.supflu.2011.02.002] that could not be compared with the current subject, due to .....".

Comments for author File: Comments.pdf

Author Response

Response to Reviewer 3 Comments
Point 1: Regarding comment #2, authors must justify what are the criteria for the selection of 50 samples. Meanwhile, if the data were available, why authors have not used it at the previous stage?
Response 1: Increasing the sample size increased the possibility of error in the accuracy of predicting in the test sample, and the results showed no statistically significant failure between a sample of 20 versus a sample of 50 subjects.

Point 2: Regarding comment #4, it is necessary to include explanations raised there in the manuscript. Accordingly, authors should mention and discuss this in the manuscript as "there are methods such response surface methodology with statistical potentials in other topics (authors should add here the suggested references, [10.1016/j.supflu.2016.04.006, /doi.org /10.1016/j.supflu.2011.02.002] that could not be compared with the current subject, due to
Response 2: The part in the discussion which describes statistical procedures for fitting a hypothesized (empirical) model to data obtained under the chosen design was extended, including suggested references.
Thank you for the constructive and well-intentioned suggestions.

Author Response File: Author Response.pdf