PONE-D-25-12300Dose-response relationships of physical activity with bone mineral density and muscle mass in visceral obesity: A metabolic heterogeneity perspectivePLOS ONE

Dear Dr. zhang,

Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel that it has merit but does not fully meet PLOS ONE’s publication criteria as it currently stands. Therefore, we invite you to submit a revised version of the manuscript that addresses the points raised during the review process.

Please submit your revised manuscript by Jul 18 2025 11:59PM. If you will need more time than this to complete your revisions, please reply to this message or contact the journal office at plosone@plos.org . When you're ready to submit your revision, log on to https://www.editorialmanager.com/pone/ and select the 'Submissions Needing Revision' folder to locate your manuscript file.

Please include the following items when submitting your revised manuscript:

• A rebuttal letter that responds to each point raised by the academic editor and reviewer(s). You should upload this letter as a separate file labeled 'Response to Reviewers'.
• A marked-up copy of your manuscript that highlights changes made to the original version. You should upload this as a separate file labeled 'Revised Manuscript with Track Changes'.
• An unmarked version of your revised paper without tracked changes. You should upload this as a separate file labeled 'Manuscript'.

If you would like to make changes to your financial disclosure, please include your updated statement in your cover letter. Guidelines for resubmitting your figure files are available below the reviewer comments at the end of this letter.

If applicable, we recommend that you deposit your laboratory protocols in protocols.io to enhance the reproducibility of your results. Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: https://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols . Additionally, PLOS ONE offers an option for publishing peer-reviewed Lab Protocol articles, which describe protocols hosted on protocols.io. Read more information on sharing protocols at https://plos.org/protocols?utm_medium=editorial-email&utm_source=authorletters&utm_campaign=protocols .

We look forward to receiving your revised manuscript.

Kind regards,

Toshio Matsumoto

Academic Editor

PLOS ONE

Journal Requirements:

When submitting your revision, we need you to address these additional requirements.

1.Please ensure that your manuscript meets PLOS ONE's style requirements, including those for file naming. The PLOS ONE style templates can be found at

https://journals.plos.org/plosone/s/file?id=wjVg/PLOSOne_formatting_sample_main_body.pdf and

https://journals.plos.org/plosone/s/file?id=ba62/PLOSOne_formatting_sample_title_authors_affiliations.pdf

2. Thank you for stating the following financial disclosure:

“This study was supported by grant from the Shenzhen Science and Technology Program (KCXFZ20230731094100001)”

Please state what role the funders took in the study.  If the funders had no role, please state: "The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript."

If this statement is not correct you must amend it as needed.

Please include this amended Role of Funder statement in your cover letter; we will change the online submission form on your behalf.

3. PLOS requires an ORCID iD for the corresponding author in Editorial Manager on papers submitted after December 6th, 2016. Please ensure that you have an ORCID iD and that it is validated in Editorial Manager. To do this, go to ‘Update my Information’ (in the upper left-hand corner of the main menu), and click on the Fetch/Validate link next to the ORCID field. This will take you to the ORCID site and allow you to create a new iD or authenticate a pre-existing iD in Editorial Manager.

4. Your ethics statement should only appear in the Methods section of your manuscript. If your ethics statement is written in any section besides the Methods, please delete it from any other section.

Additional Editor Comments:

As indicated in the comments by the three expert reviewers, although the manuscript contains some useful information, there are some issues that need to be addressed before the manuscript can be considered for publication in PLOS ONE. These include, but are not limited to, the below:

1. Physical activity levels are categorized into four levels from inactive to high-active based upon only time length per a week. However, the type and intensity of activity should be taken into account. It is important to propose which type or intensity of exercise is recommended to improve BMD and/or muscle mass.

2. Subgroup analyses were performed based upon SBP, DBP, VAI, and HbA1c. What is the rationale for using these four parameters? Is there a possibility that more comprehensive analyses including other metabolic can give better results?

3. Muscle mass is not directly measured but is estimated from the ratio of the appendicular lean mass to body mass index. This should be mentioned in the limitation.

4. Exclusion criteria is not mentioned. It is unclear whether the patients were treated for hypertension, diabetes, obesity, etc.

[Note: HTML markup is below. Please do not edit.]

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #1: Partly

Reviewer #2: Partly

Reviewer #3: Yes

**********

2. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #1: I Don't Know

Reviewer #2: I Don't Know

Reviewer #3: Yes

**********

3. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

4. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #1: Yes

Reviewer #2: Yes

Reviewer #3: Yes

**********

5. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #1: 1. The reference number ‘12’ is not complete. Please correct it.

2. “Loss of bone and muscle mass often indicates accumulation of adipose tissuee[9]. Studies in recent years have shown that obese people may co-exist with decreased muscle mass and/or BMD, constituting a complex condition of comorbidities” The relation between obesity and osteoporosis is still debatable. Historically, obesity is protective against osteoporosis. Since this is still an ongoing thesis, further studies are needed, I would revise your statement.

3. I could not see a clear exclusion criteria. I am wondering if the patients with a history of cancer, or severe comorbidities were included into the study.

4. So, the authors define VAT and SAT and the importance of their ratios. I am wondering in which statistical analysis they used this definition. They used VAI for analysis, but it is totally a different measurement, right?

5. Because NHANES is cross-sectional, causality cannot be inferred (e.g., healthier individuals may exercise more). I am wondering what kind of additional data was used for analysis. Any comorbidity scoring index etc.

6. Clustering was performed on only 4 variables (SBP, DBP, VAI, HbA1c). I am wondering why only these 4 variables were chosen and whether cluster robustness was tested.

7. It is unclear if vitamin D levels, depression scores, and smoking were included in all models. Table 2 mentions these, but the Methods section should explicitly say which covariates are included in which models.

Reviewer #2: In this study, they investigated the relationships between physical activity category levels and bone mineral density at the lumbar spine and an appendicular muscle mass parameter in 3077 subjects with visceral obesity based on the NHANES data base.

Although the paper includes some useful information, there are several issues, which should be addressed.

1. The detailed and substantial contents of classification about physical activity levels should be described in Methods, although one reference [30] was only cited.

2. The content of Subgroup analysis seemed ambiguous, which details should be explained clearly.

3. In this study, the standard methods have not used for the assessment of bone mineral density and muscle mass. This limitation should be described in Discussion.

4. The results of this study should be discussed in association with visceral obesity.

Reviewer #3: General comments

The author reported the dose-response relationship of physical activity (PA) with bone mineral density (BMD) and muscle mass in visceral obesity. This relationship was modulated by metabolic status. The most important message of this study is that, for the patients with visceral obesity, it is crucial to take an individualized approach that considers their metabolic status in addition to the amount of exercise, in order to maintain healthy bones and muscles. This report has informative and significant contents at the actual clinical setting. There are several issues that the authors should adequately address in this manuscript.

Specific comments

1) PA levels were categorized as inactive (0 min/week), low-active (1-150), moderate-active (150-300), and high-active (>300) in this study. When examining the relationship between PA and BMD/muscle mass, it is important to consider the type of exercise such as aerobic exercise, resistance exercise, or combined exercise, as well as its intensity and duration. The details are unclear in surveys of PA based on self-reported questionnaires of this cross-sectional study. The issue with this paper is that, given the wide variety of available exercise options, it lacks specific recommendations that can be suggested to the patients.

2) Subgroup analyses were conducted based on metabolic clusters, which were defined using k-means clustering according to blood pressure, visceral adiposity index, and HbA1c levels. Although metabolic clusters are being classified using blood pressure, visceral fat index, and HbA1c levels, is this classification valid? How do the authors think about the opinion that a classification based on more comprehensive data including lipid profiles and inflammatory markers yield more accurate and valid results?

3) Is whether or not patients are receiving treatment for hypertension, dyslipidemia, or diabetes mellitus taken into consideration in this analysis?

**********

6. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .

Reviewer #1: No

Reviewer #2: No

Reviewer #3: No

**********

[NOTE: If reviewer comments were submitted as an attachment file, they will be attached to this email and accessible via the submission site. Please log into your account, locate the manuscript record, and check for the action link "View Attachments". If this link does not appear, there are no attachment files.]

While revising your submission, please upload your figure files tohe manuscript record, and check for the action link "View Attachments". If this link does not appear, there are the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com/ . PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Registration is free. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email PLOS at figures@plos.org . Please note that Supporting Information files do not need this step.

Dose-response relationships of physical activity with bone mineral density and muscle mass in visceral obesity: A metabolic heterogeneity perspective

PONE-D-25-12300R1

Dear Dr. zhang,

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

Within one week, you’ll receive an e-mail detailing the required amendments. When these have been addressed, you’ll receive a formal acceptance letter and your manuscript will be scheduled for publication.

An invoice will be generated when your article is formally accepted. Please note, if your institution has a publishing partnership with PLOS and your article meets the relevant criteria, all or part of your publication costs will be covered. Please make sure your user information is up-to-date by logging into Editorial Manager at Editorial Manager®  and clicking the ‘Update My Information' link at the top of the page. If you have any questions relating to publication charges, please contact our Author Billing department directly at authorbilling@plos.org.

If your institution or institutions have a press office, please notify them about your upcoming paper to help maximize its impact. If they’ll be preparing press materials, please inform our press team as soon as possible -- no later than 48 hours after receiving the formal acceptance. Your manuscript will remain under strict press embargo until 2 pm Eastern Time on the date of publication. For more information, please contact onepress@plos.org.

Kind regards,

Toshio Matsumoto

Academic Editor

PLOS ONE

Reviewers' comments:

Reviewer's Responses to Questions

Comments to the Author

1. If the authors have adequately addressed your comments raised in a previous round of review and you feel that this manuscript is now acceptable for publication, you may indicate that here to bypass the “Comments to the Author” section, enter your conflict of interest statement in the “Confidential to Editor” section, and submit your "Accept" recommendation.

Reviewer #2: (No Response)

Reviewer #3: All comments have been addressed

**********

2. Is the manuscript technically sound, and do the data support the conclusions?

The manuscript must describe a technically sound piece of scientific research with data that supports the conclusions. Experiments must have been conducted rigorously, with appropriate controls, replication, and sample sizes. The conclusions must be drawn appropriately based on the data presented.

Reviewer #2: (No Response)

Reviewer #3: Yes

**********

3. Has the statistical analysis been performed appropriately and rigorously?

Reviewer #2: (No Response)

Reviewer #3: Yes

**********

4. Have the authors made all data underlying the findings in their manuscript fully available?

The PLOS Data policy requires authors to make all data underlying the findings described in their manuscript fully available without restriction, with rare exception (please refer to the Data Availability Statement in the manuscript PDF file). The data should be provided as part of the manuscript or its supporting information, or deposited to a public repository. For example, in addition to summary statistics, the data points behind means, medians and variance measures should be available. If there are restrictions on publicly sharing data—e.g. participant privacy or use of data from a third party—those must be specified.

Reviewer #2: (No Response)

Reviewer #3: Yes

**********

5. Is the manuscript presented in an intelligible fashion and written in standard English?

PLOS ONE does not copyedit accepted manuscripts, so the language in submitted articles must be clear, correct, and unambiguous. Any typographical or grammatical errors should be corrected at revision, so please note any specific errors here.

Reviewer #2: (No Response)

Reviewer #3: Yes

**********

6. Review Comments to the Author

Please use the space provided to explain your answers to the questions above. You may also include additional comments for the author, including concerns about dual publication, research ethics, or publication ethics. (Please upload your review as an attachment if it exceeds 20,000 characters)

Reviewer #2: (No Response)

Reviewer #3: (No Response)

**********

7. PLOS authors have the option to publish the peer review history of their article (what does this mean? ). If published, this will include your full peer review and any attached files.

If you choose “no”, your identity will remain anonymous but your review may still be made public.

Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy .

Reviewer #2: No

Reviewer #3: No

**********