A 15-year follow-up study of hip bone mineral density and associations with leisure time physical activity. The Tromsø Study 2001–2016

Saija Mikkilä; Jonas Johansson; Anna Nordström; Peter Nordström; Nina Emaus; Bjørn Helge Handegård; Bente Morseth; Boye Welde

doi:10.1371/journal.pone.0262228

Peer Review History

Original SubmissionSeptember 1, 2021
6 Oct 2021 Decision Letter - Robert Daniel Blank, Editor PONE-D-21-28316A 15-year follow-up study of hip bone mineral density and associations with leisure time physical activity. The Tromsø Study 2001-2016.PLOS ONE Dear Dr. Mikkilä, 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. Both reviewers suggest edits to your MS, which it would be desirable to address. However, please note that these are suggestions, not mandates. Please submit your revised manuscript by Nov 20 2021 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. 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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. Please review your reference list to ensure that it is complete and correct. If you have cited papers that have been retracted, please include the rationale for doing so in the manuscript text, or remove these references and replace them with relevant current references. Any changes to the reference list should be mentioned in the rebuttal letter that accompanies your revised manuscript. If you need to cite a retracted article, indicate the article’s retracted status in the References list and also include a citation and full reference for the retraction notice. [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: Yes Reviewer #2: Yes ******** 2. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: 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: No Reviewer #2: No ****** 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 ****** 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: Well written manuscript. Minor comment The sample is probably a relatively healthier population than in Australia (or the USA) judged from their BMI below (in Australia 41% of subjects in this age group are obese based on BMI https://www.aihw.gov.au/reports/australias-health/overweight-and-obesity) Study: Women had BMI of 26.7 ± 4.6 kg/m2 Men 27.1 ± 3.6 kg/m2 It is likely that the segment of this relatively non obese population that is most active is also the healthiest and would eat better, probably drink less, and possibly smoke less (although they tried to account for this). The authors are aware of this limitation and refer to it quicky in the final paragraph before the Conclusion when they say: "Also, our analysis did not include additional confounders such as dietary factors, medication affecting bone metabolism or general health status." This is a bit brief and should be expanded by saying it is possible that the more physically active cohort would most likely be the 'healthiest cohort' which is an alternative explanation for the findings. Reviewer #2: This is an interesting, rigorously conducted and well-reported study showing that higher physical activity levels are associated with greater hip aBMD in a large cohort of adults and older adults. The subjective categorisation of physical activity is a limitation of the study, however the authors have thoroughly discussed this in the limitations section. Some general and specific comments are provided below. General comments: • There are very few participants categorised as physical activity level 4. I wonder whether combining physical activity categories 3 and 4 (as was done in the Morseth et al 2010 paper; reference 18) would have any influence on the results. • It would be interesting to see if physical activity is similarly associated with femoral neck aBMD. Including femoral neck BMD data would strengthen the study. • Reporting BMD results as percentage differences/changes (as opposed to absolute values in mg/cm2) would be more easily interpreted by the reader. Specific Comments: • Page 2, line 28: Given it is a key component of the study, I think it should be made clear in the abstract that the questionnaire categorised participants into physical activity levels (as opposed to estimated volume/intensity of physical activity). Wording such as ‘Categories of physical activity were determined by questionnaire’ would be more informative. • The results section should be presented in the same order as the study aims. To align with the order of the aims presented at the end of the introduction, the ‘Changes in left total hip aBMD’ and ‘Physical activity and left total hip aBMD’ sections in the results should be swapped. • Page 16, lines 296-300: It is mentioned here that physical activity was assessed by accelerometry in a small sample in 2007-08, and in a larger sample in 2015-16. The next sentence says that objective physical activity data was not available in 2007-08. Does this mean that the data used in the Emaus et al. paper cited is not available to use in the current study? If it was available, it would be valuable to analyse the association with aBMD of objectively measured physical activity in 2007-08 and 2015-16. • Page 16, lines 297-300: The Sagelv et al. study referenced here showed only weak (albeit significant) correlations (r = 0.11 to 0.26). This should be acknowledged in this sentence. • Table 1: Descriptive labels for the 4 physical activity categories would be more informative than level 1, level 2, level 3, level 4. E.g. as in Table 4 where they are labelled as inactive, light, moderate, vigorous activity. • The footnote of Table 3 states Age groups are based on participants’ age at Tromsø6. A similar statement should also be included in the footnote for Table 2. ****** 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 [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 to 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. https://doi.org/10.1371/journal.pone.0262228.r001
Revision 1
18 Nov 2021 Author Response We thank the reviewers for very thorough and helpful comments. We have made our best efforts to address the comments and we believe that the revisions have improved the manuscript. Manuscript revisions are indicated by use of Track changes. Our responses to the reviewers are written in cursive under the respective comment and page numbers refer to the document with Track Changes. Reviewer #1: Well written manuscript. Minor comment The sample is probably a relatively healthier population than in Australia (or the USA) judged from their BMI below (in Australia 41% of subjects in this age group are obese based on BMI https://www.aihw.gov.au/reports/australias-health/overweight-and-obesity) Study: Women had BMI of 26.7 ± 4.6 kg/m2 Men 27.1 ± 3.6 kg/m2 It is likely that the segment of this relatively non obese population that is most active is also the healthiest and would eat better, probably drink less, and possibly smoke less (although they tried to account for this). The authors are aware of this limitation and refer to it quicky in the final paragraph before the Conclusion when they say: "Also, our analysis did not include additional confounders such as dietary factors, medication affecting bone metabolism or general health status." This is a bit brief and should be expanded by saying it is possible that the more physically active cohort would most likely be the 'healthiest cohort' which is an alternative explanation for the findings. Response: Thank you for taking the time to review our manuscript and for raising the issue of sample generalizability. We have now expanded this limitation about these issues regarding lifestyle and the more physically active cohort, page 16, line 307-311. Reviewer #2: This is an interesting, rigorously conducted and well-reported study showing that higher physical activity levels are associated with greater hip aBMD in a large cohort of adults and older adults. The subjective categorisation of physical activity is a limitation of the study, however the authors have thoroughly discussed this in the limitations section. Some general and specific comments are provided below. Response: Thank you for reviewing our manuscript and providing valuable feedback! General comments: • There are very few participants categorised as physical activity level 4. I wonder whether combining physical activity categories 3 and 4 (as was done in the Morseth et al 2010 paper; reference 18) would have any influence on the results. Response: By combining activity level groups 3 and 4, the results of the linear mixed models analysis become very similar to the results of the original analysis. Combining the two groups results in loss of information since we are also interested in effects concerning the highest activity level group. Thus we would prefer to not combine the groups. • It would be interesting to see if physical activity is similarly associated with femoral neck aBMD. Including femoral neck BMD data would strengthen the study. Response: The results from a linear mixed model analysis on femoral neck BMD yield very similar results and conclusions about the association between physical activity and BMD compared with the situation where total hip aBMD was used as outcome variable. This is expected since the correlation between total hip aBMD and femoral neck aBMD is approximately 0.90 on all measurement occasions. As a result of the reviewer’s suggestion, the regions included in total hip aBMD are now specified in the methods section (page 7, line 137-138) and correlation between femoral neck BMD and total hip BMD is added to the results (page 10, line 203-205). We also added associations between physical activity and femoral neck aBMD to the abstract (page 2, line 36-37), methods (page 7, line 138-139 and page 8, line 160) and results (page 10, line 202-203). Due to the high correlation between total hip aBMD and femoral neck aBMD, we have chosen not to report the femoral neck BMD linear mixed model results in the manuscript. • Reporting BMD results as percentage differences/changes (as opposed to absolute values in mg/cm2) would be more easily interpreted by the reader. Response: We agree with the reviewer and this is now added to the manuscript, table 3 (former table 2), page 12 and table 4 (former table 3), page 13. Specific Comments: • Page 2, line 28: Given it is a key component of the study, I think it should be made clear in the abstract that the questionnaire categorised participants into physical activity levels (as opposed to estimated volume/intensity of physical activity). Wording such as ‘Categories of physical activity were determined by questionnaire’ would be more informative. Response: We have now clarified the sentences, page 2, line 24-26. • The results section should be presented in the same order as the study aims. To align with the order of the aims presented at the end of the introduction, the ‘Changes in left total hip aBMD’ and ‘Physical activity and left total hip aBMD’ sections in the results should be swapped. Response: This is a good suggestion that makes the manuscript more stringent. This is now swapped in the manuscript. Table 2 is currently table 3, table 3 is currently 4 and table 4 is currently 2. • Page 16, lines 296-300: It is mentioned here that physical activity was assessed by accelerometry in a small sample in 2007-08, and in a larger sample in 2015-16. The next sentence says that objective physical activity data was not available in 2007-08. Does this mean that the data used in the Emaus et al. paper cited is not available to use in the current study? If it was available, it would be valuable to analyse the association with aBMD of objectively measured physical activity in 2007-08 and 2015-16. Response: In the Tromsø Activity sub-study, a sample of 313 men and women aged 40–44 years were randomly selected from Tromsø6 to validate the SGPALS against accelerometer. Unfortunately, only 39 participants had valid accelerometer data in both Tromsø6 and Tromsø7. Therefore, we chose not to use the accelerometer data from Tromsø6. • Page 16, lines 297-300: The Sagelv et al. study referenced here showed only weak (albeit significant) correlations (r = 0.11 to 0.26). This should be acknowledged in this sentence. Response: This is added in the manuscript now, page 16, line 302-303. • Table 1: Descriptive labels for the 4 physical activity categories would be more informative than level 1, level 2, level 3, level 4. E.g. as in Table 4 where they are labelled as inactive, light, moderate, vigorous activity. Response: Physical activity categories are now marked in Table 1, page 9-10 as in Table 2 (former Table 4), page 11. • The footnote of Table 3 states Age groups are based on participants’ age at Tromsø6. A similar statement should also be included in the footnote for Table 2. Response: This is now added to former Table 2, current Table 3. Age groups are based on baseline, therefore following footnote for the current Table 3: “Age groups are based on participants’ age at T5”, page 12, line 227. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0262228.r002
20 Dec 2021 Decision Letter - Robert Daniel Blank, Editor A 15-year follow-up study of hip bone mineral density and associations with leisure time physical activity. The Tromsø Study 2001-2016. PONE-D-21-28316R1 Dear Dr. Mikkilä, 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 for payment will follow shortly after the formal acceptance. To ensure an efficient process, please log into Editorial Manager at http://www.editorialmanager.com/pone/, click the 'Update My Information' link at the top of the page, and double check that your user information is up-to-date. If you have any billing related questions, 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, Robert Daniel Blank, MD, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): 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 #1: All comments have been addressed Reviewer #2: 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 #1: Yes Reviewer #2: Yes ****** 3. Has the statistical analysis been performed appropriately and rigorously? Reviewer #1: Yes Reviewer #2: 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 #1: No Reviewer #2: No ****** 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 #1: Yes Reviewer #2: 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 #1: All comments have been addressed satisfactorily. Well written manuscript and is ready for publication. Reviewer #2: (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 #1: No Reviewer #2: No https://doi.org/10.1371/journal.pone.0262228.r003
Formally Accepted
26 Dec 2021 Acceptance Letter - Robert Daniel Blank, Editor PONE-D-21-28316R1 A 15-year follow-up study of hip bone mineral density and associations with leisure time physical activity. The Tromsø Study 2001-2016. Dear Dr. Mikkilä: I'm pleased to inform you that your manuscript has been deemed suitable for publication in PLOS ONE. Congratulations! Your manuscript is now with our production department. If your institution or institutions have a press office, please let them know about your upcoming paper now to help maximize its impact. If they'll be preparing press materials, please inform our press team within the next 48 hours. 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. If we can help with anything else, please email us at plosone@plos.org. Thank you for submitting your work to PLOS ONE and supporting open access. Kind regards, PLOS ONE Editorial Office Staff on behalf of Professor Robert Daniel Blank Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0262228.r004

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