The bone bridge significantly affects the decrease in bone mineral density measured with quantitative computed tomography in ankylosing spondylitis

So Yun Lee; Ran Song; Hyung In Yang; Sang Wan Chung; Yeon-Ah Lee; Seung-Jae Hong; Seong Jong Yun; Sang-Hoon Lee

doi:10.1371/journal.pone.0249578

Peer Review History

Original SubmissionOctober 30, 2020
11 Jan 2021 Decision Letter - Alejandro A. Espinoza Orías, Editor PONE-D-20-33718 The Bone Bridge Significantly Affects the Decrease in Bone Mineral Density Measured with Quantitative Computed Tomography in Ankylosing Spondylitis. PLOS ONE Dear Dr. Lee, 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. The review panel was enthusiastic about this manuscript and had overall minor concerns about addressing non-clinical factors that may contribute to osteoporosis in AS patients. Although the panel is in agreement that qCT is a better method, the authors also need to reinforce the reason to not pursue DXA, since it is still considered the clinical gold standard for bone mineral measurements, and the audience of the Journal may look for that link between methods. Lastly, a power analysis also is deemed necessary to lend support to the statistical findings. Please submit your revised manuscript by Feb 21 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. 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). 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During our internal evaluation of the manuscript, we found some minor occurrences of overlapping text with the following previous publication(s), some of which you are an author, which needs to be addressed: - https://arthritis-research.biomedcentral.com/articles/10.1186/s13075-018-1731-8 - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3623474/ We would like to make you aware that copying extracts from previous publications word-for-word, especially outside the methods section, is unacceptable. In addition, the reproduction of text from published reports has implications for the copyright that may apply to the publications. Please revise the manuscript to quote or rephrase the duplicated text and cite your sources for text outside the methods section. Please note that further consideration is dependent on the submission of a manuscript that addresses these concerns about the overlap in text with published work. <h1> </h1> [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: Yes Reviewer #2: 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 ****** 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: This is a well written article examining the association between bone bridging, lumbar ROM and QCT assessed BMD. Using retrospective data the authors are able to effectively demonstrate a negative correlation between QCT BMD, bone bridging, and lumbar ROM. The discussion provides a good frame work for the utilization of this association. Osteoporosis in AS patients is likely multifactorial based on the chronic inflammatory state as well as decreasing physical activity (lumbar ROM). The limitation of this article is the relatively small data set. For example, although statistically insignificant in their evaluation, the use of TNF inhibitors differed by about 20% between the normal and low BMD groups, begging the question, would these medications have some significance in a larger data set. This article is also limited in terms of the use of QCT for the evaluation of BMD in this patient population. Although QCT appears to correlate with bone bridging and lumbar ROM, without a DXA value to compare to as an internal control (from both the hip and lumbar spine), I don’t think the rationale for utilization of QCT over DXA is entirely supported. Overall, this is an interesting article that introduces the interplay between bone bridging, physical activity (ROM), and osteoporosis in the AS population. Although it does not provide any detail of causality in regards to this interplay, this introduces a new avenue for future research on this topic. Reviewer #2: The purpose of this study was to determine whether the formation of a bone bridge correlates with low BMD measured with QCT in patients with AS. Authors concluded that the bone bridge significantly affects the decrease in bone density in patients with AS. This study could support the usefulness of early identification of bone loss to prevent spinal radiographic progression of AS. However, pathogenesis of osteoporosis could be multifactorial and bony bridge might not be the main pathology of osteoporosis in AS patients. There could be possibilities that osteoporosis is more related to socioeconomic status, occupational status, and disability caused by spinal malalignment. Author should decribe this. ****** 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. 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Revision 1
2 Mar 2021 Author Response To the Editor-in-Chief, PLOS ONE Dear Editor: First of all, thank you very much for your consideration of publication of this paper in PLOS ONE. We made efforts to follow your recommendations and suggestions as best as we could. We addressed several important concerns that the reviewers brought up and tried to revise the manuscript appropriately. We hope that our response and revision can alleviate the reviewers’ concerns. Thank you once again for your time and consideration. Sincerely Yours, Sang-Hoon Lee, MD The review panel was enthusiastic about this manuscript and had overall minor concerns about addressing non-clinical factors that may contribute to osteoporosis in AS patients. Although the panel is in agreement that qCT is a better method, the authors also need to reinforce the reason to not pursue DXA, since it is still considered the clinical gold standard for bone mineral measurements, and the audience of the Journal may look for that link between methods. Lastly, a power analysis also is deemed necessary to lend support to the statistical findings. > Thank you for your thoughtful comment. We have mentioned whether DXA use is not appropriate in AS patients. In AS, it is known that BMD is overestimated due to ossification of ligament around the vertebral body (reference #23). In the previous study, when using DXA to diagnose osteoporosis, fewer patients were diagnosed with osteoporosis than when measured by QCT. Diagnosed (reference #28). Although DXA is still the most used diagnostic method for osteoporosis, it should be considered as the diagnosis through DXA may not be as accurate as in AS. I have marked the sentences related to the first page of the discussion. We also performed a power analysis in response to your comment. As a result of post hoc analysis on the 47 patients used in this study, the power was 0.96 at ρ0 = -0.501, α = 0.05. This is added at the end of the 'Correlation between bone bridge and QCT BMD' part of the result. Reviewers' comments to the author: Reviewer #1: This is a well written article examining the association between bone bridging, lumbar ROM and QCT assessed BMD. Using retrospective data the authors are able to effectively demonstrate a negative correlation between QCT BMD, bone bridging, and lumbar ROM. The discussion provides a good frame work for the utilization of this association. Osteoporosis in AS patients is likely multifactorial based on the chronic inflammatory state as well as decreasing physical activity (lumbar ROM). The limitation of this article is the relatively small data set. For example, although statistically insignificant in their evaluation, the use of TNF inhibitors differed by about 20% between the normal and low BMD groups, begging the question, would these medications have some significance in a larger data set. > Thank you for your thoughtful comment. We agree with your point. As there have been previous studies showing that anti-TNF therapy slows down generalized bone loss in AS patients, an accurate analysis is essential that there is no difference in anti-TNF therapy between the two groups when the sample size increases. The content of the positive effect of the TNF inhibitor was mentioned in the text. This article is also limited in terms of the use of QCT for the evaluation of BMD in this patient population. Although QCT appears to correlate with bone bridging and lumbar ROM, without a DXA value to compare to as an internal control (from both the hip and lumbar spine), I don’t think the rationale for utilization of QCT over DXA is entirely supported. > Thank you for your thoughtful comment. As mentioned in the text, if there was a direct comparable DXA value, it would have been a sufficient basis for performing QCT rather than DXA in AS patients. However, it is difficult to use both methods when measuring BMD in one patient due to problems such as insurance and cost of DXA test. In the study we cited as reference # 28, it was confirmed that BMD is overestimated in DXA when compared to QCT in patients with AS due to spinal involvement. In this study, it was mentioned in a limitation that the analysis of BMD was not performed in both DXA and QCT methods. Overall, this is an interesting article that introduces the interplay between bone bridging, physical activity (ROM), and osteoporosis in the AS population. Although it does not provide any detail of causality in regards to this interplay, this introduces a new avenue for future research on this topic. Reviewer #2: The purpose of this study was to determine whether the formation of a bone bridge correlates with low BMD measured with QCT in patients with AS. Authors concluded that the bone bridge significantly affects the decrease in bone density in patients with AS. This study could support the usefulness of early identification of bone loss to prevent spinal radiographic progression of AS. However, pathogenesis of osteoporosis could be multifactorial and bony bridge might not be the main pathology of osteoporosis in AS patients. There could be possibilities that osteoporosis is more related to socioeconomic status, occupational status, and disability caused by spinal malalignment. Author should describe this. > Thank you for your thoughtful comment. We agree with your point. In the baseline characteristics analysis, one of our limitations is that the factors known to cause osteoporosis were not sufficiently identified. In response to this comment, we emphasized by adding content to the text. Attachments Attachment Submitted filename: Response to Reviewers.docx https://doi.org/10.1371/journal.pone.0249578.r002
22 Mar 2021 Decision Letter - Alejandro A. Espinoza Orías, Editor The Bone Bridge Significantly Affects the Decrease in Bone Mineral Density Measured with Quantitative Computed Tomography in Ankylosing Spondylitis. PONE-D-20-33718R1 Dear Dr. Lee, 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, Alejandro A. Espinoza Orías, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0249578.r003
Formally Accepted
8 Apr 2021 Acceptance Letter - Alejandro A. Espinoza Orías, Editor PONE-D-20-33718R1 The bone bridge significantly affects the decrease in bone mineral density measured with quantitative computed tomography in ankylosing spondylitis. Dear Dr. Lee: 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 Dr. Alejandro A. Espinoza Orías Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0249578.r004

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