Impaired bone quality characterized by apatite orientation under stress shielding following fixing of a fracture of the radius with a 3D printed Ti-6Al-4V custom-made bone plate in dogs

Keiichiro Mie; Takuya Ishimoto; Mari Okamoto; Yasumasa Iimori; Kazuna Ashida; Karin Yoshizaki; Hidetaka Nishida; Takayoshi Nakano; Hideo Akiyoshi

doi:10.1371/journal.pone.0237678

Peer Review History

Original SubmissionJune 15, 2020
24 Jul 2020 Decision Letter - Ryan K. Roeder, Editor PONE-D-20-18343 Impaired bone quality characterized by apatite orientation under stress shielding following fixing of a fracture of the radius with a 3D printed Ti-6Al-4V custom-made bone plate in dogs PLOS ONE Dear Dr. Akiyoshi, Thank you for submitting your manuscript to PLOS ONE. After careful consideration, we feel your manuscript is ready for publication after a minor revision. Please submit a revised version of the manuscript that addresses the points raised by Reviewer 1. Please submit your revised manuscript by Sep 07 2020 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. 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Protocols.io assigns your protocol its own identifier (DOI) so that it can be cited independently in the future. For instructions see: http://journals.plos.org/plosone/s/submission-guidelines#loc-laboratory-protocols We look forward to receiving your revised manuscript. Kind regards, Ryan K. Roeder, PhD 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. In your Methods section, please provide additional details regarding the dogs used in your study and ensure you have described the source. For more information regarding PLOS' policy on materials sharing and reporting, see https://journals.plos.org/plosone/s/materials-and-software-sharing#loc-sharing-materials. 3. Thank you for including your ethics statement: "The study was conducted according to the guidelines of the Experimental Animal Committee of Osaka Prefecture University (Permit number 29–104).". Please amend your current ethics statement to confirm that your named ethics committee specifically approved this study. For additional information about PLOS ONE submissions requirements for ethics oversight of animal work, please refer to http://journals.plos.org/plosone/s/submission-guidelines#loc-animal-research Once you have amended this/these statement(s) in the Methods section of the manuscript, please add the same text to the “Ethics Statement” field of the submission form (via “Edit Submission”). [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: Abstract: "flexibly" should be "properly" Abstract: "remained impaired" should be "remained different" You have no evidence of impairment, just differences in axis orientation. Line 149: "cares" should be "care" General comment: The remodeling of fracture callus (woven bone) into lamellar bone is affected by loading since osteonal orientation is affected by bone stress (see, for example, "Skeletal Tissue Mechanics Edition 2" Martin et al, discussion around Figure 6.14). A discussion of this is not necessary, but would make the results of the paper fit better into existing literature. My conclusion from your experiment is that stress shielding under a plate that is insufficient to cause an effect on BMD, can still affect the details of consolidation of the woven bone of the fracture callus (i.e., collagen and mineral long-axis directions) by affecting paths of osteonal cutting cones and, perhaps, how the osteoblasts deposit matrix. Reviewer #2: The authors presented a high-quality study of the effect of a single fracture plate for use in veterinary applications. The authors demonstrated reduced BMD and, more so, reduced apatite c-axis preferential orientation in the vicinity of the fracture site and corresponding surrounding bone plate. This reviewer does not have any additional questions. ****** 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.0237678.r001
Revision 1
28 Jul 2020 Author Response Thank you for your valuable comments regarding our manuscript. In response to the reviewers’ comments, we have revised our manuscript as described below. In the revised manuscript and this response letter, the revised sections are marked in red color. Editor: Comments 1-3 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 Answer to comments 1 Thank you for kindly comment. We have revised the manuscript and figure files naming according to PLOS ONE's style templates. 2. In your Methods section, please provide additional details regarding the dogs used in your study and ensure you have described the source. For more information regarding PLOS' policy on materials sharing and reporting, see https://journals.plos.org/plosone/s/materials-and-software-sharing#loc-sharing-materials. Answer to comments 2 Thank you for kindly comment. According to Editor’s comment, we have added the following sentences in Materials and Methods section. P. 4, line 83 The dogs belonged the kennel of Research Center for Experimental Animal Science of Osaka Prefecture University. The dogs were considered healthy based on their medical history and physical examination. 3. Thank you for including your ethics statement: "The study was conducted according to the guidelines of the Experimental Animal Committee of Osaka Prefecture University (Permit number 29–104).". Please amend your current ethics statement to confirm that your named ethics committee specifically approved this study. For additional information about PLOS ONE submissions requirements for ethics oversight of animal work, please refer to http://journals.plos.org/plosone/s/submission-guidelines#loc-animal-research Once you have amended this/these statement(s) in the Methods section of the manuscript, please add the same text to the “Ethics Statement” field of the submission form (via “Edit Submission”)." Answer to comments 3 Thank you for kindly comment. According to Editor’s comment, we have revised the following sentences about ethics statement in Materials and Methods section. P. 4, line 85 The study was conducted according to the guidelines of the Experimental Animal Committee of Osaka Prefecture University and the protocol was approved by the Experimental Animal Committee of Osaka Prefecture University (Permit number 29–104). Reviewer #1: Comments 1-3 • Abstract: "flexibly" should be "properly" • Abstract: "remained impaired" should be "remained different" You have no evidence of impairment, just differences in axis orientation. • Line 149: "cares" should be "care" Answer to comments 1-3 Thank you for kindly pointing them out. Following to the reviewer #1’s comments, we have revised the manuscript. General comment The remodeling of fracture callus (woven bone) into lamellar bone is affected by loading since osteonal orientation is affected by bone stress (see, for example, "Skeletal Tissue Mechanics Edition 2" Martin et al, discussion around Figure 6.14). A discussion of this is not necessary, but would make the results of the paper fit better into existing literature. My conclusion from your experiment is that stress shielding under a plate that is insufficient to cause an effect on BMD, can still affect the details of consolidation of the woven bone of the fracture callus (i.e., collagen and mineral long-axis directions) by affecting paths of osteonal cutting cones and, perhaps, how the osteoblasts deposit matrix. Answer to general comment Thank you for your valuable comment. As the reviewer #1 suggested, the orientation of osteon in which collagen preferentially orients along its longitudinal axis [Ascenzi A, Bonucci E. The tensile properties of single osteons. Anat Rec. 1967; 158: 375-386] should be important for the formation of preferential collagen/apatite orientation. With the reviewer #1’s comment, we felt that discussing the relationship between stress shielding and apatite orientation, by citing the existing literatures on the directional relationship between osteon and bone stress, reinforces our claim. Therefore, we have added the following sentences and references in Discussion section. P. 12, line 259 This unrecovered apatite orientation under stress shielding might be influenced by the osteon orientation. The orientation of osteon in which collagen preferentially orients along its longitudinal axis [29] corresponds with the directions of the maximum principal stress [30, 31]. Under the stress shielding, the direction of osteon would be disturbed, which further led to the low degree of collagen orientation. Since the apatite crystallizes on collagen so that its c-axis aligns with the long axis of collagen in the presence of osteocalcin [17], the apatite c-axis orientation degrades by inheriting degraded collagen orientation. Added references: 29. Heřt J, Fiala P, Petrtýl M. Osteon orientation of the diaphysis of the long bones in man. Bone. 1994; 15: 269-277. 30. Martin RB, Burr DB, Sharkey NA, Fyhrie DP. Skeletal tissue mechanics. 2nd ed. New York: Springer; 2015. 31. Ascenzi A, Bonucci E. The tensile properties of single osteons. Anat Rec. 1967; 158: 375-386. Reviewer #2: The authors presented a high-quality study of the effect of a single fracture plate for use in veterinary applications. The authors demonstrated reduced BMD and, more so, reduced apatite c-axis preferential orientation in the vicinity of the fracture site and corresponding surrounding bone plate. This reviewer does not have any additional questions. Answer to comment Thank you for your review and your encouraging comment. We will continue to devote ourselves to research activities for the development of veterinary medicine and science. We hope that the revised manuscript is suitable for publication in PLOS ONE. Sincerely yours, Hideo Akiyoshi Attachments Attachment Submitted filename: Resposes to the reviewers.DOCX https://doi.org/10.1371/journal.pone.0237678.r002
31 Jul 2020 Decision Letter - Ryan K. Roeder, Editor Impaired bone quality characterized by apatite orientation under stress shielding following fixing of a fracture of the radius with a 3D printed Ti-6Al-4V custom-made bone plate in dogs PONE-D-20-18343R1 Dear Dr. Akiyoshi, 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, Ryan K. Roeder, PhD Academic Editor PLOS ONE Additional Editor Comments (optional): Reviewers' comments: https://doi.org/10.1371/journal.pone.0237678.r003
Formally Accepted
24 Aug 2020 Acceptance Letter - Ryan K. Roeder, Editor PONE-D-20-18343R1 Impaired bone quality characterized by apatite orientation under stress shielding following fixing of a fracture of the radius with a 3D printed Ti-6Al-4V custom-made bone plate in dogs Dear Dr. Akiyoshi: 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. Ryan K. Roeder Academic Editor PLOS ONE https://doi.org/10.1371/journal.pone.0237678.r004

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