Bone and Infections: An Osteoimmunological Interplay

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

This review systematically explores the mechanisms of osteoimmunology in bone infections, covering the direct and indirect effects of bacterial and viral infections on bone remodeling. The topic of the paper has significant scientific importance and clinical value, and the content organization is relatively comprehensive, aligning with the journal's scope. However, the paper still has the following issues that need improvement.

1. There is obvious duplication of sentences between the abstract and introduction, such as the phrase "Osteoimmunology is an emerging field that explores..." in the abstract being almost identically repeated in the introduction.
2. Some sentences are verbose, such as in the abstract: "This immune response can lead to bone erosion and remodeling and recent research highlights how immune dysregulation contributes to bone infections and related diseases.", which contains multiple parallel clauses, affecting the clarity of reading.
3. The paper discusses in detail "bone remodeling in prosthetic joint infection (PJI)", but neglects other types of bone infections (such as periodontitis, osteomyelitis). Why? This may lead to an incomplete review, failing to evenly reflect the role of osteoimmunology in different infection scenarios.
4. The caption of Figure 2 is described as "osteoimmunological effect of bone infections on osteoclasts, osteoblasts and osteocytes", but the image link cannot display specific content, making it impossible for reviewers to evaluate its validity and clarity. Firstly, the morphology of osteoclasts, osteoblasts, and osteocytes in the figure does not match the well-known forms; osteoclasts show nuclei of two different colors, and some nuclei are elongated or deformed; what is drawn for osteoblasts? Reviewers cannot identify it as osteoblasts at all; osteocytes even contain multiple nuclei, which raises doubts about the authors' professionalism. Secondly, some descriptions in the figure are perplexing, such as "bacterial-inhibits osteoclast formation", "inflammatory cytokines osteogenesis", "struggle to clear", "Reservoir for bacteria". Finally, the arrows in the figure are messy, and reviewers have no idea what the authors intend to express. Therefore, Figure 2 needs to be completely redrawn, and the caption should provide a clear description of the content conveyed in the figure
5. In Section 7 "Future Directions", the authors briefly describe immune modulation-based strategies for preventing and treating bone infections. This content should be expanded into an important section of the paper rather than being placed as an outlook. The outlook should be closely integrated with the specific field of bone infections, proposing more original and feasible specific research paths or key scientific questions that urgently need to be solved.

Author Response

This review systematically explores the mechanisms of osteoimmunology in bone infections, covering the direct and indirect effects of bacterial and viral infections on bone remodeling. The topic of the paper has significant scientific importance and clinical value, and the content organization is relatively comprehensive, aligning with the journal's scope. However, the paper still has the following issues that need improvement.

1. There is obvious duplication of sentences between the abstract and introduction, such as the phrase "Osteoimmunology is an emerging field that explores..." in the abstract being almost identically repeated in the introduction.

Reply : The abstract has been completely rephrased in order to avoid repetitions or duplications

1. Some sentences are verbose, such as in the abstract: "This immune response can lead to bone erosion and remodeling and recent research highlights how immune dysregulation contributes to bone infections and related diseases.", which contains multiple parallel clauses, affecting the clarity of reading.

 Reply : The abstract has been completely rephrased in order to avoid repetitions and improve the clarity  of the text

 

1. The paper discusses in detail "bone remodeling in prosthetic joint infection (PJI)", but neglects other types of bone infections (such as periodontitis, osteomyelitis). Why? This may lead to an incomplete review, failing to evenly reflect the role of osteoimmunology in different infection scenarios.

Reply : The section 5 was extensively improved, as indicated by the new title Effect of bacterial infection on bone remodeling: lessons from prosthetic joint infections (PJI) and other bone infections. A large part was added  ( indicated in red ) describing periodontitis and osteomyelitis, as suggested by the reviewer.

1. The caption of Figure 2 is described as "osteoimmunological effect of bone infections on osteoclasts, osteoblasts and osteocytes", but the image link cannot display specific content, making it impossible for reviewers to evaluate its validity and clarity. Firstly, the morphology of osteoclasts, osteoblasts, and osteocytes in the figure does not match the well-known forms; osteoclasts show nuclei of two different colors, and some nuclei are elongated or deformed; what is drawn for osteoblasts? Reviewers cannot identify it as osteoblasts at all; osteocytes even contain multiple nuclei, which raises doubts about the authors' professionalism. Secondly, some descriptions in the figure are perplexing, such as "bacterial-inhibits osteoclast formation", "inflammatory cytokines osteogenesis", "struggle to clear", "Reservoir for bacteria". Finally, the arrows in the figure are messy, and reviewers have no idea what the authors intend to express. Therefore, Figure 2 needs to be completely redrawn, and the caption should provide a clear description of the content conveyed in the figure

Reply : as suggested by reviewers, Figure 2 was completely redrawn, in order to provide a more clear and detailed description of osteoimmunological effect of bone infections on osteoclasts, osteoblasts and osteocytes

1. In Section 7 "Future Directions", the authors briefly describe immune modulation-based strategies for preventing and treating bone infections. This content should be expanded into an important section of the paper rather than being placed as an outlook. The outlook should be closely integrated with the specific field of bone infections, proposing more original and feasible specific research paths or key scientific questions that urgently need to be solved.

Reply : Section 7 , as suggested by the reviewer, was extensively improved, adding a consistent integration (indicated in red ) of immune modulation-based strategies for preventing and treating bone infections and a dedicated new figure. For this reason the title of section 7 was converted  into Future directions of therapeutic strategies

 

 

Reviewer 2 Report

Comments and Suggestions for Authors

The article approaches osteoimmunology from a different perspective. Most studies address osteoimmunology in relation to metabolic bone disease, whereas the authors approach it from the perspective of bone infection.

This is a comprehensive narrative review that analyses the molecular aspects of the relationship between bone remodelling and infections.

Concerns

The methodology of the literature review is not indicated.

The figure should be clarified to make it more comprehensive by indicating the factors that increase or decrease.

It might be interesting to add a section showing the effect of antiresorptive drugs, especially anti-RANKL, and the infectious process.

The text should be thoroughly revised from a grammatical point of view.

Comments on the Quality of English Language

 

The text should be thoroughly revised from a grammatical point of view.

Author Response

The article approaches osteoimmunology from a different perspective. Most studies address osteoimmunology in relation to metabolic bone disease, whereas the authors approach it from the perspective of bone infection.

This is a comprehensive narrative review that analyses the molecular aspects of the relationship between bone remodelling and infections.

Concerns

1. The methodology of the literature review is not indicated.

Reply : The  literature was based on recent primary studies and reviews on osteoimmunological biomarkers . Multiple databases (PubMed/MEDLINE, Web of Science) was used and supplement with targeted searches of recent reviews and specialty journals. Include search terms combining disease (e.g., osteomyelitis), domain (e.g., osteoimmunology, biomarkers), and specific analytes (e.g., SuPAR, sCD14‑ST, RANKL/OPG).

2. The figure should be clarified to make it more comprehensive by indicating the factors that increase or decrease.

Reply : as suggested by reviewers, Figure 2 was completely redrawn, in order to provide a clearer and more detailed description of the osteoimmunological effect of bone infections on osteoclasts, osteoblasts and osteocytes

 

3. It might be interesting to add a section showing the effect of antiresorptive drugs, especially anti-RANKL, and the infectious process.

Reply : as suggested by the reviewer, the text was improved by adding a consistent description of the effect of antiresorptive drugs, especially anti-RANKL, and the infectious process ( text in red )

 

4. The text should be thoroughly revised from a grammatical point of view.

Reply : The whole text was revised by a mother tongue editor

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

no further comments

Reviewer 2 Report

Comments and Suggestions for Authors

The authors have answered by the authors