Current Trends in Adjuvant Therapies for Medication-Related Osteonecrosis of the Jaw
Round 1
Reviewer 1 Report
Manuscript ID: applsci-1648360
Title: Current trends of adjuvant therapies in MRONJ treatment
1.What is the main question addressed by the research?
To evaluate the use of adjunct therapies in the treatment of medication-related osteonecrosis of the jaw (MRONJ) patients.
2.Is it relevant and interesting?
The article is relevant and interesting.
3.How original is the topic?
The topic is current.
4.What does it add to the subject area compared with other published material?
The authors have collected and analyzed a great deal of recent data.
5.Is the paper well written?
Yes, the article is well written.
6.Is the text clear and easy to read?
Yes, but moderate English editing is required.
7.Are the conclusions consistent with the evidence and arguments presented?
Yes, the conclusions consistent with the evidence and arguments presented but further studies are necessary to confirm authors’ hypothesis.
8.Do they address the main question posed?
Yes, the Authors addressed the main question posed.
Other comments:
- English language: Moderate English editing is required.
- Abstract: To attract the reader's attention, please clarify the target of the article, and structure the abstract.
- Introduction: This section needs some improvements. I recommend reading the Meeting Report of the first Workshop of European task force on MRONJ: article by Schiodt et al [PMID: 31325201]. Please refer to wide range of medications classified as tyrosine kinase inhibitors, monoclonal antibodies (including tocilizumab), mammalian target of rapamycin inhibitors, radiopharmaceuticals, selective estrogen receptor modulators, and immunosuppressants implicated in osteonecrosis of the jaws.
I recommend Chang et al's article entitled "Current Understanding of the Pathophysiology of Osteonecrosis of the Jaw" to implement this section [PMID: 30155844].
Please refer to relationship between oncological symptoms (like numb chin syndrome) and MRONJ [PMID: 29680775]. Please refer to efficacy of drug holiday in MRONJ treatment [PMID: 32568416].
- Materials and Methods: This section was properly prepared.
- Results and Discussion: This section needs some improvements. Please discuss the use of platelet concentrates for MRONJ treatment with reference to a recent systematic review on the subject published in the EACMFS reference journal. Anyway, the use of platelet concentrate in oncological patient is at the center of a recent academic debate [PMID: 31116189]. Please discuss the efficacy of drug holiday in MRONJ treatment [PMID: 32568416].
- Conclusion: This section was properly prepared but further studies are necessary to confirm authors’ hypothesis regarding.
After making the indicated changes, I am available for a second round of peer review.
Thanks for the opportunity to review this manuscript.
Author Response
Please see the attachment. Thank you.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
The manuscript entitled “Current trends of adjuvant therapies in MRONJ treatment” submitted to Applied sciences aims to show a brief summary of adjunct therapies and to review clinical reports to suggest adjunct therapies in the treatment of MRONJ patients.
The manuscript appears interesting however, many manuscripts on ONJ treatment strategies are documented in the literature.
I have some suggestions to improve deeply the quality of the manuscript, enriching the text with further notions.
- English language: Minor spell check is required.
- Introduction: This section needs some improvements. I recommend to report to the last AAOMS update [DOI:https://doi.org/10.1016/j.joms.2022.02.008]
- “pathophysiological mechanisms of MRONJ have not been found clearly…” I suggest to refer to recent theory of MRONJ onset (influence of previous oral cavity infections, systematic condition of patients, influence of BPs on mesenchymal stem cells of oral cavity).
- I think it is necessary to mention the usefulness of early surgical treatment of patients with ONJ. In particular how early surgical management of ONJ can have a different prognosis for oncological or osteometabolic patients [DOI: 10.1016/j.joms.2020.05.037 - DOI: 10.1016/j.jcms.2018.12.014]
- A section on the use of platelet concentrates should be implemented in the text. In particular, I suggest to evidence how the use of platelet concentrate can help in solving various cases in oral and maxillofacial surgery scenarios [PMID: 18983325 - PMID: 22818655 - PMID: 32613433 - PMID: 21740370]
- Please, add an Abbreviation part at the end of the manuscript
After the suggested improvements, I think it is necessary to re-evaluate the text.
Author Response
Please see the attachment. Thank you.
Author Response File: Author Response.pdf
Reviewer 3 Report
This manuscript is an interesting review on several treatment strategies in the management of MRONJ disease.
Although there are many review on this topic, the structure of the manuscript could be interesting for the readers.
I suggest many addition and changes of the text.
- Please, be less subjective in the statements of the part of the abstract (mronj is a treatable pathology!)
- "In addition, the incidence is much higher in elder patients who had surgical dental treatments such as tooth extraction, dental implants. " I suggest to refer to a recent interesting manuscript about the infection in the onset of MRONJ [PMID: 34065104]
- "But, the pathophysiological mechanisms of MRONJ have not been found clearly ..." I suggest to report a short piece on new important theories of the onset of ONJ, in particular the influence of BP on mesenchymal stem cells in the oral cavity [DOI: 10.1177/0963689720948497 – DOI: 10.3390/ph13120423].
This part could enrich deeply the manuscript quality.
- The use of Autologous platelet concentrate is well documented in literature for the management of MRONJ.
In particular, application of APC after bone surgery may improve the quality of life limited to the short-term follow-up and reduce pain and postoperative infections.
I suggest to add a text part about this therapeutic option [DOI: 10.4103/ijdr.IJDR_689_19 - doi: 10.4317/jced.54154 - doi: 10.3390/jcm9113505 - doi:10.1097/SCS.0000000000007981 - DOI: 10.3390/jcm11030682]
This part could improve the text, in particular on treatment strategies.
Author Response
Please see the attachment.
Thank you.
Author Response File: Author Response.pdf
Reviewer 4 Report
This manuscript is a review article about the current trend in the therapy of medication-related osteonecrosis of the jaw (MRONJ). MRONJ is a severe condition and challenging to treat.
When authors talk about hyperbaric oxygen treatment, they mention only minor complications, but they need to mention also significant complications such as adverse effects of potential carcinoma residuals.
In addition, the authors did not mention anything about platelet-rich plasma therapy and vasodilatation therapy.
Since this condition does not yet have a harmonized therapy, the authors should also state the negatives of each of the mentioned therapies and, based on everything, give a conclusion.
Also, I suggest that authors write a recommendation based on the stage of MRONJ.
Without a satisfactory conclusion, the manuscript brings no novelties.
Please check the language style. I recommend that a native speaker review the manuscript. Also, please check the reference according Journal instructions.
Author Response
Please see the attachment.
Thank you.
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
Dear Authors,
I think that platelet concentrates is a relevant topic in adjuvant therapies for MRONJ management.
Please insert a section in the manuscript.
Without the manuscript it would be incomplete.
After I will be available for another round of peer review.
Author Response
Please see the attachment.
Thank you.
Author Response File: Author Response.pdf
Reviewer 2 Report
I suggest to insert a text part about the usefulness of early surgical treatment of patients with ONJ. In particular how early surgical management of ONJ can have a different prognosis for oncological or osteometabolic patients [DOI: 10.1016/j.joms.2020.05.037 - DOI: 10.1016/j.jcms.2018.12.014].
This part can enrich from a clinical point of view the text which is inherent as a topic to the suggested literature.
Reporting recent data increases the scientific validity of the text.
Without the manuscript it would be incomplete.
After I will be available for another round of peer review.
Author Response
Please see the attachment.
Thank you.
Author Response File: Author Response.pdf
Reviewer 3 Report
The authors partially followed the suggestions and revisions made by the reviewers.
Despite some modifications, the text does not seem to have improved much since the first version.
I suggest that the authors complete the reviewers' suggestions and I am available for subsequent evaluation of the manuscript.
Author Response
Please see the attachment.
Thank you.
Author Response File: Author Response.pdf
Reviewer 4 Report
I still stand by my demands from the original review. However, I don't know why authors can't write references according to the journal's instructions - I guess it's not that complicated.
Please further refine the negatives of each of the mentioned therapies.
Author Response
Please see the attachment.
Thank you.
Author Response File: Author Response.pdf
Round 3
Reviewer 1 Report
After the changes made, the article may be suitable for publication.
Author Response
We modified manuscript according to 'reviewer 3's comments'. Thank you.
Reviewer 2 Report
Manuscript is suitable for publication
Author Response
We modified manuscript according to 'reviewer 3's comments'.
Thank you.
Reviewer 3 Report
The use of Autologous platelet concentrate is well documented in literature for the management of MRONJ.
In particular, application of APC after bone surgery may improve the quality of life limited to the short-term follow-up and reduce pain and postoperative infections.
I suggest to add a text part about this therapeutic option [DOI: 10.4103/ijdr.IJDR_689_19 - doi: 10.4317/jced.54154 - doi: 10.3390/jcm9113505 - doi:10.1097/SCS.0000000000007981 - DOI: 10.3390/jcm11030682]
This part could improve the text, in particular on treatment strategies
Author Response
Please see the attachment.
Thank you.
Author Response File: Author Response.pdf
