The Assessment of the Usefulness of Platelet-Rich Fibrin in the Healing Process Bone Resorption

Round 1

Reviewer 1 Report

The manuscript of the study carried out by the authors is demonstrating the use of PRF in dental surgery aimed at preventing changes in alveolar height and width after tooth extraction. On the date of extraction, thereafter on the 10 day and 6 months, the alveolar process was measured, soft tissues healing was assessed, and imaging examinations were carried out.

I have a remark on the Materials and Methods: 

Performing bone density measurements on CBCT dataset is not reliable without BMD calibration phantoms prior to the scans. Please clarify how the calibration procedures were carried out prior to the CBCT scans on which the bone density measurements were performed and additionally, please clarify how the density values were generated from the datasets.

Author Response

Dear Reviewers,

Thank you for giving us the opportunity to submit a revised manuscript. We appreciate the time and effort that you dedicated to providing feedback on our manuscript and are grateful for the insightful comments on and valuable improvements to our paper. We have incorporated most of the suggestions to the revised manuscript (please see the attachment). Those changes are highlighted within the manuscript. Please see below for a point-by-point response to your comments and concerns.

Reviewer 1:

1.Performing bone density measurements on CBCT dataset is not reliable without BMD calibration phantoms prior to the scans. Please clarify how the calibration procedures were carried out prior to the CBCT scans on which the bone density measurements were performed and additionally, please clarify how the density values were generated from the datasets.

Thank you very much for this remark. Indeed, the limitation of this study is that the measurements were done based on the Gray Values obtained from the imaging software. During the research we had to rely on the CBCT imaging performed by the contractor and had no possibility to perform equipment calibration and further conversion steps. Therefore in the manuscript we remarked on using “dimensionless units of bone optical density” (lines 319-320) in this research. However, thanks to your comment we find it more appropriate to refer the results as the “Grayscale Values (GVs)”. Moreover, we put a remark on this limitation of the study in the Discussion section.

 

Reviewer 2:

1. line 69-72: it is not clear to the reader, please explain better the aim of the study -  I suggest to describe better the study in material and methods part. Data about it are found just in result at line 196-204. Maybe it is better to move all this part to M&M section.
   
   We added the outlined aims of the study. We removed the sentence “In this study, it was the first time the healing of homonymous teeth in the same patient with and without the use of platelet-rich fibrin had been compared on the basis of the clinical assessment of wound healing, the measurements of the alveolar process and volumetric tomography” as it is clearly stated further in Inclusion Criteria and M&M 2.2 subsection.
2. line 96 lignocaine?
   
   We are very sorry for that mistake. Lignocaine is one of the trade names for the lidocaine in our country.
3. line 103 figure quite useless

We do accede to your opinion and have removed the Figure

4. lines 158 -1 : I'm not a Medical Doctor and in my opinion the scale grades proposed is not exposed clearly and I also have some doubts about the actual usefulness and accuracy that this ARSTH scale of parameters can give.
   
   We have clarified the description of the ARSTH scale.
   Numerous healing assessment tools have been employed in the periodontal tissues research field. For example the first published index – the Healing Index (HI) by Landry et al. evaluated such parameters as: tissue color, bleeding response to palpation, presence of granulation tissue, characteristics of the incision margins and the presence of suppuration. Later on Wachtel et al. proposed the Early Healing Index (EHI) which classifies healing in 5 degrees according to wound closure and the amount of fibrin and necrosis. In 2018 Marini et al. proposed Early Wound Healing Score (EHS) which is composed of 3 parameters: clinical signs of re-epithelialization (wound closure: incision margins merged, in contact or distance between margins), clinical signs of haemostasis (absence or presence of fibrin or bledding), and clinical signs of inflammation (redness or swelling in the wound surroundings).

The ARSTH scale is designed in similar fashion, but applies also the pain score in order to track other clinical benefits. As one of the presumptions was that the PRF application might enhance soft tissue healing and improve the surgical procedure outcomes the scale was designed to reflect that.

5. lines 174-181 are not clear and in the mentioned figure 8 the point A is missing. Please explain better

The figure has been fixed and the definition of the measuring points was improved.

6. lines 272-275: I don't think is useful and correct to put this sentence

The following sentence “Authors should discuss the results and how they can be interpreted from the per-spective of previous studies and of the working hypotheses. The findings and their impli-cations should be discussed in the broadest context possible. Future research directions may also be highlighted.” Comes from the Journal template and of course should not be left in place. We do apologize for that editing mistake.

7. line 337: leukocytes are never mentioned before, in material and methods you should say if you're taking also the buffy coat or not or here introduce and explain why are you discussing talking about leukocytes   

Thank you for the remark. The sentence was not clear enough, so we changed it to: “Dohan Ehrenfest, who is the author of numerous publications on PRF, proved the high concentration of not only platelets, but also leucocytes in a PRF clot obtained according to Choukroun’s protocol [33,34]”

The PRF obtained according to Choukroun’s protocol was proved the have high concentration of  platelets and leucocytes (Dohan Ehrenfest DM, Del Corso M, Diss A, Mouhyi J, Charrier JB. Three-dimensional architecture and cell composition of a Choukroun's platelet-rich fibrin clot and membrane. J Periodontol. 2010;81(4):546-555. doi:10.1902/jop.2009.090531).

Reviewer 3:

1. In page 5, the CBCT is applied after 10 days of healing. But, in the last paragraph of 2.1. section" .The patient was subjected to CBCT examination (cone-beam computed 142 tomographies), limited to the area of the post-extraction alveoli using the Kodak 9000 ap- 143 Paratus (Figure 5)." needed to be deleted and added in section 2.2.

 

We moved this paragraph to section 2.2.

 

2. In table 3, in the alveolar height, why the alveolar height of 6 months is larger than that of 0 days instead of lower values in both groups? please clarify.

 

This is due to the methodology of height measurement. Thanks to your comment we found the term “alveolar height” in Table 3 misleading and changed it to HIC distance. This value is the distance between IC line and the alveolar lamina – the higher the value is the less bone is in place. The Table 3 contains also the rows entitled “width/height change (bone loss) where positive values represent bone loss.

 

3. How to confirm the selected area of bone density as the same point?

 

The selected methodology of defining the measuring points incorporated consisted, undeviating reference points such as adjacent teeth apexes and buccal cusps.

 

4. In table 4, why the bone density in point A in group two has very low values (11.01) in comparison with that in group one?

 

We are very thankful for pointing this out. The values in this row of Table 4 were accidentally copied from Table 3 during the formatting to the MDPI template. We do apologize for that mistake. The values have been corrected.

 

5. No significant differences between the groups grafting with and without PRP. Please explain in the discussion section.
   
   

We have observed statistically significant difference in alveolar width loss (1.49mm ± 0.84mm, vs  1.85mm ± 0.86mm) and heigh loss (1.79mm ± 0.61mm vs  1.98mm ± 0.86mm). In absolute numbers the difference might appear insignificant, but we do believe they might play the role in overall clinical success.

 

6. Why select 10 days as the baseline rather than the 0 days immediately after tooth extraction?
   
   The examination 10 days post extraction allowed for the examination of the soft tissue healing. The CBCT was performed at 10 days post extraction due to technical issues (the examination performed at remote facility by contractor), patients compliance. Moreover the CBCT after 10 days was screened for any alveolar bone damage that might occur during teeth extraction.
   
   
7. Maybe the primary closure technique maintains the socket dimensions even with no PRP grafting. Please clarify and extend the influence of surgical techniques and other parameters on the socket healing.  

 

Thank you for your remark. In order to avoid such bias both of the alveolar sockets in every patient were surgically treated in the same fashion. One of the most important factors affecting the socket healing is the preservation of the bony structures during the tooth extraction. This is emphasized in the M&M section, where the extraction was defined as minimally invasive

Author Response File: Author Response.pdf

Reviewer 2 Report

The paper is in general well written but:

- line 69-72: it is not clear to the reader, please explain better the aim of the study -  I suggest to describe better the study in material and methods part. Data about it are found just in result at line 196-204. Maybe it is better to move all this part to M&M section. - line 96 lignocaine? - line 103 figure quite useless - lines 158 -1 : I'm not a Medical Doctor and in my opinion the scale grades proposed is not exposed clearly and I also have some doubts about the actual usefulness and accuracy that this ARSTH scale of parameters can give - lines 174-181 are not clear and in the mentioned figure 8 the point A is missing. Please explain better - lines 272-275: I don't think is useful and correct to put this sentence - line 337: leukocytes are never mentioned before, in material and methods you should say if you're taking also the buffy coat or not or here introduce and explain why are you discussing talking about leukocytes   

Author Response

Dear Reviewers,

Thank you for giving us the opportunity to submit a revised manuscript. We appreciate the time and effort that you dedicated to providing feedback on our manuscript and are grateful for the insightful comments on and valuable improvements to our paper. We have incorporated most of the suggestions to the revised manuscript (please see the attachment). Those changes are highlighted within the manuscript. Please see below for a point-by-point response to your comments and concerns.

Reviewer 1:

1.Performing bone density measurements on CBCT dataset is not reliable without BMD calibration phantoms prior to the scans. Please clarify how the calibration procedures were carried out prior to the CBCT scans on which the bone density measurements were performed and additionally, please clarify how the density values were generated from the datasets.

Thank you very much for this remark. Indeed, the limitation of this study is that the measurements were done based on the Gray Values obtained from the imaging software. During the research we had to rely on the CBCT imaging performed by the contractor and had no possibility to perform equipment calibration and further conversion steps. Therefore in the manuscript we remarked on using “dimensionless units of bone optical density” (lines 319-320) in this research. However, thanks to your comment we find it more appropriate to refer the results as the “Grayscale Values (GVs)”. Moreover, we put a remark on this limitation of the study in the Discussion section.

 

Reviewer 2:

1. line 69-72: it is not clear to the reader, please explain better the aim of the study -  I suggest to describe better the study in material and methods part. Data about it are found just in result at line 196-204. Maybe it is better to move all this part to M&M section.
   
   We added the outlined aims of the study. We removed the sentence “In this study, it was the first time the healing of homonymous teeth in the same patient with and without the use of platelet-rich fibrin had been compared on the basis of the clinical assessment of wound healing, the measurements of the alveolar process and volumetric tomography” as it is clearly stated further in Inclusion Criteria and M&M 2.2 subsection.
2. line 96 lignocaine?
   
   We are very sorry for that mistake. Lignocaine is one of the trade names for the lidocaine in our country.
3. line 103 figure quite useless

We do accede to your opinion and have removed the Figure

4. lines 158 -1 : I'm not a Medical Doctor and in my opinion the scale grades proposed is not exposed clearly and I also have some doubts about the actual usefulness and accuracy that this ARSTH scale of parameters can give.
   
   We have clarified the description of the ARSTH scale.
   Numerous healing assessment tools have been employed in the periodontal tissues research field. For example the first published index – the Healing Index (HI) by Landry et al. evaluated such parameters as: tissue color, bleeding response to palpation, presence of granulation tissue, characteristics of the incision margins and the presence of suppuration. Later on Wachtel et al. proposed the Early Healing Index (EHI) which classifies healing in 5 degrees according to wound closure and the amount of fibrin and necrosis. In 2018 Marini et al. proposed Early Wound Healing Score (EHS) which is composed of 3 parameters: clinical signs of re-epithelialization (wound closure: incision margins merged, in contact or distance between margins), clinical signs of haemostasis (absence or presence of fibrin or bledding), and clinical signs of inflammation (redness or swelling in the wound surroundings).

The ARSTH scale is designed in similar fashion, but applies also the pain score in order to track other clinical benefits. As one of the presumptions was that the PRF application might enhance soft tissue healing and improve the surgical procedure outcomes the scale was designed to reflect that.

5. lines 174-181 are not clear and in the mentioned figure 8 the point A is missing. Please explain better

The figure has been fixed and the definition of the measuring points was improved.

6. lines 272-275: I don't think is useful and correct to put this sentence

The following sentence “Authors should discuss the results and how they can be interpreted from the per-spective of previous studies and of the working hypotheses. The findings and their impli-cations should be discussed in the broadest context possible. Future research directions may also be highlighted.” Comes from the Journal template and of course should not be left in place. We do apologize for that editing mistake.

7. line 337: leukocytes are never mentioned before, in material and methods you should say if you're taking also the buffy coat or not or here introduce and explain why are you discussing talking about leukocytes   

Thank you for the remark. The sentence was not clear enough, so we changed it to: “Dohan Ehrenfest, who is the author of numerous publications on PRF, proved the high concentration of not only platelets, but also leucocytes in a PRF clot obtained according to Choukroun’s protocol [33,34]”

The PRF obtained according to Choukroun’s protocol was proved the have high concentration of  platelets and leucocytes (Dohan Ehrenfest DM, Del Corso M, Diss A, Mouhyi J, Charrier JB. Three-dimensional architecture and cell composition of a Choukroun's platelet-rich fibrin clot and membrane. J Periodontol. 2010;81(4):546-555. doi:10.1902/jop.2009.090531).

Reviewer 3:

1. In page 5, the CBCT is applied after 10 days of healing. But, in the last paragraph of 2.1. section" .The patient was subjected to CBCT examination (cone-beam computed 142 tomographies), limited to the area of the post-extraction alveoli using the Kodak 9000 ap- 143 Paratus (Figure 5)." needed to be deleted and added in section 2.2.

 

We moved this paragraph to section 2.2.

 

2. In table 3, in the alveolar height, why the alveolar height of 6 months is larger than that of 0 days instead of lower values in both groups? please clarify.

 

This is due to the methodology of height measurement. Thanks to your comment we found the term “alveolar height” in Table 3 misleading and changed it to HIC distance. This value is the distance between IC line and the alveolar lamina – the higher the value is the less bone is in place. The Table 3 contains also the rows entitled “width/height change (bone loss) where positive values represent bone loss.

 

3. How to confirm the selected area of bone density as the same point?

 

The selected methodology of defining the measuring points incorporated consisted, undeviating reference points such as adjacent teeth apexes and buccal cusps.

 

4. In table 4, why the bone density in point A in group two has very low values (11.01) in comparison with that in group one?

 

We are very thankful for pointing this out. The values in this row of Table 4 were accidentally copied from Table 3 during the formatting to the MDPI template. We do apologize for that mistake. The values have been corrected.

 

5. No significant differences between the groups grafting with and without PRP. Please explain in the discussion section.
   
   

We have observed statistically significant difference in alveolar width loss (1.49mm ± 0.84mm, vs  1.85mm ± 0.86mm) and heigh loss (1.79mm ± 0.61mm vs  1.98mm ± 0.86mm). In absolute numbers the difference might appear insignificant, but we do believe they might play the role in overall clinical success.

 

6. Why select 10 days as the baseline rather than the 0 days immediately after tooth extraction?
   
   The examination 10 days post extraction allowed for the examination of the soft tissue healing. The CBCT was performed at 10 days post extraction due to technical issues (the examination performed at remote facility by contractor), patients compliance. Moreover the CBCT after 10 days was screened for any alveolar bone damage that might occur during teeth extraction.
   
   
7. Maybe the primary closure technique maintains the socket dimensions even with no PRP grafting. Please clarify and extend the influence of surgical techniques and other parameters on the socket healing.  

 

Thank you for your remark. In order to avoid such bias both of the alveolar sockets in every patient were surgically treated in the same fashion. One of the most important factors affecting the socket healing is the preservation of the bony structures during the tooth extraction. This is emphasized in the M&M section, where the extraction was defined as minimally invasive

Author Response File: Author Response.pdf

Reviewer 3 Report

The manuscript assesses and compares the dimensional changes of alveolar socket grafting with and without PRP. The experimental design is well-prepared and the results are interesting for readers. But there are some questions and viewpoints needed to be clarified.

1. In page 5, the CBCT is applied after 10 days of healing. But, in the last paragraph of 2.1. section" .The patient was subjected to CBCT examination (cone-beam computed 142 tomographies), limited to the area of the post-extraction alveoli using the Kodak 9000 ap- 143 Paratus (Figure 5)." needed to be deleted and added in section 2.2.
2. In table 3, in the alveolar height, why the alveolar height of 6 months is larger than that of 0 days instead of lower values in both groups? please clarify.
3. How to confirm the selected area of bone density as the same point?
4. In table 4, why the bone density in point A in group two has very low values (11.01) in comparison with that in group one?
5. No significant differences between the groups grafting with and without PRP. Please explain in the discussion section.
6. Why select 10 days as the baseline rather than the 0 days immediately after tooth extraction?
7.  Maybe the primary closure technique maintains the socket dimensions even with no PRP grafting. Please clarify and extend the influence of surgical techniques and other parameters on the socket healing.  

Author Response

Dear Reviewers,

Thank you for giving us the opportunity to submit a revised manuscript. We appreciate the time and effort that you dedicated to providing feedback on our manuscript and are grateful for the insightful comments on and valuable improvements to our paper. We have incorporated most of the suggestions to the revised manuscript (please see the attachment). Those changes are highlighted within the manuscript. Please see below for a point-by-point response to your comments and concerns.

Reviewer 1:

1.Performing bone density measurements on CBCT dataset is not reliable without BMD calibration phantoms prior to the scans. Please clarify how the calibration procedures were carried out prior to the CBCT scans on which the bone density measurements were performed and additionally, please clarify how the density values were generated from the datasets.

Thank you very much for this remark. Indeed, the limitation of this study is that the measurements were done based on the Gray Values obtained from the imaging software. During the research we had to rely on the CBCT imaging performed by the contractor and had no possibility to perform equipment calibration and further conversion steps. Therefore in the manuscript we remarked on using “dimensionless units of bone optical density” (lines 319-320) in this research. However, thanks to your comment we find it more appropriate to refer the results as the “Grayscale Values (GVs)”. Moreover, we put a remark on this limitation of the study in the Discussion section.

 

Reviewer 2:

1. line 69-72: it is not clear to the reader, please explain better the aim of the study -  I suggest to describe better the study in material and methods part. Data about it are found just in result at line 196-204. Maybe it is better to move all this part to M&M section.
   
   We added the outlined aims of the study. We removed the sentence “In this study, it was the first time the healing of homonymous teeth in the same patient with and without the use of platelet-rich fibrin had been compared on the basis of the clinical assessment of wound healing, the measurements of the alveolar process and volumetric tomography” as it is clearly stated further in Inclusion Criteria and M&M 2.2 subsection.
2. line 96 lignocaine?
   
   We are very sorry for that mistake. Lignocaine is one of the trade names for the lidocaine in our country.
3. line 103 figure quite useless

We do accede to your opinion and have removed the Figure

4. lines 158 -1 : I'm not a Medical Doctor and in my opinion the scale grades proposed is not exposed clearly and I also have some doubts about the actual usefulness and accuracy that this ARSTH scale of parameters can give.
   
   We have clarified the description of the ARSTH scale.
   Numerous healing assessment tools have been employed in the periodontal tissues research field. For example the first published index – the Healing Index (HI) by Landry et al. evaluated such parameters as: tissue color, bleeding response to palpation, presence of granulation tissue, characteristics of the incision margins and the presence of suppuration. Later on Wachtel et al. proposed the Early Healing Index (EHI) which classifies healing in 5 degrees according to wound closure and the amount of fibrin and necrosis. In 2018 Marini et al. proposed Early Wound Healing Score (EHS) which is composed of 3 parameters: clinical signs of re-epithelialization (wound closure: incision margins merged, in contact or distance between margins), clinical signs of haemostasis (absence or presence of fibrin or bledding), and clinical signs of inflammation (redness or swelling in the wound surroundings).

The ARSTH scale is designed in similar fashion, but applies also the pain score in order to track other clinical benefits. As one of the presumptions was that the PRF application might enhance soft tissue healing and improve the surgical procedure outcomes the scale was designed to reflect that.

5. lines 174-181 are not clear and in the mentioned figure 8 the point A is missing. Please explain better

The figure has been fixed and the definition of the measuring points was improved.

6. lines 272-275: I don't think is useful and correct to put this sentence

The following sentence “Authors should discuss the results and how they can be interpreted from the per-spective of previous studies and of the working hypotheses. The findings and their impli-cations should be discussed in the broadest context possible. Future research directions may also be highlighted.” Comes from the Journal template and of course should not be left in place. We do apologize for that editing mistake.

7. line 337: leukocytes are never mentioned before, in material and methods you should say if you're taking also the buffy coat or not or here introduce and explain why are you discussing talking about leukocytes   

Thank you for the remark. The sentence was not clear enough, so we changed it to: “Dohan Ehrenfest, who is the author of numerous publications on PRF, proved the high concentration of not only platelets, but also leucocytes in a PRF clot obtained according to Choukroun’s protocol [33,34]”

The PRF obtained according to Choukroun’s protocol was proved the have high concentration of  platelets and leucocytes (Dohan Ehrenfest DM, Del Corso M, Diss A, Mouhyi J, Charrier JB. Three-dimensional architecture and cell composition of a Choukroun's platelet-rich fibrin clot and membrane. J Periodontol. 2010;81(4):546-555. doi:10.1902/jop.2009.090531).

Reviewer 3:

1. In page 5, the CBCT is applied after 10 days of healing. But, in the last paragraph of 2.1. section" .The patient was subjected to CBCT examination (cone-beam computed 142 tomographies), limited to the area of the post-extraction alveoli using the Kodak 9000 ap- 143 Paratus (Figure 5)." needed to be deleted and added in section 2.2.

 

We moved this paragraph to section 2.2.

 

2. In table 3, in the alveolar height, why the alveolar height of 6 months is larger than that of 0 days instead of lower values in both groups? please clarify.

 

This is due to the methodology of height measurement. Thanks to your comment we found the term “alveolar height” in Table 3 misleading and changed it to HIC distance. This value is the distance between IC line and the alveolar lamina – the higher the value is the less bone is in place. The Table 3 contains also the rows entitled “width/height change (bone loss) where positive values represent bone loss.

 

3. How to confirm the selected area of bone density as the same point?

 

The selected methodology of defining the measuring points incorporated consisted, undeviating reference points such as adjacent teeth apexes and buccal cusps.

 

4. In table 4, why the bone density in point A in group two has very low values (11.01) in comparison with that in group one?

 

We are very thankful for pointing this out. The values in this row of Table 4 were accidentally copied from Table 3 during the formatting to the MDPI template. We do apologize for that mistake. The values have been corrected.

 

5. No significant differences between the groups grafting with and without PRP. Please explain in the discussion section.
   
   

We have observed statistically significant difference in alveolar width loss (1.49mm ± 0.84mm, vs  1.85mm ± 0.86mm) and heigh loss (1.79mm ± 0.61mm vs  1.98mm ± 0.86mm). In absolute numbers the difference might appear insignificant, but we do believe they might play the role in overall clinical success.

 

6. Why select 10 days as the baseline rather than the 0 days immediately after tooth extraction?
   
   The examination 10 days post extraction allowed for the examination of the soft tissue healing. The CBCT was performed at 10 days post extraction due to technical issues (the examination performed at remote facility by contractor), patients compliance. Moreover the CBCT after 10 days was screened for any alveolar bone damage that might occur during teeth extraction.
   
   
7. Maybe the primary closure technique maintains the socket dimensions even with no PRP grafting. Please clarify and extend the influence of surgical techniques and other parameters on the socket healing.  

 

Thank you for your remark. In order to avoid such bias both of the alveolar sockets in every patient were surgically treated in the same fashion. One of the most important factors affecting the socket healing is the preservation of the bony structures during the tooth extraction. This is emphasized in the M&M section, where the extraction was defined as minimally invasive

Author Response File: Author Response.pdf

Round 2

Reviewer 1 Report

Performing bone density measurements on CBCT dataset is not reliable without BMD calibration phantoms prior to the scans. 
The authors declared that no calibration was carried out prior to the CBCT scan. Comparing gray scale values gained from CBCT images without calibration and drawing statements and conclusions (Line 390-393) from these results with respect to bone density are scientifically inaccurate.

Author Response

Dear Reviewers,

Thank you for giving us the opportunity to submit a revised manuscript. We appreciate every bit of time and effort that you dedicated to reevaluate the manuscript. The latest changes are highlighted within the manuscript. Please see below for a point-by-point response to your comments and concerns.

Reviewer 1:

Performing bone density measurements on CBCT dataset is not reliable without BMD calibration phantoms prior to the scans. 
The authors declared that no calibration was carried out prior to the CBCT scan. Comparing gray scale values gained from CBCT images without calibration and drawing statements and conclusions (Line 390-393) from these results with respect to bone density are scientifically inaccurate.

Thank you very much for your effort and time dedicated to review the manuscript. We have updated it with the papers providing proof for correlation between CBCT derived GVs and primary and secondary implant stability [1–7]. Moreover contemporary there are papers assessing the socket prevention strategies with the aid of CBCT GVs measurements [8].

We hope that during the revision of the manuscript we have adequately emphasized the limitations of the CBCT study for such measurements. Also we have changed the conclusions that are drawn from these data. All of the authors, being aware of the limitation of CBCT derived GVs, believe that these measurements constitute the important part of the paper, however at your will we might delete the paragraphs on GVs measurements from the manuscript.

1. Salimov, F.; Tatli, U.; Kürkçü, M.; Akoğlan, M.; Oztunç, H.; Kurtoğlu, C. Evaluation of Relationship between Preoperative Bone Density Values Derived from Cone Beam Computed Tomography and Implant Stability Parameters: A Clinical Study. Clin Oral Implants Res 2014, 25, 1016–1021, doi:10.1111/clr.12219.
2. Ivanova, V.; Chenchev, I.; Zlatev, S.; Mijiritsky, E. Correlation between Primary, Secondary Stability, Bone Density, Percentage of Vital Bone Formation and Implant Size. Int J Environ Res Public Health 2021, 18, 6994, doi:10.3390/ijerph18136994.
3. Schnutenhaus, S.; Götz, W.; Dreyhaupt, J.; Rudolph, H.; Luthardt, R.G.; Edelmann, C. Associations among Primary Stability, Histomorphometric Findings, and Bone Density: A Prospective Randomized Study after Alveolar Ridge Preservation with a Collagen Cone. Dent J (Basel) 2020, 8, 112, doi:10.3390/dj8040112.
4. Abdulkarim, H.H.; Zeng, R.; Pazdernik, V.K.; Davis, J.M. Effect of Bone Graft on the Correlation between Clinical Bone Quality and CBCT-Determined Bone Density: A Pilot Study. J Contemp Dent Pract 2021, 22, 756–762.
5. Al-Jamal, M.F.J.; Al-Jumaily, H.A. Can the Bone Density Estimated by CBCT Predict the Primary Stability of Dental Implants? A New Measurement Protocol. J Craniofac Surg 2021, 32, e171–e174, doi:10.1097/SCS.0000000000006991.
6. Isoda, K.; Ayukawa, Y.; Tsukiyama, Y.; Sogo, M.; Matsushita, Y.; Koyano, K. Relationship between the Bone Density Estimated by Cone-Beam Computed Tomography and the Primary Stability of Dental Implants. Clin Oral Implants Res 2012, 23, 832–836, doi:10.1111/j.1600-0501.2011.02203.x.
7. Wada, M.; Suganami, T.; Sogo, M.; Maeda, Y. Can We Predict the Insertion Torque Using the Bone Density around the Implant? Int J Oral Maxillofac Surg 2016, 45, 221–225, doi:10.1016/j.ijom.2015.09.013.
8. Križaj Dumić, A.; Pajk, F.; Olivi, G. The Effect of Post‐extraction Socket Preservation Laser Treatment on Bone Density 4 Months after Extraction: Randomized Controlled Trial. Clin Implant Dent Relat Res 2021, 23, 309–316, doi:10.1111/cid.12991.

 

Reviewer 2:

The critical issues that I pointed out have been addressed and solved properly. The only thing that could be further improved is the bibliography.

I suggest, in some cases, referring to newer articles. Since PRF has been largely used in the last decade newer articles should be more updated on this topic.

Thank you for the remark – we have updated the references with newer sources.

 

Reviewer 3:
accept the revised manuscript

Thank you very much.

Author Response File: Author Response.pdf

Reviewer 2 Report

The critical issues that I pointed out have been addressed and solved properly. The only thing that could be further improved is the bibliography.

I suggest, in some cases, referring to newer articles. Since PRF has been largely used in the last decade newer articles should be more updated on this topic.

 

Author Response

Dear Reviewers,

Thank you for giving us the opportunity to submit a revised manuscript. We appreciate every bit of time and effort that you dedicated to reevaluate the manuscript. The latest changes are highlighted within the manuscript. Please see below for a point-by-point response to your comments and concerns.

Reviewer 1:

Performing bone density measurements on CBCT dataset is not reliable without BMD calibration phantoms prior to the scans. 
The authors declared that no calibration was carried out prior to the CBCT scan. Comparing gray scale values gained from CBCT images without calibration and drawing statements and conclusions (Line 390-393) from these results with respect to bone density are scientifically inaccurate.

Thank you very much for your effort and time dedicated to review the manuscript. We have updated it with the papers providing proof for correlation between CBCT derived GVs and primary and secondary implant stability [1–7]. Moreover contemporary there are papers assessing the socket prevention strategies with the aid of CBCT GVs measurements [8].

We hope that during the revision of the manuscript we have adequately emphasized the limitations of the CBCT study for such measurements. All of the authors, being aware of the limitation of CBCT derived GVs, believe that these measurements constitute the important part of the paper, however at your will we might delete the paragraphs on GVs measurements from the manuscript.

1. Salimov, F.; Tatli, U.; Kürkçü, M.; Akoğlan, M.; Oztunç, H.; Kurtoğlu, C. Evaluation of Relationship between Preoperative Bone Density Values Derived from Cone Beam Computed Tomography and Implant Stability Parameters: A Clinical Study. Clin Oral Implants Res 2014, 25, 1016–1021, doi:10.1111/clr.12219.
2. Ivanova, V.; Chenchev, I.; Zlatev, S.; Mijiritsky, E. Correlation between Primary, Secondary Stability, Bone Density, Percentage of Vital Bone Formation and Implant Size. Int J Environ Res Public Health 2021, 18, 6994, doi:10.3390/ijerph18136994.
3. Schnutenhaus, S.; Götz, W.; Dreyhaupt, J.; Rudolph, H.; Luthardt, R.G.; Edelmann, C. Associations among Primary Stability, Histomorphometric Findings, and Bone Density: A Prospective Randomized Study after Alveolar Ridge Preservation with a Collagen Cone. Dent J (Basel) 2020, 8, 112, doi:10.3390/dj8040112.
4. Abdulkarim, H.H.; Zeng, R.; Pazdernik, V.K.; Davis, J.M. Effect of Bone Graft on the Correlation between Clinical Bone Quality and CBCT-Determined Bone Density: A Pilot Study. J Contemp Dent Pract 2021, 22, 756–762.
5. Al-Jamal, M.F.J.; Al-Jumaily, H.A. Can the Bone Density Estimated by CBCT Predict the Primary Stability of Dental Implants? A New Measurement Protocol. J Craniofac Surg 2021, 32, e171–e174, doi:10.1097/SCS.0000000000006991.
6. Isoda, K.; Ayukawa, Y.; Tsukiyama, Y.; Sogo, M.; Matsushita, Y.; Koyano, K. Relationship between the Bone Density Estimated by Cone-Beam Computed Tomography and the Primary Stability of Dental Implants. Clin Oral Implants Res 2012, 23, 832–836, doi:10.1111/j.1600-0501.2011.02203.x.
7. Wada, M.; Suganami, T.; Sogo, M.; Maeda, Y. Can We Predict the Insertion Torque Using the Bone Density around the Implant? Int J Oral Maxillofac Surg 2016, 45, 221–225, doi:10.1016/j.ijom.2015.09.013.
8. Križaj Dumić, A.; Pajk, F.; Olivi, G. The Effect of Post‐extraction Socket Preservation Laser Treatment on Bone Density 4 Months after Extraction: Randomized Controlled Trial. Clin Implant Dent Relat Res 2021, 23, 309–316, doi:10.1111/cid.12991.

 

Reviewer 2:

The critical issues that I pointed out have been addressed and solved properly. The only thing that could be further improved is the bibliography.

I suggest, in some cases, referring to newer articles. Since PRF has been largely used in the last decade newer articles should be more updated on this topic.

Thank you for the remark – we have updated the references with newer sources.

 

Reviewer 3:
accept the revised manuscript

Thank you very much.

Author Response File: Author Response.pdf

Reviewer 3 Report

accept the revised manuscript

Author Response

Dear Reviewers,

Thank you for giving us the opportunity to submit a revised manuscript. We appreciate every bit of time and effort that you dedicated to reevaluate the manuscript. The latest changes are highlighted within the manuscript. Please see below for a point-by-point response to your comments and concerns.

Reviewer 1:

Performing bone density measurements on CBCT dataset is not reliable without BMD calibration phantoms prior to the scans. 
The authors declared that no calibration was carried out prior to the CBCT scan. Comparing gray scale values gained from CBCT images without calibration and drawing statements and conclusions (Line 390-393) from these results with respect to bone density are scientifically inaccurate.

Thank you very much for your effort and time dedicated to review the manuscript. We have updated it with the papers providing proof for correlation between CBCT derived GVs and primary and secondary implant stability [1–7]. Moreover contemporary there are papers assessing the socket prevention strategies with the aid of CBCT GVs measurements [8].

We hope that during the revision of the manuscript we have adequately emphasized the limitations of the CBCT study for such measurements. All of the authors, being aware of the limitation of CBCT derived GVs, believe that these measurements constitute the important part of the paper, however at your will we might delete the paragraphs on GVs measurements from the manuscript.

1. Salimov, F.; Tatli, U.; Kürkçü, M.; Akoğlan, M.; Oztunç, H.; Kurtoğlu, C. Evaluation of Relationship between Preoperative Bone Density Values Derived from Cone Beam Computed Tomography and Implant Stability Parameters: A Clinical Study. Clin Oral Implants Res 2014, 25, 1016–1021, doi:10.1111/clr.12219.
2. Ivanova, V.; Chenchev, I.; Zlatev, S.; Mijiritsky, E. Correlation between Primary, Secondary Stability, Bone Density, Percentage of Vital Bone Formation and Implant Size. Int J Environ Res Public Health 2021, 18, 6994, doi:10.3390/ijerph18136994.
3. Schnutenhaus, S.; Götz, W.; Dreyhaupt, J.; Rudolph, H.; Luthardt, R.G.; Edelmann, C. Associations among Primary Stability, Histomorphometric Findings, and Bone Density: A Prospective Randomized Study after Alveolar Ridge Preservation with a Collagen Cone. Dent J (Basel) 2020, 8, 112, doi:10.3390/dj8040112.
4. Abdulkarim, H.H.; Zeng, R.; Pazdernik, V.K.; Davis, J.M. Effect of Bone Graft on the Correlation between Clinical Bone Quality and CBCT-Determined Bone Density: A Pilot Study. J Contemp Dent Pract 2021, 22, 756–762.
5. Al-Jamal, M.F.J.; Al-Jumaily, H.A. Can the Bone Density Estimated by CBCT Predict the Primary Stability of Dental Implants? A New Measurement Protocol. J Craniofac Surg 2021, 32, e171–e174, doi:10.1097/SCS.0000000000006991.
6. Isoda, K.; Ayukawa, Y.; Tsukiyama, Y.; Sogo, M.; Matsushita, Y.; Koyano, K. Relationship between the Bone Density Estimated by Cone-Beam Computed Tomography and the Primary Stability of Dental Implants. Clin Oral Implants Res 2012, 23, 832–836, doi:10.1111/j.1600-0501.2011.02203.x.
7. Wada, M.; Suganami, T.; Sogo, M.; Maeda, Y. Can We Predict the Insertion Torque Using the Bone Density around the Implant? Int J Oral Maxillofac Surg 2016, 45, 221–225, doi:10.1016/j.ijom.2015.09.013.
8. Križaj Dumić, A.; Pajk, F.; Olivi, G. The Effect of Post‐extraction Socket Preservation Laser Treatment on Bone Density 4 Months after Extraction: Randomized Controlled Trial. Clin Implant Dent Relat Res 2021, 23, 309–316, doi:10.1111/cid.12991.

 

Reviewer 2:

The critical issues that I pointed out have been addressed and solved properly. The only thing that could be further improved is the bibliography.

I suggest, in some cases, referring to newer articles. Since PRF has been largely used in the last decade newer articles should be more updated on this topic.

Thank you for the remark – we have updated the references with newer sources.

 

Reviewer 3:
accept the revised manuscript

Thank you very much.

Author Response File: Author Response.pdf