Implant-Prosthetic Rehabilitation with Immediately Loaded Post-Extractive Implants: Retrospective Clinical Cohort Study at 18-Month Follow-Up

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

The Material and Methods section should describe which implants were used, which I think is important.

Reasons for the teeth extraction? -  it is advisable to perform an analysis concerning the diagnosis before tooth extraction, i.e. whether the teeth were extracted e.g. periodontal disease, caries complication (gangrenous tooth, or radix relicta) or trauma?

Discussion: Considering that “Placement of implants in basal bone without the use of biomaterials for bone regeneration”  and  “any gaps between the implant and vestibular wall were filled using collagen haemostatic sponges”, implant survival and possible complications should be discussed with the results from the literature in cases where the bone substitutes materials were used.

My long-time experience suggests that in the long term, the results are much more predictable with less chance of developing any of the complications when bone substitute materials are not used.

Author Response

Dear Reviewer,
Thank you for your valuable suggestions which we sincerely hope have helped to improve the paper and make it suitable for acceptance in your journal.
We remain at your disposal for any further clarifications. 
Best regards

The Material and Methods section should describe which implants were used, which I think is important.

Reasons for the teeth extraction? -  it is advisable to perform an analysis concerning the diagnosis before tooth extraction, i.e. whether the teeth were extracted e.g. periodontal disease, caries complication (gangrenous tooth, or radix relicta) or trauma?

No data were collected on the reasons for the avulsions, or rather they were not specified within the study because the aim was to evaluate the performance of post-extraction implants regardless of the extraction cause.

Discussion: Considering that “Placement of implants in basal bone without the use of biomaterials for bone regeneration”  and  “any gaps between the implant and vestibular wall were filled using collagen haemostatic sponges”, implant survival and possible complications should be discussed with the results from the literature in cases where the bone substitutes materials were used.
My long-time experience suggests that in the long term, the results are much more predictable with less chance of developing any of the complications when bone substitute materials are not used.

In accordance with the request, we have added the following section to the discussion.
In the current study, the placement of the implants was performed through basal bone, without biomaterials for bone regeneration. Any gaps between the implant surface and the buccal cortex were filled exclusively by collagen haemostatic sponges, according to a minimally invasive approach geared towards the preservation of hard and soft tissues. The results obtained in terms of implant survival rate, contained marginal bone loss and incidence of surgical and prosthetic complications are equal to, if not superior to, other studies in the literature in which biomaterials were used to fill post-extraction sockets.
In a prospective study conducted by Crespi et al. using hydroxyapatite and collagen-based biomaterials in immediately loaded post-extractive implants, a survival rate of 94.4% at 12 months was reported, with an average marginal bone resorption of 0.78 mm [31]. Similarly, Barone et al. clinically compared alveolar filling with autologous bone versus xenogenic graft in post-extractive implants, finding similar survival rates, but with more frequent peri-implant inflammation in sites treated with heterologous materials [37].
These data suggest that, in the presence of adequate residual vestibular bone thickness, an approach that avoids the use of biomaterials may guarantee comparable clinical results in terms of implant stability and reduction of complications, provided that careful surgical and prosthetic management of the site is maintained. Furthermore, the absence of biomaterials could reduce the risk of chronic inflammatory reactions or suboptimal graft integration, as reported in some systematic review studies [38,39].

Reviewer 2 Report

Comments and Suggestions for Authors

ABSTRACT

It is objective and summarizes the study carried out well, providing the most important data.

 

KEYWORDS

They are suitable for study.

 

INTRODUCTION

It addresses study techniques and materials in light of the state of the art.

 

It would be more complete if the authors had posed the necessary null hypotheses.

 

MATERIALS AND METHODS

In inclusion/exclusion factors, exclusion factors should not be the opposite of inclusion factors and authors should make these corrections.

 

In this type of study, the age of the patients is not an inclusion factor, it is a filter.

 

“…Any gaps between the implant and vestibular wall were filled using collagen haemo-167 static sponges (Spongostan, Ethicon, Somerville…” - Why were xenografts not considered to fill the gaps?

 

“…Post-operative therapy included, in addition to the prescription of antibiotics…” - What antibiotics did they consider prescribing?

 

“…Ibuprofen 600 mg, Brufen…” - It is not an analgesic, it is an anti-inflammatory drug. What dosage was considered?

 

“…The follow-up protocol included clinical and radiographic…” - What kind of x-rays did they do at the controls?

 

“…Peri-implant marginal bone loss (MBL) was assessed by analysing intraoral radio-210 graphs acquired…” - Why did they use film instead of a sensor and an image scanning program with greater analysis possibilities and accuracy?

 

“The sample analysed included smoking patients and subjects with compensated 285 systemic diseases but excluded individuals with uncompensated systemic diseases poten-286 tially affecting osseointegration and peri-implant response…” - There are many diseases whose treatment may have implications for bone remodeling or pre-surgical care. Authors should be more specific. On the other hand, a smoker is not the same as a non-smoker.

 

RESULTS

They are well described according to the protocol defined by the authors.

 

DISCUSSION

In general, the discussion addresses the analysis of the results by comparing them with those of other published studies. When posing null hypotheses, authors should address them in the discussion or conclusions.

 

CONCLUSIONS

They are well prepared. They are objective and short and address the need for longer follow-ups as is obvious.

Author Response

Dear Reviewer,
Thank you for your valuable suggestions which we sincerely hope have helped to improve the paper and make it suitable for acceptance in your journal.
We remain at your disposal for any further clarifications. 
Best regards

ABSTRACT
It is objective and summarizes the study carried out well, providing the most important data.
 
KEYWORDS
They are suitable for study.
 
INTRODUCTION
It addresses study techniques and materials in light of the state of the art.
 
It would be more complete if the authors had posed the necessary null hypotheses.

In the section Statistical methods (Materials and methods) we added the following paragraph:

To assess the influence of systemic and clinical variables on the main implant outcomes, a series of null hypotheses were formulated predicting the absence of statistically significant associations between the co-variables analysed and the clinical outcomes considered. Specifically, it was hypothesised that the presence of systemic pathology, smoking habit, implant site (anterior or posterior maxilla, anterior or posterior mandible), and type of prosthetic rehabilitation (single crown or bridge) did not significantly influence any of the following dependent variables: implant survival, marginal bone loss, peri-implant clinical parameters (such as probing depth and bleeding on probing), and incidence of surgical or prosthetic complications. More specifically, a specific null hypothesis was tested for each combination of independent variable and clinical outcome, assuming that any differences observed in the data were attributable to chance. The level of statistical significance (α) was set at 0.05; therefore, a p-value below this threshold was considered indicative of the rejection of the null hypothesis and the existence of a statistically significant association between the independent variable and the outcome under investigation.
 
MATERIALS AND METHODS
In inclusion/exclusion factors, exclusion factors should not be the opposite of inclusion factors and authors should make these corrections.
We have removed some of the exclusion criteria as opposed to inclusion criteria.
  
“…Any gaps between the implant and vestibular wall were filled using collagen haemo-167 static sponges (Spongostan, Ethicon, Somerville…” - Why were xenografts not considered to fill the gaps?
We have added the following paragraph in the discussion section:

In a prospective study conducted by Crespi et al. using hydroxyapatite and collagen-based biomaterials in immediately loaded post-extractive implants, a survival rate of 94.4% at 12 months was reported, with an average marginal bone resorption of 0.78 mm [31]. Similarly, Barone et al. clinically compared alveolar filling with autologous bone versus xenogenic graft in post-extractive implants, finding similar survival rates, but with more frequent peri-implant inflammation in sites treated with heterologous materials [37].
These data suggest that, in the presence of adequate residual vestibular bone thickness, an approach that avoids the use of biomaterials may guarantee comparable clinical results in terms of implant stability and reduction of complications, provided that careful surgical and prosthetic management of the site is maintained. Furthermore, the absence of biomaterials could reduce the risk of chronic inflammatory reactions or suboptimal graft integration, as reported in some systematic review studies [38,39].
 
“…Post-operative therapy included, in addition to the prescription of antibiotics…” - What antibiotics did they consider prescribing?

As reported in the section Implant-prosthetic rehabilitation:

Starting the day before surgery, all patients had taken antibiotic therapy (1 gram of Amoxicillin/Clarithromycin in allergic patients every 12 hours for a total of six days).
 
“…Ibuprofen 600 mg, Brufen…” - It is not an analgesic, it is an anti-inflammatory drug. What dosage was considered?

Ibuprofen had both analgesic and pain-relieving roles. The text states “analgesics as needed (Ibuprofen 600 mg, Brufen - Mylan S.p.A., Milan, Italy)” because it can be taken as needed up to a maximum of 3 times a day according to the specific posology of the drug mentioned.
 
“…The follow-up protocol included clinical and radiographic…” - What kind of x-rays did they do at the controls?
We added as follows: 
“The follow-up protocol included clinical and radiographic checks (intra-oral x rays) at one week after surgery for suture removal, at three and six months after provisional prosthetic loading, and then at three, six and twelve months after placement of the definitive prosthesis.”
 
“…Peri-implant marginal bone loss (MBL) was assessed by analysing intraoral radio-210 graphs acquired…” - Why did they use film instead of a sensor and an image scanning program with greater analysis possibilities and accuracy?
The decision to use traditional endoral radiographs on film instead of digital sensors with analysis software was dictated by a question of methodological consistency and standardisation of the radiographic protocol, as all the patients included in the study were treated in a time frame in which digital radiology was not yet systematically available at the facility where the study was conducted.

However, the use of the long cone technique associated with a centring system (XCP, Dentsply International, RINN) ensured high repeatability and reliability of the radiographic images, limiting geometric distortions and angular variations between the different follow-ups to a minimum. In addition, the films were subsequently digitised with a high-resolution scanner and analysed by two experienced operators in a blinded manner according to standardised criteria for measuring peri-implant marginal bone loss.
 
“The sample analysed included smoking patients and subjects with compensated 285 systemic diseases but excluded individuals with uncompensated systemic diseases poten-286 tially affecting osseointegration and peri-implant response…” - There are many diseases whose treatment may have implications for bone remodeling or pre-surgical care. Authors should be more specific. On the other hand, a smoker is not the same as a non-smoker.
 
RESULTS
They are well described according to the protocol defined by the authors.
 
DISCUSSION
In general, the discussion addresses the analysis of the results by comparing them with those of other published studies. When posing null hypotheses, authors should address them in the discussion or conclusions. 
Concerning null hypohtesis a specifical paragraph was added in the section results. In the discussion, the comparison with the literature was made in a discussion-oriented way.
Null hypothesis
Implant survival rate
Over the 18-month follow-up period, implant survival was significantly influenced by a number of systemic and clinical variables. In particular, smoking habit showed a statistically significant association with implant failure (p = 0.04), leading to the rejection of the null hypothesis that excluded its impact. Similarly, the presence of systemic disease also proved to be a significant determinant of implant loss (p = 0.04), leading to the rejection of the null hypothesis. An equally significant role was observed for implant site, with a higher incidence of failure in the posterior maxilla (p = 0.03), confirming the influence of local anatomy on treatment outcome. In contrast, the type of rehabilitation, i.e. the use of single crowns as opposed to bridges on distal implants, did not show a statistically significant effect on implant survival (p = 0.09), leading to the acceptance of the null hypothesis concerning this variable.
Marginal bone loss 
Marginal bone loss showed a significant development over time and was influenced by several factors. Smoking was associated with increased bone loss (p = 0.04), leading to the rejection of the null hypothesis. The presence of systemic disease also showed a negative influence on peri-implant bone maintenance (p = 0.03), thus rejecting the null hypothesis. Similarly, the implant site proved to be decisive, with the highest resorption values observed in the posterior maxilla (p = 0.03), confirming a significant correlation. Conversely, the type of rehabilitation did not show a statistically significant association with MBL (p = 0.07), and therefore the null hypothesis was accepted for this variable.
Peri-implant clinical parameters
The analysis of clinical parameters, in particular PPD, PI, BoP and suppuration, revealed significant associations with some of the co-variables analysed. Probing depth was significantly greater in smoking patients (p = 0.04) and in posterior areas, particularly in the maxilla (p = 0.02), leading to the rejection of the null hypothesis in both cases. On the other hand, no statistically significant association was found with the presence of systemic pathology (p = 0.06) nor with the type of rehabilitation (p = 0.09), confirming the null hypothesis for these two variables.
Concerning plaque index and bleeding on probing, there was also a significant correlation with smoking (p = 0.03) and implant site (p = 0.03), while there were no significant associations with the presence of systemic pathology (p = 0.07) nor with the type of rehabilitation (p = 0.08). About suppuration, the data showed a significant association with both smoking (p = 0.02) and systemic pathologies (p = 0.03), while neither implant site (p = 0.08) nor type of rehabilitation (p = 0.09) showed significant effects. Overall, the null hypotheses were rejected for smoking and systemic pathologies in relation to suppuration, but accepted for site and type of rehabilitation.
Surgical complications
Post-operative complications, although generally moderate, were significantly more frequent in smokers (p = 0.03) and in patients with systemic diseases (p = 0.02), leading to the rejection of the corresponding null hypotheses. The type of restoration also showed a significant association with the incidence of surgical complications (p = 0.04), with a higher frequency in patients treated with bridges on two distal implants. The implant site, on the other hand, did not reach statistical significance (p = 0.08), confirming the null hypothesis in this case.
Prosthetic complications
Regarding prosthetic complications, there was a significant association with the implant site (p = 0.03), particularly in the posterior region, and with the type of rehabilitation (p = 0.04), with a higher incidence in patients with bridges than in those with single crowns. In both cases, the null hypothesis was rejected. In contrast, neither smoking (p = 0.07) nor the presence of systemic diseases (p = 0.08) showed a statistically significant influence on the occurrence of these complications, leading to the acceptance of the corresponding null hypotheses.
 
CONCLUSIONS
They are well prepared. They are objective and short and address the need for longer follow-ups as is obvious.

Reviewer 3 Report

Comments and Suggestions for Authors

The manuscript: “Implant-prosthetic rehabilitation with immediately loaded post-extractive implants: retrospective clinical cohort study at 18-month follow-up” is interesting and addresses an important clinical issue. Some suggestions were made by the reviewer to further improve the study.

 

The authors need to improve the structure of the introduction. Each paragraph should be composed of 3 to 4 sentences.

 

For the formula used to determine the sample size of the study, please provide the definition of each acronym.

 

In lines 371 and 372, in the following sentence: “There were 6 smokers with systemic diseases, 13 smokers with systemic diseases and 16 non-smokers with systemic diseases.” Please revise the number of smokers with systemic diseases.

 

Please correct typos throughout the manuscript and Italian terms in table 3.

 

For the multivariate logistic regression analysis please provide the complete table with the Odds ratio, confidence interval, and p-value. Also, prior to the multivariate logistic regression, was a bivariate regression performed?

 

According to the results, the presence of risk factors related to smoking and systemic diseases was observed, which play a crucial role in the incidence of surgical and prosthetic complications. However, the number of smokers and patients with systemic diseases was lower than the number of healthy patients. The authors are encouraged to add this limitation to the discussion. After all, although there was this relationship, the low number of smokers could be a bias.

Author Response

Dear Reviewer,

Thank you for your valuable suggestions which we sincerely hope have helped to improve the paper and make it suitable for acceptance in your journal.

We remain at your disposal for any further clarifications.

Best regards

 

The manuscript: “Implant-prosthetic rehabilitation with immediately loaded post-extractive implants: retrospective clinical cohort study at 18-month follow-up” is interesting and addresses an important clinical issue. Some suggestions were made by the reviewer to further improve the study.

The authors need to improve the structure of the introduction. Each paragraph should be composed of 3 to 4 sentences.

According to your suggestion we modified the introductions’ structure.

 

For the formula used to determine the sample size of the study, please provide the definition of each acronym.

We added the following specifications:

The sample size for this study was determined through a priori power analysis to ensure an optimal balance between Type I (α = 0.05) and Type II (β) error rates. The calculation was based on an estimated effect size of 0.5 and was performed using the following formula:

n=2×(Zα/2+Zβ)2×σ2IES2n=IES22×(Zα/2​+Zβ​)2×σ2​

Where:

• n = required sample size per group;
• Z_α/2 = Z-score corresponding to the desired Type I error rate (α = 0.05, thus Z_α/2 ≈ 1.96);
• Z_β = Z-score corresponding to the desired power (1 - β; for 80% power, Z_β ≈ 0.84);
• σ² = variance of the outcome variable;
• IES = minimum expected intervention effect size (difference between group means expressed in units of standard deviation).

 

In lines 371 and 372, in the following sentence: “There were 6 smokers with systemic diseases, 13 smokers with systemic diseases and 16 non-smokers with systemic diseases.” Please revise the number of smokers with systemic diseases.

We revised and confirm.

 

Please correct typos throughout the manuscript and Italian terms in table 3.

We corrected.

 

For the multivariate logistic regression analysis please provide the complete table with the Odds ratio, confidence interval, and p-value. Also, prior to the multivariate logistic regression, was a bivariate regression performed?

 

As requested, we have now included a complete table summarizing the results of the multivariate logistic regression analysis. The table reports the odds ratios (OR), corresponding 95% confidence intervals (CI), and p-values for each independent variable included in the model. This addition can be found in the revised manuscript under the Results section (Table 4).

Prior to conducting the multivariate logistic regression, we performed bivariate logistic regression analyses for each independent variable in relation to the clinical outcomes of interest. This step was used to explore potential associations and to identify candidate variables to include in the multivariate model, in line with standard methodological practice. Only variables showing an association with a p-value < 0.15 in the bivariate analysis were retained for inclusion in the final multivariate logistic regression model to reduce the risk of overfitting.

 

According to the results, the presence of risk factors related to smoking and systemic diseases was observed, which play a crucial role in the incidence of surgical and prosthetic complications. However, the number of smokers and patients with systemic diseases was lower than the number of healthy patients. The authors are encouraged to add this limitation to the discussion. After all, although there was this relationship, the low number of smokers could be a bias.

 

Actually, of the 99 patients considered, there were only 22 patients with systemic diseases. If we consider smokers and those with systemic diseases as a whole, there were 35 patients, thus outnumbering the healthy, non-smokers.

Round 2

Reviewer 1 Report

Comments and Suggestions for Authors

My remark that “ The Material and Methods section should describe which implants were used” was not taken into account?

In any case, it is necessary to describe the type of implant used in this study. Figure 1 shows that two-piece implants with a rough surface were used, but I think the Materials and Methods section should describe which implant  Brand/s has been used. It is not clear if just one implant type was used in all of the cases.

Author Response

Dear Editor,

according to your suggestion we added in the section materials and methods the following sentence concerning kind of implants placed.

Only TTi type implants from the TT line (Winsix, Biosafin, Cefla, Imola, Ita-ly) featuring an internal hexagonal connection and a cylindrical body with a conical apex were inserted. 

 

Best regards

Reviewer 2 Report

Comments and Suggestions for Authors

Inclusion/exclusion factors - exclusion factors should not be the opposite of inclusion factors and authors should make these corrections. - For example, what the authors refer to in relation to age.

Ibuprofen is an anti-inflammatory and not a  analgesic. This is the classification!

Author Response

Dear Editor,

we correct inclusion and exclusion criteria as follows

Inclusion Criteria
•    Age over 18 years;
•    Single or partial implant-prosthetic rehabilitation with post-extraction implants subjected only to immediate loading;
•    Screw-retained prostheses;
•    Surgical procedure performed by an operator with over 20 years of experience in implantology;
•    Prosthetic rehabilitation performed by an operator with over 20 years of experience in prosthodontics;
•    Minimum follow-up of 18 months;
•    Absence of systemic diseases or presence of compensated systemic diseases;
•    Smoking patients;
•    Patients rehabilitated with implants featuring an internal hexagonal connection from the same manufacturer;
•    Placement of implants in basal bone without the use of biomaterials for bone re-generation.
Exclusion Criteria
•    Failure to adhere to recall and hygiene maintenance protocols during the follow-up period;
•    Incomplete clinical and radiographic documentation;
•    Patients with uncompensated systemic diseases developed during the follow-up period;
•    Patients enrolled in concomitant research protocols.

Thank you for your kindness and availability

Best regards