The implant-supported rehabilitation is, to date, a valid and highly predictable solution for the restoration of missing teeth. The success of this rehabilitation is based on the integration of the implants into the patient's newly formed bone through the osseointegration process. This success has been demonstrated in short and long-term success with 94.6% early success rates and an average success rate of 89.7% even after more than 10 years of function [
Despite this, the implant-prosthetic treatment has shown different short and long-term complications. Among the early failures are: lack of osseointegration, intra or postoperative infection or loss of the primary stability. Meanwhile, among long-term failure could be found: marginal bone loss (MBL), peri-implantitis, and implant overload [
Several authors have investigated the causes related to MBL [
The possible responsible factors were discussed: implant design, the neck area, implant shoulder surface treatment, surgical trauma, platform switching concept, amount of peri-implant soft tissue, surgical implant placement, residual crestal bone and microgap at the fixture-abutments interface [
The latter seems to play a key role in the process of bacterial colonization of the fixture-abutment interface. This area is widely studied in literature in terms of microgap reduction and improvement of the implant-abutment connection. Several authors analyzed the existing microgap describing values between 10 and 135
The internal hexagon connection remains in any case the most widespread and simple in terms of clinical procedures. Although new conometric and hybrid connections are able to further reduce the microgap, there are no connections able to completely eliminate this passage area during long-term clinical use [
The existing microgap could therefore lead to micromovements and bacterial infiltration which results in a peri-implant inflammatory reaction and consequent bone reassembly [
However, the respective roles of bacterial infection and host response to MBL are not yet well understood. Greater MBL can occur when the host's response is insufficient compared to the infection causing more bone resorption [
Over the years the use of rigid surgical and prosthetic protocols has allowed to reduce the microbial load during surgical and postsurgical stage in the peri-implant area. In this sense, the use of local antiseptics such as chlorhexidine (CHX) showed to be a valid support for reducing postsurgical bacterial load [
The objective of this randomized, double blind, placebo-controlled study was to radiologically compare the MBL when a 0.20% CHX gel or a placebo gel was applied to the implant-abutment interface during all surgical and prosthetic phases and for a follow-up period up to 12 months.
This article was written following the CONSORT statement for improving the quality of RCTs as shown in Figure
This prospective, randomized, controlled, double blind clinical trial study was designed according to the Declaration of Helsinki protocol. The allocation ratio was 1:1. The study was approved on 23/07/2015 by the Inter Institutional Ethics Committee of University of Chieti-Pescara, Chieti, Italy; committee report nr:14. All patients gave a written informed consent to the treatment and study recruiting. The trial was registered on clinicaltrials.gov with registration number NCT03431766.
The null hypothesis was that there were no differences between the use of CHX or placebo gel during clinical and prosthetic phase on MBL. The primary outcome was the mean marginal bone loss in single implant-supported restorations. In fact, single unit restoration was chosen to overcome possible problems resulting in patients with multiple implant restorations. MBL was used to estimate the number of patients needed to be randomized.
According to Annibali et al. 2012 [
Meanwhile, the secondary outcomes were as follows: Implant failure: implant failure was described as mobility or any infection ordering implant removal. Prosthetic failure: prosthetic failure was when it was impossible to place the ceramic restoration or its loss due to fracture or secondary implant failure. Gingival index: full mouth plaque score and bleeding on probing score recorded during each stage (4 sides per tooth). Any complications and adverse events reported during the first year.
Forty patients were selected for implant placement. Six were excluded because they did not meet the inclusion criteria. Thirty-four patients (age range 29–75 years; mean age 52,28) without significant medical anamnesis, 14 women and 20 men, all nonsmokers, were recruited as candidates for single implant placement and prosthetic rehabilitation. The patients were enrolled from December 2015 till March 2017 and were treated in the Outpatient Department of Medical, Oral and Biotechnological Sciences of the University “G. d’Annunzio” of Chieti-Pescara, Italy.
The inclusion criteria were as follows: Patients between 18 and 75 years Good systemic and oral health Need of single crown implant-supported restoration At least six months of healing after tooth extraction Cortical bone thickness > 5 mm measured by means of a cone beam computed tomography (CBCT) Adequate dimension of the attached gingiva (>2 mm) or keratinized tissue at the site selected
The exclusion criteria were as follows: Poor oral hygiene Active periodontal disease or other oral disorders Insufficient bone thickness for implant insertion Bone augmentation procedures Immediate loading protocols Uncontrolled diabetes mellitus Immune diseases Smoking Bruxism.
Patients were randomly divided into Group A (control) and Group B (test) as indicated by the randomization chart. The randomization was obtained using computer generated random numbers, centralized with sequentially sealed opaque envelopes provided by the study adviser.
The investigation team was composed by a principal investigator who designed the study and made the randomization, the surgeon who performed first and second stage surgery, examiners who performed the radiological analysis, dentist who performed the prosthetic procedure, and the statistician. Patients were informed of all the study procedures but blinded to the different gel used in the study.
The surgeon opened the sealed envelope containing the randomized group only after having inserted the implant.
During the first evaluation, all subjects were clinically examined. Radiographs and gingival index, such as, plaque and bleeding scores, were carried out for diagnostic evaluation; then the patients were scheduled for surgery procedures. All implants (Cortex classic, Cortex, Shalomi, Israel) were inserted (T0) by two skilled operators who followed a two-stage protocol and placed them according to the manufacturer's instructions. Before surgery all the patients were subject to mouth rinse of chlorhexidine digluconate solution 0.2% for 2 minutes to reduce the bacterial load and local anesthesia was given with Articaine® (Ubistesin 4% - Espe Dental AG Seefeld, Germany) associated with epinephrine (1:100.000). Eventually all patients were rehabilitated with a single implant-supported crown. During all stages either a gel containing 0.20% chx (Plak ®Gel; Polifarma Wellness Srl, Rome, Italy) or a placebo gel (Placebo, Polifarma Wellness Srl, Rome, Italy) was used. The two gels were perfectly alike in packaging, colour, and smell and nobody knew the exact location of placebo or test gel which was revealed, only after data collection was performed, by the person who prepared them. (Figure
The two gels used during every stage of the study. Gels were perfectly alike in packaging, colour, and smell.
A or B gel was placed on internal connection abutments and then a cover screw was inserted. Finally the site was sutured with nonabsorbable sutures. Cone Beam Computed Tomography evaluation (CBCT) (Vatech Ipax 3D PCH-6500, Fort Lee, NJ, USA) was performed for both preoperative (to evaluate residual bone) and postsurgical implant placement. All patients received antibiotic therapy, 2g/day for 6 days (Augmentin®; Glaxo-Smithkline Beecham, Brentford, UK).
The postoperative pain was controlled with NSAIDs, and oral hygiene instructions were given. Both gels were given to the patients, according to the protocol and applied 2 times/day until suture removal after 7 days. Implants were allowed to a submerged heal of 8 weeks. Eight weeks later, implant stability was assessed by percussion test, the second surgical stage was performed, and a healing abutment was placed (T1). Using an open tray technique an impression was made and an acrylic provisional restoration was positioned (T2, 16 weeks after surgery). Finally, porcelain fused to metal restoration was inserted 18-20 weeks after implant placement. A follow- up period of 12 months was established.
Implant success was evaluated according to the clinical and radiographic criteria of Papaspyridakos et al. 2012 [
The peri-implant and gingival index were recorded. Specifically, plaque score (PS) and bleeding on probing (BOP) were evaluated and recorded on four surfaces on each tooth at every study time points. Radiographs and clinical photographs were also recorded during every stage: visit, first implant surgery, second surgical stage, at provisional and permanent restoration positioning, and at follow-up visits (at 6 and 12 months). Also during each visit possible adverse events were recorded. In any case placebo or CHX gel was used during every implant-abutment connection. In order to compare radiographic modification of the peri-implant marginal bone, intraoral radiograph, applying the parallel ray technique, was taken immediately after implant insertion. To measure the crestal bone remodeling, intraoral analogic Rx was taken during each stage and processed on a digital software because the method was considered of high precision for scientific evaluations with a precision less than 0.1 mm [
In order to obtain a highly reproducible and faithful image, the commercially available Rinn film holders, used for intraoral radiographs applying the parallel X-ray technique, were customized using a silicone key for the exact reposition in every subject. Also, during the first radiography kilovolts, milliampere, and seconds were recorded and used every time to obtain the same radiographs. Radiographs were repeated at the implant placement (T0), at 8 weeks during second surgical stage (T1), at 12 weeks during provisional delivery (T2), at 14 weeks during restoration placement (T3), and at 12 months of follow-up (T4).
In every radiograph distance from the top of the fixture and the mesial and distal crestal bone level measured to the first bone to implant contact were recorded. The mean value between mesial and distal region was calculated for the data analysis. Also the known implants length and diameter were measured to guarantee a correct measurement even if the implant was slightly angulated on the radiograph. (Figure
A computer-assisted calibration was performed and linear measurements of MBL were Also it was measured the known implants length and diameter to guarantee a correct measurement even if the implant was slightly angulated on the radiograph.
Statistical tests were conducted with SPSS (IBM Corp., Armonk, NY, USA) and Excel (Microsoft, Redmond, WA, USA) software. The statistical tests to be used were predetermined by the study protocol. Patients were considered for statistical evaluation. Data was presented by means and standard deviations (SD). Analysis of variance (Student's t-test) was used to evaluate differences between groups. Tukey test at 5 different time points considered into the study was used to evaluate difference among groups. Significance was set to p=0.05.
Throughout the study, 40 patients were screened for inclusion and exclusion criteria. 34 patients were enrolled for single implant-supported restoration. Six patients were rejected for not meeting the inclusion criteria. Furthermore, two patients were excluded after randomization due to poor oral hygiene at the surgery appointment. A total of 16 patients were included in Group A (control group with placebo gel). Meanwhile, 16 patients were included in Group B (chlorhexidine gel) as shown in Table
Patient characteristics at study baseline.
| | | | | | | |
---|---|---|---|---|---|---|---|
1 | F | 57 | B | 3.6 | 3.8x11,5 | Normal | 35 |
2 | F | 32 | A | 1.6 | 4.2x11,5 | Poor | 40 |
4 | M | 35 | B | 3.6 | 3.8x11,5 | Normal | 30 |
5 | F | 45 | A | 1.4 | 3.8x11,5 | Poor | 35 |
6 | M | 49 | B | 1.6 | 4.2x10 | Normal | 35 |
7 | F | 51 | A | 4.6 | 4.2x11,5 | Dense | 35 |
8 | M | 67 | B | 4.6 | 4.2x10 | Normal | 45 |
10 | F | 38 | B | 3.6 | 3.8x11,5 | Dense | 40 |
11 | F | 29 | A | 1.6 | 4.2x10 | Poor | 45 |
12 | M | 70 | B | 2.4 | 3.8x11,5 | Normal | 35 |
13 | F | 68 | B | 3.6 | 4.2x11,5 | Normal | 40 |
14 | F | 56 | A | 4.7 | 3.8x10 | Normal | 45 |
15 | M | 75 | B | 3.6 | 3.8x11,5 | Dense | 50 |
16 | M | 39 | B | 4.6 | 4.2x10 | Dense | 35 |
17 | F | 40 | A | 3.6 | 3.8x10 | Dense | 30 |
18 | M | 41 | B | 1.5 | 3.8x11,5 | Poor | 35 |
19 | F | 50 | B | 4.6 | 4.2x11,5 | Normal | 30 |
20 | M | 67 | A | 3.6 | 3.8x11,5 | normal | 35 |
21 | M | 71 | A | 4.6 | 4.2x11,5 | Normal | 40 |
22 | F | 70 | B | 2.4 | 3.8x11,5 | Normal | 45 |
23 | M | 40 | A | 4.6 | 3.8x11,5 | Dense | 40 |
24 | F | 59 | A | 3.5 | 4.2x11,5 | Normal | 35 |
25 | M | 63 | A | 2.2 | 3.8x11,5 | Dense | 45 |
26 | M | 68 | B | 4.5 | 4.2x10 | Normal | 40 |
27 | M | 56 | B | 3.7 | 3.8x11,5 | Normal | 35 |
28 | F | 59 | B | 2.5 | 4.2x10 | Poor | 45 |
29 | F | 44 | A | 3.6 | 4.2x10 | Dense | 40 |
30 | M | 43 | A | 3.7 | 3.8x11,5 | Dense | 40 |
31 | M | 39 | B | 2.6 | 4.2x11,5 | Poor | 35 |
32 | M | 35 | A | 2.4 | 3.8x11,5 | Normal | 45 |
33 | F | 56 | A | 3.6 | 3.8x11,5 | Dense | 50 |
34 | M | 61 | A | 4.6 | 4.2x11,5 | Dense | 40 |
Average percentage for the different groups of plaque score (PS) and bleeding scores (BS) recorded during all phases of the study.
| | | | | | | | | | |
---|---|---|---|---|---|---|---|---|---|---|
PS | 17.45 | 17.32 | 19.34 | 18.45 | 17.34 | 18.32 | 20.32 | 19.46 | 23.45 | 23.28 |
BS | 9.2 | 8.15 | 11.32 | 12.21 | 13.45 | 13.78 | 15.21 | 16.32 | 17.25 | 18.5 |
Explanatory images of all the treatments performed (a-l). (a) Residual crest. (b) Implant insertion. (c) Measurement of residual bone. (d) Gel inserted into the fixture. (e) Suture positioning. (f) Suture removal. (g) Second surgical stage. (h) A minimal inflammatory response was present below the healing screw. (i) Impression. (j) Abutment positioning and temporary crown delivery. (k-l) Definitive ceramic restoration delivery.
At T0 (implant placement), the mean value was 0.04 ± 0.30 mm for Group A and 0.06 ± 0.22 mm for Group B, without significant statistical difference. Analysis of data showed different MBL into the two groups during the different stages as shown in Table
Table shows different MBL into the two groups during the different stages.
| | | | | | | |
---|---|---|---|---|---|---|---|
2 | 1.6 | A | 0.22 | -0.06 | -0.49 | -0.73 | -1.51 |
5 | 1.4 | A | 0.00 | -0.38 | -0.55 | -0.82 | -1.07 |
7 | 4.6 | A | 0.49 | 0.12 | -0.20 | -0.84 | -0.95 |
11 | 1.6 | A | -0.62 | -1.53 | -1.75 | -1.76 | -1.84 |
14 | 4.7 | A | -0.39 | -0.92 | -0.89 | -0.65 | -0.80 |
17 | 3.6 | A | -0.06 | -0.38 | -0.43 | -0.68 | -0.73 |
20 | 3.6 | A | 0.06 | 0.00 | -0.44 | -0.60 | -0.63 |
21 | 4.6 | A | 0.16 | -0.29 | -0.53 | -0.73 | -0.94 |
23 | 4.6 | A | -0.13 | -0.20 | -0.74 | -1.01 | -1.05 |
24 | 3.5 | A | -0.06 | -0.20 | -0.44 | -0.59 | -0.64 |
25 | 2.2 | A | 0.60 | -0.06 | -0.46 | -0.71 | -0.77 |
29 | 3.6 | A | -0.11 | -0.15 | -0.78 | -0.94 | -1.06 |
30 | 3.7 | A | 0.05 | -0.09 | -0.25 | -0.38 | -0.58 |
32 | 2.4 | A | 0.35 | -0.05 | -0.52 | -0.79 | -0.90 |
33 | 3.6 | A | 0.21 | -0.05 | -0.40 | -0.58 | -0.74 |
34 | 4.6 | A | -0.08 | -0.21 | -0.58 | -0.61 | -0.80 |
| | | | | | ||
| | | | | | ||
| |||||||
1 | 3.6 | B | 0.57 | 0.62 | 0.00 | -0.47 | -0.55 |
4 | 3.6 | B | -0.17 | 0.03 | -0.50 | -0.71 | -0.81 |
6 | 1.6 | B | 0.10 | 0.22 | -0.05 | -0.41 | -0.93 |
8 | 4.6 | B | 0.20 | 0.21 | -0.48 | -0.74 | -0.79 |
10 | 3.6 | B | -0.04 | 0.00 | -0.38 | -0.53 | -0.61 |
12 | 2.4 | B | 0.00 | 0.10 | -0.35 | -0.55 | -0.71 |
13 | 3.6 | B | -0.02 | 0.15 | -0.37 | -0.67 | -0.89 |
15 | 3.6 | B | 0.16 | 0.39 | -0.08 | -0.61 | -0.74 |
16 | 4.6 | B | 0.12 | 0.59 | -0.23 | -0.49 | -0.61 |
18 | 1.5 | B | 0.00 | -0.36 | -0.57 | -0.69 | -0.77 |
19 | 4.6 | B | 0.34 | 0.24 | 0.00 | -0.16 | -0.31 |
22 | 2.4 | B | 0.29 | 0.28 | -0.29 | -0.88 | -0.95 |
26 | 4.5 | B | -0.35 | -0.08 | -0.15 | -0.41 | -0.66 |
27 | 3.7 | B | 0.00 | -0.05 | -0.21 | -0.54 | -0.59 |
28 | 2.5 | B | 0.06 | 0.18 | -0.30 | -0.37 | -0.57 |
31 | 2.6 | B | -0.26 | -0.08 | -0.46 | -0.56 | -0.70 |
| | | | | | ||
| | | | | |
Statistical analysis compared the different MBL between the two groups in every single stage.
| 0,0435625 | T-ratio | -0,220803459 | |
| 0,0621875 | DF | 15 | |
Mean difference | -0,018625 | Prob > | 0,8282 | |
Std. error | 0,084351034 | Prob > t | 0,5859 | |
Upper 95% | 0,161164972 | Prob < t | 0,4141 | |
Lower% | 0,198414972 | |||
N | 16 | |||
Correlation | 0,211215722 | |||
| ||||
| -0,2768125 | T-ratio | -3,690326917 | |
| 0,15328125 | DF | 15 | |
Mean difference | -0,43009375 | Prob > | 0,0022 | |
Std. error | 0,116546246 | Prob > t | 0,9989 | |
Upper 95% | -0,181681306 | Prob < t | 0,0011 | |
Lower% | -0,678506194 | |||
N | 16 | |||
Correlation | 0,060006213 | |||
| ||||
| -0,62671875 | T-ratio | -4,200440951 | |
| -0,2736875 | DF | 15 | |
Mean difference | -0,35303125 | Prob > | 0,0008 | |
Std. error | 0,084046236 | Prob > t | 0,9996 | |
Upper 95% | -0,173890939 | Prob < t | 0,0004 | |
Lower% | -0,532171561 | |||
N | 16 | |||
Correlation | 0,394342209 | |||
| ||||
| -0,846 | T-ratio | -3,483100821 | |
| -0,54834375 | DF | 15 | |
Mean difference | -0,29765625 | Prob > | 0,0033 | |
Std. error | 0,085457259 | Prob > t | 0,9983 | |
Upper 95% | -0,115508414 | Prob < t | 0,0017 | |
Lower% | -0,479804086 | |||
N | 16 | |||
Correlation | 0,407963714 | |||
| ||||
| -1,033375 | T-ratio | -2,787533871 | |
| -0,69665625 | DF | 15 | |
Mean difference | -0,33671875 | Prob > | 0,0138 | |
Std. error | 0,120794496 | Prob > t | 0,9931 | |
Upper 95% | -0,079251376 | Prob < t | 0,0069 | |
Lower% | -0,594186124 | |||
N | 16 | |||
Correlation | 0,103410841 |
Radiographs from the two groups. (a-e) Patient from Group B (test group). A minimal bone gain was present at the second surgical stage. (f-j) Patient from Group A (control group).
Graphical representation of MBL during every surgical and prosthetic stage.
CONSORT 2010 Flow Diagram. Flow diagram of the progress through the phases of a parallel randomized trial of two groups.
The aim of the study was to compare the effect of a 0,20% CHX gel or placebo used during all the restoration phases on the MBL rate around implant-supported rehabilitation.
To reduce bias on both groups, only the gel used during connection decontamination was changed; the same type of implant design, surface treatment, and type of connection was used [
To the authors’ best knowledge this is the first study which investigates the effects of 0,20% CHX gel during the early stage of healing abutment connection (T1) and provisional prosthetic delivery (T2) on MBL. Until now, there was no scientific evidence to explain the mechanisms related to MBL around implants related to the use of CHX. Specifically, MBL was used as a measure of treatment success; a prognostic factor leads to capture the effect of treatment on the clinical endpoint but not to directly measure the main clinical benefit of the intervention [
Several authors have investigated the MBL around the implants demonstrating how most of the bone reabsorption occurs during the first year of loading [
According to Bateli et al., the possibility of preserving MBL requires a multifactorial approach [
Regarding the MBL the overall mean values of the two groups were 0.05 ± 0,26 mm at the baseline. Following the protocol, the implants were placed all at bone level and all by the same operator to receive high accuracy. Considering this, MBL at 12 months was -0,94 ± 0.33 mm and -0.70 ± 0.16 mm for Group A and Group B, respectively. Although there was a statistically significant difference between the groups, the values in both were in agreement with other authors [
Other authors have shown how different connections can reduce the existing microgap, improving fixture-abutment seal and reducing micromovements [
Short-term studies [
Despite the presence of several studies concerning MBL, no one has specified the time course of this reabsorption [
Likewise, in the presented results, the reduction of the microbial load has been transformed into a reduction of the inflammatory response with results in terms of MBL comparable to platform switching rehabilitation. Anyway, longer follow-up would be necessary to verify the efficacy of CHX in this rehabilitation. Romanos et al. [
In any case, the study was based on a number of patients; even if the number is statistically acceptable, it is still limited. Therefore, further investigations with more relevant sample sizes are needed. However, the patients are still under strict control and results from longer follow-up periods (5 and 10 years) should be investigated. Therefore, albeit with due caution, the CHX gel formulation used allowed us to obtain encouraging results, considering the rigid selection of patients, the protocol, the randomization technique, and the observation performed (double blind). In any case, further investigation may be necessary to have a more complete draft, like a microbiological profile or a peri-implant soft tissue analysis to assess the inflammatory status of soft tissues. It could also be useful to perform this investigation in different connection types and evaluate its effectiveness following strict decontamination protocols.
The results obtained from this randomized double blinded human-controlled study showed that the use of 0,20% CHX gel inside the connection during all surgical and prosthetic phases significantly reduces peri-implant crestal bone loss during the first year. However, the existing space between fixture and abutments remains a crucial area in bacterial colonization as a starting point for the MBL around the fixture. A rigid disinfection protocol with 0.20% CHX from the time of implant insertion to crown delivery is strongly recommended to reduce host inflammatory response and consequently MBL.
The data used to support the findings of this study are included within the article.
The authors declare that there are no conflicts of interest regarding the publication of this paper.
Bruna Sinjari and Gianmaria D’Addazio contributed equally to this work so they should be considered joint first authors.