A Radiographical and clinical comparison of immediate vs. early loading (4 weeks) implants with a new thermo-chemically treated-surface; a randomized clinical trial

International Journal of Environmental Research and Public Health Article A Radiographic and Clinical Comparison of Immediate vs. Early Loading (4 Weeks) of Implants with a New Thermo-Chemically Treated Surface: A Randomized Clinical Trial Matteo Albertini 1, Federico Herrero-Climent 2, Carmen María Díaz-Castro 3, Jose Nart 1, Ana Fernández-Palacín3, JoséVicente Ríos-Santos 4,* and Mariano Herrero-Climent 5   Citation: Albertini, M.; Herrero-Climent, F.; Díaz-Castro, C.M.; Nart, J.; Fernández-Palacín, A.; Ríos-Santos, J.V.; Herrero-Climent, M. A Radiographic and Clinical Comparison of Immediate vs. Early Loading (4 Weeks) of Implants with a New Thermo-Chemically Treated Surface: A Randomized Clinical Trial. Int. J. Environ. Res. Public Health 2021, 18, 1223. https://doi.org/10.3390/ ijerph18031223 Academic Editors: Tiziano Testori and Paul B. Tchounwou Received: 30 November 2020 Accepted: 26 January 2021 Published: 29 January 2021 Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). 1Department of Periodontology, Universitat International de Catalunya, 08017 Barcelona, Spain; [email protected] (M.A.); [email protected] (J.N.) 2Clinica Dental Herrero Climent, Calle del Dr. Fleming 54, 28036 Madrid, Spain; [email protected] 3Department of Preventive Medicine and Public Health, Faculty of Medicine, Universidad de Sevilla, Avda Sanchez Pizjuán S/N, 41009 Sevilla, Spain; [email protected] (C.M.D.-C.); [email protected] (A.F.-P.) 4 Department of Periodontics and Dental Implants, School of Dentistry, University of Seville, C/Avicena S/N, 41009 Sevilla, Spain 5Porto Dental Institute, 4150-518 Porto, Portugal; [email protected] *Correspondence: [email protected]; Tel.: +34-954481121 Abstract: Background: Implant dentistry has evolved over time, resulting in better treatment outcomes for both patients and clinicians. The aim of this trial was to test whether the immediate loading of implants with a platform-switching design influences the marginal bone level, compared to four-week loading, after one year of follow-up. Moreover, a comparison of clinical data regarding implant survival, implant stability, and patient-reported outcome measures (PROMs) was conducted. Methods: Klockner ® VEGA ® implants with a ContacTi ® surface were placed in partially edentulous patients in the posterior areas. Group A received an immediately loaded prosthesis (one week) and Group B received an early-loaded prosthesis (four weeks). All abutments were placed at the time of surgery. Radiographic and clinical data were recorded. Results: Twenty-one patients were treated (35 implants). No implants were lost during the study. The final marginal bone level did not show differences between groups. The bone loss at 12 months at the implant level was 0.00 mm for both groups (median). The final implant quotient stability (ISQ) values did not differ between groups (median 73 and 70.25), nor did the other clinical parameters or PROMs. Conclusions : The results suggest that neither of the loading protocols with the implants used influenced the marginal bone level—not the osseointegration rate, clinical conditions, or PROMs. Keywords: immediate loading; early loading; dental implants; bone–implant interface; osseointegration 1. Introduction Implant dentistry has evolved in recent decades, resulting in better treatment outcomes for both patients and clinicians. This improvement has been possible through progressive changes in each and every aspect of therapy: implant design, implant surface, prosthetic connections, abutments, materials, surgical and loading protocols, and so on [ 1 ]. In this sense, shortening the period to treatment completion has been always a main concern, including consideration of the immediate installation of the prosthesis, and, consequently, the immediate loading of the implants [ 2 , 3 ]. Immediate loading is defined as the connection of the restoration onto the implant in occlusion with the opposing dentition within the first week after implant placement; in contrast, early loading is considered when prosthesis installation takes place between the first week and two months; finally, conventional loading refers to installation that takes place later on [ 4 , 5 ]. Predictable results have been reported in terms of implant survival rates and marginal bone loss, with both immediate and early loading procedures, under some specific clinical conditions, mainly Int. J. Environ. Res. Public Health 2021,18, 1223. https://doi.org/10.3390/ijerph18031223 https://www.mdpi.com/journal/ijerph Int. J. Environ. Res. Public Health 2021,18, 1223 2 of 19 in the anterior region [ 4 , 6 ]. Even in the posterior areas, several clinical studies have shown a high implant success rate in the presence of an adequate primary stability and favorable occlusal conditions under an early loading approach [ 7 , 8 ] and, moreover, under immediate loading [9]. Considering the factors involved in implant osseointegration, it is generally accepted that the implant surface plays a major role regarding the bone healing process around dental implants. In fact, from the early days of osseointegration, the development of new surfaces has been a main issue in terms of promoting a greater rate of osseointegration, a faster bone apposition, and greater bone–implant contact [ 1 , 10 ]. In the field of implant surfaces, one of the proposals to reach these goals has been the modification of the endosseous implant surface by the deposit of a layer of diverse so-called bioactive molecules, such as hydroxyapatite (HA), bioactive glasses, and calcium phosphate [11–13]. Different manufacturing processes, including the plasma spray technique, have enabled manufacturers to obtain implants with an HA-coated surface onto titanium or titanium alloy implant bodies [ 14 , 15 ]. Although these implants, years ago, showed promising results in the short term regarding bone healing [ 16 , 17 ], diverse complications were later reported, mainly due to failures of adhesion of the HA coating, leading, finally, to bacterial microleakage and peri-implant tissue complications [ 13 , 18 , 19 ]. In 1990, Kokubo et al. proposed a titanium surface modification by means of an initial chemical treatment with alkaline solutions and a subsequent heating process at high temperatures [ 20 ]. This method has demonstrated de novo HA formation through a biomimetic reaction once the implant is in contact with the human serum, without the presence of osteoblasts [ 21 , 22 ]. In vitro experiments in a simulated body fluid model have demonstrated, by electromicroscopy, new deposits of apatite particles in implants with this surface modification [ 21 , 23 – 25 ]. This method has also shown de novo HA formation once the implant is in contact with human serum, without the presence of osteoblasts [ 21 , 22 ]. Authors have suggested that the crystalline apatite layer adhered to titanium has the potential to stimulate osteoblast migration in contact with the living bone, and, consequently, to accelerate the osseointegration process [23]. Furthermore, in vivo studies have observed de novo bone formation and increased bone–implant contact in the early stages of bone healing, in comparison to non-treated surfaces. Based on these investigations, a highly hydrophilic and osteoconductive surface was developed [ 26 , 27 ] and has been applied to dental implants for its clinical use [ 28 ], under the commercial name of ContacTi ® (Klockner Implant System, SOADCO S.L., Andorra). As already described by Aparicio et al. [29], once the implants are produced in commercially pure titanium grade 4, their surface undergoes a process of grit-blasting and acid-etching in order to obtain a moderately rough surface, followed by thermo-chemical modification. A recent clinical investigation with a bioactive HA surface showed promising results with both immediate and early loading [30]. Regarding implant morphology, years ago, the platform-switching design was introduced, meaning that the diameter of the abutment placed onto an implant is narrower than the inner wall of the implant itself [ 31 ]. The use of platform-switching has been claimed to protect from bone loss around implants and, as a consequence, to facilitate the maintenance of peri-implant tissue health [ 32 , 33 ]. In addition, whether repeated implant abutment disconnections may lead to marginal bone resorption has also been investigated, but this is, at least at the present moment, still a matter of controversy [ 34 – 36 ]. Recent studies have suggested that one single abutment connection at the time of implant surgery, the so-called one abutment–one time (OAOT), would favor peri-implant marginal bone level maintenance [ 37 – 39 ]. Under the platform-switching design, a new implant model has been marketed, named Klockner ® VEGA ® ContacTi ® (Vega-CTi) (SOADCO S.L., Andorra), featuring: (a) a 10 ◦ Morse taper internal conical connection, (b) an internal hexagon for index and anti-rotation purposes, (c) a platform-switching design, and (d) enhanced titanium, i.e., grade 4 titanium cold worked at high tension. The implant surface is the already mentioned and previously described ContacTi®. Int. J. Environ. Res. Public Health 2021,18, 1223 3 of 19 Considering the previous statements, a clinical protocol was developed to investigate the clinical performance of Vega-CTi implants. Therefore, the aim of this randomized clinical trial was, primarily, to test the null hypothesis that the immediate loading of Vega- CTi implants (less than one week) would not influence the marginal bone level, compared to four-week loading, under the concept of OAOT, one year after treatment completion. Additionally, this study obtained and compared clinical data regarding implant survival, implant stability values, and the patient-reported outcome measures (PROMs) under these loading conditions. 2. Materials and Methods The present study was originally designed as a prospective, multi-center, singleblinded, controlled clinical trial. This article presents the one-year results of the trial. 2.1. Participants Adult patients, at least 18 years old, missing at least one posterior tooth (molar or premolar) in the mandible or maxilla and willing to receive implant therapy were eligible for screening. In addition, the following inclusion criteria were required: - Undisturbed, completely healed edentulous sites, at least four months after tooth/ teeth extraction; - Adequate bone volume verified by CBCT (cone beam computed tomography) for the placement of a dental implant of at least 8 mm in length and 3.5 mm in diameter; this means at least 9 mm of bone in the vertical dimension and 6.5 mm in the horizontal dimension; - No bone regeneration procedures required; - Adequate prosthetic conditions for proper crown or bridge installation; - Natural antagonist dentition, whether restored or untreated teeth; - Presence of at least 4 mm of keratinized mucosa from the buccal to lingual side of the edentulous ridge; - Absence of oral infections, gingival inflammation, untreated periodontitis, or mucosal diseases. 2.2. General Exclusion Criteria The general exclusion criteria included: - Uncontrolled systemic diseases; - Pregnancy; - Bone-related disorders such as osteoporosis; - Drug abuse or alcoholism; - Smoking habit of >10 cigarettes per day; - Severe bruxism or severe temporomandibular junction disorders; - Previous history of implant failure. In order to enter the study, patients had to be able to understand the nature of the study, to sign an informed written consent form, and to be willing to attend the scheduled follow-up appointments. This study was conducted in accordance with the Declaration of Helsinki (1964) and its amendments for patients participating in clinical studies (Tokyo, 1975; Venice, 1983; Hong Kong, 1989; Somerset, 1996; Edinburgh, 2000). The study protocol was reviewed and approved by the ethics committee for clinical studies of the Universitat Internacional de Catalunya with reference number 500077. 2.3. Location and Clinicians Three centers in Spain (Barcelona Dental Institute Barcelona, the CEROM Clinic in Marbella, and the NCD Clinic in Barcelona) participated in the study. Three experienced dentists, one at each center, all of them familiarized with the implant system, were responsible for the surgical and prosthetic procedures (M.A., M.H., and J.N.). Before the study Int. J. Environ. Res. Public Health 2021,18, 1223 4 of 19 started, the clinicians participated in a calibration meeting to receive all the information (verbally and in writing) about the study and the assessment of the variables. 2.4. Implants and Abutments Vega-CTi implants, as already described, of 3.5, 4.0, and 4.5 mm in diameter and 8, 10, and 12 mm in length were available for the surgeries. The dimensions of the platformswitching for each implant diameter were 0.3, 0.35, and 0.6 mm, respectively. All of the restorations were installed onto abutments of 1 or 2 mm in transmucosal height, designed for screw-retained prostheses (Permanent ® Abutment, Klockner Implant System, SOADCO S.L., Andorra). No cemented restorations were used in this study. 2.5. Pre-Treatment Procedures All clinicians were asked to follow a common pre-treatment protocol, including intraoral photographs, impressions, cast models, diagnostic wax-up, intra-oral radiographs, orthopantomography, and cone beam computerized tomography. With all of this information, prosthetically guided implant placement was planned. The patients received teeth prophylaxis, including oral hygiene instructions, fullmouth plaque scores (FMPS), and full-mouth bleeding scores (FMBS). The periodontal chart was completed recording the clinical attachment level (CAL) and probing depth (PD) with a conventional periodontal probe (PCP UNC 15-Hu-Friedy). Periodontal status was assessed according to the classification proposed by Armitage 1999 [40]. 2.6. Surgical Interventions The patients received prophylactic antibiotic therapy 1 h prior to surgery (1 g of amoxicillin or 600 mg of clindamycin in case of allergy or intolerance). The patients were told to mouthwash for 1 min with a 0.12% solution of chlorhexidine (Perio Aid ® , Dentaid, Spain); later, a 2.0% solution of chlorhexidine (Bohmclorh ® , Bohm, Madrid, Spain) was applied extra-orally to the peri-oral skin. The surgeries were performed under local anesthesia with 40 mg/mL of articaine + 0.01 mg/mL of epinephrine (Artinibsa ® , Inibsa Dental, Barcelona, Spain). Then, the full-thickness flaps were raised by means of crestal and intrasulcular incisions, paying attention to preserving at least 2 mm of keratinized mucosa on the buccal and lingual or palatal aspects of the alveolar crest. The crestal bone width was measured buccolingually with a periodontal probe (PCP-UNC 15, Hu-Friedy). The bone site preparation was performed according to the manufacturer’s drilling sequence suggested for Vega-CTi implants; however, each clinician was free to adapt the final drilling according to the bone quality in order to ensure optimal primary stability. The implants were inserted using a calibrated torque wrench (Klockner Implant System, SOADCO S.L., Andorra), taking care to place the implant shoulder at least 1 mm below the crestal level at the most declining part of the bone preparation. Each clinician could decide the optimal diameter and length of the implants, considering the preoperative diagnostic procedures and the surgical evaluation of the bone volume available at the site. Bone quality was registered according to the D1-, D2-, D3-, and D4-type classifications [ 41 ]. Insertion torque (IT) and primary stability were registered after implant placement as follows: (A) Manually, by means of a calibrated torsion torque wrench (Klockner Implant System, SOADCO S.L., Andorra) at the time of placing the implant. (B) Manually, after the use of the torque wrench, according to the following criteria at the time of the abutment connection: Type A: IT > 35 N/cm, and the implant could not be rotated manually; type B: IT < 35 N/cm and the implant could not be rotated manually; type C: IT < 35 N/cm and the implant could be rotated manually; type D: the implant could be rotated manually and moved in a vertical direction. In this case (i.e., type D), the patient was excluded from the study, and a delayed loading protocol was carried out. Int. J. Environ. Res. Public Health 2021,18, 1223 5 of 19 (C) By radiofrequency, using the Osstell ® device and Osstell ® transducers (Smart-Pegs ® ) (Osstell ® , Gothenburg, Sweden) in order to obtain of the implant stability quotient (ISQ) values. The transducers were connected to the abutments, screwed at 5 N/cm. After implant installation, the straight abutments for screw-retained restorations were tightened at 20 N/cm with a dynamometric wrench (Klockner Implant System, SOADCO S.L., Andorra). The selection of the height of the abutment (1 or 2 mm) was subject to the criteria of the clinician at the time of surgery. The ISQ values for the implants in the study were recorded, both buccolingually and mesiodistally. Abutment-level impressions were taken the same day of the surgery, and screw-retained acrylic provisional restorations were prepared for all implants. Finally, healing caps were placed onto the abutments and the surgical flaps were sutured with 5/0 polyamide avoiding any tension. Antibiotic treatment was maintained for seven days (500 mg of amoxicillin or 300 mg of clindamycin for 1/8 h). Non-steroidal anti-inflammatory dexketoprofen (25 mg) was administrated every 8 h if needed, as was a gastric protector (20 mg of pantoprazole) once per day for seven days. At this point, a randomization process was performed in order to allocate the patients to Group A, in which the implants were loaded with provisional restorations within the first week after surgery, or Group B, in which the implants were loaded four weeks after surgery. The randomization was done by the toss of a coin, by an assistant who was not involved in the investigation. 2.7. Prosthetic Procedure Provisional prostheses up to three units and with no cantilever or implant–tooth junctions were inserted and tightened at 20 N/cm within the first week after implant placement in patients of Group A and after four weeks in patients of Group B. Eight weeks after implant placement, the provisional restorations were unscrewed, and definitive impressions were taken. All definitive prostheses (also up to three units and with no cantilever or implant–tooth junctions) were delivered 10–12 weeks later; the abutments were re-tightened at 30 N/cm and restoration screws at 25 N/cm with a dynamometric wrench. The occlusal screw access hole was filled with a composite material and occlusal adjustment and polishing were carried out if needed. All of the restorations, whether provisional or final, were in occlusion with the opposite dentition in the maximum intercuspation position. If there were any complications with the prostheses, they were recorded (screw loosening, abutment loosening, fracture, chipping, etc.). 2.8. Outcomes The primary outcome measure was the peri-implant marginal bone level changes. For this purpose, standardized periapical radiographs were taken at five time points: immediately after implant placement (baseline), after the temporary restoration installation (at one or four weeks), after definitive restoration installation (at 10–12 weeks), and at 6 and 12 months. Baseline radiographs were taken with the definitive abutment and the corresponding healing cap screwed. Radiographs for assessing the impression coping fit and the prosthetic components were also performed, but only for clinical purposes. Once the final crowns were in place, a customized standard holder was prepared for each implant, recording the occlusal surfaces of the adjacent and opposing teeth with acrylic resin on a parallel X-ray holder (Dentsply Rinn XCP-DS ® ) in order to obtain a consistent image projection. An independent blinded technician performed the radiographic analysis. A previous calibration procedure was carried out as follows: The same examiner measured a subset of 10 radiographs on three separate occasions, 72 h apart, to determine the intra-examiner reproducibility. An interclass coefficient of 0.99 (p< 0.05) was obtained. The radiographic peri-implant bone level changes in the X-rays were analyzed using software for image analysis (ImageJ ® , version 1.39F, U.S. National Institutes of Health). All measurements were performed using 7X magnification. Figure 1shows the reference landmarks for the X-ray analysis. In each radiograph, the most coronal part of the bone crest (C), the position of the implant shoulder (S), and the Int. J. Environ. Res. Public Health 2021,18, 1223 6 of 19 level of the first visible contact of the peri-implant bone with the implant (Fi) or abutment (Fa) were identified. The distance in millimeters from S to C was defined as the marginal bone level at the crest (MBLc), while the distance from S to Fi was defined as the marginal bone level at the implant (MBLi). The distance between S and Fa was registered as the marginal bone level at the abutment (MBLa). The MBLc distance was considered positive if the C mark was coronal to S, negative if C was apical to it, and as zero if C coincided with the implant shoulder. In the same manner, MBLi was considered negative if Fi was apical to S and as zero if Fi coincided with S or bone–abutment contact was detected. This radiographic analysis was completed by an independent researcher who did not know to which group each implant belonged. Int. J. Environ. Res. Public Health 2021, 18, x FOR PEER REVIEW 6 of 19 examiner reproducibility. An interclass coefficient of 0.99 (p < 0.05) was obtained. The radiographic peri-implant bone level changes in the X-rays were analyzed using software for image analysis (ImageJ ® , version 1.39F, U.S. National Institutes of Health). All measurements were performed using 7X magnification. Figure 1 shows the reference landmarks for the X-ray analysis. In each radiograph, the most coronal part of the bone crest (C), the position of the implant shoulder (S), and the level of the first visible contact of the peri-implant bone with the implant (Fi) or abutment (Fa) were identified. The distance in millimeters from S to C was defined as the marginal bone level at the crest (MBLc), while the distance from S to Fi was defined as the marginal bone level at the implant (MBLi). The distance between S and Fa was registered as the marginal bone level at the abutment (MBLa). The MBLc distance was considered positive if the C mark was coronal to S, negative if C was apical to it, and as zero if C coincided with the implant shoulder. In the same manner, MBLi was considered negative if Fi was apical to S and as zero if Fi coincided with S or bone–abutment contact was detected. This radiographic analysis was completed by an independent researcher who did not know to which group each implant belonged. Figure 1. Reference landmarks in the X-rays. C, bone crest; S, implant shoulder; Fi, first bone–implant contact; M, mesial; D, distal; S–C distance, marginal bone level at the crest (MBLc); S–Fi distance, marginal bone level at the implant (MBLi); S–Fa distance, marginal bone level at the abutment (MBLa). The secondary outcome measures were (a) the implant survival at 4, 8, and 12 weeks and 6 and 12 months, by just clinical examination of the presence, stability, and function of the implant/prosthesis; (b) the implant stability, by means of a comparison of the ISQ values at the corresponding follow-up visits; (c) the PROMs. Finally, three clinical variables were recorded: the modified plaque index (mPLI), the modified sulcus bleeding index (mSBI), and PD, at the mesial, distal, vestibular, and palatal/lingual aspects of the implants at 4 weeks and 3, 6, and 12 months. Figure 1. Reference landmarks in the X-rays. C, bone crest; S, implant shoulder; Fi, first bone–implant contact; M, mesial; D, distal; S–C distance, marginal bone level at the crest (MBLc); S–Fi distance, marginal bone level at the implant (MBLi); S–Fa distance, marginal bone level at the abutment (MBLa). The secondary outcome measures were (a) the implant survival at 4, 8, and 12 weeks and 6 and 12 months, by just clinical examination of the presence, stability, and function of the implant/prosthesis; (b) the implant stability, by means of a comparison of the ISQ values at the corresponding follow-up visits; (c) the PROMs. Finally, three clinical variables were recorded: the modified plaque index (mPLI), the modified sulcus bleeding index (mSBI), and PD, at the mesial, distal, vestibular, and palatal/lingual aspects of the implants at 4 weeks and 3, 6, and 12 months. 2.9. Provisional and Definitive Restoration Follow-Ups The post-loading status of the provisional and definitive restorations was assessed at each follow-up visit. The following complications were registered in the case of occurrence: mobility of the prostheses, mobility of the abutments, abutment screw loosening, the presence of porcelain chippings, the fracture of the frameworks, and the fracture of the abutments. Int. J. Environ. Res. Public Health 2021,18, 1223 7 of 19 2.10. Adverse Events Adverse events and complications related to the implant surgical treatment (“implantrelated adverse events”) such as acute or chronic pain, sensorial alterations, bone fractures, osteomyelitis, loss of osseointegration of the implant, and discomfort and local or systemic infections were recorded. “Non-implant-related adverse events” such as serious illnesses or any condition requiring hospitalization for more than one day were also recorded. 2.11. PROMs (Patient-Reported Outcome Measures) The PROMs were assessed by means of a questionnaire regarding comfort, esthetics of the restorations, chewing ability, and overall satisfaction. A four-item rating scale was used to assess the degree of satisfaction: excellent, good, fair, and poor. 2.12. Statistical Analysis Sample size was previously calculated with N Query Advisor 4.0 software (Statistical Solutions ® , Cork, Ireland) using data from previous studies with a similar design [ 42 ]. A significance level of 5% ( α = 0.05) and a statistical power of 80% were used for the analysis. Radiographic bone changes over time were considered as the primary outcome variable. Considering a mean difference of 0.25 mm of radiographic bone changes as acceptable, a standard deviation of 0.21 mm, and a dropout rate of 10%, a minimum of 20 patients for the overall sample had to be included in the study. The interclass correlation coefficients to study the consistency among the different consecutive radiographic measurements provided by the same operator on the same patients were significant with a confidence level of 95%, and they all were greater than 0.9, considering 1 as a perfect consistency. Descriptive statistics, such as the means, SEs, SDs, medians, and ranges of the measurements, were calculated for the ISQ, the marginal bone level, and the rest of the clinical values. Chi-square tests for comparing the categorical variables between two groups were applied. As the variables appeared to be parametric up to the three-month visit, Student’s t-tests and ANOVAs were used to analyze parameter evolution and to compare the values between groups. Nonparametric tests such as the Wilcoxon and Mann–Whitney tests were used to compare the data after three months. The mean differences were considered statistically significant at p ≤ 0.05 with a confidence interval of 95%. Data analysis was completed with the software package IBM SPSS 21.0 ® for Windows (IBM, SPSS, Chicago, IL, USA). Since asymmetry or bias of the data was detected, instead of using the mean and standard deviation, the variables with medians and 25th and 75th percentiles were summarized and the non-parametric Mann–Whitney test was used. The follow-up of the repeated measures was carried out with the non-parametric Friedman test in each of the study groups. 3. Results 3.1. Study Population Twenty-one patients were recruited in this randomized clinical trial from October 2015 to July 2016. A total of 35 implants were included in the study. No implants were lost, and no implant or non-implant related adverse events were observed throughout the study. Two patients (two implants) were not subjected to X-ray exposure at the six-month visit as they were pregnant at that time. Another two patients (two implants) did not attend the one-year visit. Figure 2depicts the study sample flow-chart. Int. J. Environ. Res. Public Health 2021,18, 1223 8 of 19 Int. J. Environ. Res. Public Health 2021, 18, x FOR PEER REVIEW 8 of 19 study. Two patients (two implants) were not subjected to X-ray exposure at the six-month visit as they were pregnant at that time. Another two patients (two implants) did not attend the one-year visit. Figure 2 depicts the study sample flow-chart. Figure 2. Study sample flow-chart. 3.2. Demographic Data Twelve of the 21 patients (54.2%) were men and nine (45.8%) were women, with a mean age of 52.4 years (SD: 14.6 years). No statistically significant differences between groups were observed for these variables at baseline (p = 0.205 and p = 0.382 for Groups A and B, respectively). Regarding the smoking habit, five patients (20.8%) were smokers and 19 were not (79.2%). From a periodontal point of view, four patients were healthy (16.9%), and 17 were previously treated: five for gingivitis (20.8%), eight for mild chronic periodontitis (33.3%), six for moderate chronic periodontitis (25%), and one for severe chronic periodontitis (4.2%). Again, no statistically significant differences between Groups A and B were observed for any of the parameters at baseline (p = 1 and p = 0.470, respectively). 3.3. Interventions Nine patients (42.8%) and 17 implants (48.6%) were assigned to Group A and 12 patients (57.2%) and 18 implants (51.4%) to Group B (early loading). Fourteen implants (40%) were placed in the maxilla and 21 implants (60%) in the mandible. The locations of the implants by tooth site (FDI nomenclature) are displayed in Figure 3. The location more frequent was the left lower first molar. The diameters of the implants used were 3.5 mm (five implants), 4 mm (24 implants), and 4.5 mm (six implants), while the lengths were 8 mm (nine implants), 10 mm (22 implants), and 12 mm (four implants). Recruited (n=21 subjects) Randomized (n=21 subjects, 35 implants) Excluded (n=0 subjects) Group A (Test) IMMEDIATE LOADING (n= 9 subjects, 17 implants) Group B (Control) EARLY LOADING (n= 12 subjects, 18 implants) 3-months follow-up (n= 9 subjects, 17 implants) 6-months follow-up (n= 9 subjects, 17 implants) 12-months follow-up (n= 9 subjects, 17 implants) 3-months follow-up (n= 12 subjects, 18 implants) 6-months follow-up (n= 11 subjects, 17 implants) 12-months follow-up (n= 10 subjects, 16 implants) Figure 2. Study sample flow-chart. 3.2. Demographic Data Twelve of the 21 patients (54.2%) were men and nine (45.8%) were women, with a mean age of 52.4 years (SD: 14.6 years). No statistically significant differences between groups were observed for these variables at baseline (p= 0.205 and p= 0.382 for Groups A and B, respectively). Regarding the smoking habit, five patients (20.8%) were smokers and 19 were not (79.2%). From a periodontal point of view, four patients were healthy (16.9%), and 17 were previously treated: five for gingivitis (20.8%), eight for mild chronic periodontitis (33.3%), six for moderate chronic periodontitis (25%), and one for severe chronic periodontitis (4.2%). Again, no statistically significant differences between Groups A and B were observed for any of the parameters at baseline (p= 1 and p= 0.470, respectively). 3.3. Interventions Nine patients (42.8%) and 17 implants (48.6%) were assigned to Group A and 12 patients (57.2%) and 18 implants (51.4%) to Group B (early loading). Fourteen implants (40%) were placed in the maxilla and 21 implants (60%) in the mandible. The locations of the implants by tooth site (FDI nomenclature) are displayed in Figure 3. The location more frequent was the left lower first molar. The diameters of the implants used were 3.5 mm (five implants), 4 mm (24 implants), and 4.5 mm (six implants), while the lengths were 8 mm (nine implants), 10 mm (22 implants), and 12 mm (four implants). Int. J. Environ. Res. Public Health 2021,18, 1223 9 of 19 Int. J. Environ. Res. Public Health 2021, 18, x FOR PEER REVIEW 9 of 19 Figure 3. Study sample flow-chart. Twenty-four implants (68.6%) were restored with single crowns, and 11 implants (31.4%) were part of partial fixed prostheses. Additionally, 52.9% and 47.1% of the implants were restored with single crowns and partial fixed prostheses in Group A, respectively, whereas in Group B, the distribution was 83.3% and 16.7%, respectively. Seven of the abutments placed were of 1 mm in height (five in Group A and two in Group B) and 28 were of 2 mm in height (12 in Group A and 16 in Group B). Regarding the bone quality, 20 implants (57.1%) were inserted into D2 bone (12 and 8 implants in Groups A and B, respectively) and 15 (49.2%) in D3 bone (5 and 10 implants in Groups A and B, respectively). The final IT at the implant placement is shown in Figure 4. No statistically significant differences between groups were observed in any of these variables (p > 0.05). Figure 4. Insertion torque at implant placement. 0 1 2 3 4 5 6 7 8 9 10 17 16 15 14 24 25 26 27 37 36 35 34 44 45 46 47 48 Nº of implants placed Tooth number Group A Group B 0 1 2 3 4 5 6 7 <151520253035>35 Nº of implants placed IT Group A Group B Figure 3. Study sample flow-chart. Twenty-four implants (68.6%) were restored with single crowns, and 11 implants (31.4%) were part of partial fixed prostheses. Additionally, 52.9% and 47.1% of the implants were restored with single crowns and partial fixed prostheses in Group A, respectively, whereas in Group B, the distribution was 83.3% and 16.7%, respectively. Seven of the abutments placed were of 1 mm in height (five in Group A and two in Group B) and 28 were of 2 mm in height (12 in Group A and 16 in Group B). Regarding the bone quality, 20 implants (57.1%) were inserted into D2 bone (12 and 8 implants in Groups A and B, respectively) and 15 (49.2%) in D3 bone (5 and 10 implants in Groups A and B, respectively). The final IT at the implant placement is shown in Figure 4 . No statistically significant differences between groups were observed in any of these variables (p> 0.05). Int. J. Environ. Res. Public Health 2021, 18, x FOR PEER REVIEW 9 of 19 Figure 3. Study sample flow-chart. Twenty-four implants (68.6%) were restored with single crowns, and 11 implants (31.4%) were part of partial fixed prostheses. Additionally, 52.9% and 47.1% of the implants were restored with single crowns and partial fixed prostheses in Group A, respectively, whereas in Group B, the distribution was 83.3% and 16.7%, respectively. Seven of the abutments placed were of 1 mm in height (five in Group A and two in Group B) and 28 were of 2 mm in height (12 in Group A and 16 in Group B). Regarding the bone quality, 20 implants (57.1%) were inserted into D2 bone (12 and 8 implants in Groups A and B, respectively) and 15 (49.2%) in D3 bone (5 and 10 implants in Groups A and B, respectively). The final IT at the implant placement is shown in Figure 4. No statistically significant differences between groups were observed in any of these variables (p > 0.05). Figure 4. Insertion torque at implant placement. 0 1 2 3 4 5 6 7 8 9 10 17 16 15 14 24 25 26 27 37 36 35 34 44 45 46 47 48 Nº of implants placed Tooth number Group A Group B 0 1 2 3 4 5 6 7 <151520253035>35 Nº of implants placed IT Group A Group B Figure 4. Insertion torque at implant placement. Int. J. Environ. Res. Public Health 2021,18, 1223 16 of 19 Institutional Review Board Statement: In order to enter the study, patients had to be able to understand the nature of the study, to sign an informed written consent form, and to be willing to attend the scheduled follow-up appointments. This study was conducted in accordance with the Declaration of Helsinki (1964) and its amendments for patients participating in clinical studies (Tokyo, 1975; Venice, 1983; Hong Kong, 1989; Somerset, 1996; Edinburgh, 2000). The study protocol was reviewed and approved by the ethics committee for clinical studies of the Universitat Internacional de Catalunya with reference number 500077. Informed Consent Statement: Informed consent was obtained from all subjects involved in the study. Data Availability Statement: The data presented in this study are available on request from the corresponding author. The data are not publicly available due to privacy. 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