Study design
This is a prospective equivalence randomized controlled trial with parallel groups blinded to the evaluators designed according to the SPIRIT statement [15] and reported following CONSORT guidelines [16]. The study protocol was in accordance the Helsinki Declaration of 1975, as revised in 2000, and was approved by the institutional ethics committee (Protocol 2.369.402), and the trial was registered prior to beginning (ReBEC TRIAL: RBR-35TNJ7). The study was conducted from June 2017 to June 2019.
Eligibility criteria
The adopted inclusion criteria were (1) At least 21 years old; (2) have at least one healed (≥ 6 months) tooth extraction site requiring rehabilitation; (3) adequate bone dimensions for implant placement without the need for guided bone regeneration procedures; (4) good general health, which allows for dental implant surgery; (5) availability for dental appointments at the institution; and (6) signed informed consent given by the patient.
Exclusion criteria are (1) any uncontrolled systemic diseases that prevent surgery for dental implant placement (e.g., hypertension, metabolic bone disease, diabetes); (2) need of tooth extraction in the region; (3) less than 6 months after tooth extraction; (4) need for guided bone regeneration or sinus lift for implant placement; and (5) history of radiation therapy in the head and neck.
Randomization and allocation concealment
Patients were included in the study after fulfilling all the eligibility criteria and signing the informed consent form for participation and permission to use obtained data for research purposes. Patients were randomly allocated according to the type of treatment (control group: conventional protocol for implant placement and intervention group: LLLT). The allocation process considered the implants as units and was performed using the Random Allocator software® in blocks of 6. To ensure concealment of randomization, consecutively numbered brown envelopes were used, with the following intervention draws: CONTROL and LLLT and only one researcher was involved in this process. The team of surgeons only became aware of the intervention at the time of surgery, when the envelope was opened by a blinded researcher.
Clinical procedures
All surgeries were carried out by the same group of surgeons who were specialists in oral implantology and performed all surgeries with the reflection of a flap and direct access to the bone tissue. Grade 4 titanium implants with conical geometry and morse taper connection (Alvim CM, Neodent Straumann, Curitiba, Brazil) were used in this study. Implant length and diameter were chosen based on bone availability assessed by cone-beam computed tomography.
The implants remained submerged during this period, and in the case of anterior implants, adhesively fixed bridges or removable prostheses were provided.
Study groups
Control
The implant placement protocol was made following all the steps indicated by the manufacturer and according to each case.
LLLT group
Low-level laser (Therapy XT, DMC Group, Sao Carlos, Brazil) [Gallium Aluminum Arsenide Diode (GaAlAs)] therapy with a wavelength of 808nm wavelength, a measured power output of 50mW and a spot size of 0.4cm2 were applied in six points (80 s each point of application; energy density=11 J/cm2) prior to the preparation of the bone bed and after suturing. The application points were divided into two points in the labial region where the implant would be placed (apical and cervical): two points in the lingual region (apical and cervical) and two points in the occlusal direction. The implant placement protocol followed all the steps indicated by the manufacturer, including the sequence of the drills. The total dosage including the laser application prior to the preparation of the bone bed and after the implant placement resulted in 66 J/cm2. This LLLT protocol was applied only in the dental implant placement session and is based on previous studies [11, 17].
Sample size estimation
The sample size was calculated using the inference for means tool comparing two means of the site www.stat.ubc.ca. An earlier study that assessed implant stability using the ISQ was used as the basis for this calculation [18] which reported a SD of 5.5 ISQ with expected group differences according to the bone type of 5.5 ISQ. The sample was calculated using a two-tailed comparison of two mean tests, with 90% power and 95% significance level, resulting in at least 22 implants per group. Considering possible losses, the number of included implants exceeded the sample size calculation.
Primary outcome—implant stability
The primary outcome was the implant stability quotient (ISQ), which was assessed by means of a resonance frequency analysis device (Osstell®, IntegrationDiagnostics AB, Gothenburg, Sweden). The device was handled by a single operator and was calibrated following the manufacturer’s instructions. The smartpegs were attached to the implants, and measurements were performed in triplicate at the following intervals: baseline (T0—implant placement) and at the abutment selection phase (4 to 6 months, Ta). Whenever inconsistency was observed during the ISQ assessment (e.g., lack of proper grip of the smartpegs, ISQ resulting in 0), they were excluded from the analysis. The value of insertion torque measured by the torque ratchets was also registered, in newton-centimeter (N.cm).
Secondary outcomes—radiographic marginal bone level changes
Digital periapical radiographs were made at implant placement (T0) and abutment selection phase (Ta) and were used to assess radiographical peri-implant alterations during the osseointegration period (4 to 6 months). Radiographs were performed with an intraoral X-ray positioning device by a single, previously calibrated, operator to ensure standardization. The digital files were then imported into software (ImageJ 1.47v, NIH, USA) to assess the differences in the distance between the implant platform and the alveolar bone crest in T0 and Ta. The distances were measured both in mesial and distal areas (Fig. 1) and were the average value was reported according to each implant [11]. All radiographs were assessed by a single researcher who was previously calibrated and blinded to the interventions.
Statistical analyses
Descriptive analyses with mean values and standard deviation (SD) or frequency distribution (%) were calculated for each variable. The statistical analysis was performed using Stata Software 14.2 (Stata Corporation, College Station, TX, USA). Outcome data were tested for normality by means of the Shapiro-Wilk test and found to be normally distributed. A descriptive analysis of the sample was performed, and bivariate analysis was performed to test the association between the intervention (LLLT or control) and studied outcomes using chi-square test. Possible influences of the intervention in ISQ and radiographical peri-implant alterations (Ta–T0) were tested using t test in terms of means comparisons and its variation. Implant was considered as an analysis unit. The statistical significance was set at the alpha level of 0.05.