Changes in implant stability using different site preparation techniques: Osseodensification drills versus piezoelectric surgery. A multi‐center prospective randomized controlled clinical trial

Abstract Introduction Implant stability is influenced by bone density, implant design, and site preparation characteristics. Piezoelectric implant site preparation (PISP) has been demonstrated to improve secondary stability compared with conventional drilling techniques. Osseodensification drills (OD) have been recently introduced to enhance both bone density and implant secondary stability. The objective of the present multi‐center prospective randomized controlled trial was to monitor implant stability changes over the first 90 days of healing after implant bed preparation with OD or PISP. Methods Each patient received two identical, adjacent or contralateral implants in the posterior maxilla. Following randomization, test sites were prepared with OD and control sites with PISP. Resonance frequency analysis was performed immediately after implant placement and after 7, 14, 21, 28, 60, and 90 days. Implants were then restored with single screw‐retained metal‐ceramic crowns and followed for 12 months after loading. Results Twenty‐seven patients (15 males and 12 females; mean age 63.0 ± 11.8 years) were included in final analysis. Each patient received two identical implants in the posterior maxilla (total = 54 implants). After 1 year of loading, 53 implants were satisfactorily in function (one failure in test group 28 days after placement). Mean peak insertion torque (40.7 ± 12.3 Ncm and 39.5 ± 10.2 Ncm in test and control group, respectively) and mean implant stability quotient (ISQ) value at baseline (71.3 ± 6.9 and 69.3 ± 7.6 in test and control group, respectively) showed no significant differences between the two groups. After an initial slight stability decrease, a shift to increasing ISQ values occurred after 14 days in control group and after 21 days in test group, but with no significant differences in ISQ values between the two groups during the first 90 days of healing. Conclusion No significant differences in either primary or secondary stability or implant survival rate after 1 year of loading were demonstrated between implants inserted into sites prepared with OD and PISP.

Conclusion: No significant differences in either primary or secondary stability or implant survival rate after 1 year of loading were demonstrated between implants inserted into sites prepared with OD and PISP.

K E Y W O R D S
implant site preparation, implant stability, osseodensification, piezosurgery, resonance frequency analysis What is known • Implant stability tends to decrease in the first weeks after implant placement due to periimplant bone remodeling following surgical trauma.
• Piezoelectric implant site preparation reduces stability decrease and favors earlier shifting from a decreasing to an increasing stability pattern, compared with conventional drilling.
• Osseodensification is a recently introduced, non-subtractive implant site preparation technique, aiming to increase both primary implant stability and percentage of bone at the implant surface, compared with conventional drilling.

What this study adds
• No significant differences in primary or secondary stability were demonstrated between implants inserted into sites prepared with osseodensification drills and sites prepared with piezoelectric surgery.

| INTRODUCTION
The early stage of bone repair response after dental implant insertion is a complex phenomenon in which the combined action of inflammatory cascade and immune system regulate new bone formation and neo-angiogenesis. 1 Among various factors influencing the healing process, excessive implant micro-movement may compromise osseointegration by producing large interfacial strains which, especially in low-quality bone, induce bone resorption and determine fibrous encapsulation of the fixture. [2][3][4] Therefore, one of the main goals in implant surgery is the achievement of adequate primary stability, which is strictly related to both bone quality and quantity, implant design, and implant site preparation characteristics. 5 Implant bed preparation should be performed with minimal trauma to the bone, avoiding overheating, and excessive compression of the cortical layer to prevent an excessive inflammatory phase potentially causing massive bone resorption, delayed healing or implant failure. [6][7][8] The progressive drilling technique has always been the conventional approach to implant osteotomy, using increasing-diameter twist drills rotating clockwise from 600 to 2000 rpm under copious irrigation.
Piezoelectric implant site preparation (PISP) has been proposed as an alternative technique to improve surgical control, safety, and bone healing response. Piezoelectric devices for bone surgery exploit ultrasonic vibrations of specific tips with three main features: (1) micrometric cutting with easy operative control, (2) selective cutting action on hard tissues, and (3) enhanced surgical visibility due to the cavitation effect of cooling saline solution. [9][10][11] Moreover, PISP seems to improve healing response resulting in a limited stability decrease during the first weeks after implant placement and in an earlier shifting from a decreasing to an increasing stability pattern, compared with conventional drilling. [12][13][14] Osseodensification drills (OD) is a recently introduced implant site preparation technique based on specially designed drills with large negative rake angles which, rotating counterclockwise, work as non-cutting edges to expand the implant site and compact bone at the osteotomy walls. 15 This non-subtractive approach aims to increase primary stability and maintain secondary stability of dental implants inserted into lowdensity bone compared with conventional drilling procedures. 16,17 Osseodensification protocols could help to obtain higher bone-toimplant contact and higher bone volume around implants. 18 However, most studies analyzing OD were conducted in vitro, ex vivo or on an animal model. Well-designed clinical trials on human subjects are necessary to fully elucidate the potential of this novel technique as an alternative to conventional implant site preparation in daily clinical practice. Therefore, the objective of the present randomized clinical trial was to compare stability changes of implants inserted into sites prepared using OD with implants inserted into sites prepared with PISP during the first 90 days of healing.

| Study design
The present study was a multi-center, randomized controlled clinical trial with simple randomization (1:1 allocation ratio), conducted by six experienced operators, who enrolled and treated patients from June 2020 to February 2021. The present trial was reported following CONsolidated Standards of Reporting Trials guidelines. The study protocol was designed in accordance with recommendations expressed in the Fortaleza revision (2013) of the Helsinki Declaration for investigations on human subjects. The study protocol was approved by the relevant ethical committee (Comitato Etico Regione Calabria-Sezione Area Centro n. 418/2020) and retrospectively recorded in a public registry of clinical trials (https://clinicaltrials.gov-NCT05410405). A calibration meeting was held among all the clinical centers prior to the study to discuss and standardize operative protocols. Each clinician received written instructions regarding collection of experimental parameters in order to obtain acceptable inter-examiner consistency.
All patients, after being thoroughly informed about the study protocol, the treatment plan with its alternatives and any potential risk related to the therapy, signed a written informed consent to participate in the study and authorized the use of their data for research purposes.
The present superiority trial tested the null hypothesis of no difference in primary stability between implants inserted into sites pre-

| Patient selection
All partially edentulous patients needing two adjacent or contralateral implants in pristine bone in the maxillary premolar area were screened at the clinical centers for potential participation in this trial.
General inclusion criteria were the following: (I) age >18 years; All patients received oral hygiene instruction and professional deplaquing 1 week prior to implant surgery.

| Surgical procedure
After raising a minimally invasive full-thickness flap under local anesthesia (articaine 4% with epinephrine 1:100000), an independent assessor opened the randomization sealed opaque envelope, and the assigned treatment was revealed to the surgeon. Test and control sites were prepared with the same final diameter for insertion of two identical implants (4.1 Â 8 mm or 4.1 Â 10 mm Volution, i-Res) during the same intervention. Selected implants present double-threaded conical shape, moderately rough surface treatment, platform-switched internal connection and machined implant neck.
These burs have a cutting chisel edge, a tapered shank and noncutting edges with four or more lands with a negative rake angle Sutures were removed 7 days after surgery. A blinded assessor measured ISQ following the previously described protocol at 7, 14, 21, 28, 60, and 90 days. Implants were evaluated at every visit for mobility, pain and signs of infection. At 4 months, implants were restored with screw-retained single metal-ceramic crowns and followed up for at least for 12 months after prosthetic loading.

| Predictor and outcome variables
The primary predictor variable was implant site preparation technique (OD vs PISP).

Secondary outcome measures:
• implant secondary stability pattern during the first 90 days after implant placement (ISQ); • implant survival after 1 year of prosthetic loading; • any complication or adverse event.

| Sample size and randomization
Sample size calculation was performed by means of a web-based software (https://app.sampsize.org.uk). As no previous studies comparing implant stability after OD or PISP are present in the literature, expected differences for sample size calculation were extrapolated from a recent randomized clinical trial comparing implant stability after OD or conventional drilling. 16 A sample of seven patients from each group was required to detect significant differences (confidence level 5% with a statistical power of 90%), with an expected difference in implant primary stability of 19.0 ± 8.4 Ncm.
An investigator (GT), not involved in selection or treatment of patients, arranged a computer-generated table using a balanced, randomly permuted block approach (www.random.org) to assign the two implants of each patient to the different groups (test and control).
Programmed implant sites assigned to test group had the implant bed prepared with OD, while implant sites assigned to control group had the osteotomy prepared with piezoelectric surgery. Randomization codes were enclosed in numbered, identical, sealed, opaque envelopes. Envelopes were opened after flap elevation. Treatment allocation was concealed to the two operators in charge of enrolling and treating the patients in this trial.

| Statistical analysis
An independent investigator (GT) performed data analysis using STATA 16.0 software (StataCorp). Implant stability was described at each single time point with a single ISQ value (mean of mesio-distal and bucco-palatal measurements).
The Shapiro-Wilk test was performed to assess data normality.
Intra-group differences were longitudinally analyzed using ANOVA and Scheffé tests, while inter-group comparisons were assessed using the two-sample Wilcoxon rank-sum test. The level of significance was set at a p-value lower than 0.05. Mean ISQ values at baseline (primary stability) were 71.3 ± 6.9 and 69.3 ± 7.6 in the test and control group, respectively. Two-sample Wilcoxon rank-sum test showed no significant difference between the two groups (p = 0.48).

| RESULTS
Implant stability decreased in both groups during the early healing period. The lowest peak was recorded 21 days after implant insertion for test group implants (mean ISQ 65.9 ± 7.8-7.6% decrease from mean primary stability) and 14 days after implant insertion for control group implants (mean ISQ 66.5 ± 6.7-4.9% decrease from mean primary stability).
After the third week, implant stability continued to increase constantly in both groups. However, only control group implants, at 60 and 90 days after implant insertion, showed ISQ values higher than at baseline (Figure 4).
Inter-group comparisons were performed using the two-sample Wilcoxon rank-sum test and showed no significant differences in ISQ values between the test and control group during the entire period of observation (Table 2).
Intra-group comparisons, analyzed using the Scheffé test, showed no significant differences in ISQ values at any time point both in test and in control group (p = 0.06 and p = 0.07, respectively).

| DISCUSSION
This multi-center randomized clinical trial aims to compare primary and secondary stability of implants inserted into sites prepared with OD and piezoelectric tips. Being the very first analysis comparing OD and PISP, it was possible to examine and discuss only the available evidence on OD and PISP resulting from studies in which conventional drilling was used as comparator.
The present study was designed to control variables influencing implant primary stability, in order to highlight the impact of surgical technique on the healing process. 21,22 Each patient received two identical implants (same macrotopography, microtopography, diameter, and length) in sites with similar bone quality (adjacent or contralateral teeth in the upper premolar area) and implant site preparation was performed by experienced operators who underwent a calibration session prior to the study.  This disagreement may be explained by inhomogeneity of implant design and differences in bone density among the cases of this latter study. 16 Both of these factors can heavily influence implant primary stability.
In the context of the inflammatory response to surgical trauma, analyses reporting similar survival rates for implants inserted with different implant site preparation techniques. 16,36,39,40 It must be underlined that the findings of this multi-center randomized clinical trial should be interpreted with caution due to some limitations of the present study. Factors including the limited numerosity of the sample, the selection of a specific surgical site (only lateral maxilla) and the use of a single implant type should be taken into consideration when generalizing the present results.
After analyzing data from the present study, it was not possible to reject the null hypothesis of this trial. In other words, no significant differences in implant stability were demonstrated between implants inserted into sites prepared with OD or piezoelectric surgery.

ACKNOWLEDGMENT
The present study was self-funded. The authors wish to thank Richard de Roeck for linguistic revision. Open Access Funding provided by Universita degli Studi di Roma La Sapienza within the CRUI-CARE Agreement.