Comparative evaluation of displacement of bisphosphonate-coated mini-implants in anterior en-masse retraction – A randomized control split-mouth clinical trial

INTRODUCTION

Mini-implants are widely recognized for their capacity to offer skeletal anchorage, as they proficiently stabilize the anchorage components and effectively impede the anterior displacement of molars.^[1] The long-term maintenance of the position of mini-implants under orthodontic loading in clinical practice has been a subject of ongoing debate. Multiple investigations have documented the phenomenon of mini-implant movement within the bone with the application of orthodontic forces, while maintaining the stability of the mini-implant.^[2-4] The migration of mini-implants has the potential to result in force decay and cause harm to critical structures such as the periodontium, nerves, and blood vessels.^[5,6] Different surface treatments of mini-implants have been documented to alter both the surface composition and topography, resulting in an augmentation of the implant’s surface roughness and area. Thus, this has the potential to improve the interaction between the implant and bone, resulting in greater initial stability of the implant in areas with limited bone quantity and/or quality.^[7,8]

Animal studies show that systemically administered bisphosphonates impede orthodontic tooth movement.^[9,10] These deleterious effects of bisphosphonates have been used to an advantage through localized administration to restrict (or) control the undesired tooth movement, without interfering with the desired tooth movement.^[11]

This study was done to identify if localized use of bisphosphonate as a mini-implant coating could reduce (a) mini-implant migration, (b) enhance implant stability, and (c) exhibit a favorable impact on the rate of tooth movement.

MATERIAL AND METHODS

Study design

This study followed a randomized split-mouth controlled clinical design. In each patient, one side of the maxillary arch was randomly allocated to receive a bisphosphonate-coated mini-implant, while the contralateral side received an uncoated mini-implant. Allocation of the intervention side (right or left) was performed with equal probability. Blinding was maintained for outcome assessment, wherein investigators evaluating cone beam computed tomography (CBCT) and digital model measurements were unaware of the intervention allocation. Blinding was maintained for outcome assessment, where investigators evaluating CBCT and digital model measurements were unaware of the group allocation. The research conducted was a single-blinded randomized controlled split-mouth clinical experiment, which received approval from the Institutional Ethical Review Board (SRB/ SDC/ORTHO-1906/21/TH-024). Before participating in the experiment, patients were provided with a comprehensive explanation of the proposed treatment and were required to provide informed consent. The trial was officially registered with the Clinical Trial Registry-India (CTRI/2021/11/038094). A sample size calculation was performed to achieve a statistical power of 95%, utilizing the findings from the anchorage study conducted by Liou et al. This calculation was carried out using G Power analysis software.^[2] A total sample size of 15 was obtained on calculation, and an additional 3 subjects were selected to compensate for any sample attrition. The participants were randomly assigned to either the intervention group, which received bisphosphonate-coated mini-implants, or the control group, which received uncoated mini-implants. The allocation was done with equal probability for both the right and left sides in the upper arch. The participant flow in the study is indicated in the CONSORT flow chart [Figure 1]. Inclusion criteria used were (a) patients requiring orthodontic treatment aged between 15 and 40 years, (b) upper premolar extraction with maximum anchorage, (c) crowding ≤4 mm, (d) dentoalveolar proclination, (e) no systemic or metabolic diseases or periodontal problems, and (f) healthy individuals not under medication for any other ailments.

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Figure 1: Consort flow chart.

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Evaluation of mini-implant displacement

The CBCT scans of the midface were performed immediately after the mini-implant was placed and again after 6 months (KODAK CARESTREAM CS 9600-16 X 17 FOV CBCT). Digital imaging and communications in medicine format was used to save the CBCT data.

Reconstructing the core three-dimensional (3D) anthropometric models (alveolar bone, teeth, and mini-implant) was done with the help of the materialise interactive medical image control system (MIMICS) medical imaging density segmentation software. By applying a thresholding method based on Hounsfield units, the MIMICS program was able to distinguish between tooth, bone, and mini-implant structures. The Standard Tessellation Language file format was used to export all 3D models.

The base of the orbit was assumed to be unchanged in every CBCT and used for superimposition. In the MIMICS software, 4 registration points were used to superimpose the models. Pre- and post-treatment CBCT scans were superimposed using four stable craniofacial landmarks: the base of the orbit, bilateral infraorbital rims, the anterior wall of the maxillary sinus, and the nasal floor. These structures are minimally affected by orthodontic treatment and allow reliable three-dimensional registration for assessing mini-implant displacement. Mini-implant deviations were assessed at the head and apex. The x, y, and z axes were reconfigured by the MIMICS program to signify bucco-palatal, distomesial, and vertical orientations, respectively. By comparing the pre- and post-treatment 3D coordinate values of the same two spots, we were able to derive the drift distances in all three directions [Figure 2]. Slice thickness used for CBCT was 0.3 mm. To assess reliability, 10% of measurements were repeated after 2 weeks, and intraclass correlation coefficients were calculated, showing values above 0.9.

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Figure 2: Three-dimensional superimposition of pre- and post-treatment models to measure miniimplant displacement. The distance between pre- and post-treatment models was measured at both the head and apex of the mini-implant using the difference in 3D coordinate values between the pre- and post-treatment positions along the X, Y, and Z axis. (a) Overall lateral view of the registered maxillary model showing the global coordinate system and reference landmarks. The blue arrow indicates the direction of displacement along the bucco-palatal (X) axis, the green arrow along the mesio-distal (Y) axis, and the brown arrow along the vertical (Z) axis. Green circles labelled S, A, and L represent the Superior, Anterior, and Lateral orientations respectively. The grey circle labelled W indicates the reference landmark used for registration during superimposition. (b) Close-up view of the head of the mini-implant. The red circle indicates the reference point used for displacement measurement at the implant head. (c) Close-up view of the apex of the mini-implant. The red oval indicates the reference point used for displacement measurement at the implant apex. The blue highlighted line outlines the superimposed contour and carries no statistical significance (i.e., it is a visual reference only).

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Evaluation of anterior retraction

Patients were scanned in 3D using an intraoral scanner (intraoral scanner) and a 3D reverse modeling software program. The amount of space closure in millimeters at 3 months and 6 months of retraction was recorded using digital models in STL format. Retraction rate and mini-implant migration (through CBCT) were assessed at three and 6 months to capture meaningful treatment phases while minimizing radiation and avoiding short-term fluctuations from elastomeric force decay. The distance between perpendicular lines drawn from the mid palatal line to the distal surface of the canine and to the mesial surface of the second premolar was used to determine the extraction space in the digital models [Figure 3].

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Figure 3: Measurement of the amount of space closure. The horizontal arrows represent the distance between perpendicular lines drawn from the midpalatal line to the distal surface of the canine and the mesial surface of the second premolar.

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RESULTS

Normality of the data was tested using the Shapiro–Wilk and Kolmogorov–Smirnov tests. As the data were normally distributed, parametric tests were opted.

Mini-implant displacement

Independent “t”-test and paired t-test are described in [Tables 1 and 2]. The mean head and apex mini-implant displacement in X, Y, and Z planes in bisphosphonate-coated and uncoated mini-implant groups are represented in [Figures 4 and 5], respectively.

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Figure 4: The bar graph represents the mean head mini- implant displacement in X, Y, and Z planes in bisphosphonate-coated and uncoated mini-implant groups.

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Figure 5: The bar graph represents the mean apex mini- implant displacement in X, Y, and Z planes in bisphosphonate-coated and uncoated mini-implant groups.

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Table 1: Comparison of bisphosphonate-coated and uncoated mini-implant head and apex position in X, Y, and Z planes between the two groups and within each group at baseline and 6 months.

Parameters	Groups	Baseline (Mean±SD)	6 Months (Mean±SD)	#p-value
Head X axis	Coated	60.21±5.96	60.18±5.95	0.058
	Uncoated	60.29±5.28	60.27±5.29	0.005*
	##p-value	0.917	0.904
Apex X axis	Coated	60.88±5.35	60.84±5.35	0.117
	Uncoated	60.16±5.11	60.13±5.12	0.017*
	##p-value	0.2	0.205
Head Y axis	Coated	39.53±5.31	39.10±5.66	0.06
	Uncoated	41.36±3.98	39.24±4.02	0.0*
	##p value	0.072	0.831
Apex Y axis	Coated	39.94±4.40	39.71±4.55	0.053
	Uncoated	41.72±3.86	39.91±4	0.0*
	##p value	0.053	0.749
Head Z axis	Coated	33.26±1.96	33.25±1.96	0.109
	Uncoated	33.40±1.6	33.29±1.61	0.153
	##p value	0.817	0.954
Apex Z axis	Coated	33.47±1.48	33.47±1.48	0.154
	Uncoated	33.68±1.72	33.59±1.74	0.151
	##p-value	0.762	0.857

SD: Standard deviation, ^#:indicates intra-group comparison using paired t-test, ^##indicates inter-group comparison using independent t-test, *indicates statistically significant difference (p < 0.05)

Table 2: Comparison of the bisphosphonate-coated and uncoated mini-implant head and apex displacement in X, Y, and Z planes between the two groups.

Parameter	Group	Mean	Standard deviation	p-value
Head X-axis deviation	Coated	0.034	0.064	0.489
	Uncoated	0.021	0.025
Apex X-axis deviation	Coated	0.039	0.090	0.664
	Uncoated	0.027	0.039
Head Y-axis deviation	Coated	0.175	0.108	0.00*
	Uncoated	0.802	0.266
Apex Y-axis deviation	Coated	0.072	0.067	0.00*
	Uncoated	0.656	0.253
Head Z-axis deviation	Coated	0.005	0.012	0.116
	Uncoated	0.128	0.292
Apex Y-axis deviation	Coated	0.003	0.008	0.127
	Uncoated	0.096	0.222

Statistical significance level set at p< 0.05, *indicates statistically significant difference (p< 0.05)

Rate of anterior retraction

The results of independent “t”-test and paired “t”-test comparing the amount of space closure between bisphosphonate-coated and uncoated mini-implant groups at the two time intervals are described in [Table 3 and Figure 6].

Table 3: Independent sample “t” test comparing the amount of space closure among bisphosphonate-coated and uncoated mini-implants.

Parameters	Groups	Baseline (Mean±SD)	3 Months (Mean±SD)	6 Months (Mean±SD)	p-value
Retraction rate	Coated	6.26±0.55	2.5±1.0	5.8±0.81	0.00*
	Uncoated	6.02±0.611	1.6±0.73	4.8±1.01	0.00*
	p-value	0.28	0.009*	0.007*

The p-value indicates that there was a significant difference between the intervention and control groups at all time intervals, SD: Standard deviation, *indicates statistically significant difference (p< 0.05)

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Figure 6: The bar graph represents the mean rate of space closure in the bisphosphonate-coated and uncoated mini-implant group at three different time intervals.

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DISCUSSION

This study demonstrates that bisphosphonate-coated mini-implants exhibit reduced displacement in the mesio-distal plane and an enhanced rate of anterior retraction. These outcomes suggest that the coating may improve primary stability and anchorage preservation. Previous animal studies have shown that local bisphosphonate application can reduce tooth movement at the application site. Our findings align with prosthodontic and orthopedic research showing increased implant stability with bisphosphonate-loaded mesoporous coatings.

In our clinical setting, coated implants experienced less mesial migration, likely due to improved osseointegration. Uncoated implants showed measurable displacement that could compromise anchorage.

However, several limitations exist: First, periodontal health was not assessed throughout the study, which may influence implant displacement. Second, although CBCT imaging involves radiation exposure, it was justified in this study to enable accurate three-dimensional superimposition using stable craniofacial landmarks for assessment of mini-implant displacement. Third, our conclusions should be interpreted cautiously, given measurement limitations.

Past literature on surface modifications such as silver or hydroxyapatite coatings has shown mixed outcomes. Further long-term, controlled studies are needed to assess clinical significance and optimal coating protocols.

Several studies have consistently demonstrated that all types of bisphosphonates administered locally inhibited orthodontic tooth movement at the site of application in animal studies.^[16-19] The addition of a mesoporous titanium dioxide layer that has been dip-coated with bisphosphonate has been shown to increase implant stability in several types of prosthodontic and orthopedic implants.^[20,21] In this study, we employed this novel approach to form a mesoporous titanium dioxide layer on the mini-implant which is dip-coated with bisphosphonate. This modification was implemented to enhance the durability of the bisphosphonate during the self-drilling process. However, the detailed characterization of this modified coating is not within the scope of the present publication. Animal studies using bisphosphonate-loaded mesoporous coatings have demonstrated improved osseointegration, increased implant fixation, and reduced implant migration without systemic drug effects.^[20,21]

After redefining the coordinate system and registering the pre- and post-treatment 3D models, the miniscrews’ 3D displacements could be calculated. The findings of the study indicated that the mini-implant exhibited displacement in the course of the force applied, whereas any displacements observed in the bucco-palatal or vertical planes were deemed insignificant. There was a significant amount of mini-implant displacement in the Y plane in the uncoated mini-implant group. While the bisphosphonate-coated mini-implant showed no significant difference, suggesting prevention of mini-implant migration. Mini-implants measuring 2×7 mm were surgically implanted into the zygomatic crest in an experiment done by Liou et al. Mini-implant tail exhibited inclination, measuring 1 mm in both millimeters in backward and forward directions. Extrusion was used on the mini-implants, which caused them to lean forward by around 1 mm.^[2] Using 451 oblique lateral cephalometric radiographs, Santiago et al. found no movement in the locations of mini-implants after canine retraction.^[22] Both studies by Liou et al. 2004^[2] and Santiago et al. 2009^[22] used two-dimensional radiographs, which is a questionable assessment method, in addition to having certain well-known limitations. El-Beialy et al. found mean mini-implant migration of 1.08 and 0.82 mm in the head and tail, respectively, while evaluating canine retraction using computed tomography (CT).^[23,24] Displacement ranged from 0.17 mm at the head to 4.12 mm at the tail, with the minimum being 0.34 mm. Head mean displacements of 0.23 and 0.91 mm apically were found in a previous work by Liu et al., which were consistent with our own.^[24]

Regarding the retraction rate, bisphosphonate-coated mini-implants showed a significantly greater amount of space closure, suggesting enhanced efficiency of anterior retraction due to improved anchorage control. To our knowledge, this is the first randomized split-mouth clinical trial evaluating the effect of bisphosphonate-coated mini-implants on both mini-implant displacement and the rate of en masse anterior retraction. In keeping with the MBT treatment paradigm, the rate of tooth movement was used to determine the efficacy of mass retraction rather than the retraction of individual canines. Given that the experiment was completed over the course of the full retraction period, the en-masse retraction model is preferred over the two-step retraction model, which takes more time for space closure.^[15,25] Our present findings showed that there was a significant difference in the rate of space closure between the bisphosphonate-coated and uncoated groups (p < 0.05). The mean rate of space closure in the bisphosphonate-coated mini-implant group was 2.5 ± 1.0 mm at the end of 3 months and 5.8 ± 0.81 mm at the end of 6 months. The mean rate of space closure in the uncoated mini-implant group was 1.6 ± 0.73 mm at the end of 3 months and 4.8 ± 1.01 mm at the end of 6 months. The amount of space closure on the side of the bisphosphonate-coated mini-implants was significantly greater compared to the space closure on the side with the uncoated implants, showing that the reduction of implant migration has a positive effect on the rate of space closure. Since different studies use different methods of evaluation, we cannot make any direct comparisons regarding the space closure rate results. In the study conducted by Al-Sibaie and Hajeer, individuals requiring maximum anchorage experienced an average retraction rate of 0.35 mm per month over a period of 12.9 months. This investigation aimed to assess the efficacy of en-masse retraction utilizing mini-implant anchorage with individual canine retraction employing conventional anchorage.^[25] When Basha et al. compared traditional retraction to retraction utilizing orthodontic micro-implants, they found that the latter took 6.0 months to achieve a mean retraction rate of 0.85 mm/month.^[15] The mean retraction rates obtained in our study at the end of 3 and 6 months showed that the amount of space closure was not consistent each month. In this study, standardized hooks with an average height of 7–8 mm were used which were nearly at the level of the height of the implant placement. In this study, the significant difference in migration of the coated and uncoated implants was in the mesio-distal direction which is along the line of action of the force. It is expected that altering the line of action of the force, either by adjusting the height of the retraction hooks or by modifying the placement height of the implants, may potentially result in a change in the migration direction of the implant. Nevertheless, a comprehensive assessment of this matter would necessitate additional clinical research.

CONCLUSION

Based on the findings of the study, it was observed that the application of a bisphosphonate coating on mini-implants effectively reduced their migration in the mesio-distal direction when used for en-masse retraction purposes. In addition, it was found that bisphosphonate-coated mini-implants exhibited a significantly higher rate of space closure, indicating a greater retraction rate compared to the uncoated implant side. These findings indicate that decreasing micro-implant migration during mass anterior retraction can significantly increase the rate of gap closure.