How Does Orthodontic Mini-Implant Thread Minidesign Influence the Stability?—Systematic Review with Meta-Analysis

Background: Clinical guidelines are lacking for the use of orthodontic mini-implants (OMIs) in terms of scientific evidence referring to the choice of proper mini-design. Thus, the present study aimed to investigate to what extent orthodontic mini-implant thread design influences its stability. Methods: Search was conducted in five search engines on 10 May. Quality assessment was performed using study type specific scales. Whenever possible, meta-analysis was performed. Results: The search strategy identified 118 potential articles. Twenty papers were subjected to qualitative analysis and data from 8 papers—to meta-analysis. Studies included were characterized by high or medium quality. Four studies were considered as low quality. No clinical studies considering the number of threads, threads depth, or TSF have been found in the literature. Conclusions: Minidesign of OMIs seems to influence their stability in the bone. Thread pitch seems to be of special importance for OMIs retention—the more dense thread—the better stability. Thread depth seems to be of low importance for OMIs stability. There is no clear scientific evidence for optimal thread shape factor. Studies present in the literature vary greatly in study design and results reporting. Research received no external funding. Study protocol number in PROSPERO database: CRD42022340970.


Introduction
A few decades ago, introducing skeletal anchorage revolutionized orthodontic treatment dogma and significantly broadened therapeutic possibilities [1]. With the use of orthodontic mini-implants (OMIs), it is possible to achieve direct or indirect anchorage for a specific tooth movement as well as skeletal anchorage for facemasks or hybrid maxillary expansion appliances [2,3]. Thus, the possibility of orthodontic treatment is increased, less patient's compliance may be required to obtain a treatment goal and the need for orthognathic surgery may be reduced [4]. The increasing popularity of orthodontic OMIs is due to a simplicity of the surgical technique, easy acceptance of OMIs by patients, and low cost regarding the effect achieved [5]. Innovative materials and technologies to improve implants primary stability are an intense research topic in dentistry [6]. The use of skeletal anchorage has been the subject of above 1500 scientific papers published in the recent two decades [7], and manufacturers provide more and more innovative solutions. As a result, multiple systematic reviews regarding the influence of OMIs geometry on treatment success rate can be found, generalizing and assessing multiple factors [7][8][9][10][11] and thematically specific [12,13]. Clinical guidelines can be found in the literature referring to the influence of macrodesign of OMIs on success rate.

Eligibility Criteria
For the present systematic review, the following inclusion criteria were applied: Type of study: prospective clinical and animal studies, in-vitro studies, finite element analysis. Results of the study: pull-out strength, removal torque Object of the study: evaluation of the influence of orthodontic mini-implant design on its stability Subject of the study: orthodontic mini-implants The following exclusion criteria were as follows: Studies not referring to the design of orthodontic mini-implants, in-vivo retrospective studies, ex-vivo studies not using finite element analysis, case reports, reviews, authors' opinions, conference reports, studies lacking effective statistical analysis, studies considering the type of material used, studies evaluating the effectiveness of specific orthodontic movement with the use of skeletal anchorage, studies evaluating the influence of biological factors on skeletal anchorage effectiveness. No language restriction was applied.

Quality Assessment
According to the PRISMA statements evaluation of methodological quality must be performed in order to properly assess the strength of evidence provided by the included studies, as methodological flaws can result in biases [14].
Due to a wide range of types of studies that were finally included in this review (animal studies, finite element analysis, in-vitro studies) the authors decided to use three types of specific quality assessment tools-SYRCLE for animal studies [19], Methodological Quality Assessment of Single-Subject Finite Element Analysis Used in Computational Orthopedics for finite element analysis (MQSSFE) [20] and QUIN for in-vitro studies [21]. While assessing the studies according to the SYRACLE assessment tool, 10 different types of bias were evaluated that possibly could have occurred. Two authors independently assessed the risk of bias by scoring "+" if there was no risk of bias in the assessed category, "−" if the possibility of bias occurred, and "?" when it was impossible to assess wherever it occurred or not. MQSSFE consists of 37 questions and is evaluated independently by two researchers. If there was no risk of bias, "YES" was entered, and "No" if there was a risk of bias. If the researchers disagree on a point in the checklist, a half point is issued for a given checklist question. In the case of the QUIN assessment tool, two independent authors (MJ and MM) evaluated independently each of the 12 criteria as adequately specified = 2 points, inadequately specified = 1 point, not specified = 0 points, and not applicable = exclude criteria from the calculation. Then, the scores were summarized to obtain a total score for a particular in vitro study. The scores thus obtained were used to grade the in vitro study as high, medium, or low risk (>70% = low risk of bias, 50% to 70% = medium risk of bias, and <50% = high risk of bias).

Meta-Analysis
Meta-analysis was performed with the R statistical software (R Foundation, Vienna, Austria), ver.4.1.2 [22] using a random-effect model via metafor R package [23], with Mean Differences (MD) and 95% confidence intervals (95% CI) being calculated as effect estimates. Heterogeneity was assessed quantitatively using I2-statistics and Cochran's Q [24]. The results were considered statistically significant at p < 0.05. Publication bias was estimated using a funnel plot.

Results of the Search
The search strategy identified 118 potential articles: 20 from PubMed, 45 from PubMed Central, 23 from Scopus, 18 from Web of Science, and 12 from Embase. At the beginning of the analysis, 22 duplicates were removed, and 96 titles and abstracts were analyzed. Subsequently, 61 papers were excluded because they did not meet the inclusion criteria (completely different subject; studies regarding other factors affecting MI stability, systematic reviews). Of the remaining 34 papers, only 1 could not be retrieved. Fourteen studies had to be excluded, because they were not relevant to the subject of the study (discussing a different topic, not including taper design into the evaluated factors, retrospective analysis, or in one study-lack of an effective statistical analysis). Thus, finally, 20 papers were subjected to qualitative analysis, and data from 6 papers were subjected to meta-analysis. Two in-vitro studies did not provide exact resulting values, giving only the relationships between the tested parameters. The latter five studies did not provide sufficient data. The whole procedure is described in Prisma 2020 Flow Diagram (Figure 1. Flow diagram) The main characteristics of each included study are presented in Table 1.  [27] 3D finite element analysis Four types of titanium grade V OMIs with different design parameters Screw type 1 had a 0.4-mm thread depth and a 7 tapered core at the 5 uppermost threads. Screw type 2 had a 0.4-mm thread depth and a 0 tapered core (cylindrical core).
Screw type 3 had a 0.4-mm thread depth and a 7 tapered core at the 3 uppermost threads. Screw type 4 had a 0.32-mm thread depth and a 7 tapered core at the 3 uppermost threads. To evaluate the effect of thread depth on primary stability, the thread depths of the mini-implants were set at 0. 16 Mini-implants with greater thread depths, smaller tapers, and shorter taper lengths generated higher maximum stresses on the bone and thread elements. These mini-implants had larger relative displacements, as well. Pullout resistance increased as thread depth increased from 0.16 to 0.32 mm. However, the pullout resistance decreased as thread depth exceeded 0.32 mm. Pullout resistance also decreased as taper degrees and taper lengths decreased. High stresses were distributed on the uppermost threads at the neck of the mini-implants close to the bone margin in all conditions. Maximum insertion torque was observed in the first and the third OMIs. The conical section improved the initial stability by creating compressive stress and additional friction in the surrounding bone. With increasing each millimeter and each degree in the conical section's length and angle, the lateral displacement decreased by 2.3 and 1.8mm, respectively. The length and angle of the non-threaded part does not significantly control the lateral displacement. The higher the pitch of the mini-implant, the higher the lateral displacement (increases by 1.3-2.2mm). It is necessary to consider the minimum possible value for the pitch according to the threads' shape. The removal torque of the taper shape was lower than the removal of torque of the dual-thread shape. The dual-thread shape showed a low insertion torque and a gentle increase of insertion torque. The dual-thread shape also showed a higher removal torque on the broad range than the cylindrical and taper shapes. Long mini-implants need higher insertion torque than short mini-implants. Dual-thread shape may need improvement for reducing the long insertion time to decrease the stress to the surrounding tissue.
Gracco et al. 2012 [32] In-vitro study 35 OMIs (7 in each group) five different designs in thread shape (reverse buttress, buttress, 75 • joint profile with flutes, trapezoidal and rounded) Pull out strength form artificial bone block from polyurethane foam block

Pull out strength [N]
The thread shape influenced the resistance to pullout and, therefore, the primary stability of miniscrews. The buttress reverse thread shape (about 192 There is a direct positive correlation between the increase in TSF (depth/pitch), the miniscrew pull-out strength and maximum insertion torque The mini-implants with a shorter pitch distance and an insertion angle of 30 • presented a better primary stability (torque) in artificial bone of a higher density. The mini-implants with a longer pitch distance and an insertion angle of 45 • were found to be more stable in artificial bone of lower density, when performing evaluation with the Periotest. The strain between the single-thread and dual-thread type miniscrews was similar at a cortical bone thickness of 1.0mm, but the discrepancy between miniscrew types widened to >10,000 µstrain with increasing cortical bone thicknesses. Self-drilling dual-thread miniscrews provide better initial mechanical stability, but their design may cause excessive strain that is over the physiological bone remodeling level (>1mm cortical bone) at the bone-implant interface of thick cortical bone layers. Larger pitch width, flank, thread angle, apical face angle, and/or lead angle led to a higher primary stability, while a smaller thread shape factor (depth/width) improved primary stability.
Katić et al. 2017 [39] In-vitro study Orthoimplant type with a larger diameter, smaller pitch and shorter taper length has a better primary stability, and lower stresses within the mini-implants and surrounding comparing to other groups tested. The favorable insertion angulation found was 90 • , as it provides better primary stability and low stresses in the mini-implant and surrounding bone under orthodontic loading. The design of the mini-implant affects the insertion torque and pulling force. The bone quality at the implant insertion point is important for primary stability; thus, the increase in the cortical bone thickness significantly increases the pulling force.

Quality Assessment
The results of the assessment are presented in Tables 2-4.      From the quality analysis performed, it can be concluded that 1 animal study [25] and 2 finite element analyses are at high risk of bias [27,29], and most of the in-vitro studies are at medium bias risk. Two finite element analyses and two in-vitro studies should be considered at low risk [28,30,35,39].

Meta-Analysis
Even if studies included in the review may seem possible to be included in meta-analysis they had to be excluded since they presented only correlations between the examined factors, not specific values. [35,41] In the other study there was a different research material used (human cadaver heads). [42] This is a significant loss for the study, because the studies mentioned were designed similarly, and the number of OMIs tested was significant. Each of the included studies was based on the same polyurethane foam block in case of artificial bone and in case of animal bone-on similar species of animals in similar conditions on similar insertion depth. The data used to perform meta-analysis are summarized in Table 5. N1/N2 are numbers of OMIs in the left/right part of the table. Negative values of MD mean smaller dimensions of a given diameter in OMIs in the left part of the data table. Table 5. Meta-analysis of in-vitro studies of peak load for pull-out strength-artificial bone model.

Dimension of Thread Pitch
[mm]

Dimension of Thread Pitch
[mm]

Meta-Analysis of In-Vitro Studies of Peak Load for Pull-Out Strength Regarding Thread Depth (A) artificial bone model
There is small insignificant (p = 0.117) negative effect size. Study results are inconsistent-heterogeneity is significant (p < 0.001), and more than 98% of the variability comes from heterogeneity ( Figure 6). The funnel plot confirms high heterogeneity, asymmetry suggests some publication bias (Figure 7). There is small insignificant (p = 0.117) negative effect size. Study resul inconsistent-heterogeneity is significant (p < 0.001), and more than 98% of the vari comes from heterogeneity ( Figure 6). The funnel plot confirms high heteroge asymmetry suggests some publication bias (Figure 7).

(B) animal bone model
There is small insignificant (p = 0.243) negative effect size. Study res inconsistent-heterogeneity is significant (p = 0.001), and more than 76% of the va comes from heterogeneity ( Figure 8). The funnel plot does not suggest publicat ( Figure 9). There is small insignificant (p = 0.243) negative effect size. Study results are inconsistent-heterogeneity is significant (p = 0.001), and more than 76% of the variability comes from heterogeneity ( Figure 8). The funnel plot does not suggest publication bias (Figure 9).

(B) animal bone model
There is small insignificant (p = 0.243) negative effect size. Study re inconsistent-heterogeneity is significant (p = 0.001), and more than 76% of the v comes from heterogeneity ( Figure 8). The funnel plot does not suggest publica ( Figure 9).   [38,44].
There is small insignificant (p = 0.243) negative effect size. Study inconsistent-heterogeneity is significant (p = 0.001), and more than 76% of the comes from heterogeneity (Figure 8). The funnel plot does not suggest publ ( Figure 9).  There is small significant (p = 0.027) negative effect size. Study results are inconsistent-heterogeneity is significant (p < 0.001), and more than 97% of the variability comes from heterogeneity ( Figure 10). The funnel plot confirms high heterogeneity, asymmetry suggests some publication bias ( Figure 11).

Thread Shape Factor (A) artificial bone model
There is small significant (p = 0.027) negative effect size. Study results are inconsistent-heterogeneity is significant (p < 0.001), and more than 97% of the variability comes from heterogeneity ( Figure 10). The funnel plot confirms high heterogeneity, asymmetry suggests some publication bias ( Figure 11).

(B) animal bone model
There is small significant (p = 0.033) positive effect size. Study results are inconsistent-heterogeneity is significant (p = 0.030), and more than 67% of the variability comes from heterogeneity ( Figure 12). The funnel plot confirms high heterogeneity, asymmetry suggests some publication bias ( Figure 13). Figure 10. Forest plot for evalutaion of thread shape factor infulence on pull-out strentght in artifical bone model studies [33,34,41].
(A) artificial bone model There is small significant (p = 0.027) negative effect size. Study results are inconsistent-heterogeneity is significant (p < 0.001), and more than 97% of the variability comes from heterogeneity ( Figure 10). The funnel plot confirms high heterogeneity, asymmetry suggests some publication bias ( Figure 11).

(B) animal bone model
There is small significant (p = 0.033) positive effect size. Study results are inconsistent-heterogeneity is significant (p = 0.030), and more than 67% of the variability comes from heterogeneity ( Figure 12). The funnel plot confirms high heterogeneity, asymmetry suggests some publication bias ( Figure 13). There is small significant (p = 0.033) positive effect size. Study results are inconsistent-heterogeneity is significant (p = 0.030), and more than 67% of the variability comes from heterogeneity ( Figure 12). The funnel plot confirms high heterogeneity, asymmetry suggests some publication bias ( Figure 13).   Forest plot for evalutaion of thread shape factor infulence on pull-out strentght in animal bone model studies [38,44].

Discussion
Although there are many systematic reviews concerning different geometric characteristics of OMIs, the present paper is the first referring to their minidesign. First of all, it should be pointed out that no clinical study considering the number of threads, threads depth, or TSF has been found in the literature. The only papers found correlating the minidesign of OMIs to their physical characteristics are animal studies, in-vitro studies, and 3D finite element analysis. Thus, the authors of the present systematic review must have based their clinical recommendations on indirect evidence.
Moreover, there is a well-designed split-mouth study discussing other factors, that may influence OMI stability, for instance, chemical treatment of screw surfaces [44]. Another study shows that increasing penetration depth of OMIs results in better retention [45], whereas increased abutment head distance from cortical plate leads to decreased retention [45]. Moreover, TADs inclination angle of 60 to 70° to the cortical plate was reported as the most retentive insertion angle [46,47]. Insertion at a right angle or more oblique from the line of force reduces retention of TADs.
In the present review with meta-analysis, the studies included are characterized mainly by the medium quality of evidence. This may result from the types of studies included. In the studies included the researchers had a possibility to carefully design every step of a trial, including the study material, procedure, and examination, leaving less possibility of biases than in clinical trials, where the subjects may much more frequently behave differently than planned. The shortcomings of in-vitro studies included were mainly

Discussion
Although there are many systematic reviews concerning different geometric characteristics of OMIs, the present paper is the first referring to their minidesign. First of all, it should be pointed out that no clinical study considering the number of threads, threads depth, or TSF has been found in the literature. The only papers found correlating the minidesign of OMIs to their physical characteristics are animal studies, in-vitro studies, and 3D finite element analysis. Thus, the authors of the present systematic review must have based their clinical recommendations on indirect evidence.
Moreover, there is a well-designed split-mouth study discussing other factors, that may influence OMI stability, for instance, chemical treatment of screw surfaces [44]. Another study shows that increasing penetration depth of OMIs results in better retention [45], whereas increased abutment head distance from cortical plate leads to decreased retention [45]. Moreover, TADs inclination angle of 60 to 70 • to the cortical plate was reported as the most retentive insertion angle [46,47]. Insertion at a right angle or more oblique from the line of force reduces retention of TADs.
In the present review with meta-analysis, the studies included are characterized mainly by the medium quality of evidence. This may result from the types of studies included. In the studies included the researchers had a possibility to carefully design every step of a trial, including the study material, procedure, and examination, leaving less possibility of biases than in clinical trials, where the subjects may much more frequently behave differently than planned. The shortcomings of in-vitro studies included were mainly lack of sample size calculation, randomization, and blinding of the results evaluation. Some of the studies have only discussed the proportions of the ongoing phenomena, without providing specific values. The present meta-analysis provides very interesting results of the calculated effect. The high heterogeneity could not have been disclosed. Various implants were tested in different environments, including a digital analysis environment. A similar problem was observed in another recently published meta-analysis on OMIs [48]. Therefore, the studies included were classified according to their design in terms of the environment. Moreover, studies included had to meet the requirement of including minimum of three study groups of subjects for comparison (required for meta-analysis). It is surprising that all the studies carried out on the artificial bone model are characterized by an enormous heterogeneity, and all funnel plots are indicating publication bias. On the contrary, studies performed on the animal model are characterized by lower I 2 and funnel plots do not indicate bias. Additionally, the results of artificial bone model studies are in contradiction to studies performed on an animal model. Both studies on the artificial bone model and those on the animal model indicate that smaller thread pitch is correlated with higher pull-out strength values. However, the results in the animal model are more homogeneous.
Referring to studies included only in the systematic review, Topcuoglu et al. found that a smaller thread pitch is correlated with higher removal torque values [25]. A smaller thread pitch prevents lateral displacement when orthodontic force is exerted [30]. The same was indicated by Budsabong et al. in their in-vitro study [43]. This fact additionally strengthens the result of the meta-analysis. Dastenaei et al. in a 3D finite element analysis point out that thread pitch also increases the stability of OMIs, but with thread pitch density that is too high, the implant may be more prone to fracture [28]. Similar results were observed regarding thread depth. In both groups of studies, it was stated that thread depth does not significantly influence pull-out strength, e.g., the primary stability of the implant. However, also here the results on the animal model are more homogeneous. There is no clear indication regarding TSF. Studies on the artificial bone model stated that smaller TSF was correlated with better stability, whereas studies on the animal bone model stated that bigger TSF was correlated with better stability. Both groups are characterized by high I 2 and the funnel plot suggests publication bias, thus there is no clear scientific evidence regarding an optimal TSF. In the studies regarding MIT, it was found that a smaller thread pitch was correlated with higher MIT values. What is worth mentioning is that in all studies included examined OMIs were made of titanium grade V which is proof of the wide recognition of this material in orthodontics [49]. An important factor that may affect the clinical effectiveness of OMI is also its head, which should be accessible to the clinician and make fixing wire or elastics easy and efficient (e.g., button for the elastics, slot for wire) [50]. An interesting element that should also be taken into account is the thread shape. Gracco et al. [32] indicate reverse butter shape, and Yashwant [40]-trapezoidal fluted and reverse butter shape as shapes ensuring the greatest stability. Clear conclusions can be drawn from the review that clinicians should use OMIs with smaller thread pitch to obtain maximum anchorage with high primary stability and avoid OMIs lateral displacement during therapy. However, one should remember that excessive thread pitch (<0.45mm) may cause significant strain within the bone due to sparse stress distribution and disturb the physiological bone remodeling process. Minidesign features such as thread depth or TSF do not seem to be very clinically significant in view of the available knowledge. Another interesting factor could be the collar shape. Clinically, implants with a wider neck exhibit better long-term retention [51]. Miniscrew design could be of special importance in patients, who might have compromised miniscrew retention resulting from previous treatment influencing bone metabolism, including chemotherapy [52]. Finally, it should be mentioned that digital treatment planning, mesh superimposition (intraoral scans + CBCT), and CAD-Cam technologies, including CBCT, and planned guided insertion, may be other important factors influencing miniscrew stability [53,54]. It has been proven that implants inserted through 3D guides were characterized by better stability [55].
The limitations of the present study come from the number of studies present in the literature, the difference in study design, different results reporting, and a lack of proper clinical studies. More studies are needed in the future to accurately detect and determine the effect size of a given minidesign characteristic.

1.
Minidesign of orthodontic mini-implant-that is characteristics such as OMI thread pitch, OMI thread depth, and OMI thread shape should be considered when choosing optimal miniscrews for orthodontic anchorage.

2.
Thread pitch seems to be of special importance for OMIs retention-OMIs with a more dense thread-should be preferred due to their superior stability. 3.
Thread depth seems to be of low importance for OMIs stability.

4.
There is no clear scientific evidence referring to the optimal tread shape factor. 5.
Studies present in the literature vary greatly in study design and way of reporting results. The results of in-vitro tests carried out on animal models are more consistent than those carried out on artificial bone models.