INTRODUCTION

Anchorage is the most important factor that improves the quality of treatment and treatment results in orthodontics.^1–3 Orthodontic miniscrews are increasingly used by orthodontists to provide absolute temporary anchorage without patient compliance during orthodontic treatment.^3–6 Miniscrews can provide sufficient and stable anchorage and produce orthopedic effects without reciprocal tooth movements during treatment.^3,7

Miniscrews can be loaded immediately because stability is supported by the mechanical retention between the implant and the bone tissue. However, magnitude, direction, and pattern of orthodontic force could influence stability.⁸ In the literature, conflicting results were found related to amount of force. Carrillo et al.^9,10 reported that the miniscrews on the side of the mouth immediately loaded with lighter forces were significantly more stable than those subjected to heavier forces in their studies. In contrast, significantly higher success rates were found for miniscrews loaded with 100 or 200 g than unloaded miniscrews and those loaded with 50 g in the study of Liu et al.¹¹

Peri-miniscrew crevicular fluid (PMCF) is an inflammatory exudate that is secreted in the crevice between a miniscrew and peri implant tissue. Its composition is similar to other body fluids, such as gingival crevicular fluid, and contains inflammatory biomarkers, growth factors, and other proteins. The content of PMCF is analogous to that released in the gingival crevicular fluid during orthodontic tooth movement, and both are affected by bone remodeling processes.^7,12,13

Interleukin-4 (IL-4) is a potent downregulator of macrophage function that inhibits the expression and release of proinflammatory cytokines. IL-4 inhibits the receptor activator of nuclear factor kappa–B ligand induced osteoclastogenic process and suppresses bone resorption. Additionally, IL-4 plays important roles in inflammatory and immune responses.^14,15 Bone alkaline phosphatase (BALP) is related to osteoblastic activity and is a marker of bone formation. BALP is associated with early stages of osteogenesis.¹⁶ C-telopeptide fragment of type I collagen (CTX-I) is a biochemical marker of osteoclastic activity that is generated in the degradation of bone collagen and therefore regarded as a bone resorption marker.¹⁷

No published studies have assessed the IL-4, BALP, and CTX-I levels around miniscrews in response to application of different amounts of orthodontic force. Therefore, the aim of this study was to evaluate IL-4, BALP, and CTX-I levels in PMCF during orthodontic tooth movement between 75 and 150 g of distalization force.

MATERIALS AND METHODS

Clinical Procedures

Orthodontic preadjusted edgewise brackets with 0.022-inch slots (Gemini, 3M Unitek, Monrovia, Calif) and segmented stainless steel archwires with 0.019 × 0.025 inch were placed on the upper posterior teeth, and the second premolars and the first molars were ligated together before canine distalization. Miniscrews (8 mm long, 1.5 mm diameter; Aarhus Anchorage System, American Orthodontics, Sheboygan, Wisc) were placed bilaterally into the interradicular bone between the maxillary second premolars and first molars in the attached gingiva below the mucogingival junction as described by Park.¹⁸ The right and left maxillary canines were moved distally using either 75 or 150 g of force. Distalization force delivered by NiTi closed-coil spring (American Orthodontics) was applied horizontally between the miniscrew and the canine immediately after insertion of the miniscrew (Figure 1). The force was activated and calibrated every fourth week by a force strain gauge.

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RESULTS

Thirty miniscrews were placed randomly in 15 periodontally healthy subjects using the split-mouth study design. All miniscrews survived and no infection was observed through the termination of the study period.

Clinical Findings

Comparisons of the clinical measurements, including PD, PBI, PI, and GI. for the sampling sites at all time points are shown in Table 1. The PD level at T4 was significantly higher in the 75 g force group than the 150 g force group, while a significantly increased PI score was found in the 150 g force group compared with the 75 g force group (P < .05). There were no significant differences between the force levels for clinical measurements at the other time points (P > .05). There were no significant differences among time points for the PD level and the GI score in either force group or for the PBI and the PI scores in the 150 g force group (P > .05). Although a significant result was obtained for the PBI score in the 75 g force group (P = .026), there was no significant difference between T0 and the other time points. The interaction of force and time was insignificant for all clinical measurements (P > .05).

Table 1 Comparisons of the Clinical Measurements for the Sampling Sites at All Time Points^a

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Biochemical Findings

Comparisons of the biochemical measurements, including BALP, CTX-I, and IL-4 levels, for the sampling sites at all time points are shown in Table 2. There was no significant difference between the force groups at all time points with respect to BALP, CTX-I. and IL-4 levels (P > .05). There was no significant difference among time points for either force group in terms of BALP and IL-4 levels (P > .05). The CTX-I level at T3 was significantly higher than at T0 for both force groups (P < .05). Time and force interaction was insignificant for all biochemical measurements (P > .05).

Table 2 Comparisons of the Biochemical Measurements for the Sampling Sites at All Time Points^a

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DISCUSSION

Miniscrews have been widely used to provide absolute temporary anchorage for guiding orthodontic tooth movement, but less information is available about the biomolecular mechanism that affects miniscrew stability.^6,7,19 It is important to know the tissue reactions to applied orthodontic forces for keeping the miniscrews stable. In the literature, many studies have assessed proinflammatory cytokines^6,13,19 and bone remodeling markers⁷ in PMCF for evaluating the health status of miniscrews. This was the first study to examine different amounts of force to clarify the interaction between force and peri-miniscrew tissues by determining BALP, CTX-I (bone turnover markers). and IL-4 (antiinflammatory cytokine) levels in PMCF.

It is known that oral hygiene and prevention of inflammation are crucial factors for stability of miniscrews.^2,20 In patients with poor oral hygiene, the plaque around the miniscrews caused inflammation and early loss of the surrounding bone. PD, PBI, GI, and PI scores were investigated in the present study. Statistical differences were detected at only one time point (T4) between groups. These slight changes were not likely to be of clinical relevance because scores were generally at a low level as a consequence of proper daily oral hygiene.

To date, various studies have focused on the optimum force magnitude for canine distalization. The first study by Storey and Smith²¹ reported an optimum force of 150 to 200 g for distalization of the canines. Iwasaki et al.²² recommended that optimum force should be less than 100 g, Ricketts²³ advocated 75 g, and Lee²⁴ recommended 150 to 200 g as the optimum force value for canine distalization. Boester and Johnston²⁵ reported 140 to 300 g, and Paulsen et al.²⁶ used 50 to 75 g for canine distalization. It is known that light forces are more biologic and painless.¹ In this study, 75 and 150 g of force were compared for canine distalization as a light and heavy force within optimal force limits.

Both BALP and CTX-I levels are diagnostic markers of bone turnover. There is no published study on the levels of BALP and CTX-I in the PMCF to date. Although the BALP level remained unchanged, the CTX-I level on day 7 was higher than the before loading level for both force groups in this study. During the first few weeks after miniscrew insertion, osteoclasts remove older, damaged bone. Elevated CTX-I level at this time is associated with increased osteoclastic activity.

IL-4 is a potent downregulator of macrophage function that inhibits the secretion of pro-inflammatory cytokines such as IL-1, IL-6, and tumor necrosis factor. Lack of IL-4 may cause the accumulation of macrophages and high production of IL-1b, tumor necrosis factor–α, and prostaglandin E2 in human monocytes, which leads to bone resorption.²⁷ In this study, the IL-4 level did not significantly change during the study period and between the force groups. These results showed that orthodontic force might have a minimal effect on initial bone modeling, subsequent remodeling and miniscrew anchorage stability.²⁸

Carrillo et al.¹⁰ reported that miniscrews immediately loaded with 50 g (100% stable) were more stable than those loaded with 100 g (94.4% stable). In contrast, higher (100%) success has been found for miniscrews loaded with 100 and 200 g than for the same miniscrews loaded with 50 g in the study of Liu et al. (77%).²⁹ In the current study, all miniscrews survived. and stability of the miniscrews was 100%. Inconsistent results like these suggest interactions with other factors that could have been responsible for the different success rates observed. The previous studies comparing the effects of different forces on miniscrews reported that osseointegration was independent of force magnitudes.^30,31 Similarly, this study found no significant difference for biochemical markers between the force groups. It is possible that the magnitude of forces used in this study was within the optimal force limits so the results were not affected.

CONCLUSIONS

• In this study, 75 g and 150 g of orthodontic force were within the optimal range for canine distalization, and there was no difference between them in biochemical markers of bone turnover.

• The results of this study should be confirmed with longer study periods and various bone remodeling biomarkers and cytokines to explain the interaction between force and peri-miniscrew tissues.

• Also, rate of tooth movement, pain. and patient comfort should be taken into account when selecting the appropriate force.