Three-Dimensional Evaluation of Treatment Effects and Post-Treatment Stability of Maxillary Molar Intrusion Using Temporary Anchorage Devices in Open Bite Malocclusion.

Background: We investigated treatment outcomes and post-treatment stability in 10 patients with an anterior open bite and nonsurgical orthodontics. Methods: The patients underwent maxillary molar intrusion using temporary anchorage devices (TADs) to deepen the overbite due to mandibular autorotation. Lateral cephalograms and dental cast models were obtained before treatment (T0), immediately after it (T1), and >1 year after it (T2). Skeletal and dental cephalometric changes and three-dimensional movements of the maxillary dentitions were evaluated. Results: At T0, cephalometric analysis indicated that patients had skeletal class I with tendencies for a class II jaw relationship and a skeletal open bite. During active treatment (T0 to T1), the maxillary first molar intruded by 1.6 mm, the mandibular first molar extruded by 0.3 mm, the Frankfort-mandibular plane angle decreased by 1.1°, and the overbite increased by 4.1 mm. Statistically significant changes were observed in the amount of vertical movement of the maxillary first molar, Frankfort-mandibular plane angle, and overbite. Three-dimensional (3D) dental cast analysis revealed that the maxillary first and second molars intruded, whereas the anterior teeth extruded, with the second premolar as an infection point. In addition, the maxillary molar was tipped distally by 2.9° and rotated distally by 0.91°. Statistically significant changes were observed in the amount of vertical movement of the central incisor, lateral incisor, canine and first molar, and molar angulation. From T1 to T2, no significant changes in cephalometric measurements or the 3D position of the maxillary dentition were observed. The maxillary and mandibular dentitions did not significantly change during post-treatment follow-up. Conclusions: Maxillary molar intrusion using mini-screws is an effective treatment for open bite correction, with the achieved occlusion demonstrating 3D stability at least 1 year after treatment.

Three-dimensional morphologic analysis of the maxillary alveolar bone after anterior tooth retraction with temporary anchorage devices.

OBJECTIVES: To investigate three-dimensional (3D) morphologic changes in the alveolar bone around the maxillary central incisors of patients who underwent premolar extraction and subsequent anterior tooth retraction using temporary anchorage devices (TADs). MATERIALS AND METHODS: The subjects consisted of 16 patients with bimaxillary protrusion. The maxillary anterior teeth were retracted using sliding or loop mechanics and TADs for anchorage reinforcement. Cephalograms and computed tomography scans taken pretreatment and posttreatment were registered with respect to the palatal structures. The movement of the maxillary central incisors and morphologic changes in the anterior alveolar bone were evaluated quantitatively. RESULTS: Displacement in the palatal direction was observed in the alveolar bone around the incisors and the interdental septum. The displacement and bone remodeling/tooth movement ratio were larger on the labial side than the palatal side, and decreased progressively from the crest to apex level. The bone thickness was significantly increased on the labial side and decreased on the palatal side. CONCLUSIONS: Regional differences exist in morphologic changes of the alveolar bone during anterior tooth retraction using TADs. Attention should be paid to the crest region of the palatal alveolar bone because of its small original thickness and low remodeling activity.

Mechanical properties and biocompatibility of a novel miniscrew made of Zr70Ni16Cu6Al8 bulk metallic glass for orthodontic anchorage.

The purpose of the present study was to fabricate a miniscrew possible for clinical application using Zr70Ni16Cu6Al8 bulk metallic glass (BMG), which has high mechanical strength, low elastic modulus, and high biocompatibility. First, the elastic moduli of Zr-based metallic glass rods made of Zr55Ni5Cu30Al10, Zr60Ni10Cu20Al10, Zr65Ni10Cu17.5Al7.5, Zr68Ni12Cu12Al8, and Zr70Ni16Cu6Al8 were measured. Zr70Ni16Cu6Al8 had the lowest elastic modulus among them. Then, we fabricated Zr70Ni16Cu6Al8 BMG miniscrews with diameters from 0.9 to 1.3 mm, conducted a torsion test, and implanted them into the alveolar bone of beagle dogs to compare insertion torque, removal torque, Periotest, new bone formation around the miniscrew, and failure rate compared with 1.3 mm diameter Ti-6Al-4 V miniscrew. The Zr70Ni16Cu6Al8 BMG miniscrew exhibited a high torsion torque even if the miniscrew had a small diameter. Zr70Ni16Cu6Al8 BMG miniscrews with a diameter of 1.1 mm or less had higher stability and lower failure rate than 1.3 mm diameter Ti-6Al-4 V miniscrews. Furthermore, the smaller diameter Zr70Ni16Cu6Al8 BMG miniscrew was shown, for the first time, to have a higher success rate and to form more new bone around the miniscrew. These findings suggested the usefulness of our novel small miniscrew made of Zr70Ni16Cu6Al8 BMG for orthodontic anchorage.

Vibration accelerates orthodontic tooth movement by inducing osteoclastogenesis via transforming growth factor-ß signalling in osteocytes.

BACKGROUND: We previously found the conditions of supplementary vibration that accelerated tooth movement and induced bone resorption in an experimental rat tooth movement model. However, the molecular biological mechanisms underlying supplementary vibration-induced orthodontic tooth movement are not fully understood. Transforming growth factor (TGF)-ß upregulates osteoclastogenesis via induction of the receptor activator of nuclear factor kappa B ligand expression, thus TGF-ß is considered an essential cytokine to induce bone resorption. OBJECTIVES: The aim of this study is to examine the role of TGF-ß during the acceleration of orthodontic tooth movement by supplementary vibration. MATERIALS AND METHODS: In experimental tooth movement, 15 g of orthodontic force was loaded onto the maxillary right first molar for 28 days. Supplementary vibration (3 g, 70 Hz) was applied to the maxillary first molar for 3 min on days 0, 7, 14, and 21. TGF-ß receptor inhibitor SB431542 was injected into the submucosal palatal and buccal areas of the maxillary first molars once every other day. The co-culture of RAW264.7 cells and MLO-Y4 cells was used as an in vitro osteoclastogenesis model. RESULTS: SB431542 suppressed the acceleration of tooth movement and the increase in the number of osteoclasts by supplementary vibration in our experimental rat tooth movement model. Immunohistochemical analysis showed supplementary vibration increased the number of TGF-ß1-positive osteocytes in the alveolar bone on the compression side during the experimental tooth movement. Moreover, vibration-upregulated TGF-ß1 in MLO-Y4 cells induced osteoclastogenesis. CONCLUSIONS: Orthodontic tooth movement was accelerated by supplementary vibration through the promotion of the production of TGF-ß1 in osteocytes and subsequent osteoclastogenesis.

Effect of vibration on orthodontic tooth movement in a double blind prospective randomized controlled trial.

The purpose of the present study was to investigate the effect of vibration on orthodontic tooth movement and safety assessment based on our previous basic research in animal experiments. A double-blind prospective randomized controlled trial using split-mouth design was conducted in patients with malocclusion. The left and right sides of maxillary arch were randomly assigned to vibration (TM + V) and non-vibration (TM) groups. After leveling, vibrations (5.2 ± 0.5 g-forces (gf), 102.2 ± 2.6 Hertz (Hz)) were supplementary applied to the canine retracted with 100 gf in TM + V group for 3 min at the monthly visit under double-blind fashion, and the canine on the other side without vibration was used as TM group. The amount of tooth movement was measured blindly using a constructed three-dimensional dentition model. The amount of canine movement per visit was 0.89 ± 0.55 mm in TM group (n = 23) and 1.21 ± 0.60 mm in TM + V group (n = 23), respectively. There was no significant difference of pain and discomfort, and root resorption between the two groups. This study indicates that static orthodontic force with supplementary vibration significantly accelerated tooth movement in canine retraction and reduced the number of visits without causing side effects.

Scleraxis upregulated by transforming growth factor-ß1 signaling inhibits tension-induced osteoblast differentiation of priodontal ligament cells via ephrin A2.

During tooth movement in orthodontic treatment, bone formation and resorption occur on the tension and compression sides of the alveolar bone, respectively. Although the bone formation activity increases in the periodontal ligament (PDL) on the tension side, the PDL itself is not ossified and maintains its homeostasis, indicating that there are negative regulators of bone formation in the PDL. Our previous report suggested that scleraxis (Scx) has an inhibitory effect on ossification of the PDL on the tension side through the suppression of calcified extracellular matrix formation. However, the molecular biological mechanisms of Scx-modulated inhibition of ossification in the tensioned PDL are not fully understood. The aim of the present study is to clarify the inhibitory role of Scx in osteoblast differentiation of PDL cells and its underlying mechanism. Our in vivo experiment using a mouse experimental tooth movement model showed that Scx expression was increased during early response of the PDL to tensile force. Scx knockdown upregulated expression of alkaline phosphatase, an early osteoblast differentiation marker, in the tensile force-loaded PDL cells in vitro. Transforming growth factor (TGF)-ß1-Smad3 signaling in the PDL was activated by tensile force and inhibitors of TGF-ß receptor and Smad3 suppressed the tensile force-induced Scx expression in PDL cells. Tensile force induced ephrin A2 (Efna2) expression in the PDL and Efna2 knockdown upregulated alkaline phosphatase expression in PDL cells under tensile force loading. Scx knockdown eliminated the tensile force-induced Efna2 expression in PDL cells. These findings suggest that the TGF-ß1-Scx-Efna2 axis is a novel molecular mechanism that negatively regulates the tensile force-induced osteoblast differentiation of PDL cells.

A comparative assessment of orthodontic treatment outcomes of mild skeletal Class III malocclusion between facemask and facemask in combination with a miniscrew for anchorage in growing patients: A single-center, prospective randomized controlled trial.

OBJECTIVES: To investigate the hypothesis that there is difference in the treatment outcomes of milder skeletal Class III malocclusion between facemask and facemask in combination with a miniscrew in growing patients. MATERIALS AND METHODS: Patients were randomly divided into two groups. In one group, the patients were treated with facemask therapy (FM group: 12 males, eight females, average age: 10 years, 5 months ± 1 year, 8 months). In the other group, patients were treated with facemask therapy along with a miniscrew (FM+MS group: 12 males, seven females, average age: 11 years, 1 month ± 1 year, 3 months). A lingual arch with hooks was fixed to the maxillary arch in both groups and a protractive force of 500 g was applied from the facemask to the hooks. The patients were instructed to use the facemask for 12 hours per day. In the FM+MS group, a miniscrew was inserted into the palate and fixed to the lingual arch. RESULTS: Mobility and loosening of the miniscrew were not observed during treatment. Lateral cephalometric analysis showed that SNA, SN-ANS, and ANB values were significantly increased in the FM+MS group compared with those for the FM group (SNA, 1.1° SN-ANS, 1.3° ANB, 0.8°). Increase in proclination of maxillary incisors was significantly greater in the FM group than in the FM+MS group (U1-SN, 5.0°). CONCLUSIONS: During treatment of milder skeletal Class III malocclusion, facemask therapy along with a miniscrew exhibits fewer negative side effects and delivers orthopedic forces more efficiently to the maxillary complex than facemask therapy alone.

Improvement of Open Bite and Stomatognathic Function in an Axenfeld- Rieger Syndrome Patient by Orthodontic Sectional Arch Mechanics: Clinical Considerations and the Risk of Orthodontic Tooth Movement.

Orthodontists need to understand the orthodontic risks associated with systemic disorders. Axenfeld-Rieger syndrome (ARS) is a rare autosomal dominant disorder with genetic and morphological variability. The risks of orthodontic treatment in ARS patients have been unclear. Here we describe the correction of an anterior open bite in a 15-year-old Japanese female ARS patient by molar intrusion using sectional archwires with miniscrew implants. An undesirable development of external apical root resorption (EARR) was observed in all intrusive force-applied posterior teeth during the patient's orthodontic treatment, suggesting that ARS patients have a higher risk of EARR than the general population.

Vibration enhances osteoclastogenesis by inducing RANKL expression via NF-κB signaling in osteocytes.

To shorten the duration of orthodontic treatment it is important not only to reduce risks such as dental caries, periodontal disease, and root resorption, but also to decrease pain and discomfort caused by a fixed appliance. Several studies have investigated the effect of vibration applied to fixed appliances to accelerate tooth movement. Although it was reported that vibration accelerates orthodontic tooth movement by enhancing alveolar bone resorption, the underlying cellular and molecular mechanisms remain unclear. In this study, we investigated the effects of vibration on osteoclastogenesis in vitro and in vivo. Vibration applied to pre-osteoclast cell line RAW264.7 cells enhanced cell proliferation but did not affect their differentiation into osteoclasts. Osteocytes in bone are known to be mechanosensitive and to act as receptor activator of nuclear factor kappa B (NF-κB) ligand (RANKL). Therefore, in the present study, vibration was applied to cells from the osteocyte-like cell line MLO-Y4. In MLO-Y4 cells, vibration induced phosphorylation of the inhibitor of NF-κB (IκB) and caused nuclear localization of NF-κB p65. Additionally, vibration increased RANKL mRNA expression, but did not affect osteoprotegerin (OPG) mRNA expression in MLO-Y4 cells, thus resulting in an increased RANKL/OPG ratio. Consistent with these findings, vibration applied during experimental tooth movement increased NF-κB activation and RANKL expression in osteocytes on the compression side of alveolar bone in vivo, whereas vibration had no such effects on the tension side. Furthermore, in a co-culture of MLO-Y4 cells and RAW264.7 cells, vibration applied to MLO-Y4 cells enhanced osteoclastogenesis. These findings suggest that vibration could accelerate orthodontic tooth movement by enhancing osteoclastogenesis through increasing the number of pre-osteoclasts and up-regulating RANKL expression in osteocytes on the compression side of alveolar bone via NF-κB activation.

Insulin-like growth factor 1 modulates bioengineered tooth morphogenesis.

Regenerative therapy to replace missing teeth is a critical area of research. Functional bioengineered teeth have been produced by the organ germ method using mouse tooth germ cells. However, these bioengineered teeth are significantly smaller in size and exhibit an abnormal crown shape when compared with natural teeth. The proper sizes and shapes of teeth contribute to their normal function. Therefore, a method is needed to control the morphology of bioengineered teeth. Here, we investigated whether insulin-like growth factor 1 (IGF1) can regulate the sizes and shapes of bioengineered teeth, and assessed underlying mechanisms of such regulation. IGF1 treatment significantly increased the size of bioengineered tooth germs, while preserving normal tooth histology. IGF1-treated bioengineered teeth, which were developed from bioengineered tooth germs in subrenal capsules and jawbones, showed increased sizes and cusp numbers. IGF1 increased the number of fibroblast growth factor (Fgf4)-expressing enamel knots in bioengineered tooth germs and enhanced the proliferation and differentiation of dental epithelial and mesenchymal cells. This study is the first to reveal that IGF1 increases the sizes and cusp numbers of bioengineered teeth via the induction of enamel knot formation, as well as the proliferation and differentiation of dental epithelial and mesenchymal cells.

Biosafety, stability, and osteogenic activity of novel implants made of Zr70Ni16Cu6Al8 bulk metallic glass for biomedical application.

Superior mechanical and chemical properties of Zr70Ni16Cu6Al8 bulk metallic glass (BMG) demonstrate its promise as a novel biomaterial for fabrication of implants. The aim of the present study was to validate mechanical, chemical, and biological properties of Zr70Ni16Cu6Al8 BMG through comparison with titanium (Ti). Our data indicated higher tensile strength, lower Young's modulus, and reduced metal ion release of Zr70Ni16Cu6Al8 BMG compared with Ti. Biosafety of bone marrow mesenchymal cells on Zr70Ni16Cu6Al8 BMG was comparable to that of Ti. Next, screw-type implant prototypes made of Zr70Ni16Cu6Al8 BMG were fabricated and inserted into rat long bones. Zr70Ni16Cu6Al8 BMG implants indicated a higher removal-torque value and lower Periotest value compared with Ti implants. In addition, higher amounts of new bone formation and osseointegration were observed around Zr70Ni16Cu6Al8 BMG implants compared with Ti implants. Moreover, gene expression analysis displayed higher expression of osteoblast- and osteoclast-associated genes in the Zr70Ni16Cu6Al8 BMG group compared with the Ti group. Importantly, loading to implants upregulated bone formation, as well as osteoblast- and osteoclast-associated gene expression in the peri-implant area. No significant difference in concentrations of Ni, Al, Cu, and Zr in various organs was shown between in the Zr70Ni16Cu6Al8 BMG and Ti groups. Collectively, these findings suggest that Zr70Ni16Cu6Al8 BMG is suitable for fabricating novel implants with superior mechanical properties, biocompatibility, stability, and biosafety compared with Ti. STATEMENT OF SIGNIFICANCE: Titanium is widely used to fabricate orthopedic and dental implants. However, Titanium has disadvantages for biomedical applications in regard to strength, elasticity, and biosafety. Recently, we developed a novel hypoeutectic Zr70Ni16Cu6Al8 BMG, which has superior mechanical and chemical properties. However, the validity of Zr70Ni16Cu6Al8 BMG for biomedical application has not been cleared. The aim of the present study was to validate the mechanical, chemical, and biological properties of Zr70Ni16Cu6Al8 BMG for biomedical applications through comparison with Titanium. The present study clarifies that Zr70Ni16Cu6Al8 BMG has good mechanical properties, corrosion resistance, and osteogenic activity, which are necessary features for biomedical applications. The present study provides for the first time the superiority of Zr70Ni16Cu6Al8 BMG implants to Titanium implants for biomedical applications.

Synergistic acceleration of experimental tooth movement by supplementary high-frequency vibration applied with a static force in rats.

Several recent prospective clinical trials have investigated the effect of supplementary vibration applied with fixed appliances in an attempt to accelerate tooth movement and shorten the duration of orthodontic treatment. Among them, some studies reported an increase in the rate of tooth movement, but others did not. This technique is still controversial, and the underlying cellular and molecular mechanisms remain unclear. In the present study, we developed a new vibration device for a tooth movement model in rats, and investigated the efficacy and safety of the device when used with fixed appliances. The most effective level of supplementary vibration to accelerate tooth movement stimulated by a continuous static force was 3 gf at 70 Hz for 3 minutes once a week. Furthermore, at this optimum-magnitude, high-frequency vibration could synergistically enhance osteoclastogenesis and osteoclast function via NF-κB activation, leading to alveolar bone resorption and finally, accelerated tooth movement, but only when a static force was continuously applied to the teeth. These findings contribute to a better understanding of the mechanism by which optimum-magnitude high-frequency vibration accelerates tooth movement, and may lead to novel approaches for the safe and effective treatment of malocclusion.

In vivo expression and regulation of genes associated with vascularization during early response of sutures to tensile force.

Sutures are fibrous tissues that connect bones in craniofacial skeletal complexes. Cranio- and dentofacial skeletal deformities in infant and adolescent patients can be treated by applying tensile force to sutures to induce sutural bone formation. The early gene expression induced by mechanical stress is essential for bone formation in long bones; however, early gene expression during sutural bone formation induced by tensile force is poorly characterized. In vivo studies are essential to evaluate molecular responses to mechanical stresses in heterogeneous cell populations, such as sutures. In this paper we examined in vivo early gene expression and the underlying regulatory mechanism for this expression in tensile-force-applied cranial sutures, focusing on genes involved in vascularization. Tensile force upregulated expression of vascular factors, such as vascular endothelial growth factor (Vegf) and endothelial cell markers, in sutures within 3 h. The expression of connective tissue growth factor (Ctgf) and Rho-associated coiled-coil containing protein kinase 2 (Rock2) was also upregulated by tensile force. A CTGF-neutralizing antibody and the ROCK inhibitor, Y-27632, abolished tensile-force-induced Vegf expression. Moreover, tensile force activated extracellular signal-related kinase 1/2 (ERK1/2) signaling in sagittal sutures, and the ERK1/2 inhibitor, U0126, partially inhibited tensile-force-induced Ctgf expression. These results indicate that tensile force induces in vivo gene expression associated with vascularization early in tensile-force-induced sutural bone formation. Moreover, the early induction of Vegf gene expression is regulated by CTGF and ROCK2.

Scleraxis and osterix antagonistically regulate tensile force-responsive remodeling of the periodontal ligament and alveolar bone.

The periodontal ligament (PDL) is a mechanosensitive noncalcified fibrous tissue connecting the cementum of the tooth and the alveolar bone. Here, we report that scleraxis (Scx) and osterix (Osx) antagonistically regulate tensile force-responsive PDL fibrogenesis and osteogenesis. In the developing PDL, Scx was induced during tooth eruption and co-expressed with Osx. Scx was highly expressed in elongated fibroblastic cells aligned along collagen fibers, whereas Osx was highly expressed in the perialveolar/apical osteogenic cells. In an experimental model of tooth movement, Scx and Osx expression was significantly upregulated in parallel with the activation of bone morphogenetic protein (BMP) signaling on the tension side, in which bone formation compensates for the widened PDL space away from the bone under tensile force by tooth movement. Scx was strongly expressed in Scx(+)/Osx(+) and Scx(+)/Osx(-) fibroblastic cells of the PDL that does not calcify; however, Scx(-)/Osx(+) osteogenic cells were dominant in the perialveolar osteogenic region. Upon BMP6-driven osteoinduction, osteocalcin, a marker for bone formation was downregulated and upregulated by Scx overexpression and knockdown of endogenous Scx in PDL cells, respectively. In addition, mineralization by osteoinduction was significantly inhibited by Scx overexpression in PDL cells without affecting Osx upregulation, suggesting that Scx counteracts the osteogenic activity regulated by Osx in the PDL. Thus, Scx(+)/Osx(-), Scx(+)/Osx(+) and Scx(-)/Osx(+) cell populations participate in the regulation of tensile force-induced remodeling of periodontal tissues in a position-specific manner.

Decreased alveolar bone turnover is related to the occurrence of root resorption during experimental tooth movement in dogs.

OBJECTIVE: To investigate the relationship between root resorption (RR) and bone turnover in two different types of tooth movement in dogs. MATERIALS AND METHODS: A total of 16 dogs in two different groups were used. Tooth movement of dog premolars resulted from approximately 200 g of force. Histomorphometric analysis of premolar roots was assessed after 4 and 12 weeks of tooth movement by comparing nonresorptive to resorptive surfaces. RESULTS: Histomorphometric analysis indicated a significant decrease in the bone formation rate in the root resorptive areas, which resulted in decreased bone volume after 12 weeks. The threshold to detect RR in periapical radiographs was about 1.0 mm(2). CONCLUSIONS: A sustained mechanical load, due to the prolonged stress and strain of continuous mechanics, induces elevated bone metabolic activity, such as the bone turnover (remodeling) and change in bone volume (modeling). Therefore, our data support the hypothesis that increased RR is related to decreased bone formation (turnover) in high stress areas exposed to prolonged orthodontic tooth movement.

Compressive force-produced CCN2 induces osteocyte apoptosis through ERK1/2 pathway.

Osteocytes produce various factors that mediate the onset of bone formation and resorption and play roles in maintaining bone homeostasis and remodeling in response to mechanical stimuli. One such factor, CCN2, is thought to play a significant role in osteocyte responses to mechanical stimuli, but its function in osteocytes is not well understood. Here, we showed that CCN2 induces apoptosis in osteocytes under compressive force loading. Compressive force increased CCN2 gene expression and production, and induced apoptosis in osteocytes. Application of exogenous CCN2 protein induced apoptosis, and a neutralizing CCN2 antibody blocked loading-induced apoptosis. We further examined how CCN2 induces loaded osteocyte apoptosis. In loaded osteocytes, extracellular signal-regulated kinase 1/2 (ERK1/2) was activated, and an ERK1/2 inhibitor blocked loading-induced apoptosis. Furthermore, application of exogenous CCN2 protein caused ERK1/2 activation, and the neutralizing CCN2 antibody inhibited loading-induced ERK1/2 activation. Therefore, this study demonstrated for the first time to our knowledge that enhanced production of CCN2 in osteocytes under compressive force loading induces apoptosis through activation of ERK1/2 pathway.

Evaluation of optimal length and insertion torque for miniscrews.

INTRODUCTION: The purpose of this article was to test the theory that short miniscrews will decrease the possibility of damaging the root, but the failure rate will increase. METHODS: One hundred eighty-six miniscrews (diameter, 1.3 × 5 mm, n = 63; 6 mm, n = 62; 7 mm, n = 61) were placed in 105 consecutive patients. Multislice computed tomography and cone-beam computed tomography scans were taken before and after miniscrew placement. Insertion torque was measured at miniscrew placement. RESULTS: The success rate of the miniscrews in the maxilla (93.4%) was higher than that in the mandible (70.3%). A significantly lower success rate with 5-mm miniscrews was observed compared with 6-mm and 7-mm miniscrews in the mandible. Miniscrews placed in less than approximately 3.8 mm of bone and those within 1.4 mm of the root had significantly higher failure rates. Miniscrews placed with insertion torque greater than 10 Ncm had a tendency for a lower success rate. CONCLUSIONS: The optimum lengths of miniscrews of a diameter of 1.3 mm are 5 mm in the maxilla and 6 mm in the mandible. They should be placed at a distance from the root with insertion torque less than 10 Ncm for safe orthodontic anchorage without failure.

Analgesic effects of the non-nitrogen-containing bisphosphonates etidronate and clodronate, independent of anti-resorptive effects on bone.

Nitrogen-containing bisphosphonates (NBPs) have greater anti-bone-resorptive effects than non-nitrogen-containing bisphosphonates (non-NBPs). Hence, NBPs are the current first-choice drug for osteoporosis. However, NBPs carry a risk of osteonecrosis of jaws. Some animal and human studies suggest that non-NBPs may have anti-bone-resorptive effect-independent analgesic effects, but there has been no detailed comparison between NBPs and non-NBPs. Here, we compared the analgesic effects of several non-NBPs and NBPs, using (a) writhing responses induced in mice by intraperitoneal injection of 1% acetic acid, (b) acetic acid-induced neuronal expression of c-Fos, (c) acetic acid-induced elevation of blood corticosterone, and (d) hindpaw-licking/biting responses induced by intraplantar injection of capsaicin. Among the NBPs and non-NBPs tested, only etidronate and clodronate displayed clear analgesic effects, with various routes of administration (including the oral one) being effective. However, they were ineffective when intraperitoneally injected simultaneously with acetic acid. Intracerebroventricular administration of etidronate or clodronate, but not of minodronate (an NBP), was also effective. The effective doses of etidronate and clodronate were much lower in writhing-high-responder strains of mice. Etidronate and clodronate reduced acetic acid-induced c-Fos expression in the brain and spinal cord, and also the acetic acid-induced corticosterone increase in the blood. Etidronate and clodronate each displayed an analgesic effect in the capsaicin test. Etidronate and clodronate displayed their analgesic effects at doses lower than those inducing anti-bone-resorptive effects. These results suggest that etidronate and clodronate exert potent, anti-bone-resorptive effect-independent analgesic effects, possibly via an interaction with neurons, and that they warrant reappraisal as safe drugs for osteoporosis.

Increase of CGRP-containing nerve fibers in the rat periodontal ligament after luxation.

The distribution of calcitonin gene-related peptide (CGRP) was examined in the periodontal ligament (PDL) after experimental luxation injury of the rat first molar tooth. The luxational injury increased the number of CGRP-immunoreactive (IR) nerve fibers. At 3-7 days, numerous CGRP-IR nerve fibers appeared throughout the injured PDL. These nerve fibers terminated as free nerve endings within resorption cavities. Immunohistochemistry for receptor activity modifying protein 1 (RAMP1) also demonstrated that the subunit of CGRP receptor was expressed by periodontal cells adjacent to the alveolar bone in the intact and injured PDL. RAMP1-IR cells were divided into two types; small cells with single nucleus and large cells with 2-6 nuclei. After the luxational injury, both types of RAMP1-IR cells abundantly appeared within resorption cavities. As a result, the treatment increased the number of large RAMP1-IR cells at 3-7 days and small RAMP1-IR cells at 7 days. In addition, a double immunofluorescence analysis demonstrated that CGRP-IR nerve fibers were seen away from RAMP1-IR cells in the intact PDL. After the traumatic injury, however, CGRP-IR nerve fibers appeared in the close vicinity of small and large RAMP1-IR cells at 5-7 days. The morphology and distribution of RAMP1-IR cells suggest that they contain osteoblasts and osteoclasts. By affecting osteoclasts and osteoblasts, CGRP may have effects on bone remodeling in the luxated PDL.