Suppression of the NLRP3 Inflammasome through Activation of the Transient Receptor Potential Channel Melastatin 2 Promotes Osteogenesis in Tooth Extraction Sockets of Periodontitis.

This study explored the role of transient receptor potential channel melastatin 2 (TRPM2)-mediated activation of NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) inflammasome in osteogenesis during healing of tooth extraction sockets. Tooth extraction socket tissue samples were collected from patients with or without periodontitis. In a TRPM2 knockout mouse model of socket healing, mice with or without periodontitis and their wild-type littermates were used for comparing the socket healing phenotypes. Micro-computed tomography imaging, three-dimensional reconstruction of the sockets, and hematoxylin and eosin staining for histopathologic analysis were performed. Immunofluorescence, immunohistochemistry, and Western blot analysis were used for evaluation of protein expression; the mRNA levels were evaluated by quantitative RT-PCR. Osteogenic, chondrogenic, and adipogenic differentiation potential of human bone marrow mesenchymal stem cells (BMMSCs) was evaluated. Calcium deposition was evaluated using Alizarin Red S staining. NLRP3 and CASP1 were up-regulated in tooth sockets of periodontitis patients. NLRP3 knockdown promoted the osteogenic differentiation of maxillary BMMSCs under inflammatory conditions. TRPM2 was up-regulated in the tooth extraction socket tissue of periodontitis. Inhibiting TRPM2 expression mitigated the NLRP3 inflammasome and its deleterious effect on osteogenesis. Activation of the TRPM2 ion channel regulated osteogenesis of BMMSCs under inflammatory conditions via Ca2+ influx, the mitochondrial dynamics, and pyroptosis. Targeting the TRPM2/Ca2+/NLRP3 axis could be beneficial in the healing process of the tooth extraction sockets of patients with periodontitis.

Expression pattern of sonic hedgehog signaling and calcitonin gene-related peptide in the socket healing process after tooth extraction.

Sonic Hedgehog (SHH), a neural development inducer, plays a significant role in the bone healing process. Calcitonin gene-related peptide (CGRP), a neuropeptide marker of sensory nerves, has been demonstrated to affect bone formation. The roles of SHH signaling and CGRP-positive sensory nerves in the alveolar bone formation process have been unknown. Here we examined the expression patterns of SHH signaling and CGRP in mouse socket by immunohistochemistry and immunofluorescence analysis. We found that the expression level of SHH peaked at day 3 and was then decreased at 5 days after tooth extraction. CGRP, PTCH1 and GLI2 were each expressed in a similar pattern with their highest expression levels at day 5 and day 7 after tooth extraction. CGRP and GLI2 were co-expressed in some inflammatory cells and bone forming cells. In some areas, CGRP-positive neurons expressed GLI2. In conclusion, SHH may affect alveolar bone healing by interacting with CGRP-positive sensory neurons and thus regulate the socket's healing process after tooth extraction.

Photothermal stress triggered by near-infrared-irradiated carbon nanotubes up-regulates osteogenesis and mineral deposition in tooth-extracted sockets.

PURPOSE: The bone regenerative healing process is often prolonged, with a high risk of infection particularly in elderly and diseased patients. A reduction in healing process time usually requires mechanical stress devices, chemical cues, or laser/thermal therapies. Although these approaches have been used extensively for the reduction of bone healing time, the exact mechanisms involved in thermal stress-induced bone regeneration remain unclear. METHODS: Photothermal stress (PTS) stimulation was carried out using a novel photothermal device, composed of an alginate gel (AG) including carbon nanotubes (CNT-AGs) and their irradiator with near-infrared (NIR) light. We investigated the effects of optimal hyperthermia on osteogenesis, its signalling pathway in vitro and mineral deposition in tooth-extracted sockets in vivo. RESULTS: The PTS (10 min at 42 °C, every day), triggered by NIR-induced CNT, increased the activity of alkaline phosphatase (ALP) in mouse osteoblast MC3T3-E1 cells in a time-dependent manner compared with the non-thermal stress control. PTS significantly induced the expression of osteogenic-related molecules such as ALP, RUNX2 and Osterix in a time-dependent manner with phosphorylated mitogen-activated protein kinases (MAPK). PTS increased the expression of heat shock factor (HSF) 2, but not HSF1, resulting in activation of heat shock protein 27. PTS significantly up-regulated mineral deposition in tooth-extracted sockets in normal and ovariectomised osteoporotic model mice in vivo. CONCLUSIONS: Our novel CNT-based PTS up-regulated osteogenesis via activation of heat shock-related molecules, resulting in promotion of mineral deposition in enhanced tooth-extracted sockets.

Hypertension modifies OPG, RANK, and RANKL expression during the dental socket bone healing process in spontaneously hypertensive rats.

OBJECTIVE: The aim of this study was to evaluate the dental socket bone healing process by histomorphometric and immunohistochemical analysis of osteoprotegerin (OPG), receptor activator of nuclear factor-κß (RANK), and receptor activator of nuclear factor-κß ligand (RANKL) proteins in spontaneously hypertensive rats (SHR). MATERIALS AND METHODS: Under general anesthesia, 25 Wistar rats and 25 SHRs underwent upper right incisor extraction. Rats were euthanized after 7, 14, 21, 28, or 42 days of dental extractions. Histomorphometric and immunohistochemical analyses of OPG, RANK, and RANKL proteins were performed. RESULTS: Histomorphometric results showed decreased bone healing and reduced bone trabecular thickness in SHRs. Immunohistochemical reactions showed intense RANKL and RANK immunolabeling at 14 and 28 postoperative days and mild OPG immunolabeling at 7, 14, and 21 days after surgery in SHRs. CONCLUSION: The results of this study show that RANK, RANKL, and OPG immunolabeling was altered in SHRs, and these results are associated with bone healing delay and decreased trabecular thickness in SHRs. CLINICAL RELEVANCE: Hypertension alters the expression of RANK, RANKL, and OPG and delays the socket bone healing process. These alterations could influence some dental procedures such as orthodontic treatment and implant placement.

Alterations in phosphorus, calcium and PTHrP contribute to defects in dental and dental alveolar bone formation in calcium-sensing receptor-deficient mice.

To determine whether the calcium-sensing receptor (CaR) participates in tooth formation and dental alveolar bone development in mandibles in vivo, we examined these processes, as well as mineralization, in 2-week-old CaR-knockout (CaR(-/-)) mice. We also attempted to rescue the phenotype of CaR(-/-) mice by genetic means, in mice doubly homozygous for CaR and 25-hydroxyvitamin D 1alpha-hydroxylase [1alpha(OH)ase] or parathyroid hormone (Pth). In CaR(-/-) mice, which exhibited hypercalcemia, hypophosphatemia and increased serum PTH, the volumes of teeth and of dental alveolar bone were decreased dramatically, whereas the ratio of the area of predentin to total dentin and the number and surface of osteoblasts in dental alveolar bone were increased significantly, as compared with wild-type littermates. The normocalcemia present in CaR(-/-);1alpha(OH)ase(-/-) mice only slightly improved the defects in dental and alveolar bone formation observed in the hypercalcemic CaR(-/-) mice. However, these defects were completely rescued by the additional elimination of hypophosphatemia and by an increase in parathyroid hormone-related protein (PTHrP) expression in the apical pulp, Hertwig's epithelial root sheath and mandibular tissue in CaR(-/-); Pth(-/-) mice. Therefore, alterations in calcium, phosphorus and PTHrP contribute to defects in the formation of teeth and alveolar bone in CaR-deficient mice. This study indicates that CaR participates in the formation of teeth and in the development of dental alveolar bone in mandibles in vivo, although it appears to do so largely indirectly.

[Ridge preservation after tooth extraction: what do we know today].

Following tooth removal, varying amounts of bone resorption take place due to qualitative and quantitative changes that occur at the alveolar bone around the extraction site. Alveolar bone is a tooth dependent structure and therefore, after a tooth is extracted, dimensional bone reduction takes place both, horizontally and vertically resulting in changes that may lead to esthetic and functional problems. Such deformities of the alveolar ridge may compromise future implant placement as well as esthetic results when a fixed partial denture is constructed in a visible area. In order to preserve ridge dimensions following tooth extraction, particularly where future implant placement is planned, ridge/socket preservation is recommended. Ridge/socket preservation is any procedure undertaken at the time of or following an extraction that is designed to minimize external resorption of the ridge and maximize bone formation within the socket. In certain situations it not advisable to perform ridge preservation at the time of tooth extraction thus, preservation is delayed by few weeks (6-8). This paper reviews the various socket/ridge preservation techniques and the diverse materials used to fill those deficient tissues or prevent their collapse. Scientific literature review is discussed.

Development of a rat model of bisphosphonate-related osteonecrosis of the jaw (BRONJ).

The purpose of this study was to develop a rat model predictive of bisphosphonate-related osteonecrosis of the jaw (BRONJ) after exodontias. Thirty female rats were randomized into 2 groups, control and experimental. The experimental group received 2 intravenous injections of zoledronate (20 µg/kg). The mesial root of the right mandibular first molar was extracted. Rats were euthanized at 0, 4, and 8 weeks. Bone mineral density (BMD), collagen breakdown (pyridinium [PYD]), vascular regeneration (VEGF), and histology were examined. A trend toward higher PYD values was suggested in control vs experimental groups after wounding. Serum VEGF increased significantly after wounding for both control and experimental groups. After 8 weeks, VEGF continued to rise for the experimental group only. In the extraction socket area, BMD was significantly lower after wounding in control vs. zoledronate-treated rats. Histology sections from experimental groups showed bacteria and bone necrosis. Consistent findings of BRONJ features similar to those in humans were observed after zoledronate treatment.

[Significance of the Magnesium in the hard tissues such as Bone and Teeth].

In latest year, the relationship between whole body osteoporosis and jawbone osteoporosis, and also the relationship between bone density from whole body and jawbone have been recognized. As Mg is related to the bone density of whole body and the weakness of alveolar bone, it deeply connects to the denture treatment and the convalescence after implant treatment. It related to avoid losing teeth during the suppression of acid solubility of enamel, too. For the importance to control the absorption of alveolar bone which can support the teeth, it is necessary to have more consideration on Mg in the relationship between whole body's bone and alveolar bone.

Malondialdehyde levels in dental follicles of asymptomatic impacted third molars.

PURPOSE: Increased levels of reactive oxygen species lead to oxidative stress and tissue damage. Malondialdehyde (MDA) is one of many low-molecular-weight endproducts of lipid peroxidation that increases with oxidative stress. The aim of this study was to determine oxidative stress in dental follicles (DFs) of radiologically asymptomatic impacted third molars (ITMs) using MDA. MATERIALS AND METHODS: This study involved 40 DFs of 40 patients referred for clinically and radiographically asymptomatic ITMs. Forty healthy gingival tissues in the same patients were obtained during surgical removal of teeth as a control group. DF widths on periapical radiographs narrower than 2.5 mm were included in the study. All tissues samples were analyzed for MDA as an indicator of oxidative stress. RESULTS: Levels of MDA were significantly higher in DFs from ITMs than those from healthy gingival tissues of the same patients (P < .01). CONCLUSION: The results suggest that significant oxidative stress may occur in DFs of asymptomatic ITMs. The findings suggest that increased MDA may play an important role in oxidative stress in DFs. In light of these preliminary findings of the present study, further investigations and comprehensive studies are required to determine the role of antioxidants that scavenge free radicals in DFs.

Effect of low-level laser therapy on the healing process after tooth replantation: a histomorphometrical and immunohistochemical analysis.

Success of tooth replantation is limited because part of the replanted tooth is lost because of progressive root resorption. This study used histomorphometry and immunohistochemistry to evaluate the effect of low-level laser therapy (LLLT) on the healing process of rat teeth replanted after different extra-oral periods, simulating immediate and delayed replantation. Sixty Wistar rats (Rattus norvegicus albinus) had their maxillary right incisors extracted and randomly assigned to six groups (n = 10): C4, C30 and C45, in which the teeth were replanted 4 min (immediate), 30 min (delayed) and 45 min (delayed) after extraction, respectively, and L4, L30 and L45, in which the teeth were replanted after the same extra-alveolar times, but the root surfaces and the alveolar wounds were irradiated with a gallium-aluminum-arsenate (GaAlAs) diode laser before replantation. The animals were sacrificed after 60 days. The anatomic pieces containing the replanted teeth were obtained and processed for either histomorphometrical analysis under optical microscopy or immunohistochemical expression of receptor activator of nuclear factor Kappa-B (RANK), and its ligand (RANKL), osteoprotegerin (OPG) and tartrate-resistant acid phosphatase (TRAP) proteins. Areas of external replacement and inflammatory root resorption were observed in all groups, without statistically significant differences (P > 0.05). Ankylosis was more frequent in L30 than in C30 (P < 0.05). RANKL immunostaining predominated over RANK and OPG immunostaining in both groups with immediate tooth replantation (P < 0.05). For the 45-min extra-alveolar time, however, there was greater evidence of RANK immunostaining compared to RANKL for both control and laser-treated groups (P < 0.05). Positive TRAP immunostaining predominated in L4 and L30 (P < 0.05). In conclusion, under the tested conditions, the treatment of the root surface and the alveolar wound with LLLT did not improve the healing process after immediate and delayed tooth replantation in rats.

[From an immediate implant placement in the post-extraction phase towards immediate loading application: current status].

The fresh extraction socket site in the immediate post-extraction phase possesses unique characteristic wound healing cascade. Marked horizontal and vertical resorption of the edentulous ridge occurred shortly following tooth extraction. In periodontally involved teeth, when partial/full socket wall destruction is evident, the ingrowth of connective tissue into the extraction site is unavoidable leading to a deficient ridge. The use of bone substitute materials aiming to preserve the alveolar ridge by stabilizing the blood clot, thus maintaining the volume of the site and at the same time serves as an osteoconductive scaffold which facilitates continual bone formation. immediate Implant placement, is also a reliable, predictable, and successful procedure. Comparative studies regarding immediate implant placement vs. delayed placement (healed sites) reported similar high survival rate for both procedures. The addition of nonfunctional immediate provisionalization (clearance of all contacts in centric occlusion and during eccentric movements to avoid full functional loading of the implant during healing) achieving an instant aesthetic solution, has been shown to have predictable results. However, a meticulous surgical protocol should be followed. In recent years, an immediate functional loading of cross-arch splinted implants proved to be a reliable and successful approach. Moreover evidence-based data comparing immediate, early and delayed loading failed to show significant difference between those treatment modalities. Apparently, primary stability of implants is an important factor in achieving predictable success. It seems that the addition of controlled loading did not impair those results. A systematic review of the current literature related to this procedure showed a survival rate of over 95% in 34 prospective/retrospective studies. Since clinical parameters were proved to be equal whether implants were placed immediate post-extraction or delayed in a healed alveolar ridge, it appears that cross-arch immediate loading of implants placed in extraction and/or healed edentulous ridges is a predictable procedure with long term stability of the results.

Malnutrition delayed wound healing after tooth extraction by HMGB1-related prolonged inflammation.

Malnutrition causes prolonged inflammation, resulting in delayed wound healing. High mobility group box-1 (HMGB1) is a damage-associated molecular pattern that is present in the nuclei of macrophages and is secreted into the extracellular milieu in response to stimuli. It stimulates the production of interleukin-1ß (IL-1ß) through the receptors for advanced glycation end products (RAGE), inducing an inflammatory response, which is an essential response to initiate wound healing. We hypothesized that malnutrition may interfere with this cascade, causing abnormal inflammation and ultimately delaying wound healing. We used tooth-extracted mice with malnutrition fed with low-casein diet for two weeks. On days 3 and 7 after tooth extraction, the wound tissue was histologically observed and analyzed for several factors in the inflammation-regeneration lineage, including IL-1ß, mesenchymal stem cells, myeloperoxidase activity, HMGB1, macrophage polarization, and adenosine 5-triphosphate (ATP). On day 7, delayed wound healing was observed with the following findings under malnutrition conditions: decreased mRNA expression of genes for regeneration and mesenchymal stem cell (MSC) accumulation, an obvious increase in myeloperoxidase and IL-1ß mRNA expression, an increase in HMGB1 levels, and an increase in ATP concentration in tissues with elevated proportion of M2 macrophages. These results suggest that the significantly increased secretion of HMGB1 associated with the upregulated production of ATP and IL-1ß secretion via the RAGE pathway may interfere with the resolution of inflammation and wound healing under the state of malnutrition.

Healing of tooth extraction sockets in the streptozotocin diabetic rat model: Induction of cartilage by BMP-6.

Cartilage does not form in the tooth extraction socket of the normal rat. The aim of the study was to determine if adding BMP-6 to the extraction socket would cause chondrogenic differentiation in the diabetic rat. A group of 8-week-old rats were injected intraperitoneally with a diabetogenic agent, streptozotocin, and a control group received citrate buffer only. Three weeks later, the maxillary molar teeth were extracted and either BMP-6 or saline applied to the extraction sockets. Rats from each group were killed on days 3, 5, 7, and 9 after tooth extraction. In the diabetic rats treated with BMP-6, there was a cellular subperiosteal reaction at day 3 in the extra-alveolar tissues, which by day 7 had formed a large mass of cartilage. Cartilage was induced in the subperiosteal region of the socket extra-alveolar bone following the application of BMP-6 in the diabetic rat.

Role of p53 deficiency in socket healing after tooth extractions.

p53 is known to advance the cell arrest and cell senescence in human tumors. In this study, we displayed that osteogenic ability of p53-knockout (p53-/-) mice was significantly increased in the tooth extraction socket compared with wild-type (WT) counterparts. Bone marrow mesenchymal stem cells (BM-MSCs) from mandibular were collected and exhibited with elevated proliferation potential and colony-forming units compared with the control, as well as stronger mineral deposits and osteogenic markers. Besides, the bone mass and bone parameter in p53-/- mice were markedly enhanced compared with the counterpart after extractions by micro-CT. Masson's trichrome staining and immunohistochemistry also revealed that new bone filling and osterix/osteocalcin (Osx/OCN)-immunopositive staining in p53-/- mice were remarkably increased at each time point. Furthermore, consistent with the enhanced osteogenic markers, the angiogenic marker of blood vessels (alpha smooth muscle actin, α-SMA) was significantly elevated in p53-/- mice in contrast to WT mice. Importantly, we found that the osteoclast numbers exhibited an increased trend in p53-/- mice compared with WT mice during socket healing. Collectively, our result suggest that p53 deficiency could promote the osteogenesis and angiogenesis in the tooth extraction socket and might lend possibility for p53-based therapeutic approaches in acceleration of extraction bone healing.

The use of TLR2 modified BMSCs for enhanced bone regeneration in the inflammatory micro-environment.

The repair of periodontal bone tissue defects in patients with periodontitis is one of the major challenges for dentists. Stem cell-based bone regeneration has been considered as a promising strategy to restore the lost periodontal bone tissue. However, the local inflammatory environment of periodontal tissue affects stem cell-based periodontal bone regeneration. Toll-like receptor 2 (TLR2), a member of the TLR family, plays an important role in regulating immunoreaction. Previous studies have shown that the activation of TLR2 signaling pathway is involved in enhancing tissue vascularization and wound healing. However, the mechanisms underlying the therapeutic effects of TLR2 on regulating bone marrow stromal cells (BMSCs) mediated periodontal bone tissue regeneration still need to be further investigated. In this study, we tested the effect of TLR2 on regulating BMSCs mediated alveolar bone regeneration by establishing a TLR2 gene-modified canine BMSCs using a lentivirus. Activation of TLR2 significantly enhanced the expression of hypoxia-inducible factor-1α (HIF-1α) and bone morphogenetic protein 2 (BMP-2) and then upregulated the expression of their downstream osteogenic and angiogenic related gene in BMSCs. TLR2-BMSCs mediated bone regeneration in canine tooth extraction sockets under an inflammatory environment demonstrated that activation of the TLR2 signaling pathway significantly stimulated BMSCs meditated angiogenesis and osteogenesis.

Modeling and remodeling of human extraction sockets.

INTRODUCTION: The available studies on extraction wound repair in humans are affected by significant limitations and have failed to evaluate tissue alterations occurring in all compartments of the hard tissue defect. AIM: To monitor during a 6-month period the healing of human extraction sockets and include a semi-quantitative analysis of tissues and cell populations involved in various stages of the processes of modeling/remodeling. MATERIAL AND METHODS: Twenty-seven biopsies, representative of the early (2-4 weeks, n=10), intermediate (6-8 weeks, n=6), and late phase (12-24 weeks, n=11) of healing, were collected and analysed. RESULTS: Granulation tissue that was present in comparatively large amounts in the early healing phase of socket healing, was in the interval between the early and intermediate observation phase replaced with provisional matrix and woven bone. The density of vascular structures and macrophages slowly decreased from 2 to 4 weeks over time. The presence of osteoblasts peaked at 6-8 weeks and remained almost stable thereafter; a small number of osteoclasts were present in a few specimens at each observation interval. CONCLUSIONS: The present findings demonstrated that great variability exists in man with respect to hard tissue formation within extraction sockets. Thus, whereas a provisional connective tissue consistently forms within the first weeks of healing, the interval during which mineralized bone is laid down is much less predictable.

Dense hydroxyapatite inserted into postextraction sockets: a histologic and histomorphometric 20-year case report.

BACKGROUND: The biologic behavior, i.e., the degradation of hydroxyapatite (HA) in the human body, is of relevance for clinicians. The present investigation is a long-term (20-year) histologic and histomorphometric evaluation of dense HA used in postextraction sockets. METHODS: Dense HA particles were used in a patient in postextraction alveolar sockets to maintain the alveolar ridge height. The patient returned after 20 years for implant treatment. A ridge remodeling was necessary during implant insertion surgery, and the HA/bone tissue was harvested with bone-cutting forceps from the canine and premolar area. The specimen was processed for histology and histomorphometry at the Implant Retrieval Centre, Dental School, University of Chieti-Pescara. RESULTS: Most of the particles (56%) were surrounded partially by bone, whereas some particles (39%) were surrounded completely. At higher magnification, bone was in close contact with the particles, and neither gaps nor fibrous tissues were present at the bone-biomaterial interface. Microscopically, the particles had a dense appearance. In only a few fields, it was possible to observe that the outer part of some particles had detached from the original particles' surface. Histomorphometry showed that bone represented 25.4% +/- 3.2%, marrow spaces represented 41.3% +/- 5.2%, and residual HA particles represented 38.1% +/- 4.1%. CONCLUSIONS: Intimate binding between bone and HA particles was present after a long-term implantation period (20 years). The fact that HA particles were surrounded closely by bone is very promising for the long-term stability of the augmentation.

Micro-computed tomography for evaluating alveolar bone resorption induced by hyperocclusion.

PURPOSE: Occlusal trauma, resulting in the destruction of alveolar bone, is a form of periodontal disease caused by excessive mechanical stress (MS) during hyperocclusion. Previously, we showed that CC chemokine ligand (CCL) 2/CCR2 receptor axis plays a crucial role in MS-dependent osteoclastogenesis. However, in the previous work, we were unable to precisely measure changes in alveolar bone profiles. In the present study, we sought to establish a precise method for evaluating alveolar bone resorption induced by hyperocclusion using micro-computed tomography. METHODS: Under anesthesia, a stainless steel wire was attached to the molars of 5-week-old C57/BL6 wild-type (WT) mice, CCL2-/- mice, and CCR2-/-mice to induce occlusal force overload. At days 0 and 7, hard tissue samples were harvested and analyzed by micro-computed tomography. RESULTS: In the WT mice, bone mineral density of the alveolar bone was significantly decreased at day 7 as compared with day 0, with marked alveolar bone resorption observed. Similarly, significant alveolar bone resorption was observed in the CCL2-/- and CCR2-/- mice at day 7 as compared with day 0. CONCLUSIONS: Micro-computed tomographic images can be used to measure changes in bone mineral density in a mouse model of hyperocclusion. This method may be useful for further investigating bone changes in other periodontal disease research fields.

Rapid orthodontic tooth movement aided by alveolar surgery in beagles.

INTRODUCTION: It has been reported that oral surgery can accelerate orthodontic tooth movement. The purpose of this study was to evaluate the effects of alveolar surgery that undermines interseptal bone in orthodontic tooth movement. METHODS: Ten male beagles, aged 12 to 15 months, were used in this study. Extraction of the mandibular second premolar and alveolar surgery to reduce the osteal resistance on the mesial side of the extraction socket were performed on the experimental side; on the control side, only the second premolar was extracted. The first premolars were distalized against the third premolars with orthodontic nickel-titanium coil springs on the both sides. The beagles were killed in the first, second, third, fourth, and eighth weeks after orthodontic force application. RESULTS: The first premolar on the experimental side moved more rapidly than that on the control side (P <.01). Tissue slices were obtained for histological evaluation. No obvious root resorption and no irreversible injury to the pulp were observed on either side. Active and extensive bone resorption in the compressive area and bone deposition in the tension area were observed on the experimental sides. CONCLUSIONS: Self-fluorescence checks showed that more new bone was deposited in the tension area of the experimental side than on the control side (P <.05). These results suggest that alveolar surgery might be an effective and safe way to aid orthodontic tooth movement.

Long-term therapy with intravenous zoledronate increases the number of nonattached osteoclasts.

The purpose of this study was to investigate the influence of long-term therapy with intravenous zoledronate (ZA) on the healing of extraction sockets in rats. Forty rats, divided into groups C (Control) and Z (Zoledronate), received intravenous injections of either saline solution or ZA for 24 weeks. Their right maxillary incisor was extracted. Euthanasia was performed at 7 or 28 days postoperative. Histomorphometric (Newly Formed Bone Area) and immunohistochemical (RANKL, OPG and TRAP) analyses were performed. Data were statistically analyzed (ANOVA, Tukey's test and Kruskal-Wallis, Dunn's Multiple Comparison test).Groups C and Z showed similar new bone area, RANKL and OPG immunolabeling. The number of TRAP-positive multinucleated cells was significantly higher in Group Z than in Group C at 28 days. A significantly higher proportion of nonattached osteoclasts were seen in Group Z than in Group C at both periods of analysis. Long-term therapy with intravenous ZA stimulated nonattached osteoclast formation in extraction sockets in rats, thus decreasing local bone resorption. However, it did not influence bone formation by osteoblasts.