Biomechanical analysis of alveolar bones with compromised quality supporting a 4-unit implant bridge; a possible association with implant-related sequestration (IRS).

OBJECTIVES: This study aimed to investigate the strain in the bone surrounding dental implants supporting a 4-unit bridge and assess the role of excessive strain as a possible risk factor for implant related sequestration (IRS) or peri-implant medication-related osteonecrosis of the jaw (PI-MRONJ). MATERIALS AND METHODS: A 3D-mandibular model was constructed using computed tomography and segmented it into cortical and cancellous bones. The 4-unit implant-supported bridges replacing the mandibular posteriors were constructed, and each featuring two, three, and four implants, respectively. The Young's modulus was assigned based on the quality of the bone. A maximum occlusal force of 200 N was applied to each implant in the axial and in a 30-degree oblique direction. RESULTS: The maximum principal strain of the fatigue failure range (> 3000 µÎµ) in the bone was analyzed. The volume fraction of fatigue failure was higher in poor-quality bone compared to normal bone and oblique load than in axial load. An increasing number of implants may dissipate excessive strain in poor-quality bones. CONCLUSIONS: Occlusal force applied to poor-quality bone can result in microdamage. Given that unrepaired microdamage may initiate medication-related osteonecrosis of the jaw, long-term occlusal force on fragile bones might be a risk factor. CLINICAL RELEVANCE: When planning implant treatment for patients with compromised bone status, clinical modifications such as strategic placement of implants and optimization of restoration morphology should be considered to reduce excessive strain which might be associated with IRS or PI-MRONJ.

Effect of agents affecting bone homeostasis on short- and long-term implant failure.

OBJECTIVES: To review the current evidence on the relationship between agents that affect bone homeostasis and dental implant failures. MATERIALS AND METHODS: Electronic searches for bisphosphonates, denosumab, methotrexate, corticosteroids, romosozumab, sunitinib, and bevacizumab were performed using PubMed, MEDLINE (OVID), EMBASE (OVID), Cochrane Central Register of Controlled Trials (Cochrane Library), Cochrane Oral Health Group Trials Register (Cochrane Library) and Web of Science (Thomson Reuters). Manual searches were also conducted to complement the digital searches for recent issues. RESULTS: Previous publications suggested that bisphosphonates do not compromise the survival of dental implants. However, one study documented an increased risk of implant failure in patients who had received high-dose of intravenous bisphosphonate therapy after implant rehabilitation. There has been an issue of MRONJ around implants in patients who have successfully received implant therapy before and after antiresorptive therapy, leading to late implant failure. Despite evidence on the detrimental effects of denosumab, methotrexate and corticosteroids on bone metabolism, their role in implant survival is not conclusive. CONCLUSIONS: At present, there is insufficient evidence to establish a potential connection between agents that affects bone homeostasis and implant failure. However, some studies have reported negative results for implant therapy. In addition, implant-related sequestration in patients who received anti-resorptive therapy, despite of successful osseointegration, is also noticeable. Although limited studies are available at present, clinicians should still carefully consider the potential hazards and take appropriate precautions to minimize the risks associated with the medications and implant therapy.

Group 3 ITI Consensus Report: Materials and antiresorptive drug-associated outcomes in implant dentistry.

OBJECTIVES: The aim of Working Group 3 was to address the influence of both material- and anti-resorptive drug- related factors on clinical and biological outcomes and complications in implant dentistry. Focused questions were addressed on (a) implant materials other than titanium (alloy)s, (b) transmucosal abutment materials and (c) medications affecting bone metabolism were addressed. MATERIALS AND METHODS: Three systematic reviews formed the basis for discussion in Group 3. Consensus statements and clinical recommendations were formulated by group consensus based on the findings of the systematic reviews. Patient perspectives and recommendations for future research were also conveyed. These were then presented and accepted following further discussion and modifications as required by the plenary. RESULTS: Zirconia is a valid alternative to titanium as material for implant and transmucosal components, allowing soft and hard tissue integration with clinical outcomes-identified by implant survival, marginal bone loss and peri-implant probing depths-up to 5-years comparable to titatnium. However, most of the evidence for zirconia implants is based on 1-piece implants limiting the indication range. Furthermore, based on expert opinion, zirconia transmucosal components might be preferred in the esthetic zone. In patients receiving low-dose bisphosphonate therapy, the rate of early implant failure is not increased, while the long-term effects remain poorly studied. Although it has not been sufficiently addressed, similar outcomes can be expected with low-dose denosumab. A drug holiday is not recommended when considering implant placement in patients treated with low-dose ARD. However, the specific therapeutic window, the cumulative dose and the administration time should be considered. Access to peri-implant supportive care is mandatory to prevent peri-implantitis-related medication-related osteonecrosis of the jaw (MRONJ) or implant-related sequestra (IRS). In patients receiving low-dose anti-resorptive drugs (ARD) therapy, the risk of complications related to implant placement is high, and implant procedures in this specific population should be strictly treated in a comprehensive multidisciplinary center. Finally, healthy dental implants should not be removed before low or high-dose ARD. CONCLUSIONS: Zirconia implants can be an alternative to titanium implants in selected indications. However, the current state of evidence remains limited, especially for 2-piece implant designs. Administration of low-dose ARD did not show any negative impact on early implant outcomes, but careful follow-up and supportive care is recommended in order to prevent peri-implant MRONJ and IRS. Implant placement in high-dose patients must be strictly considered in a comprehensive multidisciplinary center.

EMD-liquid contributes to tissue thickness gain in soft tissue augmentation using a collagen matrix.

OBJECTIVES: To investigate the function of enamel matrix derivative (EMD)-liquid compared to EMD-gel (original Emdogain® with polyglycolic acid-carrier) in inducing soft tissue regeneration using a rat dorsal model. MATERIAL AND METHODS: Four subcutaneous pouches were created through dorsal skin incisions in 18 female Wistar rats and randomly allocated to the following groups: (1) sterile saline + non-crosslinked collagen matrix (CM), (2) EMD-gel + CM, and (3) EMD-liquid + CM. After 2 and 4 weeks of healing, the specimens were harvested and stained with Goldner's trichrome, hematoxylin and eosin, and were immunohistochemically stained with an anti-CD31 antibody. RESULTS: The EMD-liquid group showed the thickest connective tissue compared to the other groups, with statistical significance both at 2 (p < 0.001) and 4 weeks (p = 0.011 and 0.023, respectively). The number of multinucleated giant cells was not significantly different among the groups for both periods. Moreover, there was a tendency to have more blood vessels over a longer period, and the highest number of blood vessels was observed in the EMD-liquid group at 4 weeks (p = 0.009 and 0036, respectively). CONCLUSION: EMD-liquid-treated CM is advantageous compared to using CM alone or EMD-gel-treated CM, owing to the histomorphometric results that show significantly increased soft tissue thickness and number of blood vessels when EMD-liquid was pre-primed to CM. CLINICAL RELEVANCE: EMD with a liquid carrier may be an appropriate biologic supplement to provide cell-inducing properties to the CM scaffold and is clinically more beneficial for phenotype modification therapy than CM only and EMD-gel-treated CM.

Is implant surgery a risk factor for osteonecrosis of the jaw in older adult patients with osteoporosis? A national cohort propensity score-matched study.

OBJECTIVES: This study aimed to investigate the association between dental implant therapy and osteonecrosis of the jaw (ONJ) in osteoporotic patients and the relationship between tooth extraction, dental implantation, and ONJ. MATERIAL AND METHODS: This retrospective cohort study used the Customized Health Information Data from the National Health Insurance Corporation in South Korea. The study population included patients older than 70 years with a history of osteoporosis; the cases included patients who had undergone dental implant surgery between July 2014 and July 2016 with specific procedure codes. The case and control cohorts were stratified by tooth extraction because it was the strongest risk factor to consider in this study. Each group of patients was matched using the propensity score. To investigate the relationship between dental implants and ONJ, a Cox proportional hazard model was applied to socio-economic factors, comorbidities, and bisphosphonates (BPs). All analyses were conducted using SAS statistical software. RESULTS: Based on the fully adjusted model, the propensity score-matched osteoporosis patients with dental implants had a 0.51 times hazard ratio of osteonecrosis. On the contrary, tooth extraction was associated with a higher risk of ONJ (HR = 5.89). The patients with rheumatoid arthritis (RA) and those using BPs had a higher HR, respectively, 6.80 and 4.09 HR (p < .001). CONCLUSIONS: Dental implantation was not a risk factor and patients with implants show rather lower ratios. However, older osteoporotic Korean patients who had undergone tooth extraction had higher risks of ONJ. A significantly higher risk of ONJ was associated with RA and BPs as well.

Effect of enamel matrix derivative liquid combined with synthetic bone substitute on bone regeneration in a rabbit calvarial model.

OBJECTIVES: This study aimed to verify the effectiveness of EMD-liquid in combination with a synthetic bone substitute in a rabbit calvarial model. MATERIAL AND METHODS: Four 7-mm outer diameter circular slits were created in the calvaria of 10 New Zealand white rabbits, and polycarbonate cylinders were inserted into the slits. Two experimental groups were established: (1) EMD-liquid + bone substitute (Osteon III®; biphasic calcium phosphate (BCP), ß-TCP/HA = 40:60) and (2) saline + bone substitute (Osteon III®; BCP). The cylinders were filled with saturated graft materials and covered with polycarbonate caps. Micro-CT and histomorphometric evaluation were conducted. RESULTS: In the histomorphometric analysis, new bone formation was significantly higher in the bone substitute (BS) + EMD-liquid group than in the BS only group at both 5 and 10 weeks (p < 0.01). There were statistically significant differences in the material area between the bone substitute and bone substitute + EMD-liquid groups at only 5 weeks (p < 0.05). The BS + EMD-liquid group demonstrated reduced material area to a greater extent. In micro-CT analysis, the BS + EMD-liquid group (27.04 ± 8.06 at 5 weeks, 28.49 ± 9.22 at 10 weeks) showed a significantly higher percentage of mineralized tissue volume at both 5 and 10 weeks (p < 0.05) than the BS only group. CONCLUSION: EMD-liquid enhances new bone formation when combined with BCP bone substitute in an animal model. Moreover, the EMD-liquid + BS has significantly lesser material area than BS alone, indicating accelerated graft degradation. Further studies on types of graft materials are required to verify the effect of EMD-liquid and to optimize its regenerative potential. CLINICAL RELEVANCE: This study suggests that EMD-liquid may have beneficial effect on bone regeneration with synthetic bone substitute.

Axial Triangle of the Maxillary Sinus, and its Surgical Implication With the Position of Maxillary Sinus Septa During Sinus Floor Elevation: A CBCT Analysis.

The aim of this study was to measure the convexity of the lateral wall of the maxillary (Mx) sinus and identify the locational distribution of antral septa in relation to the zygomaticomaxillary buttress (ZMB), in order to suggest another anatomical consideration and surgical modification of sinus floor elevation procedures. This study was designed as a cross-sectional study, and a total of 134 patients and 161 sinuses containing edentulous alveolar ridges were analyzed. The angle between the anterior and lateral walls of the Mx sinus (lateral sinus angle [LSA]), and the angle between the midpalatal line and the anterior sinus wall (anterior sinus angle [ASA]) were measured. Mean LSAs and ASAs were 105.9° ± 9.86° and 58.4° ± 6.43°, respectively. No significant difference between left and right sides was found (LSA, P = .420; right = 105.5° ± 9.27°; left = 105.5° ± 9.27° and ASA, P = .564; right = 57.9° ± 6.80°; left = 58.8° ± 6.02°). The prevalence of septa was 37.3%, and it was most frequently noted in the second molar region (32.8%), followed by the first molar (20.9%), retromolar (16.4%), and second premolar regions (14.9%). Septa were most frequently located posterior to the ZMB (49.2%), while ZMB was mostly located in the first molar region (66.4%). Narrow LSAs may complicate the surgical approach to the posterior maxilla, especially when sinus elevation should be used in the second molar region. Considering the occasional presence of antral septa, membrane elevation may be complicated when a septum is encountered during the procedure. These results suggest that 3-dimensional examination of the convexity of the Mx sinus should be performed preoperatively to choose proper surgical techniques and minimize surgical complications.

Bisphosphonates hinder osteoblastic/osteoclastic differentiation in the maxillary sinus mucosa-derived stem cells.

OBJECTIVES: Although bisphosphonates (BPs) are known to be associated with osteonecrosis of the maxilla, the precise effects of BPs on bone metabolism in human maxillary sinus mucosal cells (HMSMCs) are not yet known. The purposes of this study were to examine the effects of the BPs zoledronate (ZOL) and alendronate (ALN) on osteoblastic and osteoclastic differentiation in HMSMCs and to investigate the signaling pathways involved. MATERIALS AND METHODS: The effects of ZOL and ALN were assessed for osteoblast differentiation by alkaline phosphatase (ALP) activity, alizarin red staining, and RT-PCR for genes encoding Runx2 and osterix. Receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclast differentiation in bone marrow macrophages (BMMs) was also examined. RESULTS: ZOL and ALN both suppressed osteoblastic differentiation, as evidenced by their effects on ALP activity, mineralization nodule formation, and the mRNA expression levels of osteoblastic transcript factors. The RANKL/osteoprotegerin ratio in HMSMCs was increased by ALN, whereas ZOL had the opposite effect. Conditioned medium obtained from ALN-treated HMSMCs stimulated osteoclast formation and upregulated NFATc1 expression, whereas conditioned medium from ZOL-treated cells did not. ALN was more cytotoxic and stimulated apoptosis more strongly than ZOL. BPs decreased the protein levels of the non-canonical Wnt signaling protein Wnt5a and calmodulin-dependent kinase II. Moreover, recombinant human Wnt5a reversed the effects of BPs on osteoblastic and osteoclastic differentiation. CONCLUSION: This study is the first demonstration that BPs exert negative effects on osteoblastic and osteoclastic processes via the non-canonical Wnt pathway in HMSMSCs. CLINICAL RELEVANCE: It suggests that patients taking BPs during the period of maxillary sinus lifting and amentation should be given special attention.

Effects of an oral bisphosphonate and three intravenous bisphosphonates on several cell types in vitro.

OBJECTIVE: To analyze the influence of an oral bisphosphonate and compare the potency to intravenous bisphosphonates on various cell types as regards the rarity of bisphosphonate-associated osteonecrosis of the jaw (BP-ONJ) caused by oral bisphosphonate. MATERIALS AND METHODS: A viability assay (MTT), a migration assay (Boyden chamber), and an apoptosis assay (Caspase-Glo® 3/7) were performed to analyze the effect of bisphosphonates on human fibroblasts, umbilical vein endothelial cells (HUVEC), and osteoblasts. RESULTS: Alendronate and intravenous bisphosphonates suppressed cell viability and migration, and induced apoptosis in all tested cell types. Alendronate had a greater impact than ibandronate on the characteristics in fibroblasts and osteoblasts but not as strong as zoledronate. CONCLUSIONS: The incidence of BP-ONJ in oral bisphosphonate treatment is reported to be much lower than that in intravenous bisphosphonates. However, the influences of alendronate on human cells were at least as strong as ibandronate, although it was lower than zoledronate. CLINICAL RELEVANCE: Alendronate showed strong enough effects to suppress human somatic cells and was comparable to certain intravenous bisphosphonates in potency. This study suggests that the lower incidence of BP-ONJ in alendronate treatment is not originated by its potency, but might be due to the low bioavailability of alendronate, lower dosing on a daily basis, and having no additional therapies.

A 10-Year Cone Beam Computerized Tomography Observation of the Buccal Bony Wall of an Immediately Placed Implant at the Anterior Maxilla: A Case Report.

Since the introduction of immediate implant placements, the buccal bony wall has been a major consideration for success due to its correlation with soft tissue contour and color. This report presents the stability of the buccal wall thickness of an immediately placed implant at the anterior maxilla over 10 years. Although the width of the buccal wall decreased at the 2-year post-op follow-up, it remained stable afterward according to cone beam computerized tomography (CBCT) scans. Hence, this report suggests that ensuring adequate bony wall thickness with bone augmentation and fixture position may promise the longevity of the buccal bony wall and surrounding soft tissue in an immediate implant placement.

Engineering three dimensional micro nerve tissue using postnatal stem cells from human dental apical papilla.

The in vitro generation of cell-based three dimensional (3D) nerve tissue is an attractive subject to improve graft survival and integration into host tissue for neural tissue regeneration or to model biological events in stem cell differentiation. Although 3D organotypic culture strategies are well established for 3D nerve tissue formation of pluripotent stem cells to study underlying biology in nerve development, cell-based nerve tissues have not been developed using human postnatal stem cells with therapeutic potential. Here, we established a culture strategy for the generation of in vitro cell-based 3D nerve tissue from postnatal stem cells from apical papilla (SCAPs) of teeth, which originate from neural crest-derived ectomesenchyme cells. A stem cell population capable of differentiating into neural cell lineages was generated during the ex vivo expansion of SCAPs in the presence of EGF and bFGF, and SCAPs differentiated into neural cells, showing neural cell lineage-related molecular and gene expression profiles, morphological changes and electrophysical property under neural-inductive culture conditions. Moreover, we showed the first evidence that 3D cell-based nerve-like tissue with axons and myelin structures could be generated from SCAPs via 3D organotypic culture using an integrated bioprocess composed of polyethylene glycol (PEG) microwell-mediated cell spheroid formation and subsequent dynamic culture in a high aspect ratio vessel (HARV) bioreactor. In conclusion, the culture strategy in our study provides a novel approach to develop in vitro engineered nerve tissue using SCAPs and a foundation to study biological events in the neural differentiation of postnatal stem cells. Biotechnol. Bioeng. 2017;114: 903-914. © 2016 Wiley Periodicals, Inc.

A retrospective study of osteomyelitis and osteonecrosis of the jaws and its etiologic implication of bisphosphonate in Asians.

OBJECTIVE: The objective of this study were to find the annual case trend of inflammatory jawbone diseases and to investigate the impact of medication-related osteonecrosis of the jaws (MRONJ). MATERIAL AND METHODS: A retrospective study of 372 patients diagnosed with inflammatory jawbone condition except for alveolar osteitis from 2007 to 2015 was initiated. History taking and investigation of etiologic factors MRONJ, osteoradionecrosis (ORN), odontogenic infection, foreign body, and trauma were investigated. A separate analysis showed the number of MRONJ cases in two age groups (under 70 years; 70 years and over) and serum C-terminal peptide (s-CTX) values that were found. RESULTS: The results showed that the number of MRONJ cases was significantly larger in the older age group (p < 0.05). Regarding gender and sites of lesions, MRONJ was significantly frequent in the female and the mandible (p < 0.05). The R 2 values for the regression analysis for MRONJ (R 2 = 0.9234) and odontogenic etiology (R 2 = 0.0427) signified linear increase in the number of MRONJ cases, whereas bone lesions due to traditional odontogenic etiology stayed stationary. CONCLUSION: The number of MRONJ has escalated, and most of the patients are elderly people. The current trend of inflammatory conditions of the jaw may have changed since the advent of MRONJ. CLINICAL RELEVANCE: Long-term bisphosphonate therapy became a major risk factor for the osteomyelitis and osteonecrosis of the jaws. Thorough medical history, taking would be essential and communication with prescribing physicians should be emphasized during the dental treatment planning.

Orthodontic Treatment in Conjunction with Twin-bock Treatment and Growth Hormone Therapy in Silver Russell Syndrome.

Silver-Russell syndrome (SRS) is a very rare genetic disorder characterized by intrauterine growth retardation, short stature, and typical craniofacial abnormalities including micrognathia. While growth hormone (GH) therapy in children with SRS significantly improves somatic growth, functional orthopedic treatment can also be effective in adolescents with mandibular deficiency. We report the effects of Phase 1 functional orthopedic treatment of a twin-block appliance in conjunction with GH administration in a 9-year-old boy with GH deficiency and SRS, and the result of the subsequent Phase 2 orthodontic treatment.

Volume stability of hydroxyapatite and ß-tricalcium phosphate biphasic bone graft material in maxillary sinus floor elevation: a radiographic study using 3D cone beam computed tomography.

OBJECTIVES: The purpose of this study was to confirm volume stability of biphasic calcium phosphate (BCP) through the changes of grafted volume over the time by 3D CT analyzing software program. PATIENTS AND METHODS: Fifteen patients, 16 sinuses who were scheduled a staged implantation through sinus floor elevation (SFE)-lateral window technique from 2009 to 2011 were included in the study. Of the 15 patients, eight were male and seven were female (mean age 50.1). For sinus floor augmentation, BCP with local blood was packed loosely into the maxillary sinus and the grafted site was covered with a collagen membrane. For the evaluation of volume change, 3D CBCT scans were taken five times at pre-operatively (To), post-op 1 week (T1), 1 month (T2), 3 months (T3), and 6 months (T4). 3D image processing software (OnDemand3DTM software) was used for this study. The time sequential change was statistically evaluated. RESULT: 84.32% grafted BCP is maintained until post-op 6 month (T4), and the average volume loss is 207.7 mm(3) (about 0.21 cc). Statistically, a significant volume change (decreasing) was observed in three groups (T2-T1, T3-T2, T4-T3). CONCLUSION: Biphasic calcium phosphate, as a synthetic material, has high volume stability and is a predictable graft material for the successful SFE. Although some limitations of the 3D analyzing software program, it is a fast, simple, relatively accurate and promising approach to quantifying long-term changes in the grafted area.

Three-dimensional evaluation of the pharyngeal airway using cone-beam computed tomography following bimaxillary orthognathic surgery in skeletal class III patients.

OBJECTIVE: The study aims to evaluate the pharyngeal airway space (PAS) following bimaxillary surgery in skeletal class III patients and to compare the changes in PAS between genders using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: In all, 38 patients (16 male and 22 female) with skeletal class III malocclusion underwent bimaxillary surgery. CBCT scans were acquired approximately 1 month before surgery, 3 months after surgery, and 6 months after surgery. The oropharyngeal volume and the minimum cross-sectional area (CSA) were characterized using the InVivoDental imaging software package at each time point. RESULTS: The volume and minimum CSA decreased significantly postoperatively, which was maintained until 6 months postoperatively (p < 0.01). The location of the minimum CSA tended to move into the retropalatal and retroglossal areas postoperatively. A strong correlation between volume and minimum CSA was found. The amount of mandibular setback was not correlated with the change in the airway. By gender, significant decreases in both the volume and minimum CSA were found in females (p < 0.05) but not in males. CONCLUSION: Bimaxillary surgery significantly affects PAS. Gender differences should also be considered when considering changes in PAS. CLINICAL RELEVANCE: An awareness of the effects of bimaxillary setback surgery on the airway should be considered when implementing an orthognathic treatment plan.

Piezoelectric Trapezoidal Osteotomy for the Retrieval of a Displaced Dental Implant in the Osteoporotic Mandibular Body.

A female patient in her mid-seventies was referred to our department for the removal of a displaced implant within the right posterior mandible. A trapezoidal window was made using a piezoelectric device. The implant was extracted, and the osteotomized window was replaced without fixation. Caution should be exercised during implant placement in patients with osteoporosis because of the risk of implant displacement. Displaced implants can be easily retrieved by piezoelectric trapezoidal osteotomy.

Fabricating a tooth- and implant-supported maxillary obturator for a patient after maxillectomy with computer-guided surgery and CAD/CAM technology: A clinical report.

An obturator prosthesis with insufficient retention and support may be improved with implant placement. However, implant surgery in patients after maxillary tumor resection can be complicated because of limited visibility and anatomic complexity. Therefore, computer-guided surgery can be advantageous even for experienced surgeons. In this clinical report, the use of computer-guided surgery is described for implant placement using a bone-supported surgical template for a patient with maxillary defects. The prosthetic procedure was facilitated and simplified by using computer-aided design/computer-aided manufacture (CAD/CAM) technology. Oral function and phonetics were restored using a tooth- and implant-supported obturator prosthesis. No clinical symptoms and no radiographic signs of significant bone loss around the implants were found at a 3-year follow-up. The treatment approach presented here can be a viable option for patients with insufficient remaining zygomatic bone after a hemimaxillectomy.

From newborn to toddler: report of two cases of congenital granular cell tumor.

A congenital granular cell tumor (CGCT) is an uncommon benign soft tissue lesion that usually arises from the alveolar ridge in newborns. It can severely interfere with the respiratory and feeding systems, if left untreated. We present the cases of 2 newborn infants with protruded intraoral tumors that severely compromised breastfeeding. The tumors were removed by water laser without the need for suturing or pain medication. Histopathologic assessment was performed for definitive diagnosis, and the children were followed until full primary dentition was observed without any sign of CGCT recurrence.

Could zoledronic acid prevent root resorption in replanted rat molar?

BACKGROUND/AIM: In this study, we evaluated whether zoledronate could suppress the progression of external root resorption in rat due to delayed replantation by inhibiting osteoclastic activity. Also, we estimated the optimal dosage of zoledronate in root treatment of the rat model for a maximum effect of zoledronate. MATERIAL AND METHODS: Maxillary first molars in Sprague Dawley rats (N = 84) were extracted, dried for 60 min, and then replanted. The rats were divided into 6 groups (1 mM alendronate, and 1, 5, 10, 20, 40 µM zoledronate). At 4 and 8 weeks postreplantation, the animals were sacrificed and evaluated by radiographic and histological analysis. RESULTS AND CONCLUSION: There were no significant differences at 4 weeks. However, at 8 weeks, 10, 20, and 40 µM ZOL showed more increased radiopaque and smaller periapical lesion in radiographic analysis. In histological analysis, all groups showed similar inflammatory root resorption rate at 4 weeks. However, at 8 weeks, 20 and 40 µM ZOL showed lower rate than those of other groups (P < 0.05). In concerning of replacement resorption, there were no significant differences statistically. In this animal experiment, zoledronate was capable of limiting the occurrence of root resorption in delayed replantation model. In particular, 20 µM dosage of zoledronate solution showed the most effective dose in long-term follow up and might be suitable for inhibition of root resorption in delayed tooth replantation.