Comparison of dental plaque flora between intellectually disabled patients and healthy individuals: a cross-sectional study.

Periodontal diseases, including gingivitis, are highly prevalent in individuals with intellectual disability (ID). In particular, gingivitis can be difficult to cure owing to the lack of patient cooperation. Here, we evaluated differences in the oral bacterial flora between individuals with ID (n = 16) and healthy controls (n = 14) to facilitate the development of strategies for the prevention of periodontal disease in people with ID. Our results showed no significant difference in the number of decayed, missing, and filled teeth between the two groups. However, there were significant differences in the median papillary-marginal-attached index, plaque index, and gingival index between groups (P < 0.0001). Additionally, the mean probing depth in the ID group was significantly higher than that in the control group (P < 0.0001). The diversity of oral flora in people with ID and concurrent gingivitis was significantly lower than that of healthy individuals without periodontal disease. The relative abundances of Tannerella spp. and Treponema spp. were significantly higher in the ID group than in the control group at the genus level (P = 0.0383 and 0.0432, respectively), whereas that of Porphyromonas spp. was significantly lower in the ID group (P < 0.0001). Overall, our findings provided important insights into differences in the oral microbiota between patients with ID and healthy controls.

Comparative analysis of the retention force and deformation of PEEK and PEKK removable partial denture clasps with different thicknesses and undercut depths.

STATEMENT OF PROBLEM: The retentive force and deformation of milled polyetheretherketone (PEEK) and polyetherketoneketone (PEKK) removable partial denture (RPD) frameworks are not well understood. PURPOSE: The purpose of this in vitro study was to assess the retentive force and deformation of PEEK and PEKK Akers clasps with different designs and undercut depths. MATERIAL AND METHODS: A master model containing the first and second molar abutments was used to design Akers clasps of different cross-sectional dimensions, undercut depths (0.5 and 0.75 mm), and materials. The components of the removable partial denture framework also included an occlusal rest and were manufactured using a milling machine (n=5). The fatigue resistance of the Akers clasps was measured before and after deformation regarding the retentive forces. RESULTS: The PEEK2-U50 clasp had the largest retentive force with no significant difference among all groups before and after the insertion and removal cycle. In addition, the increased cross-sectional dimensions of the design resulted in significant differences in retentive forces between the PEEK1 and PEEK2 groups and between the PEEK and PEKK materials. CONCLUSIONS: Increasing the clasp's cross-sectional dimensions significantly impacted retentive forces, especially between different PEEK groups and between PEEK and PEKK materials.

Entire Dental Arch Mesial Movement after Extraction of Maxillary Right Central Incisor due to Root Fracture Treated with Temporary Anchorage Devices.

This case report describes a 19-year-old woman with skeletal Class I crowding and an unsalvageable maxillary right central incisor. She visited our clinic with the chief complaint of mobility of the maxillary right central incisor due to a traffic accident. After extraction of the maxillary right central incisor, the space was closed orthodontically. All the maxillary right teeth were moved mesially with an elastic chain attached to a palatal lever arm which was connected to palatal temporary anchorage devices (TADs). After orthodontic treatment had been completed, the maxillary right lateral incisor and peg-shaped left lateral incisor were restored with a porcelain laminate veneer. The maxillary right canine was morphologically reshaped and built up with composite resin. Consequently, esthetically ideal occlusion and functional lateral guidance with uncontacted molars were obtained. These results show that mesial movement of the entire dental arch with TADs is a useful orthodontic treatment option in patients in whom the maxillary central incisor has been extracted.

Effect of CD146+ SHED on bone regeneration in a mouse calvaria defect model.

OBJECTIVE: Stem cells from human exfoliated deciduous teeth (SHED) have bone regeneration ability and potential therapeutic applications. CD146, a cell adhesion protein expressed by vascular endothelial cells, is involved in osteoblastic differentiation of stem cells. The effect of CD146 on SHED-mediated bone regeneration in vivo remains unknown. We aimed to establish efficient conditions for SHED transplantation. MATERIALS AND METHODS: SHED were isolated from the pulp of an extracted deciduous tooth and cultured; CD146-positive (CD146+ ) and CD146-negative (CD146- ) populations were sorted. Heterogeneous populations of SHED and CD146+ and CD146- cells were transplanted into bone defects generated in the skulls of immunodeficient mice. Micro-computed tomography was performed immediately and 4 and 8 weeks later. Histological and immunohistochemical assessments were performed 8 weeks later. RESULTS: Bone regeneration was observed upon transplantation with CD146+ and heterogeneous populations of SHED, with significantly higher bone regeneration observed with CD146+ cells. Bone regeneration was higher in the CD146- group than in the control group, but significantly lower than that in the other transplant groups at 4 and 8 weeks. Histological and immunohistochemical assessments revealed that CD146+ cells promoted bone regeneration and angiogenesis. CONCLUSION: Transplantation of CD146+ SHED into bone defects may be useful for bone regeneration.

Occlusal Trauma and Bisphosphonate-Related Osteonecrosis of the Jaw in Mice.

Osteonecrosis of the jaw (ONJ) is a serious adverse event that is associated with antiresorptive agents, and it manifests as bone exposure in the maxillofacial region. Previous clinical reports suggest that mechanical trauma would trigger ONJ in a manner that is similar to tooth extractions. To the best of our knowledge, there have been few detailed pathophysiological investigations of the mechanisms by which occlusal/mechanical trauma influences ONJ. Here, we developed a novel mouse model that exhibits ONJ following experimental hyperocclusion and nitrogen-containing bisphosphonate (N-BP) treatment. This in vivo model exhibited ONJ in alveolar bone, particularly in the mandible. Moreover, the experimental hyperocclusion induced remarkable alveolar bone resorption in both mouse mandible and maxilla, whereas N-BP treatment completely prevented alveolar bone resorption. In this study, we also modeled trauma by exposing clumps of mesenchymal stem cells (MSCs)/extracellular matrix complex to hydrostatic pressure in combination with N-BP. Hydrostatic pressure loading induced lactate dehydrogenase (LDH) release by calcified cell clumps that were differentiated from MSCs; this LDH release was enhanced by N-BP priming. These in vivo and in vitro models may contribute further insights into the effect of excessive mechanical loading on ONJ onset in patients with occlusal trauma.

Simulation and navigation of living donor hepatectomy using a unique three-dimensional printed liver model with soft and transparent parenchyma.

Three-dimensional printed liver models have been used for preoperative simulation. Unlike the standard three-dimensional system on a monitor, the three-dimensional printed model can be observed from any angle manually; therefore, surgeons can obtain a clear image directly from the model. We herein report the use of a unique three-dimensional liver model with a soft and transparent liver parenchyma. Through the parenchyma, the surgeons can observe the intrahepatic vessels and perform incisions in the model as a preoperative simulation. In this study, we applied this model to donor hepatectomy, which under most circumstances requires meticulous attention to detail. The actual processes and uses of a three-dimensional liver model in clinical surgery for liver transplantation are presented.

Occlusal support is associated with nutritional improvement and recovery of physical function in patients recovering from hip fracture.

OBJECTIVE: This study aimed to elucidate the association between occlusal support and nutritional improvement and recovery of activities of daily living (ADLs) among elderly patients recovering from hip fracture. BACKGROUND: Many patients with hip fracture are malnourished, and malnutrition is associated with poor functional outcomes. Poor oral status is one reason for malnutrition because loss of occlusal support leads to masticatory disorders and can cause nutrient deficiencies. METHODS: We evaluated 202 elderly patients aged 65 years and older (mean age, 84.9 ± 7.9 years). We assessed nutritional status using the Mini Nutritional Assessment-Short Form and ADLs using functional independence measure (FIM) scores. Occlusal support was recorded in accordance with the Eichner Index. We categorised participants into two groups according to the presence or absence of occlusal support, and statistical analyses were performed to investigate the differences between the groups. RESULTS: One group contained 152 participants (mean age, 85.5 ± 7.4 years) with occlusal support, and the other group contained 50 participants (mean age, 83.0 ± 8.9 years) without occlusal support. The group with occlusal support had greater gain of FIM and higher FIM efficiency than did the other group. Multivariate analyses showed that occlusal support was independently associated with nutritional improvement [odds ratio (OR) = 4.00, 95% confidence intervals (CI) = 1.90-8.43] and motor FIM efficiency (R2  = .338, P < .001). CONCLUSIONS: Our findings suggest that occlusal support is associated with nutritional improvement and the recovery of ADLs in patients recovering from hip fracture.

Comparison of the bone regeneration ability between stem cells from human exfoliated deciduous teeth, human dental pulp stem cells and human bone marrow mesenchymal stem cells.

Cleft lip and palate is the most common congenital anomaly in the orofacial region. Autogenous iliac bone graft, in general, has been employed for closing the bone defect at the alveolar cleft. However, such iliac bone graft provides patients with substantial surgical and psychological invasions. Consequently, development of a less invasive method has been highly anticipated. Stem cells from human exfoliated deciduous teeth (SHED) are a major candidate for playing a significant role in tissue engineering and regenerative medicine. The aim of this study was to elucidate the nature of bone regeneration by SHED as compared to that of human dental pulp stem cells (hDPSCs) and bone marrow mesenchymal stem cells (hBMSCs). The stems cells derived from pulp tissues and bone marrow were transplanted with a polylactic-coglycolic acid barrier membrane as a scaffold, for use in bone regeneration in an artificial bone defect of 4 mm in diameter in the calvaria of immunodeficient mice. Three-dimensional analysis using micro CT and histological evaluation were performed. Degree of bone regeneration with SHED relative to the bone defect was almost equivalent to that with hDPSCs and hBMSCs 12 weeks after transplantation. The ratio of new bone formation relative to the pre-created bone defect was not significantly different among groups with SHED, hDPSCs and hBMSCs. In addition, as a result of histological evaluation, SHED produced the largest osteoid and widely distributed collagen fibers compared to hDPSCs and hBMSCs groups. Thus, SHED transplantation exerted bone regeneration ability sufficient for the repair of bone defect. The present study has demonstrated that SHED is one of the best candidate as a cell source for the reconstruction of alveolar cleft due to the bone regeneration ability with less surgical invasion.

Human odontogenic epithelial cells derived from epithelial rests of Malassez possess stem cell properties.

Epithelial cell rests of Malassez (ERM) are quiescent epithelial remnants of the Hertwig's epithelial root sheath (HERS) that are involved in the formation of tooth roots. ERM cells are unique epithelial cells that remain in periodontal tissues throughout adult life. They have a functional role in the repair/regeneration of cement or enamel. Here, we isolated odontogenic epithelial cells from ERM in the periodontal ligament, and the cells were spontaneously immortalized. Immortalized odontogenic epithelial (iOdE) cells had the ability to form spheroids and expressed stem cell-related genes. Interestingly, iOdE cells underwent osteogenic differentiation, as demonstrated by the mineralization activity in vitro in mineralization-inducing media and formation of calcification foci in iOdE cells transplanted into immunocompromised mice. These findings suggest that a cell population with features similar to stem cells exists in ERM and that this cell population has a differentiation capacity for producing calcifications in a particular microenvironment. In summary, iOdE cells will provide a convenient cell source for tissue engineering and experimental models to investigate tooth growth, differentiation, and tumorigenesis.

Accuracy of a three-dimensional dentition model digitized from an interocclusal record using a non-contact surface scanner.

OBJECTIVES: For orthodontic treatment, it is important to assess the dental morphology, as well as the position and inclination of teeth. The aim of this article was to develop an efficient and accurate method for the three-dimensional (3D) imaging of the maxillary and mandibular dental morphology by measuring interocclusal records using an optical scanner. MATERIALS AND METHODS: The occlusal and incisal morphology of participants was registered in the intercuspal position using a hydrophilic vinyl polysiloxane and digitized into 3D models using an optical scanner. Impressions were made of the maxilla and mandible in alginate materials in order to fabricate plaster models and created into 3D models using the optical scanner based on the principal triangulation method. The occlusal and incisal areas of the interocclusal records were retained. The buccal and lingual areas were added to these regions entirely by the 3D model of the plaster model. The accuracy of this method was evaluated for each tooth, with the dental cast 3D models used as controls. RESULTS: The 3D model created from the interocclusal record and the plaster model of the dental morphology was analysed in 3D software. The difference between the controls and the 3D models digitized from the interocclusal records was 0.068±0.048mm, demonstrating the accuracy of this method. LIMITATIONS: The presence of severe crowding may compromise the ability to separate each tooth and digitize the dental morphology. CONCLUSIONS: The digitization method in this study provides sufficient accuracy to visualize the dental morphology, as well as the position and inclination of these teeth.

Inhibition of RANKL-dependent cellular fusion in pre-osteoclasts by amiloride and a NHE10-specific monoclonal antibody.

The functions of Na(+) /H(+) exchangers (NHEs) during osteoclastic differentiation were investigated using the NHE inhibitor amiloride and a monoclonal antibody (MAb). Compared with sRANKL-stimulated control cells, amiloride decreased the number of large TRAP-positive osteoclast cells (OCs) with ≥10 nuclei and increased the number of small TRAP-positive OCs with ≤10 nuclei during sRANKL-dependent osteoclastic differentiation of RAW264.7 cells. NHE10 mRNA expression and OC differentiation markers were increased by sRANKL stimulation in dose- and time-dependent manners. NHEs 1-9 mRNA expression was not increased by sRANKL stimulation. Similar to amiloride, a rat anti-mouse NHE10 MAb (clone 6B11) decreased the number of large TRAP-positive OCs, but increased the number of small TRAP-positive OCs. These findings suggested that inhibition of NHEs by amiloride or an anti-NHE10 MAb prevented sRANKL-promoted cellular fusion. The anti-NHE10 MAb has the potential for use as an effective inhibitor of bone resorption for targeted bone disease therapy.

Involvement of ERK and p38 MAPK pathways on Interleukin-33-induced RANKL expression in osteoblastic cells.

The receptor activator of NF-κB ligand (RANKL)/osteoprotegerin (OPG) system is a well-known key factor in osteoclast differentiation, and osteoblastic lineage cells are the major sources of RANKL and OPG in local bone tissue. Recently, a new molecule from the interleukin (IL)-1 family, IL-33, was identified. Here, we report the possible involvement of IL-33 in RANKL and OPG expression, and the signaling pathways that are required for maximal IL-33-induced RANKL expression in MC3T3-E1 osteoblastic cells. Stimulation with IL-33 increased the mRNA expression and secretion of RANKL in MC3T3-E1 cells. The IL-33-induced RANKL mRNA expression was inhibited by an anti-IL-33 monoclonal antibody. Furthermore, ERK and p38 MAPK inhibitors, but not a JNK inhibitor, suppressed IL-33-induced RANKL mRNA expression. On the other hand, IL-33 had no effect on OPG mRNA expression and protein secretion. These results taken together suggest that IL-33 stimulates RANKL expression through mechanisms dependent on the ERK and p38 MAPK pathways in MC3T3-E1 cells.

Wisdom Tooth Autotransplantation for the Missing Maxillary Central Incisors Using a 3D-Printed Replica: A Case Report.

In this case report, we describe a 19-year-old man who underwent an autotransplantation of a lower third molar into the extracted region of his upper central incisors. Due to trauma, the patient's upper right and left central incisors had been extracted. He visited our clinic and requested to perform autotransplantation of his own teeth into the upper central incisor part because he wanted to use his natural teeth. So, we decided to extract his lower right third molar and autotransplant it into the extraction part of the upper central incisors. Immediately after extraction of the lower right third molar, the tooth was autotransplanted into the upper anterior region using a 3D-printed resin replica of the donor tooth and artificial sockets of the recipient site. Then, the root canal treatment was performed, and a temporary crown was set. Next, orthodontic treatment was done to flatten the curve of Spee. After completing the orthodontic treatment, a final prosthodontic restoration was set on the autotransplanted tooth. Four years later, the autotransplanted tooth remained stable with a healthy periodontium. This case demonstrates that if a patient has a request to use their natural teeth, autotransplantation of a wisdom tooth into the anterior region can be a useful method to replace the missing teeth.

Effects of various functional monomers' reaction on the surface characteristics and bonding performance of polyetheretherketone.

PURPOSE: Polyetheretherketone (PEEK) is a new polymeric material that has received significant attention in dentistry because of its mechanical properties, biocompatibility, and aesthetics. However, the bonding performance of PEEK to other materials is not preferable. This study aimed to analyze the variations in the surface characteristics of PEEK under the chemical action of primers containing different functional monomers or polymers and to evaluate the bonding performance of PEEK and dental cement. METHODS: Disk-shaped PEEK samples were prepared by dental milling, blasting with alumina oxide, and covering with primers containing functional monomers or polymers. The surface characteristics of the samples were analyzed by microscopy and spectroscopy. The shear bond strength (SBS) between PEEK and dental cement, with and without thermocycling, was tested using a universal testing machine. Finally, the data were statistically analyzed and compared. RESULTS: Functional monomers or polymers were successfully bonded to the surface of PEEK. This treatment significantly improved its hydrophilicity and surface free energy (P < 0.05). The primer containing pentaerythritol triacrylate had the highest SBS without thermocycling (13.89 MPa). Meanwhile, the primers containing urethane dimethacrylate (UDMA) and methyl methacrylate (MMA) (abbreviated as the HC group) showed the highest SBS and lowest reduction (25.51%) after thermocycling. Notably, all the testing groups achieved the ISO10477 standard of 5 MPa. After thermocycling, adhesive failure accounted for the largest proportion of failures in all the groups except the HC group. CONCLUSIONS: The chemical priming treatment can significantly improve the SBS of PEEK and dental cement. Moreover, a primer containing both UDMA and MMA can provide improved bonding for PEEK materials.

In vitro study of optimal removable partial denture clasp design made from novel high-performance polyetherketoneketone.

PURPOSE: This study aimed to investigate the retentive force and deformation of double Akers' polyetherketoneketone (PEKK) clasps on removable partial dentures (RPDs) with varying designs and undercut depths. METHODS: Thirty double Akers' PEKK clasps with two different widths and heights (Groups I and II) were fabricated using computer-aided design and computer-aided manufacturing (CAD/CAM). Each design was further subdivided (n = 5) into three undercut depths (0.25, 0.50, and 0.75 mm). The retentive force of the clasps was measured after 10 years of clinical use (15,000 insertion/removal cycles), and the deformation of the clasp tips was analyzed before and after cycling. RESULTS: Clasps with 0.50-mm and 0.75-mm undercut depths exhibited greater initial retentive forces (3.15-3.51 N) compared to those in the 0.25-mm undercut group (2.40-2.80 N). Group I maintained consistent retentive forces over the cycles (P = 0.345), whereas Group II showed declining forces after the initial use (P < 0.003). In both groups, the 0.50-mm undercut exhibited a greater retentive force than the 0.25-mm (P < 0.001 and P < 0.004, respectively), with no significant differences between the 0.50-mm and 0.75-mm undercut depths. Despite a lower initial retentive force, the 0.25-mm undercut showed less deformation and clasp tip wear. CONCLUSIONS: The PEKK clasps did not exhibit significantly reduced retentive forces or permanent deformations after 15,000 fatigue cycles. These results suggest that the PEKK polymer displays superior mechanical properties as an esthetic clasp material, and clasps with 0.50-mm and 0.75-mm undercut depths are recommended for long-term clinical use.

Trisomy 12 compromises the mesendodermal differentiation propensity of human pluripotent stem cells.

Trisomy 12 is one of the most frequent chromosomal abnormalities in cultured human pluripotent stem cells (hPSCs). Although potential oncogenic properties and augmented cell cycle caused by trisomy 12 have been reported, the consequences of trisomy 12 in terms of cell differentiation, which is the basis for regenerative medicine, drug development, and developmental biology studies, have not yet been investigated. Here, we report that trisomy 12 compromises the mesendodermal differentiation of hPSCs. We identified sublines of hPSCs carrying trisomy 12 after their prolonged culture. Transcriptome analysis revealed that these hPSC sublines carried abnormal gene expression patterns in specific signaling pathways in addition to cancer-related cell cycle pathways. These hPSC sublines showed a lower propensity for mesendodermal differentiation in embryoid bodies cultured in a serum-free medium. BMP4-induced exit from the self-renewal state was impaired in the trisomy 12 hPSC sublines, with less upregulation of key transcription factor gene expression. As a consequence, the differentiation efficiency of hematopoietic and hepatic lineages was also impaired in the trisomy 12 hPSC sublines. We reveal that trisomy 12 disrupts the genome-wide expression patterns that are required for proper mesendodermal differentiation.

Comparison of the accuracy of different handheld-type scanners in three-dimensional facial image recognition.

PURPOSE: Handheld-type scanners are widely used in clinical practice. This study examined the accuracy of handheld-type scanners using plaster statues to assess their performance in facial recognition. METHODS: Twelve 4-mm zirconia balls as measuring points were attached to the facial portions of three types of plaster statue. Six digital facial images of each plaster statue were obtained using one of the following five handheld-type scanners: Artec Eva, Artec Spider, Bellus 3D FaceApp, SNAP, and Vectra H1. Four-millimeter spherical objects were manually placed at the measurement points on the scanned data generated using computer-aided design software and coordinate positions were measured using a contact-type high-resolution three-dimensional measurement device. Consequently, the discrepancy between the distance measured using the contact-type device and that measured using the handheld-type scanner was calculated. The scanning time, processing time, and deviation of the distance between the measuring points were analyzed using two-way analysis of variance and t-test with Bonferroni correction. RESULTS: The scanning and processing times ranged from 15.2 to 42.2 s and 20.7 to 234.2 s, respectively. Overall, 97% of all measured distances by Spider were within ±1.00% deviation; 79%, Vectra; 73%, Eva; 70%, Bellus; and 42%, SNAP. CONCLUSIONS: The performance of handheld-type scanners using plaster statues varied among the different scanners. The scanning time of Eva and the processing time of Bellus were significantly shorter than those of other scanners. Furthermore, Spider exhibited the best accuracy, followed by Eva, Vectra, Bellus, and SNAP.

Effect of Lacticaseibacillus rhamnosus L8020 on the abundance of periodontal pathogens in individuals with intellectual disability: a randomized clinical trial.

OBJECTIVES: Gingivitis refers to inflammation of the gingiva and its connective tissues. Research has revealed a higher prevalence of gingivitis in individuals with intellectual disability than in healthy individuals. Milk fermented with Lacticaseibacillus rhamnosus L8020 (L8020 yogurt) inhibits the accumulation of periodontal disease-related pathogens in vitro and alleviates the symptoms of periodontal disease. The aim of this study was to investigate the influence of L8020 yogurt on oral microbiota and the abundance of four periodontal pathogens (Tannerella forsythia, Porphyromonas gingivalis, Prevotella intermedia, and Treponema denticola) and on the microbiota in individuals with intellectual disability and gingivitis. METHOD AND MATERIALS: Forty-one outpatients with intellectual disability participated in this study. To examine the effects of daily consumption of L8020 yogurt, the patients were randomly divided into L8020 (test group, n = 21) and placebo (n = 20) yogurt groups. All patients consumed 80 g of yogurt for 12 weeks. Oral examination was performed before the first intake of yogurt and dental plaque was collected before and after the intake of yogurt. DNA was extracted from dental plaque and subjected to next-generation sequencing. RESULTS: The relative abundance of T forsythia was significantly lower in the test group than in the placebo group. Additionally, the relative abundance of the four pathogens reduced after 84 days of consuming L8020 yogurt compared with that after consuming placebo yogurt. CONCLUSION: Mixing L rhamnosus L8020 with probiotic products that are consumed daily would be effective in suppressing the increase in periodontal disease-causing bacteria and beneficial for individuals with intellectual disability.

Construction of orthodontic setup models on a computer.

INTRODUCTION: Orthodontic setup models are usually limited to the display of teeth, with no information about the roots. The purpose of this article is to present a method for visualizing the tooth roots in setup models by integrating information from cone-beam computed tomography and a laser scanner. The reproducibility of the integration was evaluated. METHODS: The records of 5 patients were used in this study. Three-dimensional digital models were generated from the dental casts. Tooth models were generated from the cone-beam computed tomography slices. The 3-dimensional models were superimposed on the crowns of the teeth in the tooth models and integrated. The integrated 3-dimensional tooth model and 3-dimensional setup model were registered. The reproducibility of the integration was evaluated for each tooth. Unpaired Student t tests were performed on the data between the anterior and posterior teeth, and between the right and left teeth. RESULTS: The discrepancy among the integrated 3-dimensional models at the final positions after we used this technique was 0.025 ± 0.007 mm. There was a significant difference in the distance between the anterior and posterior teeth (P <0.05). However, the average distances between the anterior and posterior teeth were small: 0.023 ± 0.007 and 0.028 ± 0.007 mm, respectively. No significant difference was found between the right and left teeth (P = 0.831). CONCLUSIONS: The methods presented in this study provide a reproducible visualization of tooth roots in virtual setup models by registering accurate crown models to cone-beam computed tomography scans.

Lansoprazole and zoledronate delays hard tissue healing of tooth extraction sockets in dexamethasone-treated mice.

Proton pump inhibitors (PPIs) are among the most commonly prescribed medicines for the management of acid-related gastrointestinal diseases. Osteonecrosis of the jaw (ONJ) is a serious adverse event that is associated with the use of antiresorptive and antiangiogenic agents. According to previous clinical reports, the use of PPIs contributes to the pathogenesis of severe ONJ that requires surgery. Here, we investigated the effects of lansoprazole (LP) or LP in combination with zoledronate (ZOL) on ONJ development in mice. C57BL/6J mice were administered ZOL (125 µg/kg intravenously, twice weekly) and/or LP (10 mg/kg intraperitoneally; 3 weeks of 3 consecutive days followed by 1 day off). One week after initiation of the study, the first molar was atraumatically extracted. Concurrently with ZOL administration, dexamethasone (Dex) was administered (5 mg/kg intraperitoneally, twice weekly). Micro-computed tomography and histological evaluation were performed to characterize femoral structures, tooth extraction sockets, and osteonecrosis areas. The results showed that ZOL/Dex significantly increased bone mass compared to saline/Dex, while the simultaneous administration of LP and ZOL/Dex diminished the ZOL-induced enhancement of bone mass. In the alveolar bone around the tooth extraction socket, necrotic bone was significantly increased in the LP/Dex group compared to the saline/Dex group. However, no signs of more severe ONJ-like lesions were observed following combined administration of LP and ZOL/Dex, other than an increase in the number of non-attached TRAP-positive cells. Our findings in a mouse model suggest that LP use can be a risk factor for the development of ONJ.