Mechanical insights into jawbone characteristics under chronic kidney disease: A comprehensive nanoindentation approach.

The mechanical properties of the jawbone play a critical role in determining the successful integration of dental prostheses. Chronic kidney disease (CKD) has been identified to abnormally accelerate bone turnover rates. However, the impact of CKD on the mechanical characteristics of the jawbone has not been extensively studied. This study sought to evaluate the time-dependent viscoelastic behaviors of rat jawbones, particularly in the scenarios both with and without CKD. We hypothesized that CKD might compromise the bone's innate toughening mechanisms, potentially owing to the time-dependent viscoelasticity of the bone matrix proteins. The maxillary and mandibular bones of Wistar rats were subjected to nanoindentation and Raman micro-spectroscopy. Load-hold-displacement curves from the cortical regions were obtained via nanoindentation and were mathematically characterized using a suitable viscoelastic constitutive model. Raman micro-spectroscopy was employed to identify nuanced vibrational changes in local molecular structures induced by CKD. The time course of indenter penetration onto cortical bones during the holding stage (creep behavior) can be mathematically represented by a series arrangement of the Kelvin-Voigt bodies. This configuration dictates the overall viscoelastic response observed during nanoindentation tests. The CKD model exhibited a reduced extent of viscoelastic contributions, especially during the initial ramp loading phase in both the maxillary and mandibular cortical bones. The generalized Kelvin-Voigt model comprises 2 K-Voigt elements that signify an immediate short retardation time (τ1) and a subsequent prolonged retardation time (τ2), respectively. Notably, the mandibular CKD model led to an increase in the delayed τ2 alongside an increase in non-enzymatic collagen cross-linking. These suggest that, over time, CKD diminishes the bone's capability for supplementary energy absorption and dimensional recovery, thus heightening their susceptibility to fractures.

Impact of CAD/CAM Material Thickness and Translucency on the Polymerization of Dual-Cure Resin Cement in Endocrowns.

The objective of this study is to evaluate the impact of the thickness and translucency of various computer-aided design/computer-aided manufacturing (CAD/CAM) materials on the polymerization of dual-cure resin cement in endocrown restorations. Three commercially available CAD/CAM materials-lithium disilicate glass (e.max CAD), resin composite (CERASMART), and a polymer-infiltrated ceramic network (ENAMIC)-were cut into plates with five different thicknesses (1.5, 3.5, 5.5, 7.5, and 9.5 mm) in both high-translucency (HT) and low-translucency (LT) grades. Panavia V5, a commercial dual-cure resin cement, was polymerized through each plate by light irradiation. Post-polymerization treatment was performed by aging at 37 °C for 24 h under light-shielding conditions. The degree of conversion and Vickers hardness measurements were used to characterize the polymerization of the cement. The findings revealed a significant decrease in both the degree of conversion and Vickers hardness with increasing thickness across all CAD/CAM materials. Notably, while the differences in the degree of conversion and Vickers hardness between the HT and LT grades of each material were significant immediately after photoirradiation, these differences became smaller after post-polymerization treatment. Significant differences were observed between samples with a 1.5 mm thickness (conventional crowns) and those with a 5.5 mm or greater thickness (endocrowns), even after post-polymerization treatment. These results suggest that dual-cure resin cement in endocrown restorations undergoes insufficient polymerization.

Chronic kidney disease compromises structural and mechanical properties of maxillary cortical bone in a rat model.

PURPOSE: This study aimed to investigate the effects of chronic kidney disease (CKD) on the structural and mechanical properties of the maxillary and mandibular cortical bone. METHODS: The maxillary and mandibular cortical bones from CKD model rats were used in this study. CKD-induced histological, structural, and micro-mechanical alterations were assessed using histological analyses, micro-computed tomography (CT), bone mineral density (BMD) measurements, and nanoindentation tests. RESULTS: Histological analyses indicated that CKD caused an increase in the number of osteoclasts and a decrease in the number of osteocytes in the maxilla. Micro-CT analysis revealed that CKD induced a void volume/cortical volume (%) increase, which was more remarkable in the maxilla than in the mandible. CKD also significantly decreased the BMD in the maxilla. In the nanoindentation stress-strain curve, the elastic-plastic transition point and loss modulus were lower in the CKD group than that in the control group in the maxilla, suggesting that CKD increased micro fragility of the maxillary bone. CONCLUSIONS: CKD affected bone turnover in the maxillary cortical bone. Furthermore, the maxillary histological and structural properties were compromised, and micro-mechanical properties, including the elastic-plastic transition point and loss modulus, were altered by CKD.

Development of zirconia-based polymer-infiltrated ceramic network for dental restorative material.

Polymer-infiltrated ceramic network (PICN) materials have gained considerable attention as tooth restorative materials owing to their mechanical compatibility with human teeth. However, the mechanical strength of contemporary PICN materials is lower than those of conventional resin composites and ceramics. This study aims to develop novel high-strength PICN for use as a dental restorative material. Zirconia-based PICN (EXP) was fabricated using 3 mol% yttria tetragonal polycrystalline zirconia powder and resin monomers via slip casting, followed by sintering and polymer infiltration. Comprehensive analyses of the microstructure, mechanical properties, and physicochemical properties of EXP were performed using scanning electron microscopy with energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, inorganic content measurements, three-point bending test, Vickers hardness test, two-body wear test, shear bond strength (SBS) test, surface free energy analysis, and water sorption/solubility test. Commercially available computer-aided design/computer-aided manufacturing (CAD/CAM) materials, including resin composite (CERASMART), silicate-based PICN (ENAMIC), and zirconia ceramic (e.max ZirCAD), were used for comparison. The analyses highlight the dual network structure of EXP, which comprised a zirconia skeleton and an infiltrated resin phase. EXP exhibits a flexural strength of 346.0 ± 46.0 MPa, flexural modulus of 44.0 ± 3.7 GPa, and Vickers hardness of 440.1 ± 51.2 VHN. The mechanical properties of EXP are significantly higher than those of CERASMART and ENAMIC but lower than those of ZirCAD. Notably, the EXP hardness closely mimics that of the human enamel. The wear volume, SBS, and water sorption/solubility of EXP are comparable to those of CERASMART and ENAMIC. Therefore, EXP has potential applications as a tooth restorative material.

5- to 15-Year Survival of Immediately Loaded Implants in Fully Edentulous Maxillae: A Multilevel Analysis in a Retrospective Cohort Study.

PURPOSE: Although immediate-loading implant (ILI) treatment is a general treatment strategy for fully edentulous maxillae, long-term evidence is required. The purpose of this study was to evaluate the long-term clinical results of, and risk factors for, ILI treatment in fully edentulous maxillae. MATERIALS AND METHODS: ILI treatments of maxillae using 526 implants in 117 patients were reviewed retrospectively. The longest and mean observation periods were 15 years and 9.2 years, respectively. Kaplan-Meier survival curve analysis, log-rank tests, and multilevel mixed-effects parametric survival analysis were used for statistical analyses. RESULTS: Overall, 38 of 526 implants failed in 23 patients, and the estimated 15-year cumulative implant-level and patient-level survival rates were 90.7% and 73.7%, respectively. The cumulative implant survival rate was significantly higher in female patients than in male patients. Sex, implant length, and implant diameter were significantly associated with implant survival. CONCLUSION: ILI treatment of completely edentulous maxillae demonstrated viable long-term clinical outcomes. Male sex, shorter implant length, and narrow implant diameter negatively affected implant survival. Int J Oral Maxillofac Implants 2023;38:516-522. doi: 10.11607/jomi.10310.

Bond Strength of Sandblasted PEEK with Dental Methyl Methacrylate-Based Cement or Composite-Based Resin Cement.

Poly-ether-ether-ketone (PEEK) is commonly employed in dental prostheses owing to its excellent mechanical properties; however, it is limited by its low bond strength with dental resin cement. This study aimed to clarify the type of resin cement most suitable for bonding to PEEK: methyl methacrylate (MMA)-based resin cement or composite-based resin cement. For this purpose, two MMA-based resin cements (Super-Bond EX and MULTIBOND II) and five composite-based resin cements (Block HC Cem, RelyX Universal Resin Cement, G-CEM LinkForce, Panavia V5, and Multilink Automix) were used in combination with appropriate adhesive primers. A PEEK block (SHOFU PEEK) was initially cut, polished, and sandblasted with alumina. The sandblasted PEEK was then bonded to resin cement with adhesive primer according to the manufacturer's instructions. The resulting specimens were immersed in water at 37 °C for 24 h, followed by thermocycling. Subsequently, the tensile bond strengths (TBSs) of the specimens were measured; the TBSs of the composite-based resin cements after thermocycling were found to be zero (G-CEM LinkForce, Panavia V5, and Multilink Automix), 0.03 ± 0.04 (RelyX Universal Resin Cement), or 1.6 ± 2.7 (Block HC Cem), whereas those of Super-Bond and MULTIBOND were 11.9 ± 2.6 and 4.8 ± 2.3 MPa, respectively. The results demonstrated that MMA-based resin cements exhibited stronger bonding to PEEK than composite-based resin cements.

Influence of the thickening agent contained in a phosphoric acid etchant on bonding between feldspar porcelain and resin cement with a silane coupling agent.

Phosphoric acid (PA) etchants are widely used for the bonding pretreatment of teeth; however, their influences on the bonding between glass-ceramics and resin cement have not been clarified yet. This study investigated the effect of a thickening agent on the bonding strength between feldspar porcelain treated with a PA etchant and resin cement with a silane coupling agent. The experiments were performed using two PA etchants: commercial one and prepared one consisting a PA aqueous solution and poly(ethylene glycol) thickening agent. The samples were evaluated by shear bond strength testing, scanning electron microscopy, and Fourier-transform infrared spectroscopy. The obtained results revealed that the thickening agent adhered to the porcelain surface and inhibited cement bonding. Meanwhile, PA remained on the surface due to the presence of the thickening agent and activated the silane coupling agent. Overall, the PA etchant did not improve the bond durability.

Functional tooth number in the posterior region associated serum ucOC levels.

PURPOSE: The purpose of this study was to investigate serum undercarboxylated osteocalcin (ucOC) levels in partially edentulous patients scheduled to receive implant treatment and determine the association between ucOC levels, vegetable intake, vitamin K, dietary fiber intake, and functional tooth number in the posterior region (p-FTN). METHODS: A total of 46 patients (20 male and 26 female, 61.9 ± 12.7 years old) were included. The association among serum ucOC levels, vegetable intake, vitamin K and dietary fiber intake was assessed using Spearman's rank correlation coefficient and binary logistic regression analysis. RESULTS: In total, 35% of patients (16/46 subjects) showed an abnormally high ucOC level (≧ 4.5 ng/mL). p-FTN showed a weak positive correlation with vegetable intake, vitamin K and dietary fiber intake (r = 0.28, 0.21, and 0.14, respectively) and a significant negative correlation with ucOC levels (r = - 0.51). Multivariate analysis demonstrated that p-FTN as well as vitamin K intake showed a significant negative association with serum ucOC levels. CONCLUSIONS: More than one-third of patients showed abnormally high ucOC levels. p-FTN showed a negative association with serum ucOC levels, which indicated the possibility that oral status affected bone quality.

Periodontal status is associated with oral function in community-dwelling older adults, independent of dentition status.

OBJECTIVE: To determine whether periodontal status is associated with oral function, including masticatory performance and occlusal force, among community-dwelling older adults. BACKGROUND: Although a potential association between periodontal status and oral function has been reported, variations in the root surface area (RSA) of each tooth have not been considered. METHODS: We used data from a population-based study involving community-dwelling older adults. The RSA with periodontal ligament (RSA-PL), which quantifies the RSA attached to the periodontal ligament and alveolar bone, was calculated based on full-mouth periodontal examination. Masticatory performance was assessed using spectrophotometric measurement of the color (a* value) of color-changing chewing gum. The bilateral maximal occlusal force (MOF) was measured using a pressure-sensitive sheet and dedicated software. The associations of the RSA-PL, a quantitative marker of periodontal tissue support, with the a* value and MOF were assessed using linear regression models. RESULTS: The analyses included data from 250 adults [60.8% women; age, mean (standard deviation) 82.5 (5.0) years]. On average, the study participants had an RSA-PL of 26.3 cm2 , a* value of 25.0, and an MOF value of 555.1 N. After adjustments for potential confounders, including dentition status, age, sex, dental visit regularity, smoking status, physical activity level, depressive symptoms, a history of stroke or diabetes mellitus, and body mass index, the RSA-PL was found to be associated with the a* value [coefficient (per 1 cm2 increase): 0.16, 95% confidence interval (CI) 0.10-0.22)] and MOF (coefficient: 9.2, 95% CI 5.3-13.1). CONCLUSION: This study demonstrated that greater amounts of remaining tooth-supporting structures, indicated by higher RSA-PL values, were associated with better masticatory performance and a higher occlusal force among community-dwelling older adults.

Dental Poly(methyl methacrylate)-Based Resin Containing a Nanoporous Silica Filler.

Poly(methyl methacrylate) (PMMA)-based resins have been conventionally used in dental prostheses owing to their good biocompatibility. However, PMMA-based resins have relatively poor mechanical properties. In the present study, a novel nanoporous silica filler was developed and introduced into PMMA-based resins to improve their mechanical properties. The filler was prepared by sintering a green body composed of silica and an organic binder, followed by grinding to a fine powder and subsequent silanization. The filler was added to photocurable PMMA-based resin, which was prepared from MMA, PMMA, ethylene glycol dimethacrylate, and a photo-initiator. The filler was characterized by scanning electron microscopy (SEM), X-ray diffraction analysis, nitrogen sorption porosimetry, and Fourier transform infrared (FT-IR) spectroscopy. The PMMA-based resins were characterized by SEM and FT-IR, and the mechanical properties (Vickers hardness, flexural modulus, and flexural strength) and physicochemical properties (water sorption and solubility) were evaluated. The results suggested that the filler consisted of microparticles with nanopores. The filler at 23 wt % was well dispersed in the PMMA-based resin matrix. The mechanical and physicochemical properties of the PMMA-based resin improved significantly with the addition of the developed filler. Therefore, such filler-loaded PMMA-based resins are potential candidates for improving the strength and durability of polymer-based crown and denture base.

A new mandibular deformation index predicts amount of bone deformation in edentulous patients treated with an implant-supported fixed prosthesis.

PURPOSE: The present study was performed to examine the mandibular deformation during mouth opening in edentulous patients, treated with an implant-supported fixed prosthesis using strain gauges, and identify factors affecting deformation. METHODS: Twenty patients with a fully edentulous mandible who received either 4 or ≥6 implants were included. The distal-most implants were placed mesial to the mental foramen (premolar region) in patients with 4 implants and distal to the mental foramen (molar region) in patients with ≥6 implants. Mandibular deformation during mouth opening was measured using strain gauges in two directions: anteroposterior direction and lateral direction between the distal-most implants on the left and right sides (arch width). The mandibular anatomy was evaluated using computed tomography. RESULTS: Arch width reduction between the left and right implants during mouth opening ranged from 47.38 to 512.80 µm; the range of deformation was 0.12 to 15.14 µm in the anteroposterior direction. Furthermore, a significant positive correlation was noted between arch width reduction in the premolar region and the ratio between the symphyseal bone height and width (P = 0.0003, r = 0.72). CONCLUSION: The reduction in arch width was higher in the molar region than in the premolar region during mouth opening. Moreover, the reduction could be high in the mandibular symphyseal bone because of its greater height and lesser width. The ratio between the symphyseal bone height and width is defined as the mandibular deformation index (MDI) and is used to predict the rate of mandibular bone deformation.

Development of Dental Poly(methyl methacrylate)-Based Resin for Stereolithography Additive Manufacturing.

Poly(methyl methacrylate) (PMMA) is widely used in dental applications. However, PMMA specialized for stereolithography (SLA) additive manufacturing (3D-printing) has not been developed yet. This study aims to develop a novel PMMA-based resin for SLA 3D-printing by mixing methyl methacrylate (MMA), ethylene glycol dimethacrylate (EGDMA), and PMMA powder in various mixing ratios. The printability and the viscosity of the PMMA-based resins were examined to determine their suitability for 3D-printing. The mechanical properties (flexural strength and Vickers hardness), shear bond strength, degree of conversion, physicochemical properties (water sorption and solubility), and cytotoxicity for L929 cells of the resulting resins were compared with those of three commercial resins: one self-cured resin and two 3D-print resins. EGDMA and PMMA were found to be essential components for SLA 3D-printing. The viscosity increased with PMMA content, while the mechanical properties improved as EGDMA content increased. The shear bond strength tended to decrease as EGDMA increased. Based on these characteristics, the optimal composition was determined to be 30% PMMA, 56% EGDMA, 14% MMA with flexural strength (84.6 ± 7.1 MPa), Vickers hardness (21.6 ± 1.9), and shear bond strength (10.5 ± 1.8 MPa) which were comparable to or higher than those of commercial resins. The resin's degree of conversion (71.5 ± 0.7%), water sorption (19.7 ± 0.6 µg/mm3), solubility (below detection limit), and cell viability (80.7 ± 6.2% at day 10) were all acceptable for use in an oral environment. The printable PMMA-based resin is a potential candidate material for dental applications.

Myogenic differentiation 1 and transcription factor 12 activate the gene expression of mouse taste receptor type 1 member 1.

OBJECTIVES: Myogenic differentiation 1 (Myod1) is involved in the expression of taste receptor type 1 member 1 (Tas1r1) during myogenic differentiation. Further, the target genes of Myod1 participate in transcriptional control, muscle development, and synaptic function. We examined, for the first time, the function of Myod1 in the transcriptional regulation of Tas1r1. METHODS: ENCODE chromatin immunoprecipitation and sequencing (ChIP-seq) data of myogenically differentiated C2C12 cells were analyzed to identify the Myod1 and transcription factor 12 (Tcf12) binding sites in the Tas1r1 promoter region. Luciferase reporter assays, DNA affinity precipitation assays, and co-immunoprecipitation assays were also performed to identify the functions of Myod1, Tcf12, and Krüppel-like factor 5 (Klf5). RESULTS: Based on ENCODE ChIP-seq, Myod1 bound to the Tas1r1 promoter region containing E-boxes 1-3. Luciferase reporter assays revealed that site-directed E-box1 mutations significantly reduced promoter activation induced by Myod1 overexpression. According to the DNA affinity precipitation assay and co-immunoprecipitation assay, Myod1 formed a heterodimer with Tcf12 and bound to E-box1. Further, Klf5 bound to the GT box near E-box1, activating Tas1r1 expression. CONCLUSIONS: During myogenic differentiation, the Myod1/Tcf12 heterodimer, in collaboration with Klf5, binds to E-box1 and activates Tas1r1 expression.

Microstructural and mechanical recovery of bone in ovariectomized rats: The effects of menaquinone-7.

The loss of bone quantity and quality in postmenopausal female patients can be a problem for dental treatment. A sufficient intake of nutrients such as calcium, magnesium, and vitamins D and K is likely correlated with the mechanical properties of bone. In particular, vitamin K2, also called menaquinone (MK), inhibits bone loss in postmenopausal women. Here we demonstrate the microstructural and mechanical properties of bone recovery in ovariectomized (OVX) rats during MK-7 administration. Bilateral ovariectomy and a sham operation were performed on 14-week-old female SPF Wistar rats. MK-4 and -7 were orally administered at 30 mg/kg daily for 12 weeks. The femur was used for the 3-point bending test and microstructural analysis of the cancellous bone by micro-CT, and the mandibular cortical bone for the evaluation of mechanical properties on a nanoscale. Micro-computed tomography revealed irregular trabecular architecture, hollow marrow cavities, and sparse trabecular bone in the femurs of the OVX group. Trabecular bone structure analysis showed that the MK-7 group had greater bone volume per tissue volume (BV/TV) and a higher trabecular number than the OVX group. The bulk-scale 3-point bending test did not allow the mechanical properties between OVX and OVX/MK7 groups to be discerned, yet at the smallest level, the elastic-plastic transition point of the nanoindentation stress-strain curve of the mandibular cortical bone was higher in the MK-7 group than in the OVX group. These findings suggest that MK-7 enables bone microstructural and mechanical recovery in the OVX model.

Local administration of HMGB-1 promotes bone regeneration on the critical-sized mandibular defects in rabbits.

Reconstruction of a critical-sized osseous defect is challenging in maxillofacial surgery. Despite novel treatments and advances in supportive therapies, severe complications including infection, nonunion, and malunion can still occur. Here, we aimed to assess the use of a beta-tricalcium phosphate (ß-TCP) scaffold loaded with high mobility group box-1 protein (HMGB-1) as a novel critical-sized bone defect treatment in rabbits. The study was performed on 15 specific pathogen-free New Zealand rabbits divided into three groups: Group A had an osseous defect filled with a ß-TCP scaffold loaded with phosphate-buffered saline (PBS) (100 µL/scaffold), the defect in group B was filled with recombinant human bone morphogenetic protein 2 (rhBMP-2) (10 µg/100 µL), and the defect in group C was loaded with HMGB-1 (10 µg/100 µL). Micro-computed tomography (CT) examination demonstrated that group C (HMGB-1) showed the highest new bone volume ratio, with a mean value of 66.5%, followed by the group B (rhBMP-2) (31.0%), and group A (Control) (7.1%). Histological examination of the HMGB-1 treated group showed a vast area covered by lamellar and woven bone surrounding the ß-TCP granule remnants. These results suggest that HMGB-1 could be an effective alternative molecule for bone regeneration in critical-sized mandibular bone defects.

PICN Nanocomposite as Dental CAD/CAM Block Comparable to Human Tooth in Terms of Hardness and Flexural Modulus.

Polymer infiltrated ceramic network (PICN) composites are an increasingly popular dental restorative material that offer mechanical biocompatibility with human enamel. This study aimed to develop a novel PICN composite as a computer-aided design and computer-aided manufacturing (CAD/CAM) block for dental applications. Several PICN composites were prepared under varying conditions via the sintering of a green body prepared from a silica-containing precursor solution, followed by resin infiltration. The flexural strength of the PICN composite block (107.8-153.7 MPa) was similar to a commercial resin-based composite, while the Vickers hardness (204.8-299.2) and flexural modulus (13.0-22.2 GPa) were similar to human enamel and dentin, respectively. The shear bond strength and surface free energy of the composite were higher than those of the commercial resin composites. Scanning electron microscopy and energy dispersive X-ray spectroscopic analysis revealed that the microstructure of the composite consisted of a nanosized silica skeleton and infiltrated resin. The PICN nanocomposite block was successfully used to fabricate a dental crown and core via the CAD/CAM milling process.

Xerostomia aggravates ligation-induced peri-implantitis: A preclinical in vivo study.

OBJECTIVES: Previous studies have indicated that xerostomia is a critical factor affecting periodontitis; nonetheless, it is controversial whether xerostomia impairs peri-implant tissue. The objective of this experimental study was to evaluate the effect of xerostomia on the peri-implant hard and soft tissues in the rat model. MATERIALS AND METHODS: Implants were placed in bilateral maxillae of male Wistar rats. The animals underwent submandibular and sublingual gland resection on both sides (DRY group) or sham operation (CTR group). Silk ligatures were placed around one side of abutments, which were randomly selected in each animal. The effects of xerostomia were assessed using micro-CT, histological analysis, real-time PCR, and 16S rRNA-based metagenomic analysis. RESULTS: Ligation with silk thread caused bone resorption around implants. Although xerostomia itself did not induce bone resorption, it significantly enhanced silk ligature-mediated bone resorption around implants. Histological analysis and real-time PCR indicated that xerostomia induced inflammation and osteoclastogenesis around implants with silk ligatures. Furthermore, it altered the microbiota of the plaque on the silk thread around implants. CONCLUSION: Xerostomia accelerates mucosal inflammation and osteoclastogenesis, which aggravates bone resorption around implants.

Effects of metformin on the prevention of bisphosphonate-related osteonecrosis of the jaw-like lesions in rats.

PURPOSE: In this study, we aimed to investigate the effect of glucose metabolism on bone healing after tooth extraction in an osteoporosis rat model administered zoledronic acid (ZA) and dexamethasone (DX). METHODS: In total, 24 male Wistar rats (4 weeks old) were randomly assigned to four groups: Control (subcutaneous physiological saline), ZD (subcutaneous ZA and DX twice a week), Ins+ZD (subcutaneous insulin followed by ZD treatment), and Met+ZD (oral metformin followed by ZD treatment). Blood was collected every two weeks . Two weeks after treatment initiation, the first molar tooth on the right maxilla was extracted from all rats. Four weeks later, the rats were sacrificed, and bone healing was assessed. Maxillae samples were fixed and scanned using micro-computed tomography for quantifying areas of bone defects. Hematoxylin-eosin and tartrate-resistant acid phosphatase (TRAP) staining were performed to evaluate bone apoptosis and osteoclast number. RESULTS: In all experimental groups, body weight was statistically lower than that in the Control group, with no changes observed in uncarboxylated osteocalcin concentrations. The radiological analysis revealed that insulin or metformin administration improved healing in the tooth extraction socket (p < 0.01). Histological examination revealed that the osteonecrosis area was reduced in the Ins+ZD and Met+ZD groups (p < 0.01). TRAP staining presented increased osteoclast numbers in the ZD group when compared with that observed in the Control. CONCLUSIONS: Tooth extraction with long-term ZA and DX administration inhibited bone remodeling and induced bisphosphonate-related osteonecrosis of the jaw-like lesions. Metformin exerted protective effects ag ainst osteonecrosis of the jaw.

Effect of aging on bone metabolism: the involvement of complement C1q.

Purpose Impairment of normal bone remodeling affects the successful osseointegration of dental implants. Recently, it has been reported that complement C1q level increases with age and delays wound healing by modulating Wnt signaling. As Wnt signaling is known to play an essential role in bone remodeling, we hypothesized that aging-dependent increases in C1q affect bone remodeling. In this study, we examined whether C1q affects the differentiation of bone-forming osteoblasts and bone-resorbing osteoclasts, and investigated whether C1q could modify cellular signaling, including the Wnt/ß-catenin pathway in these cells.Methods Osteogenic differentiation of MC3T3-E1 cells was assessed using alkaline phosphatase staining. Differentiation of osteoclasts from mouse bone marrow cells was assessed using tartrate-resistant acid phosphatase staining. Activation of canonical Wnt signaling and protein phosphorylation was monitored using Western blotting.Results C1q, at 5-15 µg/mL promoted osteoclast fusion, whereas it did not affect the differentiation of osteoblasts. On the other hand, a higher concentration of C1q (50 µg/mL) suppressed both bone morphogenetic protein-2-induced osteogenic differentiation and osteoclast formation. C1q did not induce an obvious activation of Wnt/ ß-catenin signaling in either pre-osteoblasts or pre-osteoclasts, contrary to previous reports using other tissues. Instead, C1q upregulated the receptor activator of nuclear factor-kappa B ligand (RANKL)-induced phosphorylation of Akt.Conclusions C1q could affect cellular signaling and modify the differentiation of osteoblasts and osteoclasts, depending on the concentration. Therefore, an increase in C1q with age could be one of the factors that determine the prognosis of treatment of elderly patients.