Publications by authors named "Ryuji Hosokawa"

67 Publications

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

J Mech Behav Biomed Mater 2021 Aug 21;120:104571. Epub 2021 May 21.

Division of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Japan.

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.
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http://dx.doi.org/10.1016/j.jmbbm.2021.104571DOI Listing
August 2021

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

Sci Rep 2021 Apr 26;11(1):8950. Epub 2021 Apr 26.

Division of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Kitakyushu, Fukuoka, Japan.

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 (β-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 β-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 β-TCP granule remnants. These results suggest that HMGB-1 could be an effective alternative molecule for bone regeneration in critical-sized mandibular bone defects.
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http://dx.doi.org/10.1038/s41598-021-88195-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8076241PMC
April 2021

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

Materials (Basel) 2021 Mar 3;14(5). Epub 2021 Mar 3.

Division of Biomaterials, Department of Oral Functions, Kyushu Dental University, Fukuoka 803-8580, Japan.

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.
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http://dx.doi.org/10.3390/ma14051182DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7959134PMC
March 2021

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

Clin Oral Implants Res 2021 May 12;32(5):581-589. Epub 2021 Mar 12.

Division of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Kitakyushu, Japan.

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.
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http://dx.doi.org/10.1111/clr.13727DOI Listing
May 2021

Effects of alumina airborne-particle abrasion on the surface properties of CAD/CAM composites and bond strength to resin cement.

Dent Mater J 2021 Mar 19;40(2):431-438. Epub 2020 Nov 19.

Division of Biomaterials, Department of Oral Functions, Kyushu Dental University.

The purpose of this study is to clarify physical and chemical changes in surfaces of CAD/CAM composites caused by alumina airborne-particle abrasion and its effect on adhesive bonding. Our study involved three dispersed filler (DF)-based and a polymer-infiltrated ceramic network (PICN)-based CAD/CAM composites. Changes in the surface morphologies of the composites were examined, and surface free energy (SFE) analysis was performed based on Owens-Wendt theory. The influence of the abrasion on the bond strengths of CAD/CAM composites to the resin cement was characterized by shear bond strength (SBS) test. The abrasion increased the roughness of the composites. The SFE analysis showed that the abrasion significantly increased the dispersive component but decreased the polar component of the SFE associated with the DF-based composites, while no change occurred for those of the PICN-based composite. The abrasion slightly improved the SBSs for the DF-based composites but not that of the PICN-based composite.
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http://dx.doi.org/10.4012/dmj.2020-023DOI Listing
March 2021

Effect of aging on bone metabolism: the involvement of complemen t C1q.

J Prosthodont Res 2020 Oct 29. Epub 2020 Oct 29.

Division of Applied Pharmacology, Kyushu Dental University, Kitakyushu.

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/β-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/ β-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.
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http://dx.doi.org/10.2186/jpr.JPOR_2019_644DOI Listing
October 2020

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

J Prosthodont Res 2020 Sep 15. Epub 2020 Sep 15.

Division of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Fukuoka.

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.
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http://dx.doi.org/10.2186/jpr.JPOR_2019_629DOI Listing
September 2020

The relationship between masticatory performance and intakes of foods and nutrients in Japanese male workers: A cross-sectional study.

J Oral Rehabil 2020 Sep 25;47(9):1142-1149. Epub 2020 Jul 25.

Division of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Fukuoka, Japan.

Background: Although many studies have been conducted on the relationship between masticatory performance and nutrient ingestion in the elderly, few large-scale studies have been carried out using relatively young individuals.

Objectives: The objective of this study was to clarify the association between the masticatory performance evaluated by the gummy-jelly test, not by visual examination, and nutrient ingestion state based on the brief self-administered diet history questionnaire (BDHQ).

Methods: This was a cross-sectional survey of 540 male workers. Somatometry, blood pressure measurement, blood test and medical interview were performed as a periodic health check-up. In the dental check-up, an oral examination, gummy-jelly test (glucosensor) and survey of ingested food and nutrients using BDHQ were performed. The participants were classified into two groups with low and normal values of masticatory performance. Participants with a score on the gummy-jelly test below 150 mg/dL or 150 mg/dL or higher were included in the low and normal groups, respectively.

Results: Two hundred and forty-eight participants (45.8%) had low masticatory performance, and 292 (53.2%) had normal masticatory performance. The intakes of some minerals and vitamins, such as calcium, vitamin D, vitamin B , small fish with bones and non-oily fish, were significantly lower in the low masticatory group than in the normal group. In contrast, the intake of sugar for coffee and tea and that of chicken were significantly higher in the low masticatory group than in the normal group.

Conclusion: This study suggested that low masticatory performance can affect nutrient intake, which may cause non-communicable diseases.
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http://dx.doi.org/10.1111/joor.13039DOI Listing
September 2020

Combined effect of poor appetite and low masticatory function on sarcopenia in community-dwelling Japanese adults aged ≥ 75 years: A 3-year cohort study.

J Oral Rehabil 2020 May 8;47(5):643-650. Epub 2020 Mar 8.

Division of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Fukuoka, Japan.

Objective: This study aimed to investigate the longitudinal association of the combination of poor appetite (PA) and low masticatory function (LMF) with sarcopenia in community-dwelling older adults.

Methods: In total, 173 community-dwelling Japanese adults aged ≥ 75 years participated in the 3-year cohort study. Appetite assessment using the Simplified Nutritional Appetite Questionnaire (SNAQ) and masticatory function assessment using spectrophotometric measurement of differences in gum colour before and after masticating colour-changeable chewing gum (ΔE*ab) were performed at baseline. SNAQ score of ≤ 14 was defined as PA. The lowest tertile of ΔE*ab was defined as LMF. Follow-up examinations were administered annually over a 3-year period to determine sarcopenia incidence, which was defined by the criteria proposed by the Asian Working Group for Sarcopenia. Adjusted hazard ratios (HRs) of sarcopenia incidence according to the presence of PA and LMF were calculated using Cox proportional hazards regression models.

Results: At baseline, 81 participants (46.8%) had neither PA nor LMF, 34 (19.7%) had PA alone, 35 (20.2%) had LMF alone, and 23 (13.3%) had both PA and LMF. On follow-up, 31 participants (17.9%) developed sarcopenia. After adjusting for covariates, the adjusted HR for sarcopenia in participants with both PA and LMF was 4.4 (95% confidence interval = 1.6-12.2) compared with those without PA or LMF. PA or LMF alone was not significantly associated with sarcopenia development.

Conclusions: Coexisting PA and LMF increase the risk of sarcopenia development among community-dwelling Japanese adults aged ≥ 75 years.
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http://dx.doi.org/10.1111/joor.12949DOI Listing
May 2020

Kif1c regulates osteoclastic bone resorption as a downstream molecule of p130Cas.

Cell Biochem Funct 2020 Apr 30;38(3):300-308. Epub 2019 Dec 30.

Division of Molecular Signaling and Biochemistry, Department of Health Improvement, Kyushu Dental University, Kitakyushu, Japan.

Podosome formation in osteoclasts is an important initial step in osteoclastic bone resorption. Mice lacking c-Src (c-Src ) exhibited osteopetrosis due to a lack of podosome formation in osteoclasts. We previously identified p130Cas (Crk-associated substrate [Cas]) as one of c-Src downstream molecule and osteoclast-specific p130Cas-deficient (p130Cas ) mice also exhibited a similar phenotype to c-Src mice, indicating that the c-Src/p130Cas plays an important role for bone resorption by osteoclasts. In this study, we performed a cDNA microarray and compared the gene profiles of osteoclasts from c-Src or p130Cas mice with wild-type (WT) osteoclasts to identify downstream molecules of c-Src/p130Cas involved in bone resorption. Among several genes that were commonly downregulated in both c-Src and p130Cas osteoclasts, we identified kinesin family protein 1c (Kif1c), which regulates the cytoskeletal organization. Reduced Kif1c expression was observed in both c-Src and p130Cas osteoclasts compared with WT osteoclasts. Kif1c exhibited a broad tissue distribution, including osteoclasts. Knockdown of Kif1c expression using shRNAs in WT osteoclasts suppressed actin ring formation. Kif1c overexpression restored bone resorption subsequent to actin ring formation in p130Cas osteoclasts but not c-Src osteoclasts, suggesting that Kif1c regulates osteoclastic bone resorption in the downstream of p130Cas (191 words). SIGNIFICANCE OF THE STUDY: We previously showed that the c-Src/p130Cas (Cas) plays an important role for bone resorption by osteoclasts. In this study, we identified kinesin family protein 1c (Kif1c), which regulates the cytoskeletal organization, as a downstream molecule of c-Src/p130Cas axis, using cDNA microarray. Knockdown of Kif1c expression using shRNAs in wild-type osteoclasts suppressed actin ring formation. Kif1c overexpression restored bone resorption subsequent to actin ring formation in osteoclast-specific p130Cas-deficient (p130Cas ) osteoclasts but not c-Src osteoclasts, suggesting that Kif1c regulates osteoclastic bone resorption in the downstream of p130Cas.
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http://dx.doi.org/10.1002/cbf.3476DOI Listing
April 2020

The effects of hyperglycaemia on peri-implant tissues after osseointegration.

J Prosthodont Res 2020 Apr 15;64(2):217-223. Epub 2019 Dec 15.

Division of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Graduate School, Japan.

Purpose: We assessed the effects of hyperglycaemia induced by streptozotocin (STZ) on peri-implantitis developing after implant osseointegration.

Methods: Thirty-six male Wistar rats (4 weeks old) were used. We placed titanium implants 4 weeks after extraction of the maxillary first molars. Healing abutments were attached 4 weeks later. After osseointegration was confirmed, the rats were divided into control, hyperglycaemia (STZ), and STZ with insulin (STZ+INS) groups. Hyperglycaemia was induced by a single injection of 50mg/kg STZ. Silk ligatures were placed on only the right sides (i.e. ligature sides), not on the left sides. Peri-implant tissues extracted at 4 weeks post-ligation were analysed both radiologically (via micro-computed tomography) and histologically (via toluidine blue staining). Total RNA was also extracted and analysed by quantitative PCR to detect TNF-α, IL-1β and the receptor of advanced glycation end products (RAGE). Additionally, advanced glycation end products (AGEs) were measured by ELISA.

Results: Radiological and histological analyses showed that bone loss on the non-ligature sides was significantly greater in the STZ than the control group. However, on the ligature sides, bone loss was greater than on the non-ligature sides, and no significant difference was evident among the three groups. The levels of mRNAs encoding TNF-α, IL-1β, RAGE, and AGEs on the ligature sides were significantly upregulated (all P<0.05) in the STZ compared to the control group.

Conclusions: Although hyperglycaemia could be associated with bone loss around implants with increased AGE production and RAGE expression, hyperglycaemia does not become a triggering factor of ligature induced peri-implantitis.
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http://dx.doi.org/10.1016/j.jpor.2019.07.007DOI Listing
April 2020

Cost of establishing a general dentistry department in a small or medium-sized hospital.

J Oral Sci 2019 Nov 5;61(4):558-559. Epub 2019 Oct 5.

Towa Hospital.

To contribute to future dental healthcare policies, this study compiled data on hospital expenses and follow-ups conducted after a hospital dentistry department was established. In addition, the management status and reports on the utility and challenges of establishing a dentistry department were analyzed. The dentistry department was established through fund raising and inaugurated in May 2009. The depreciation period was set at 7 years, and income and expenditure during the 7 years 8 months after opening were compiled. In total, 17.22 million yen was needed for the dentistry department. The average income from dental care was 21.59 million yen per year, and expenditure amounted to 21.54 million yen per year. The findings indicated that a general dentist able to systemically manage patients was essential in a chronic-care hospital. Moreover, the present findings indicate that if general dentistry consultations were performed without excessive investments, after adjusting for personnel expenses, such an initiative would neither yield considerable income nor produce a substantial deficit. Finally, it is imperative to develop staff who are familiar with the costs and management of hospital dentistry and to increase medical fees for consultations with elderly patients.
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http://dx.doi.org/10.2334/josnusd.18-0261DOI Listing
November 2019

Correlation between microstructure of CAD/CAM composites and the silanization effect on adhesive bonding.

J Mech Behav Biomed Mater 2020 01 18;101:103441. Epub 2019 Sep 18.

Division of Biomaterials, Department of Oral Functions, Kyushu Dental University, Fukuoka, 803-8580, Japan.

The aim of this study was to investigate the relationship between the microstructure of a CAD/CAM composite and the silanization effect on adhesive bonding, using surface free energy (SFE) analysis. Six commercial CAD/CAM composites, as well as control samples of two glass-ceramics and a resin, were investigated. The samples were characterized by morphological observations and SFE analysis. The bonding characteristics of the samples with the resin-cement were evaluated according to the silanization effect, which was determined from the ratio between the shear-bond strengths for the sample groups, with and without a silane-primer application. The composites were classified into two groups in terms of their microstructure; ENAMIC exhibits a polymer-infiltrated-ceramic-network (PICN) structure, while the other composites have a dispersed-filler (DF) structure. The dispersive component of the SFE was significantly lower in the PICN composite than in the DF composites. On the other hand, the polar component of the SFE was significantly higher in the PICN composite than in the DF composites. These SFE components were similar to those of glass-ceramics for the PICN composite and to those of the resin for the DF composites. The silanization effect increased linearly with the polar component or with a decrease in the dispersive component. Additionally, the silanization effect increased with the inorganic content. As a result, the silanization effect was found to be the highest for the PICN structure of ENAMIC. The results revealed that the silanization effect on the adhesive bonding is more effective for a PICN composite than for a DF composite.
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http://dx.doi.org/10.1016/j.jmbbm.2019.103441DOI Listing
January 2020

Pentosidine correlates with nanomechanical properties of human jaw bone.

J Mech Behav Biomed Mater 2019 10 4;98:20-25. Epub 2019 Jun 4.

Division of Oral Reconstruction and Rehabilitation, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka, 803-8580, Japan.

Initial intimate apposition between implant fixtures and host bone at the surgical site is a critical factor for osseointegration of dental implants. The advanced glycation end products accumulated in the jaw bone could lead to potential failure of a dental implant during the initial integration stage, because of the inferior bone mechanical property associated with the abnormal collagen cross-linking at the material level. Here, we demonstrate the lowered creep deformation resistance and reduced dimensional recovery of jaw bone in line with high levels of pentosidine accumulation in the bone matrix which likely correlate with the pentosidine level in blood plasma. Peripheral blood samples and cortical bone samples at the surgical site were obtained from patients scheduled for dental implants in the mandible. The pentosidine levels in blood plasma were assessed. Subsequently, the relative pentosidine levels and the mechanical properties of the jaw bone were quantified by Raman microspectroscopy and nanoindentation, respectively. The nanoindentation tests revealed less creep deformation resistance and reduced time-dependent dimensional recovery of bone samples with the increase in the relative pentosidine level in the bone matrix. Higher tan δ values at the various frequencies during the dynamic indentation tests also suggested that viscoelasticity is associated with the relative intensity of pentosidine in the jaw bone matrix. We found a positive correlation between the pentosidine levels in blood plasma and the bone matrix, which in turn reduced the mechanical property of the jaw bone at the material level. Increased creep and reduced dimensional recovery of the jaw bone may diminish the mechanical interlocking of dental implants during the initial integration stage. Given the likely correlation between the plasma pentosidine level and the mechanical properties of bone, measurement of the plasma pentosidine level could serve as a new index to assess jaw bone matrix quality in advance of implant surgery.
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http://dx.doi.org/10.1016/j.jmbbm.2019.06.002DOI Listing
October 2019

Implant-supported fixed prosthesis improves nutrient intake in patients with partial edentulous posterior regions.

J Prosthodont Res 2019 Oct 18;63(4):411-414. Epub 2019 Apr 18.

Division of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Kitakyushu, Japan.

Purpose: This study investigated changes in food and nutrient intake after implant-supported fixed prosthesis treatment in patients with partial edentulous posterior regions.

Methods: This study included 30 patients who received implant treatment with fixed prostheses in the posterior region. Food and nutrient intake was evaluated using a brief self-administered diet history questionnaire at baseline and post-implant treatment, and the results were statistically analyzed.

Results: Treatment with implant-supported fixed prostheses in patients with posterior edentulous conditions tended to increase the amounts of soy products and vegetables consumed: in particular, intake of carrot and squash was significantly increased. The total energy, protein, lipid, and carbohydrate intakes were comparable between baseline and post-implant treatment. On the other hand, the vegetable protein, α-carotene, daidzein, and genistein intakes were significantly increased, and dietary fiber and β-carotene intakes tended to be increased in patients with implant-supported fixed prostheses.

Conclusions: Implant-supported fixed prostheses in patients with posterior edentulous conditions affected food intake, resulting in improved nutrient intake.
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http://dx.doi.org/10.1016/j.jpor.2019.03.007DOI Listing
October 2019

Krüppel-like factor 5 (Klf5) regulates expression of mouse T1R1 amino acid receptor gene (Tas1r1) in C2C12 myoblast cells.

Biomed Res 2019 ;40(2):67-78

Division of Anatomy, Department of Health Promotion, Kyushu Dental University.

T1R1 and T1R3 are receptors expressed in taste buds that detect L-amino acids. These receptors are also expressed throughout diverse organ systems, such as the digestive system and muscle tissue, and are thought to function as amino acid sensors. The mechanism of transcriptional regulation of the mouse T1R1 gene (Tas1r1) has not been determined; therefore, in this study, we examined the function of Tas1r1 promoter in the mouse myoblast cell line, C2C12. Luciferase reporter assays showed that a 148-bp region upstream of the ATG start codon of Tas1r1 had a promoter activity. The GT box in the Tas1r1 promoter was conserved in the dog, human, mouse, and pig. Site-directed mutagenesis of this GT box significantly reduced the promoter activation. The GT box in promoters is a recurring motif for Sp/KLF family members. RNAi-mediated depletion of Sp4 and Klf5 decreased Tas1r1 expression, while overexpression of Klf5, but not Sp4, significantly increased Tas1r1 expression. The ENCODE data of chromatin immunoprecipitation and sequencing (ChIP-seq) showed that Klf5 bound to the GT box during the myogenic differentiation. Furthermore, the Klf5 knockout cell lines led to a considerable decrease in the levels of Tas1r1 expression. Collectively, these results showed that Klf5 binds to the GT box in the Tas1r1 promoter and regulates Tas1r1 expression in C2C12 cells.
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http://dx.doi.org/10.2220/biomedres.40.67DOI Listing
August 2019

Efficacy of electric-powered cleaning instruments in edentulous patients with implant-supported full-arch fixed prostheses: a crossover design.

Int J Implant Dent 2019 Mar 26;5(1). Epub 2019 Mar 26.

Division of Oral Reconstruction and Rehabilitation, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-Ku, Kitakyushu City, Fukuoka, 803-8580, Japan.

Background: The aim of this study was to evaluate the plaque removal efficacies of electric toothbrushes and electric dental floss compared with conventional manual toothbrushing in cleaning the fitting surface of an All-on-4™ concept (Nobel Biocare, Zürich-Flughafen, Switzerland) implant-supported fixed dental prosthesis (FDP).

Methods: Nine patients with maxillary edentulous arches participated in the study. We investigated two electric-powered brushes (Sonicare Diamond Clean®, Koninklijke Philips N.V., Amsterdam, the Netherlands [SD group], and the Oral-B Professional Care Smart Series 5000®, Braun GmbH, Kronberg, Germany [OralB group]) and one electric dental floss unit (Air Floss®, Koninklijke Philips N.V. [AF group]). A manual toothbrush (Tuft24® MS, OralCare Inc., Tokyo, Japan) was used by the control group. The fitting surface of the FDP was stained to allow visualization of the entire accumulated plaque area. Both the buccal and palatal portions of the plaque area were assessed before and after brushing to evaluate each instrument's plaque removal rate using a crossover study design. Two-week washout periods were employed between each evaluation.

Results: The plaque removal rates were 53.5 ± 8.5%, 70.9 ± 6.5%, 75.4 ± 6.3%, and 74.4 ± 4.2% for the control, AF, OralB, and SD groups, respectively. When participants were divided into two groups based on their plaque removal rates with a manual toothbrush (poor brushing and good brushing), the poor brushing group showed significant improvement in the plaque removal rate when using electric-powered toothbrushes. The plaque removal rates for the buccal area were significantly higher for the OralB and SD groups than for the manual brushing group (control group), with rates of 52.8 ± 7.9%, 70.1 ± 7.3%, 77.7 ± 6.5%, and 79.5 ± 3.7% for the control, AF, OralB, and SD groups, respectively. The plaque removal rates in the palatal area were consistently lower than those in the buccal area for each of the three electric instruments.

Conclusions: The results suggest that patients who are not adept at manual toothbrushing may potentially improve their removal of plaque from the fitting surfaces of FDPs by using electric toothbrushes.
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http://dx.doi.org/10.1186/s40729-019-0164-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434005PMC
March 2019

Submandibular gland-specific inflammaging-induced hyposalivation in the male senescence-accelerated mouse prone -1 line (SAM-P1).

Biogerontology 2019 08 25;20(4):421-432. Epub 2019 Jan 25.

Division of Oral Reconstruction and Rehabilitation, Kyushu Dental University, 2-6-1 Manazuru, Kokurakita-ku, Kitakyushu, Fukuoka, 803-8580, Japan.

Aging has pronounced effects on mammalian tissues and cells, but the impacts of aging on salivary gland function are relatively unknown. This study aims to evaluate the effects of aging on submandibular gland (SMG) and parotid gland (PG) functions in the male senescence-accelerated mouse. In vivo analysis at the systemic level revealed that salivary secretion induced by pilocarpine, a muscarinic agonist, from the SMG was significantly decreased in aged mice, whereas salivary secretion from the PG was not affected. To evaluate organ-level function, the SMG was perfused with the muscarinic agonists carbachol and calcium ionophore A23187 ex vivo to induce salivary secretion, and decreased saliva production was also observed in the aged SMG. Histological analysis revealed the presence of CD4-positive lymphocytes infiltrating the aged SMG. Furthermore, real-time PCR revealed that the aged SMG exhibited accelerated cell aging, increased levels of the inflammatory cytokine interleukin-6, and decreased mRNA levels of the water channel protein aquaporin-5 (AQP5). In summary, these results demonstrate that SMG function in aged mice was diminished, and that cell senescence, chronic inflammation, and the decreased gene expression of AQP5 are the likely causes of hyposalivation in the SMG of aged mice.
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http://dx.doi.org/10.1007/s10522-019-09797-3DOI Listing
August 2019

Long-term dexamethasone treatment diminishes store-operated Ca entry in salivary acinar cells.

Int J Oral Sci 2019 01 3;11(1). Epub 2019 Jan 3.

Division of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Kitakyushu, Fukuoka, 803-8580, Japan.

Corticosteroids are used in the treatment of many diseases; however, they also induce various side effects. Dexamethasone is one of the most potent corticosteroids, and it has been reported to induce the side effect of impaired salivary gland function. This study aimed to evaluate the effects of dexamethasone on mouse submandibular gland function to gain insight into the mechanism of dexamethasone-induced salivary hypofunction. The muscarinic agonist carbachol (CCh) induced salivary secretion and was not affected by short-term dexamethasone treatment but was decreased following long-term dexamethasone administration. The expression levels of the membrane proteins Na-K-2Cl cotransporter, transmembrane member 16A, and aquaporin 5 were comparable between the control and long-term dexamethasone treatment groups. The CCh-induced increase in calcium concentration was significantly lower in the presence of extracellular Ca in the long-term dexamethasone treatment group compared to that in the control group. Furthermore, CCh-induced salivation in the absence of extracellular Ca and Ca ionophore A23187-induced salivation was comparable between the control and long-term dexamethasone treatment groups. Moreover, salivation induced by the Ca-ATPase inhibitor thapsigargin was diminished in the long-term dexamethasone treatment group. In summary, these results demonstrate that short-term dexamethasone treatment did not impair salivary gland function, whereas long-term dexamethasone treatment diminished store-operated Ca entry, resulting in hyposalivation in mouse submandibular glands.
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http://dx.doi.org/10.1038/s41368-018-0031-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315037PMC
January 2019

Is Anterior Guidance a Key Factor on Planning Implant Treatment for Free-End Missing in the Posterior Mandible?

J Oral Implantol 2019 Apr 12;45(2):100-105. Epub 2018 Dec 12.

1   Division of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Graduate School, Fukuoka, Japan.

To perform safe implant treatment, the anatomical structure and bone quality at implant placement sites are evaluated based on a patient's computerized tomography (CT) data, but there is no definite method to determine placement sites and the appropriate number of implants. The objective of this study was to investigate the influence of the number and arrangement of implants on the stress distribution in 3-unit posterior fixed partial dentures for the posterior mandible by mechanical analysis using the finite element method. Three-dimensional finite element analysis models were constructed from the CT data of a patient with missing mandibular teeth (Nos. 35, 36, 37). Implant placement was simulated under various conditions. Superstructures were connected and fixed with a titanium frame. As the loading conditions, 400 N vertical and lateral loads (45° on the lingual side and 45° on the buccal side) were applied to the upper areas of Nos. 35, 36, and 37, and the stress distribution and frame displacement were evaluated. When a vertical force was applied, no difference of the von Mises stress was noted among the 5 experimental conditions. When lateral force was applied from the lingual and buccal sides at 45°, the stress was higher than that induced by vertical force under all conditions, and it was especially high under mesial and distal cantilever conditions. When displacement of the titanium frame was measured, the displacement caused by lateral force was greater than that due to vertical force. In addition, comparison between long and short distal cantilever bridges revealed that displacement of the titanium frame tended to be smaller when the short cantilever was used. These findings suggested that the stress on peri-implant tissues and displacement of the titanium frame vary depending on the configuration and number of implants, with greater stress and more marked displacement of the titanium frame being induced by lateral force when the number of implants is reduced and a cantilever bridge is selected.
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http://dx.doi.org/10.1563/aaid-joi-D-17-00237DOI Listing
April 2019

OSC35: Relationship between Occlusal Support and Total Dietary Fiber Intake.

J Indian Prosthodont Soc 2018 Oct;18(Suppl 1):S22-S23

Division of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Kitakyushu, Japan.

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http://dx.doi.org/10.4103/0972-4052.244626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238445PMC
October 2018

OSC16: Effects of Streptozotocin-induced Diabetes Mellitus on Peri-implantitis.

J Indian Prosthodont Soc 2018 Oct;18(Suppl 1):S13-S14

Division of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Kitakyushu, Japan.

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http://dx.doi.org/10.4103/0972-4052.244606DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6238428PMC
October 2018

Ten-year survival of immediate-loading implants in fully edentulous mandibles in the Japanese population: a multilevel analysis.

J Prosthodont Res 2019 Jan 12;63(1):35-39. Epub 2018 Nov 12.

Division of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Kitakyushu, Fukuoka, Japan.

Purpose: To evaluate the long-term clinical results of and risk factors for immediate-loading implant treatment of completely edentulous mandibles.

Methods: We retrospectively studied 220 implants in 52 patients who received immediate-loading implants in fully edentulous mandibles. Kaplan-Meier survival analyses, log-rank tests, and multilevel mixed-effects parametric survival analysis was used for statistical analyses.

Results: Thirteen of implants in seven patients failed, and the 10-year cumulative implant survival rate was 93.9 % and significantly (p=0.049) higher in women than in men. None of the predictor variables were significantly associated with implant survival, although sex tended to be associated with implant survival.

Conclusions: Immediate-loading implant treatment for completely edentulous mandibles had acceptable clinical results in the long term. Although we could not identify significant risk factors, we established a multilevel mixed-effects parametric survival analysis with the immediate-loading implant survival data.
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http://dx.doi.org/10.1016/j.jpor.2018.04.001DOI Listing
January 2019

The effectiveness of an occlusal disclosure sheet to diagnose sleep bruxism: A pilot study.

Cranio 2019 Jan 27;37(1):5-11. Epub 2017 Nov 27.

a Department of Oral Reconstruction and Rehabilitation , Kyushu Dental University , Fukuoka , Japan.

Objective: To evaluate the utility of vacuum-pressed, BruxChecker sheets for the diagnosis of sleep bruxism.

Methods: Twenty subjects participated in this study. Tooth contact during sleep was recorded using a 0.1 mm-thick polyvinyl chloride sheet called BruxChecker. The area of the BruxChecker in which the red dye was removed was measured. In addition, the EMG activity of the masseter muscle during sleep was recorded. The numbers of bruxism bursts and episodes were counted, and their correlations with the peeled area of the red dye on the BruxChecker were evaluated.

Results: The number of bruxism bursts and episodes/hr significantly correlated with the peeled area at all cut-off values. The peeled area significantly correlated with the number of phasic type bruxism episodes but not with tonic or mixed type bruxism episodes.

Discussion: Since the BruxChecker peeled area reflected phasic type sleep bruxism, the sheets may be useful in sleep bruxism screening.
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http://dx.doi.org/10.1080/08869634.2017.1408194DOI Listing
January 2019

The effects of Lactobacillus reuteri probiotics combined with azithromycin on peri-implantitis: A randomized placebo-controlled study.

J Prosthodont Res 2018 Jan 26;62(1):89-96. Epub 2017 Jul 26.

Department of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Japan.

Purpose: The aim of this randomized placebo-controlled clinical study was to investigate the effects of a probiotic tablet containing Lactobacillus reuteri in peri-implantitis patients.

Methods: Subjects comprised 30 patients with mild to moderate peri-implantitis. A baseline clinical examination and microbiological assessment were conducted, followed by an antibiotics treatment (azithromycin, 500mg, once a day for 3 days). Subjects were divided into probiotic and placebo groups. The clinical examination and bacterial sampling were performed 0, 4, 12 and 24 weeks after the intake of probiotics. The clinical examination included probing pocket depth (PPD), bleeding on probing (BOP), the modified plaque index (mPI), and modified bleeding index (mBI). The number of bacteria was assessed using the PCR-invader method. The Wilcoxon rank-sum test and Wilcoxon signed-rank test with Bonferroni corrections were used for data analyses.

Results: Although the number of bacteria decreased after the administration of azithromycin in both groups, they increased again thereafter. No significant difference was observed in bacterial numbers between the two groups. Although PPD in the probiotics group was significantly lower at 4 and 24 weeks than at 0 weeks (p<0.05), a significant decrease did not occur in the placebo group. The mBI score at 24 weeks was significantly lower in the probiotics group than in the placebo group (p<0.05). No significant difference was observed in BOP or mPI between the two groups.

Conclusion: These results suggested that probiotics prevent inflammation by affecting host responses rather than improving microbial flora in peri-implant sulci in peri-implantitis patients.
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http://dx.doi.org/10.1016/j.jpor.2017.06.006DOI Listing
January 2018

Prostanoid-dependent spontaneous pain and PAR-dependent mechanical allodynia following oral mucosal trauma: involvement of TRPV1, TRPA1 and TRPV4.

Mol Pain 2017 01;13:1744806917704138

Kyushu Dental University.

Abstract: During dental treatments, intraoral appliances frequently induce traumatic ulcers in the oral mucosa. Such mucosal injury-induced mucositis leads to severe pain, resulting in poor quality of life and decreased cooperation in the therapy. To elucidate mucosal pain mechanisms, we developed a new rat model of intraoral wire-induced mucositis and investigated pain mechanisms using our proprietary assay system for conscious rats. A thick metal wire was installed in the rats between the inferior incisors for one day. In the mucosa of the mandibular labial fornix region, which was touched with a free end of the wire, traumatic ulcer and submucosal abscess were induced on day 1. The ulcer was quickly cured until next day and abscess formation was gradually disappeared until five days. Spontaneous nociceptive behavior was induced on day 1 only, and mechanical allodynia persisted over day 3. Antibiotic pretreatment did not affect pain induction. Spontaneous nociceptive behavior was sensitive to indomethacin (cyclooxygenase inhibitor), ONO-8711 (prostanoid receptor EP1 antagonist), SB-366791, and HC-030031 (TRPV1 and TRPA1 antagonists, respectively). Prostaglandin E2 and 15-deoxyΔ12,14-prostaglandin J2 were upregulated only on day 1. In contrast, mechanical allodynia was sensitive to FSLLRY-NH2 (protease-activated receptor PAR2 antagonist) and RN-1734 (TRPV4 antagonist). Neutrophil elastase, which is known as a biased agonist for PAR2, was upregulated on days 1 to 2. These results suggest that prostanoids and PAR2 activation elicit TRPV1- and TRPA1-mediated spontaneous pain and TRPV4-mediated mechanical allodynia, respectively, independently of bacterial infection, following oral mucosal trauma. The pathophysiological pain mechanism suggests effective analgesic approaches for dental patients suffering from mucosal trauma-induced pain.
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http://dx.doi.org/10.1177/1744806917704138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5407658PMC
January 2017

Salivary gland hypofunction in KK-A type 2 diabetic mice.

J Diabetes 2018 Jan 9;10(1):18-27. Epub 2017 May 9.

Department of Prosthodontics, Matsumoto Dental University, Nagano, Japan.

Background: Hypofunction of different organs in the body is associated with diabetes, including in the oral cavity. Diabetes is often associated with xerostomia, but the underlying mechanism is not well characterized. Thus, the mechanisms underlying diabetes-induced xerostomia were investigated in this study in KK-A mice as an experimental model of type 2 diabetes.

Methods: The mechanisms involved in diabetes-induced xerostomia were investigated using the ex vivo glandular perfusion technique, histological analysis, and immunohistochemical and intracellular signaling analyses.

Results: Ex vivo submandibular gland secretions from KK-A mice decreased by 30% following stimulation with 0.3 μmol/L carbachol (CCh), a cholinergic agonist. Acinar cell weight was comparable between KK-A and control mice, whereas duct cell weight was significantly greater in KK-A mice. Concentrations of Na and Cl in the secreted saliva decreased significantly in KK-A mice, supporting the finding of increased ductal tissue in KK-A mice. Immunohistochemistry revealed no significant differences between KK-A and control mice in terms of the expression of Cl and water channels, Na -K -2Cl cotransporters, and membrane proteins critical for fluid secretion. Cellular signaling analysis revealed that the increase in [Ca ] in response to 0.3 μmol/L CCh was reduced by 30% in KK-A mice, although there was no significant difference in the thapsigargin (1.0 μmol/L)-induced increase in store-depleted calcium between KK-A and control mice.

Conclusions: These results demonstrate that submandibular fluid secretion is diminished in KK-A mice because of a diminished increase in [Ca ] . Duct cell weight increased in KK-A mice, possibly leading to increased ion reabsorption and thus decreased Na and Cl concentrations in the secreted saliva.
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http://dx.doi.org/10.1111/1753-0407.12548DOI Listing
January 2018

The effect of low-intensity pulsed ultrasound on wound healing using scratch assay in epithelial cells.

J Prosthodont Res 2016 Oct 26;60(4):308-314. Epub 2016 Mar 26.

Department of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Japan.

Purpose: Low-intensity pulsed ultrasound (LIPUS) is widely used in medical fields because it shortens the time required for biologic wound healing in fracture treatment. Also, in dental fields, LIPUS should be effectively employed for implant treatment. However, most of the relevant reports have been published on its effects on bone formation around implants, and the effects of LIPUS on soft tissue healing remain unclear. In the present study, we examined the effects of LIPUS on soft tissue healing using gingival epithelial cells.

Methods: Gingival epithelial cells were cultured on a dish, followed by LIPUS exposure at a frequency of 3MHz for 15min. The cells were counted with a hemocytometer, and a scratch assay was conducted by measuring the closing area of the scratch wound using a microscope. Following LIPUS exposure, total RNA was collected for microarray analysis. In addition, real-time PCR was performed to examine the mRNA expression level of integrin α6β4. Furthermore, total protein was collected to examine the protein expression level of integrin α6β4 by western blotting.

Results: The cell count and scratch assay demonstrated that LIPUS exposure promoted cell proliferation and scratch-wound closure. Microarray analysis demonstrated the increased expression levels of adhesion-related genes, including integrin. Real-time PCR analysis demonstrated that LIPUS exposure significantly up-regulated the mRNA expression level of integrin α6β4. Western blotting showed intense staining of integrin α6β4.

Conclusion: LIPUS exposure promotes wound closure in the scratch assay and up-regulates the expression level of integrin α6β4 as compared with the control.
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http://dx.doi.org/10.1016/j.jpor.2016.03.002DOI Listing
October 2016

Changes in oral health-related quality of life during implant treatment in partially edentulous patients: A prospective study.

J Prosthodont Res 2016 Oct 8;60(4):258-264. Epub 2016 Mar 8.

Department of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Japan.

Purpose: The aim of this prospective study was to evaluate the changes in oral health-related quality of life (OHRQoL) during implant treatment for partially edentulous patients, and to evaluate the influence of the type of partially edentulous arch.

Methods: Twenty patients with a small number of lost teeth (fewer than 4 teeth) who underwent implant treatment were selected. Chronological QOL change during implant treatment was measured. The subjects completed the shortened Japanese version of the Oral Health Impact Profile (OHIP-J14) before the surgery (T0), 1 week after the surgery (T1), 1 week after interim prosthesis placement (T2), and 1 week after definitive prosthesis placement (T3). Complete data of the twenty subjects were analyzed with the Wilcoxon signed-rank test.

Results: The total OHIP-J14 score was significantly reduced only at T3 (P<0.05). "Physical pain" and "Physical disability" scores significantly decreased at T3, and "Psychological discomfort" scores also significantly dropped at T2. However, "Functional limitation" scores significantly increased at T1. "Psychological disability", "Social disability", and "Handicap" scores remained the same. On the other hand, in the comparison depending on the type of partially edentulous arch, the total OHIP-J14 score significantly decreased at T3 in the unilateral free-end edentulous space, whereas no significant difference was observed in the bounded edentulous space.

Conclusion: Although there is a temporary functional limitation after implant placement in overall OHRQoL improvement was observed after the definitive prosthesis placement. Moreover, implant treatment was more effective in the unilateral free-end edentulous space.
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http://dx.doi.org/10.1016/j.jpor.2016.01.010DOI Listing
October 2016

Strategies for alveolar ridge reconstruction and preservation for implant therapy.

J Prosthodont Res 2015 Oct 26;59(4):220-8. Epub 2015 May 26.

Department of Oral Reconstruction and Rehabilitation, Kyushu Dental University, Japan.

Purpose: In dental implant treatment, ridge preservation and immediate or early implant placement are recommended to minimize bone resorption after tooth extraction and achieve esthetic outcomes. However, there is no consensus concerning the efficacy of this surgical method. There is also no consensus on the efficacy of bone and soft tissue grafts and surgical methods for alveolar ridge reconstruction.

Study Selection: This paper reports ridge alteration in the anterior maxilla after tooth extraction, and summarizes the efficacy of various ridge preservation methods and immediate or early implant placement as alveolar ridge preservation methods to minimize bone resorption after tooth extraction. The advantages and complications of alveolar ridge reconstruction methods, and the efficacy and surgical method of soft tissue graft are reviewed.

Results: The anterior maxilla is in the esthetic zone, and the thickness of the bone on the labial side around the natural tooth is less than 1mm in many cases. Therefore, it is impossible to prevent bone resorption completely, even if ridge preservation and immediate or early implant placement are performed after tooth extraction. It is necessary to obtain stable and long-term esthetics by combining connective tissue and free gingival grafts, in addition to hard tissue augmentation.

Conclusions: It is important to consider the burden and level of satisfaction of patients, such as in terms of donor site morbidity in hard and soft tissue grafting, and to pay attention to appropriate indications to avoid overtreatment.
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http://dx.doi.org/10.1016/j.jpor.2015.04.005DOI Listing
October 2015