Shinichiro Kuroshima

Hokkaido University | Hokudai · Department of Crown and Bridge Prosthodontics

Objectives Intermittent administration of parathyroid hormone (PTH) increases systemic bone mass. However, the effect of PTH on osseous and soft tissue healing around implants in osteoporosis patients remains unclear. This study aimed to investigate the effects of PTH on tissue healing around implants in ovariectomized rats and to compare systemic...

Purpose: This systematic review aimed to evaluate the effects of implant placement sites on the biomechanical behavior of implant-assisted removable partial dentures (IARPDs) using finite element analysis (FEA). Study selection: Two reviewers independently conducted manual searches of the PubMed, Scopus, and ProQuest databases for articles investig...

Purpose: This scoping review aimed to systematically map research regarding implant-assisted removable partial dentures (IARPDs), and identify existing gaps in knowledge. Study selection: Two reviewers independently conducted a search of the MEDLINE-PubMed and Scopus databases according to the Preferred Reporting Items for Systematic Review and Met...

The pathophysiology, pathogenesis, histopathology, and immunopathology of medication-related osteonecrosis of the jaw (MRONJ) Stage 0 remain unclear, although 50% of MRONJ Stage 0 cases could progress to higher stages. The aim of this study was to investigate the effects of zoledronate (Zol) and anti-vascular endothelial cell growth factor A (VEGFA...

Since the initial description of medication-related osteonecrosis of the jaw (MRONJ) almost two decades ago, the potential pathophysiology and risk factors have been elaborated on in many investigations and guidelines. However, the definitive pathophysiology based on scientific evidence remains lacking. Consequently, the optimal clinical treatment...

Background: Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a potentially intractable disease with no definitive pathophysiology and treatment and prevention strategies. Cell-based therapy is one of the useful methods for resolving intractable diseases. This study aimed to investigate whether time-selective depletion and transplantation...

Objectives: This study aimed to investigate the effects of early loads on bone quality and quantity around implants and to compare the effects of early loads on bone quality and quantity with the effects of conventional loads. Materials and methods: Grade IV-titanium implants with buttress threads were placed in rat maxillary bone 4 weeks after...

The pathophysiology, histopathology, and immunopathology of bisphosphonate-related osteonecrosis of the jaw (BRONJ) Stage 0 remain unclear. The aim of this study was to investigate the effects of high-dose bisphosphonates on tooth extraction socket healing by creating a murine model of BRONJ Stage 0-like lesions using 8-week-old female C57BL/6J mic...

Background Medication-related osteonecrosis of the jaw (MRONJ), which was first reported as bisphosphonate-related osteonecrosis of the jaw (BRONJ) in bisphosphonate users, is a rare but severe soft and hard tissue disease induced by several types of medications. There has been a deluge of information about MRONJ, such as epidemiology, risk factors...

Lactoferrin (LF) has attracted great attention due to its various bioactivities, which depend on the degree of saturation with different cations. This study focused on the synergistic effect of LF and Zn²⁺ on human gingival fibroblasts (hGFs), considering antioxidant activities, cell proliferation, and collagen gene expression levels in these cells...

Purpose: The aim of the present study was to investigate the effects of chemotherapeutic/bisphosphonate combination therapy with tooth extraction on gene expression patterns of fresh extraction wounds during initial stages prior to their diagnosis as bisphosphonate-related osteonecrosis of the jaw (BRONJ)-like lesions in mice. Methods: Female C57BL...

Introduction: After the onset of bone metastasis, tumor cells appear to modify surrounding microenvironments for their benefit, and particularly, the levels of circulating fibroblast growth factor (FGF) 23 in patients with tumors have been highlighted. Materials and methods: We have attempted to verify if human breast carcinoma MDA-MB-231 cells...

Dental implant treatment in patients prescribed medications is associated with bisphosphonate-related osteonecrosis of the jaw (BRONJ) around the implants. However, there is no scientific information on how bisphosphonate and/or steroid therapies affect wound healing around implants after implant placement. The aim of this study was to histopatholo...

Background To explore the effects of topographical modification of titanium substrates at submicron level by oxalic acid treatment on bone quality and quantity around dental implants in rabbit tibiae. Methods A total of 60 blasted CP-grade IV titanium dental implants were used. Twenty-eight control implant surfaces were treated with a mixture of H...

Background: There is insufficient evidence for the efficacy of silicone soft reliner on the obturator prosthesis after maxillectomy for oral malignant tumors. Objective: To verify the efficacy of silicone soft reliner on the obturator prosthesis after maxillectomy, by evaluating masticatory performance and quality of life (QoL). Methods: This...

Denosumab-related osteonecrosis of the jaw (DRONJ), which mainly occurs in cancer patients receiving anti-receptor activator NF-kappaB ligand (RANKL) antibody, reduces oral health-related quality of life. However, the exact mechanisms of and definitive treatment strategies for DRONJ remain unknown. We hypothesized that cessation of denosumab heals...

Background: Treatment for most patients with head and neck cancers includes ionizing radiation with or without chemotherapy. This treatment causes irreversible damage to salivary glands in the irradiation field accompanied by a loss of fluid-secreting acinar cells and a considerable decrease of saliva secretion. There is currently no adequate conv...

Peri-implantitis is an inflammatory disease with a relevant focus on the long-term success of dental implants and implant-supported prostheses. The present study focuses on the antibacterial effect of the silver nanoparticle and investigated the suppression of dental plaque adhesion on implant abutment and/or superstructure by micro-wave assistant...

OBJECTIVES Intermittent injection of parathyroid hormone (PTH) is used to treat osteoporosis. The concept of bone quality was updated 20 years ago; however, these updates have not been adopted in implant dentistry. This study aimed to investigate the effects of intermittent administration of PTH on bone quality around implants in rat tibiae. METHO...

There is limited information about denosumab-related osteonecrosis of the jaw (DRONJ), unlike bisphosphonate-related ONJ (BRONJ). The mode of action is clearly different between denosumab and bisphosphonates. DRONJ occurs mainly following tooth extraction in cancer patients treated with the combination of denosumab and other drugs including chemoth...

Optical technology has provided a paradigm shift in implant dentistry. However, there is little information about the use of optical technology in implant dentistry, since this technology is relatively new and has been evolving under the current conditions. In the present narrative literature review, the effects of intraoral scanners (IOSs) use on...

Background: There are currently no effective treatments available for patients with irreversible loss of salivary gland (SG) function caused by radiation therapy for head and neck cancer. In this study, we have developed an effective culture method to enhance the anti-inflammatory and vasculogenic phenotypes of peripheral blood mononuclear cells (...

Objective: The aim of this comprehensive systematic review and meta-analysis was to investigate the pathology and pathogenesis of medication-related osteonecrosis of the jaw (MRONJ) in rodents. Background: Medication-related osteonecrosis of the jaw occurs in patients taking antiresorptive drugs, such as bisphosphonates and denosumab, and anti-a...

In this study, we attempted to localize the immunoreactivities of podoplanin/E11/gp38 and CD44, a counterpart possessing a high affinity to podoplanin/E11/gp38, as well as endomucin-immunoreactive blood vessels in the regions of odontoblast layers and the underlying sub-odontoblastic layers in murine tooth germs. Endomucin-reactive small blood vess...

Background: Definitive treatment strategies for bisphosphonate-related osteonecrosis of the jaw (BRONJ) have not been developed. Cell-based therapy is an attractive treatment method for intractable diseases in the medical and dental fields; however, approval has been challenging in dentistry. Recently, we developed quality- and quantity (QQ)-contr...

In this study, we aimed to clarify the role of ascorbic acid in collagen synthesis in periodontal ligaments using osteogenic disorder Shionogi (ODS)/ShiJcl-od/od rats lacking L-gulonolactone oxidase. These rats cannot synthesize ascorbic acid in vivo. Eight-week-old ODS/ShiJcl-od/od male rats were administered ascorbic acid solution at a concentrat...

Background: Antiresorptive agents such as bisphosphonates and denosumab, as well as angiogenesis inhibitors, may induce medication-related osteonecrosis of the jaw (MRONJ). However, the exact mechanisms of MRONJ are unclear and definitive treatment strategies have not yet been developed. Moreover, the aging population requiring antiresorptive agen...

Objective The latest survey by Japanese Society of Oral and Maxillofacial Surgeons suggested that the number of medication related osteonecrosis of the jaw (MRONJ) patients who received oral bisphosphonate, mostly for postmenopausal osteoporosis, may exceed that by intravenous bisphosphonate for cancer treatment. Consequently, the number of female...

Purpose: The aim of this review article was to present the current concept of “bone quality” which was stated to be important parameters for bone diagnosis other than BMD by the National Institute of Health (NIH), based on collagen fibers, biological apatite, and bone cells. Results: The term “bone quality” has been considered to be synonymous with...

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) worsens oral health-related quality of life. Most BRONJ occurs in multiple myeloma or metastatic breast cancer patients treated with bisphosphonate/chemotherapeutic combination therapies. Cyclophosphamide (CY), an alkylating chemotherapeutic drug, is used to treat multiple myeloma, although it...

Greater understanding and acceptance of the new concept “bone quality”, which was proposed by the National Institutes of Health and is based on bone cells and collagen fibers, are required. The novel protein Semaphorin3A (Sema3A) is associated with osteoprotection by regulating bone cells. The aims of this study were to investigate the effects of m...

The aim was to clarify whether marginal grooves on dental implants affect osseointegration, bone structure and the alignment of collagen fibers determining bone quality under loaded condition. Anodized Ti-6Al-4V alloy dental implants with and without marginal grooves were used (3.7 × 8.0 mm; test and control implants, respectively). Fourth premolar...

Osteonecrosis of the jaw (ONJ), which is a rare but severe adverse effect, mainly occurs in oncology patients receiving chemotherapeutic agents and bisphosphonates. However, the combined impact of chemotherapy and bisphosphonates on wound healing after tooth extraction remains unknown. The aim of this study was to determine the precise etiology of...

The precise pathoetiology and effective treatment strategies for bisphosphonate-related osteonecrosis of the jaw (BRONJ) remain unknown. Transplantation of noncultured stromal vascular fraction (SVF) cells has been shown to be a useful method for regenerative medicine in place of stem cell therapy. This study investigated the effects of noncultured...

Purpose: The aim of this study was to present the current concept of bone quality based on the proposal by the National Institutes of Health (NIH) and some of the cellular and molecular factors that affect bone quality. Study selection: This is a literature review which focuses on collagen, biological apatite (BAp), and bone cells such as osteob...

Osteocytes play important roles in controlling bone quality as well as preferential alignment of biological apatite c-axis/collagen fibers. However, the relationship between osteocytes and mechanical stress remains unclear due to the difficulty of three-dimensional (3D) culture of osteocytes in vitro. The aim of this study was to investigate the ef...

The aim was to investigate the effect of groove designs on bone quality under controlled-repetitive load conditions for optimizing dental implant design. Anodized Ti-6Al-4V alloy implants with -60° and +60° grooves around the neck were placed in the proximal tibial metaphysis of rabbits. The application of a repetitive mechanical load was initiated...

Purpose: The aim of this study was to investigate effects of implant neck design on the original concept of osseointegration and bone formation when applying mechanical repetitive loading by bone-integrated implants. Materials and methods: Twenty-eight anodized Ti-6Al-4V alloy implants with +60° or -60° grooves in the implant neck were placed in...

Osteocytes are crucial cells that control bone responses to mechanical loading. However, the effects of mechanical loading on osteocytes around dental implants are unclear. The aim of this study was to investigate whether mechanical loading via bone-integrated implants influences osteocyte number and morphology in the surrounding bone. Fourteen ano...

Teriparatide is a synthetic polypeptide hormone that contains the 1-34 amino acid fragment of the recombinant human parathyroid hormone that stimulates bone formation. Currently, it is approved only for the treatment of osteoporosis. The outcomes of daily teriparatide injections for the treatment of bisphosphonate-related osteonecrosis of the jaw i...

Denosumab, a human monoclonal antibody (mAb) that neutralizes receptor activator for nuclear factor κB ligand (RANKL), is associated with osteonecrosis of the jaw. However, the effect of denosumab on oral wounds is unclear. The aim was to determine the effect of anti-RANKL mAb on oral wounds and bone marrow. The direct effect of the mAb on fibrobla...

Background Bone mechanical function is regulated by bone quality and bone mineral density (BMD) that reflect bone strength. The preferential alignment of biological apatite (BAp) c-axis/collagen fibers and osteocytes is a determinant factor of bone quality. However, the effect of mechanical loading on bone quality around dental implants is unclear....

Administration of intermittent parathyroid hormone (PTH) promoted healing of tibial osseous defects and tooth extraction wounds and prevented the development of necrotic lesions in rats on a combined bisphosphonate and steroid regimen. Osteonecrosis of the jaw (ONJ) has emerged in association with antiresorptive therapies. The pathophysiology of ON...

Osteonecrosis of the jaw (ONJ) is a serious adverse event that occurs predominantly in patients on both antiresorptive and antineoplastic therapies. However, how these combination therapies are connected to the high frequency of ONJ in this particular patient population is unclear. This study's aim was to determine a mechanism of ONJ associated wit...

Background: Patients with osteoporosis who receive tooth extractions are typically on either oral bisphosphonate or parathyroid hormone (PTH) therapy. Currently, the consequence of these therapies on hard- and soft-tissue healing in the oral cavity is not clearly defined. The aim of this study is to determine the differences in the therapeutic eff...

Intermittent parathyroid hormone (PTH) administration increases systemic and craniofacial bone mass. However, the effect of PTH therapy on healing of tooth extraction sites is unknown. The aims of this study were to determine the effect of PTH therapy on tooth extraction socket healing and to examine whether PTH intra-oral injection promotes healin...

Objective: The majority of ONJ cases occur after tooth extractions in patients on intravenous antiresorptive therapy. Those patients typically have a history of multiple chemotherapy and steroid therapy. However, the effect of chemotherapeutics and steroids on the pathophysiology of ONJ is unclear. The objective of this study was to investigate the...

Objectives: Osteonecrosis of the jaw (ONJ) is a devastating condition that has emerged in association with antiresorptive therapies. The pathophysiology of ONJ is unknown and no established cure currently exists. The objective of this study was to determine whether PTH therapy prevents the development of ONJ-like lesions in tooth extraction sockets...

The bone anabolic effect of parathyroid hormone (PTH) therapy is blunted when used in patients who were previously on bisphosphonate treatment. Osteocytes may play a role in the bisphosphonate silencing effect on PTH therapy since bisphosphonates have been shown to reach the lacunocanalicular system. In vivo osteocyte studies pose a significant cha...

Objective: The quality and quantity of bone formed in tooth extraction sockets impact implant therapy. Therefore, the establishment of a new approach to enhance bone formation and to minimize bone resorption is important for the success of implant therapy. In this study, we investigated whether intermittent parathyroid hormone (PTH) therapy enhanc...

Osteoclasts are key players in the maintenance of bone, which is an endocrine target and organ. Bisphosphonates, used for the management of metastatic bone diseases and osteoporosis, suppress osteoclasts. However, the impact of continuously suppressed osteoclasts is unknown. In this study, mice received zoledronic acid (ZA) for 13 months, nearly ha...

Objectives: The interaction between hematopoietic and mesenchymal cell populations is well controlled in the bone marrow microenvironment. However, mechanisms in which hematopoietic cells communicate with osteoblasts during homeostasis are unknown. In this study we investigated the effects of bone marrow hematopoietic cells (BMHCs) on the mineraliz...

Coexpression of desmosomal proteins and vimentin has been reported in a specific mesenchymal phenotype. This study investigated the expression of vimentin-binding desmosomal proteins in human dental pulp fibroblasts (DPF) and odontoblasts. The dental pulp has no cells expressing desmocollin (DSC) 1-3, desmoglein (DSG) 1-3, junction plakoglobin (JUP...

The cys-cys (C-C) chemokine ligand 21 is a member of the C-C chemokines that constitute a group of heparin-binding cytokines with a pattern of four or six conserved cysteines. The CCL21 is known to be expressed in secondary lymphoid tissues, however it has rarely been reported for the expression on peripheral lymphatic vessels in somatic tissue. He...

The osteogenic cell type of human periodontal ligament fibroblasts (PDLF) undergoes senescence at finite population doubling numbers unrelated to donor ages. This study investigated telomere lengths of osteogenic PDLF from differently aged donors and alterations of the osteoblast-like properties in the aged PDLF with short telomeres. Telomere lengt...

The Toll-like receptor (TLR) is a part of the innate immune system sensing pathogen-associated molecular patterns (PAMPs). Recently, TLRs 2 and 4 have been demonstrated for the ligand engagements, which result in the induction of cytokines. Here we investigated the expression of TLRs 2 and 4 on lymphatic vessels producing cys-cys chemokine ligand 2...