• Journal of Periodontal and Implant Science
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• v.31 no.4
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• pp.713-726
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• 2001

Bisphosphonate가 백서 발치와의 치유과정에 미치는 영향에 대해 관찰하고자 생후 2개월 된 Sprague-Dawley계의 백서 18마리를 사용하여, 실험군과 대조군 모두 발치를 용이하게 하고 외상을 최소화 하기 위해 발치 전에 하루 ${\beta}-Aminoproprionitrile(APN)$ 0.2g/㎏을 5일간 투여한 후 발치하고, 감염방지를 위해 매일 1.5㎎/㎏ ampicillin을 3일 동안 근육주사 하였다. 실험군에서는 Biosphosphonate 1㎎/㎏을, 대조군에서는 vehicle(0.9%saline)을 1주에 3회씩 2주 동안 피하 주사하였으며, 각 군은 발치 후 1주, 2주, 4주 간격으로 3마리씩 희생시켜 H&E 염색에 의한 조직학적인 관찰, TRAP 염색에 의한 파골 세포의 활성, 경도 측정기에 의한 경도 측정을 통해 다음과 같은 결과를 얻었다. 1. 각 주간의 전반적인 치유양상은 시간이 경과함에 따라 실험군과 대조군 공히 유사한 치조골 회복 양상을 보였다. 2. 파골 세포의 활성은 1주, 4주 군에서는 실험군과 대조군에서 유사한 양상을 나타내었으나, 2주 군에서는 실험군에서 대조군에 비해 감소된 파골 세포 활성 양상을 관찰 할 수 있었다. 3. 경도측정에서는 모든 군에서 대조군에 비해 실험군에서 유의성 있는 증가 양상을 보였으며, 시간경과에 따른 경도의 차이에서는 1주군과 4주군 간에서 대조군에 비해 실험군에서 통계학적으로 유의성 있는 증가 양상을 보였다.(p<0.05) 이상의 연구를 통해 Bisphosphonate가 백서 발치와의 치유과정과 파골 세포의 활성에 영향을 미치며, 치유된 발치와의 경도를 증가시키는 것으로 나타났다.

• Clinical Pain
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• v.19 no.2
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• pp.111-115
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• 2020

We report a case of a healthy 38-year-old man presenting with insufficiency fracture of proximal tibia associated with unrecognized osteoporosis. Radiologic bone DEXA (Dual Energy X-ray Absorptiometry) assessment revealed osteoporosis, but the patient displayed no apparent risk factors for insufficiency fractures and osteoporosis except for a history of smoking. Following right proximal tibial open reduction and internal fixation, the patient commenced smoking cessation and began taking alendronate. The patient was treated for gait rehabilitation, which included quadriceps strengthening exercises and his condition improved with independent walking. This report highlights an unusual site of proximal tibial insufficiency fractures and the potential effect of smoking on low bone mineral density in a young male patient.

• International Journal of Industrial Entomology and Biomaterials
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• v.30 no.1
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• pp.17-25
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• 2015

This study aimed to investigate the effects of silk fibroin on bone metabolism in ovariectomized rats. A total of 30 Sprague-Dawley rats were randomized into sham-operated (SHAM), ovariectomized control (OVX), alendronate (OVX+ALEN, 10 mg/kg body weight/d), low silk fibroin (OVX+SF100, 100 mg/kg body weight/d), and high silk fibroin (OVX+SF300, 300 mg/kg body weight/d) groups. All the rats were fed by gavage for 12 wk. At the end of 12 wk, blood and urine were collected for analysis of bone turnover markers, and bone mineral density (BMD) was measured by micro-computed tomography. The results show that the OVX group (p < 0.05) displayed the highest mean body weight gain. Among the five groups, serum levels of bone alkaline phosphatase (ALP) and urine levels of deoxypyridinoline (DPD) were highest in the OVX group (p < 0.05). Bone ALP levels in the ALEN group were significantly lower than that of the silk-treated groups. On the other hand, DPD levels were not significantly different between the ALEN and silk-fibroin-treated groups (p < 0.05). The trabecular BMD was significantly higher in the ALEN and silk-treated groups compared to the OVX group (p < 0.05). In conclusion, this study showed that silk fibroin has similar effects as alendronate, which is used in osteoporosis medication. Therefore silk fibroin might be a new candidate for the prevention and treatment of osteoporosis in patients.

• Bulletin of the Korean Chemical Society
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• v.31 no.9
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• pp.2561-2564
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• 2010

The accurate determination of bisphosphonate levels in bone and biological fluids is important in both clinical and pharmacological/toxicological studies; however, the quantitative analysis of the bisphosphonate is difficult because its concentration is quite low in most of biological sample. A novel fluorescent chemosensor (FCS)-based measurement method of bisphosphaonate levels using Naphta-diDPA-$2Zn^{2+}$ (NadDPA-$2Zn^{2+}$, DPA = dipycolylamine), an excellent FCS previously used for detecting PPi, was developed. By the FCS method, the concentration of bisphosphonates having no fluorophores can be determined analyzed with sufficient sensitivity. The results of this study indicate that the FCS-based measurement can be a useful method to analyze bisphosphonates in biological samples.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.32 no.5
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• pp.478-483
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• 2010

Bisphosphonates are synthetic analogue and have high affinity on bone remodeling site. Since they have a long half-reduction time, they accumulate at bone and act for a long time. They are widely used in osteo-porosis derived from imflammatory bowel disease or postmenopausal osteoporosis patient for bone mineral density improvement. In addition, they neutralize hypercalcemia owing to bone metastasis of malignancy. However, a jaw bone necrosis was recently reported in some patients who have taken bisphosphonates for a long time. It is called Bisphosphonate Related Osteonecrosis of Jaws (BRONJ). It can come spontaneous-ly, but more often after oral surgery including tooth extraction. In this case, a 80-year-old woman was treated with bisphosphonate (sodium alendronate) for 2 years to improve bone mineral density. She had her left lower second molar tooth extracted at local clinic. After extraction, she had inflammatory symptoms like a pain, a cheek swelling, and a discharge of pus. She was referred to our clinic for treatment. We treated meticulously from dressing to surgery. After following up about 1.5 years, the jaw lesion was successfully healed. So we report this case.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.34 no.5
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• pp.550-554
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• 2008

Bisphosphonates (BPs) are a class of agent used to treat patient with osteoporosis or malignant bone metastases. BPs can be categorized into 2 groups: nitrogen-containing and non-nitrogen containing. Nitrogen-containing BPs are considered to have more toxicity. Despite their clinical benefits, bisphosphonate-related osteonecrosis of jaw(BRONJ) is a significant complication to patients receveing these drugs. Since the first description of BRONJ in 2003 by Marx, the number of reports on BRONJ has been rapidly increasing. BRONJ is considered as an emerging problem in oral & maxillofacial surgery. Generally, osteonecrosis in the maxilla is rare, however BRONJ is found both in the maxilla and the mandible. This is an important feature of BRONJ compared to common infectious osteomyelitis of the jaw. Growing number of case reports, suggest that bisphosphonate therapy may cause exposed, necrotic bone. BRONJ has simillar features compared to IORN (infected osteoradionecrosis). BRONJ has meaningful features established through the interestigation on histopathologic and radiographic findings. These features have an impact on treatment plan and prognosis. This presentation contemplates on features of histopathologic and radiographic findings in bisphosphonate-related osteonecrosis of the jaw.

• International Journal of Oral Biology
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• v.41 no.2
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• pp.89-96
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• 2016

Tooth development shows dynamic morphological changes from the stages of cap to hard tissue formation and is strictly regulated during development. In the present study, we compared expression and localization of 3 major enamel matrix proteins in rats: amelogenin, enamel and ameloblastin. DD-PCR and RT-PCR revealed differential expression of the major proteins from the cap stage to root stage. Immunofluorescence staining results indicated that amelogenin was not detected in either inner enamel epithelium or reduced enamel epithelium, but highly immunoreactive in preameloblasts and ameloblasts; in addition, it was sporadically expressed in preodontoblasts abutting preameloblasts. Ameloblastin expression was also observed in not only differentiated ameloblasts but also osteoblasts. Immunoreactivity to ameloblastin in ameloblasts was strong in Tomes' processes. Enamelin was exclusively localized along the entire newly formed and maturing enamel. Enamelin was largely localized in near Tomes' processes and enamel rods in maturing enamel. Alendronate treatment resulted in down-regulation of amelogenin and ameloblastin at both transcription and translation levels; whereas, enamelin expression was unchanged in response to the treatment. These results suggested that amelogenin, ameloblastin and enamelin might be implicated in cell differentiation, adhesion of ameloblasts to enamel and enamel crystallization during enamel matrix formation, respectively.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.38 no.3
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• pp.152-159
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• 2012

Objectives: This study evaluated bisphosphonate-related osteonecrosis of the jaws (BRONJ) in patients diagnosed with malignant bone tumors. Demographic findings, laboratory, and radiographic analyses were performed to characterize disease severity and progression. Materials and Methods: Patients who had been diagnosed with BRONJ (2005-2010) at the authors' hospital according to the American Association of Oral and Maxillofacial Surgeons were investigated. Twenty-one patients (12 with multiple myelomas, 7 with breast cancer, and 2 with prostate cancer) who had been treated with bisphosphonates (BPs) for malignant bone tumors were included. Radiographic evaluations with a panorama, computed tomography, whole body bone scan, and laboratory findings were evaluated for erythrocyte sedimentation rate (ESR), c-reactive proteins (CRPs), and c-terminal cross-linked telopeptides (CTXs). Results: The average age of the patients was 64.3 (range 51-80), and they were treated with BPs for an average of $35{\pm}19$ months before BRONJ was diagnosed. Types of BPs were zolendronic acid (81%, intravenous [IV]), pamidronate (4.8%, IV), zoledronic acid+pamidronate (4.8%, IV), alendronate (4.8%, per os [PO]), and ibadronate (4.75%, PO). Extraction (67%) and persistent irritation of dentures (20%) were the most common triggering factors. BRONJ in the mandible was reported in 62% of the cases, in the maxilla 24%, and both 14%. BRONJ occurred more frequently in patients with multiple myelomas (n=12, 57.1%). Most of the patients revealed an advanced BRONJ stage; Stage I (n=2, 9%), Stage II (n=13, 62%), and Stage III (n=6, 29%). Conclusion: The differences of the ESR, CRP, and CTX values between the BRONJ-recurring and non-recurring patients after the treatment were not evident. Later stage BRONJ patients showed lower CTX levels. A drug holiday after the diagnosis of BRONJ did not remarkably influence the surgical outcomes. However, the limited number of patients in the study should be considered.

• Restorative Dentistry and Endodontics
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• v.44 no.2
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• pp.17.1-17.10
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• 2019

Objectives: Root resorption is an unexpected complication after replantation procedures. Combining anti-osteoclastic medicaments with retrograde root filling materials may avert this resorptive activity. The purpose of this study was to assess effects of a cathepsin K inhibitor with calcium silicate-based cements on osteoclastic activity. Methods: MC3T3-E1 cells were cultured for biocompatibility analyses. RAW 264.7 cells were cultured in the presence of the receptor activator of nuclear factor-kappa B and lipopolysaccharide, followed by treatment with Biodentine (BIOD) or ProRoot MTA with or without medicaments (Odanacatib [ODN], a cathepsin inhibitor and alendronate, a bisphosphonate). After drug treatment, the cell counting kit-8 assay and Alizarin red staining were performed to evaluate biocompatibility in MC3T3-E1 cells. Reverse-transcription polymerase chain reaction, tartrate-resistant acid phosphatase (TRAP) staining and enzyme-linked immunosorbent assays were performed in RAW 264.7 cells to determine the expression levels of inflammatory cytokines, interleukin $(IL)-1{\beta}$, IL-6, tumor necrosis $factor-{\alpha}$ ($TNF-{\alpha}$) and prostaglandin E2 (PGE2). Data were analyzed by one-way analysis of variance and Tukey's post hoc test (p < 0.05). Results: Biocompatibility results showed that there were no significant differences among any of the groups. RAW 264.7 cells treated with BIOD and ODN showed the lowest levels of $TNF-{\alpha}$ and PGE2. Treatments with BIOD + ODN were more potent suppressors of inflammatory cytokine expression (p < 0.05). Conclusion: The cathepsin K inhibitor with calcium silicate-based cement inhibits osteoclastic activity. This may have clinical application in preventing inflammatory root resorption in replanted teeth.

• BMB Reports
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• v.52 no.9
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• pp.572-576
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• 2019

Bisphosphonates are the mainstay of therapy worldwide for osteoporosis. However, bisphosphonates also have limitations. The objective of this study was to determine the role of miR-101-3p/Rap1b signal pathway in osteoclast differentiation after treatment with bisphosphonates. Our results revealed that miR-101-3p was an important regulator in bisphosphonates treated-osteoclasts. When miR-101-3p was down-regulated in bone marrow-derived macrophage-like cells (BMMs), the development of mature osteoclasts was promoted, and vice versa. However, alendronate decreased multinucleated cell number regardless of whether miR-101-3p was knocked down or over-expressed. TRAP activity assay confirmed the above results. Luciferase assay indicated that miR-101-3p was a negative regulator of Rap1b. Western blot analysis revealed that protein expression level of Rap1b in BMMs transfected with OV-miR-101-3p was lower than that in BMMs transfected with an empty vector. Rap1b overexpression increased TRAP-positive multinucleated cells, while Rap1b inhibition decreased the cell numbers. In vivo data showed that miR-101-3p inhibited osteoclast differentiation in ovariectomized mice while overexpressed of Rap1b blocked the differentiation. Taken together, our data demonstrate that miR-101-3p/Rap1b signal pathway plays a key role in osteoclast differentiation after treatment with bisphosphonates.