• Journal of the Korean Chemical Society
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• v.43 no.3
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• pp.294-301
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• 1999

Geminal bisphosphonates have been well known to be effective inhibitors of various calciumrelated disorders such as Paget's disease, hypercalcemia of malignancy, and osteoporosis. To synthesize bisphosphonates, we have used the pentacovalent oxaphospholene prepared from methyl vinyl ketone and triethyl-phosphite. Υ-Ketobisphosphonates are obtained by bromination, applied Westheimer reaction, and hydrolysis of synthesized oxaphospholene. This compound was converted to the N-alkylated Υ-aminobisphosphonates by the reductive amination. Conversion of the resulting secondary amine to the tertiary one, followed by introduction of the second alkyl group on the nitrogen, was led to the synthesis of new N,N'-dialkylated Υ-aminobisphosphonates.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.41 no.6
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• pp.332-337
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• 2015

Dental infections and maxillary sinusitis are the main causes of osteomyelitis. Osteomyelitis can occur in all age groups, and is more frequently found in the lower jaw than in the upper jaw. Systemic conditions that can alter the patient's resistance to infection including diabetes mellitus, anemia, and autoimmune disorders are predisposing factors for osteomyelitis. We report a case of uncommon broad maxillary osteonecrosis precipitated by uncontrolled type 2 diabetes mellitus and chronic maxillary sinusitis in a female patient in her seventies with no history of bisphosphonate or radiation treatment.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.49 no.3
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• pp.135-141
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• 2023

Objectives: This study aimed to develop and validate machine learning (ML) models using H₂O-AutoML, an automated ML program, for predicting medication-related osteonecrosis of the jaw (MRONJ) in patients with osteoporosis undergoing tooth extraction or implantation. Patients and Methods: We conducted a retrospective chart review of 340 patients who visited Dankook University Dental Hospital between January 2019 and June 2022 who met the following inclusion criteria: female, age ≥55 years, osteoporosis treated with antiresorptive therapy, and recent dental extraction or implantation. We considered medication administration and duration, demographics, and systemic factors (age and medical history). Local factors, such as surgical method, number of operated teeth, and operation area, were also included. Six algorithms were used to generate the MRONJ prediction model. Results: Gradient boosting demonstrated the best diagnostic accuracy, with an area under the receiver operating characteristic curve (AUC) of 0.8283. Validation with the test dataset yielded a stable AUC of 0.7526. Variable importance analysis identified duration of medication as the most important variable, followed by age, number of teeth operated, and operation site. Conclusion: ML models can help predict MRONJ occurrence in patients with osteoporosis undergoing tooth extraction or implantation based on questionnaire data acquired at the first visit.

• Journal of Trauma and Injury
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• v.37 no.1
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• pp.89-96
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• 2024

The indications for total hip replacement are increasing and not limited to osteoarthritis. Total hip replacement may also be done for trauma and pathological fractures in patients otherwise physiologically fit and active. This trend has led to an inevitable rise in complications such as periprosthetic femoral fracture. Periprosthetic femoral fracture can be challenging due to poor bone quality, osteoporosis, and stress fractures. We present a case of periprosthetic femoral fracture in a 71-year-old woman with some components of an atypical femoral fracture. The fracture was internally fixed but was subsequently complicated by infection, implant failure needing revision, and later stress fracture. She was on a bisphosphonate after her index total hip replacement surgery for an impending pathological left proximal femur fracture, and this may have caused the later stress fracture. Unfortunately, she then experienced implant breakage (nonunion), which was treated with a biplanar locking plate and bone grafting. The patient finally regained her premorbid mobility 13 months after the last surgery and progressed satisfactorily towards bony union.

• Clinical and Experimental Pediatrics
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• v.60 no.12
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• pp.403-407
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• 2017

Purpose: Quadriplegic children with cerebral palsy are more susceptible to osteoporosis because of various risk factors that interfere with bone metabolism. Pamidronate is effective for pediatric osteoporosis, but there are no guidelines for optimal dosage or duration of treatment in quadriplegic children with osteoporosis. We aimed to evaluate the efficacy of low-dose pamidronate treatment in these patients. Methods: Ten quadriplegic patients on antiepileptic drugs (6 male, 4 female patients; mean age, $10.9{\pm}5.76years$), with osteoporosis and gross motor function classification system level V, were treated with pamidronate (0.5-1.0 mg/kg/day, 2 consecutive days) every 3-4 months in a single institution. The patients received oral supplements of calcium and vitamin D before and during treatment. The lumbar spine bone mineral density (BMD) z score and biochemical markers of bone metabolism were measured regularly during treatment. Results: The main underlying disorder was perinatal hypoxic brain damage (40%, 4 of 10). The mean cumulative dose of pamidronate was $4.49{\pm}2.22mg/kg/yr$, and the mean treatment period was $10.8{\pm}3.32months$. The BMD z score of the lumbar spine showed a significant increase from $-4.22{\pm}1.24$ before treatment to $-2.61{\pm}1.69$ during treatment (P=0.008). Alkaline phosphatase decreased during treatment (P=0.037). Significant adverse drug reactions and new fractures were not reported. Conclusion: Low-dose pamidronate treatment for quadriplegic children with cerebral palsy increased lumbar BMD and reduced the incidence of fracture.

• Imaging Science in Dentistry
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• v.49 no.4
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• pp.281-286
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• 2019

Purpose: The purpose of this study was to evaluate the morphology of the mandibular cortex in cases of medication-related osteonecrosis of the jaw (MRONJ) in patients with osteoporosis or bone metastases using a computer programme. Materials and Methods: Fifty-four patients with MRONJ (35 with osteoporosis and 19 with bone metastases) were examined using panoramic radiography. The morphology of the mandibular cortex was evaluated using a computer programme that scanned the mandibular inferior cortex and automatically assessed the mandibular cortical index (MCI) according to the thickness and roughness of the mandibular cortex, as follows: normal (class 1), mildly to moderately eroded (class 2), or severely eroded (class 3). The MCI classifications of MRONJ patients with osteoporosis or bone metastases were evaluated with the Pearson chi-square test. In these analyses, a 5% significance level was used. Results: The MCI of MRONJ patients with osteoporosis(class 1: 6, class 2: 15, class 3: 14) tended to be higher than that of patients with bone metastases(class 1: 14, class 2: 5, class 3: 0)(P=0.000). Conclusion: The use of a computer programme to assess mandibular cortex morphology may be an effective technique for the objective and quantitative evaluation of the MCI in MRONJ patients with osteoporosis or bone metastases.

• Journal of Veterinary Clinics
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• v.28 no.4
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• pp.375-386
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• 2011

Polygoni Multiflori Radix (PMR), a dried root tuber of Polygonum multiflorum Thunberg with bioactivities in bone metabolism is one of the most famous tonic traditional medicines. To observe in vivo anti-osteoporotic efficacy of PMR extracts, we orally administered once a day for 28 days (Qd ${\times}$ 28) to bilateral ovariectomized (OVX)-induced osteoporosis ddY mice after 1 week of recovery periods at 125, 250 and 500 mg/kg (of body weight). A positive control drug, Alendronate (FOSA) 10 mg/kg-dosing group was added. As results of OVX-induced osteoporotic process, estrogen-deficient osteoporotic changes were also dramatically decreased in all PMR extracts-dosing groups. Especially middle dosage of PMR extracts, 250 mg/kg constantly and significantly (p < 0.01 or p < 0.05) inhibited the loss of bone strength and bone quality. Based on the results, it was concluded that PMR extracts (125, 250 or 500 mg/kg; orally dosing) has relatively good favorable effect to prevention and/or treatment of OVX-induced osteoporosis. Therefore, although the efficacy was slighter than that of Alendronate on the inhibition of bone loss, it is expected that PMR extracts will be promising as a new anti-osteoporotic agents for prevent the fracture induced in osteoporotic patients because natural herbal medicine origin PMR extracts will be dose not show serious side effects especially the problem in upper alimentary irritation by bisphosphonate and hypercalcaemia of parathyroid hormone analogs.

• Journal of Microbiology and Biotechnology
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• v.16 no.1
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• pp.37-45
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• 2006

Treatment with exopolymers of Aureobasidium pullulans SM-2001 containing $\beta-1,3/1,6-glucan$ inhibited osteoclastogenesis of bone marrow stem cells in a co-culture system with calvariae osteoblastic cells. In addition, the treatment increased mineral deposition in osteoblastic cells. These two observations prompted us to evaluate whether the exopolymers could be used as an anti-osteoporotic agent, and efficacy of the exopolymers to prevent bone loss was compared with alendronate, a bisphosphonate, in ovariectomized mice prone to osteoporosis. Administration of the exopolymers to the ovariectomized mice resulted in improved effects on femur weight and histomorphometric changes of femur such as trabecular bone volume (TBV), trabecular bone thickness (TBT), and cortical bone thickness (CBT). In conclusion, the exopolymers treatment inhibited bone loss from osteoporosis induced by ovariectomy, and the effect was comparable to alendronate administration.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.41
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• pp.26.1-26.7
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• 2019

Background: The aim of this study was to investigate clinical and pharmacoepidemiologic characteristics of medicationrelated osteonecrosis of the jaw. Methods: The study population is comprised of 86patients who were diagnosed with ONJ at Ewha Womans University Mokdong Hospital from 2008 to 2015. Factors for epidemiologic evaluation were gender, age, location of lesion, and clinical history. The types of bisphosphonates, duration of intake, and the amount of accumulated dose were evaluated for therapeutic response. Clinical symptoms and radiographic images were utilized for the assessment of prognosis. Results: Among the 86 patients, five were male, whereas 81 were female with mean age of 73.98 (range 45-97). Location of the lesion was in the mandible for 58 patients and maxilla in 25 patients. Three patients had both mandible and maxilla affected. This shows that the mandible is more prone to the formation of ONJ lesions compared to the maxilla. ONJ occurred in 38 cases after extraction, nine cases after implant surgery, six cases were denture use, and spontaneously in 33 cases. Seventy-six patients were taking other drugs aside from drugs indicated for osteoporosis. Most of these patients were diagnosed as osteoporosis, rheumatic arthritis, multiple myeloma, or had a history of cancer therapy. Higher weighted total accumulation doses were significantly associated with poorer prognosis (P < 0.05). Conclusion: Dose, duration, route, and relative potency of bisphosphonates are significantly associated with treatment prognosis of osteonecrosis of the jaw.

• Journal of Dental Rehabilitation and Applied Science
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• v.32 no.2
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• pp.93-101
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• 2016

The average life expectancy has been increased, so the proportion of elderly patients that visit to the dental clinic for prosthetic restoration has increased. Elderly patients have various chronic diseases. Recent trends show an increase of osteoporosis in elderly patients, and thus, the number of osteoporosis patients is expected to escalate. Currently, the most widely used drug for osteoporosis is bisphosphonate. However, osteonecrosis of the jaw has been reported as a side effect derived from longterm oral administration or injection treatment of the drug. Surgical dental treatment was the main cause of medication related osteonecrosis of the jaw (MRONJ). As MRONJ is very difficult to cure, it is important to take preventive measures. Surgical operation may be needed for the mouth preparation before prosthetic restoration. For successful treatment, the dentist should have a full understanding of osteoporosis and show a continued interest toward this disease for careful management.