• Korean Journal of Acupuncture
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• v.37 no.2
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• pp.63-75
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• 2020

Objectives : Osteoporosis is the most common bone disease and osteoporosis fracture is the leading cause of decreased life. Bisphosphonate and selective estrogen receptor modulators are the best choice of treatment for osteoporosis. However, when used for a long time, they increase the probability of side effect such as osteonecrosis of the jaw. Thus, it is crucial to develop alternative medicine to treat osteoporosis. Gentianae Macrophyllae Radix, a herbal medicine, is mainly to treat rheumatoid arthritis. However, the effect of the water extract of Gentianae Macrophyllae Radix (w-GM) on osteoporosis has not been investigated. Thus, we examine whether w-GM can inhibit osteoclast differentiation and bone resorption on receptor activator of nuclear factor kappa-B (NF-κB) ligand (RANKL)-treated RAW 264.7 cells. In this study, RAW 264.7 cells were used as an osteoclast differentiation model by treating them with RANKL. Methods : RAW 264.7 cells were used to determine the effect of w-GM on osteoclast differentiation and bone resorption. The number of tartrate-resistant acid phosphatase (TRAP)-positive cells, TRAP activity and pit formation assay were examined. In addition, protein expressions were measured by western blot and mRNA expressions were analyzed by reverse transcription polymerase chain reaction. Results : Treatment with w-GM inhibited the number of TRAP-positive cells, TRAP activity and pit area. In addition, w-GM decreased protein expression such as mitogen-activated protein kinase, NF-κB, c-Fos and nuclear factor of activated T-cells cytoplasmic 1 (NFATc1). It also inhibited the mRNA levels such as c-Fos, NFATc1, TRAP, NF-κB, calcitonin receptor and cathepsin K in RANKL-treated RAW 264.7 cells. Conclusions : These results suggest that w-GM has inhibitory effects via osteoclast differentiation, thus it could be a new medication for osteoporosis.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.46 no.1
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• pp.19-27
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• 2020

Objectives: Pentoxifylline (PTX) is a methylxanthine derivative that has been implicated in the pathogenesis of peripheral vessel disease and intermittent lameness. The purpose of this study was to investigate the effect of PTX and tocopherol in patients diagnosed with osteoradionecrosis (ORN), bisphosphonate-related osteonecrosis of the jaw (BRONJ), and chronic osteomyelitis using digital panoramic radiographs. Materials and Methods: This study was performed in 25 patients who were prescribed PTX and tocopherol for treatment of ORN, BRONJ, and chronic osteomyelitis between January 2014 and May 2018 in Seoul National University Dental Hospital. Radiographic densities of the dental panorama were compared prior to starting PTX and tocopherol, at 3 months, and at 6 months after prescription. Radiographic densities were measured using Adobe Photoshop CS6 (Adobe System Inc., USA). Blood sample tests showing the degree of inflammation at the initial visit were considered the baseline and compared with results after 3 to 6 months. Statistical analysis was performed using the Mann-Whitney test and repeated measurement ANOVA using IBM SPSS 23.0 (IBM Corp., USA). Results: Eight patients were diagnosed with ORN, nine patients with BRONJ, and the other 8 patients with chronic osteomyelitis. Ten of the 25 patients were men, average age was 66.32±14.39 years, and average duration of medication was 151.8±80.65 days (range, 56-315 days). Statistically significant increases were observed in the changes between 3 and 6 months after prescription (P<0.05). There was no significant difference between ORN, BRONJ, and chronic osteomyelitis. Only erythrocyte sedimentation rate (ESR) was statistically significantly lower than before treatment (P<0.05) among the white blood cell (WBC), ESR, and absolute neutrophil count (ANC). Conclusion: Long-term use of PTX and tocopherol can be an auxiliary method in the treatment of ORN, BRONJ, or chronic osteomyelitis in jaw.

• Journal of Korean Neurosurgical Society
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• v.61 no.4
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• pp.494-502
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• 2018

Objective : The loosening of pedicle screws (PS) is one of the frequent problems of spinal surgery in the patients with osteoporosis. Previous studies had revealed that intermittent injection of teriparatide could reduce PS loosening by improving bone mass and quality when their patients took parathyroid hormone for a considerable duration before surgery. However, although the teriparatide is usually used after spine surgery in most clinical situations, there was no report on the efficacy of teriparatide treatment started after spine surgery. The purpose of this retrospective study was to examine the efficacy of teriparatide treatment started immediately after lumbar spinal surgery to prevent pedicle screw loosening in patients with osteoporosis. Methods : We included 84 patients with osteoporosis and degenerative lumbar disease who underwent transforaminal interbody fusion and PS fixation and received parathyroid hormone or bisphosphonate (BP) postoperatively. They were divided into teriparatide group (daily injection of $20{\mu}g$ of teriparatide for 6 months, 33 patients, 172 screws) and BP group (weekly oral administration of 35 mg of risedronate, 51 patients, 262 screws). Both groups received calcium (500 mg/day) and cholecalciferol (1000 IU/day) together. The screw loosening was evaluated with simple radiographic exams at 6 and 12 months after the surgery. We counted the number of patients with PS loosening and the number of loosened PS, and compared them between the two groups. Clinical outcomes were evaluated using visual analog scale (VAS) and Oswestry disability index (ODI) preoperatively, and at 12 months after surgery. Results : There was no significant difference in the age, sex, diabetes, smoking, bone mineral density, body mass index, and the number of fusion levels between the two groups. The number of PS loosening within 6 months after surgery did not show a significant difference between the teriparatide group (6.9%, 12/172) and the BP group (6.8%, 18/272). However, during 6-12 months after surgery, it was significantly lower in the teriparatide group (2.3%, 4/172) than the BP group (9.2%, 24/272) (p<0.05). There was no significant difference in the number of patients showing PS loosening between the teriparatide and BP groups. The teriparatide group showed a significantly higher degree of improvement of the bone mineral density (T-score) than that of BP group (p<0.05). There was no significant difference in the pre- and post-operative VAS and ODI between the groups. Conclusion : Our data suggest that the teriparatide treatment starting immediately after lumbar spinal fusion surgery could reduce PS loosening compared to BP.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.41
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• pp.6.1-6.10
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• 2019

Background: Osteomyelitis is an intraosseous inflammatory disease characterized by progressive inflammatory osteoclasia and ossification. The use of quantitative analysis to assist interpretation of osteomyelitis is increasingly being considered. The objective of this study was to perform early diagnosis of osteomyelitis on digital panoramic radiographs using basic functions provided by picture archiving and communication system (PACS), a program used to show radiographic images. Methods: This study targeted a total of 95 patients whose symptoms were confirmed as osteomyelitis under clinical, radiologic, pathological diagnosis over 11 years from 2008 to 2017. Five categorized patients were osteoradionecrosis, bisphosphonate-related osteonecrosis of jaw (BRONJ, suppurative and sclerosing type), and bacterial osteomyelitis (suppurative and sclerosing type), and the control group was 117 randomly sampled. The photographic density in a certain area of the digital panoramic radiograph was determined and compared using the "measure area rectangle," one of the basic PACS functions in INFINITT PACS^® (INFINITT Healthcare, Seoul, South Korea). A conditional inference tree, one type of decision making tree, was generated with the program R for statistical analysis with SPSS^®. Results: In the conditional inference tree generated from the obtained data, cases where the difference in average value exceeded 54.49 and the difference in minimum value was less than 54.49 and greater than 12.81 and the difference in minimum value exceeded 39 were considered suspicious of osteomyelitis. From these results, the disease could be correctly classified with a probability of 88.1%. There was no difference in photographic density value of BRONJ and bacterial osteomyelitis; therefore, it was not possible to classify BRONJ and bacterial osteomyelitis by quantitative analysis of panoramic radiographs based on existing research. Conclusions: This study demonstrates that it is feasible to measure photographic density using a basic function in PACS and apply the data to assist in the diagnosis of osteomyelitis.

• Journal of Periodontal and Implant Science
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• v.34 no.4
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• pp.733-746
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• 2004

The present study aimed to examine the effects of topical application of alendronate with a collagen membrane on the healing of the calvarial defect in rats, which has a good experimental design for the healing of tissue destruction, To study the effect of alendronate on bone healing, the collagen membrane containing $200{\mu}g$ alendronate was inserted in the defects of the right side and collagen membrane treated with physiologic saline was inserted in the defects of the left side. After 1, 2 and 4 weeks, observation of histologic feature after H&E staining, cell counting after TRAP staining, and hardness measurement(Knoop) were performed. In histologic finding, similar features were shown for both test and control groups each week. In cell counting only the 1 week test groups showed significant reduction of TRAP(+)cells than control groups(p<0.01) and the control groups showed statistically significant difference for 1, 2, 4weeks(p<0.05). In hardness measurement, The 2 week test groups showed significant higher hardness than control groups.(p<0,05) and not 4 weeks. There was significant increase of hardness for both groups as time goes by.(p<0.0l) Therefore local application of alendronate with collagen membrane was somewhat effective in reducing osteoclastic activity and increasing hardness in the early stage of healing. Further investigation concerning the actual effect of alendronate for bony healing will be necessary to apply the clinical cases

• The Journal of Korean Academy of Prosthodontics
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• v.53 no.2
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• pp.150-156
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• 2015

As dental implant treatment becomes popular for both partial and complete edentulous patients, old people with complex systemic diseases also tend to prefer implant-assisted-overdenture or implant-supported-fixed prostheses to conventional complete denture. In this case, 77-year-old female who was on medication for hypertension and osteoporosis and paralyzed on right side due to stroke visited for implant-assisted-overdenture on lower jaw. After oral and radiographic examination, root-assisted magnet overdenture on upper jaw and implant-assisted magnet overdenture on lower jaw are planned. Consequently, overdentures using self-adjusting magnetic attachment(SA) system on both jaws resulted in recovering satisfying function and retention, which is enable to insert and remove with only one hand.

• Journal of Periodontal and Implant Science
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• v.50 no.2
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• pp.121-131
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• 2020

Purpose: Dental implant-associated medication-related osteonecrosis of the jaw has been frequently reported in patients administered bisphosphonates (BPs) to prevent osteoporosis. The aim of this study was to investigate the effect of intermittent administration of parathyroid hormone (PTH) on peri-implant bone in the maxillae of ovariectomized rats systemically administered BPs. Methods: Thirty 8-week-old female Sprague-Dawley rats were randomly divided into 3 groups. The OVX-ZP group included ovariectomized rats administered 60 ㎍/kg of zoledronate once a week for 6 weeks and 30 ㎍/kg PTH after implant installation. The OVX-Z group included ovariectomized rats administered 60 ㎍/kg of zoledronate once a week for 6 weeks and saline after implant installation, and the control group included rats that underwent a sham operation and were then administered saline. Rats were sacrificed 4 weeks after implant placement for histomorphometric and micro-computed tomography (CT) analyses. Results: The average bone area percentage was greater in the OVX-ZP group than in the OVX-Z group (53.4%±4.0% vs. 28.9%±9.5%, P=0.01). The bone-to-implant contact ratio was 50.8%±1.4% in the OVX-ZP group and 16.9%±2.4% in the OVX-Z group (P=0.012). The average bone volume ratio as shown on micro-CT was 31.3%±19.8% in the OVX-ZP group and 19.4%±9.3% in the OVX-Z group (P=0.045). The OVX-ZP and OVX-Z groups displayed similar trabecular thickness (0.06±0.004 mm vs. 0.06±0.002 mm) (P>0.05) and trabecular separation (0.21±0.02 mm vs. 0.29±0.13 mm) (P>0.05). However, the number of trabeculae in the OVX-ZP group was significantly higher than that in the OVX-Z group (4.3±1.33/㎣ vs. 2.2±0.19/㎣) (P=0.024). Conclusions: The present findings indicate that intermittently-administered PTH can promote peri-implant bone formation and suggest that PTH administration may aid in effective treatment for medication-related osteonecrosis of the jaw after dental implantation.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.5
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• pp.3337-3343
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• 2013

This systematic review was conducted to assess the efficacy and safety of bisphosphonates for prevention and treatment of osteopenia or osteoporosis in men with non-metastatic prostate cancer receiving androgendeprivation therapy. We searched for randomised controlled trials (RCTs) of bisphosphonates compared with placebo from Pubmed, Embase, the Cochrane Library, and ISI - Science Citation Index. Meta-analyses of prespecified outcomes (bone mineral density, fractures, and adverse events) were performed using Review Manager. Ten RCTs with a total patient population of 1,017 were identified. There was generally more improvement in bone mineral density of the lumbar spine for patients who received bisphosphonate treatment than placebo or other medical treatment at 12 months (WMD 6.02,95%CI 5.39 to 6.65). Similar effects were also observed for total hip, trochanter or femoral neck bone mineral density. However, there was no significant reduction in fractures. Fever and gastrointestinal symptoms were the most common adverse events (10.4% vs. 1.2%; 0.10% vs. 0.03%). Currently, our meta-analysis suggested that oral and intravenous bisphosphonates caused a rapid increase in spine and hip or femoral BMD in non-metastatic prostate cancer patients receiving androgen-deprivation therapy. Fever and gastrointestinal symptoms were common with the use of bisphosphonates. These short-term trials (maximum of 12 months) did not show fracture reduction. In future, more efficient performance of higher quality, more rigorous, large sample, long-term randomised controlled trials (>12 months) are needed where outcomes are detailed.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.46 no.3
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• pp.191-196
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• 2020

Objectives: Beyond the original application approved by the U.S. Food and Drug Administration, recombinant human bone morphogenetic protein-2 (rhBMP-2) is used for medication-related osteonecrosis of the jaw (MRONJ) treatment because of its bone remodeling enhancement properties. The purpose of the study was to investigate the bone formation effect of rhBMP-2/absorbable collagen sponge (ACS) in patients with MRONJ. Materials and Methods: In this retrospective cohort study, 26 female patients diagnosed with MRONJ and who underwent mandibular sequestrectomy at Ajou University Dental Hospital from 2010 to 2018 were included. The experimental group was composed of 18 patients who received rhBMP-2/ACS after sequestrectomy, while the control group was composed of 8 patients who did not receive rhBMP-2/ACS after sequestrectomy. A total dose of 0.5 mg of rhBMP-2 was used in the experimental group at a concentration of 0.5 mg/mL. Follow-up panoramic X-rays were taken immediately after the surgery and more than 6 months after the surgery. Using those X-rays, a radiographic index of bone defect area was calculated using the modified Ihan Hren method, which measures radiographic density of the normal bone and the defect site. Results: This study suggests that rhBMP-2 contributes to new bone formation. The mean radiographic index immediately after surgery and more than 6 months after the surgery for the experimental group was 68.4% and 79.8%, respectively. The mean radiographic index immediately after surgery and more than 6 months after the surgery for the control group was 73.4% and 76.7%, respectively (Wilcoxon signed rank test, P>0.05). The mean radiographic index increased 11.4% in the experimental group and 3.27% in the control group (Mann-Whitney U-test, P<0.05). Conclusion: Based on the results, use of rhBMP-2/ACS on bone defect sites after sequestrectomy could be a successful strategy for treatment of MRONJ patients.

• Journal of Bone Metabolism
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• v.25 no.4
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• pp.195-211
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• 2018

Background: To develop guidelines and recommendations to prevent and treat glucocorticoid (GC)-induced osteoporosis (GIOP) in Korea. Methods: The Korean Society for Bone and Mineral Research and the Korean College of Rheumatology have developed this guideline based on Guidance for the Development of Clinical Practice Guidelines ver. 1.0 established by the National Evidence-Based Healthcare Collaborating Agency. This guideline was developed by adapting previously published guidelines, and a systematic review and quality assessment were performed. Results: This guideline applies to adults aged ${\geq}19years$ who are using or plan to use GCs. It does not include children and adolescents. An initial assessment of fracture risk should be performed within 6 months of initial GC use. Fracture risk should be estimated using the fracture-risk assessment tool (FRAX) after adjustments for GC dose, history of osteoporotic fractures, and bone mineral density (BMD) results. All patients administered with prednisolone or an equivalent medication at a dose ${\geq}2.5mg/day$ for ${\geq}3months$ are recommended to use adequate calcium and vitamin D during treatment. Patients showing a moderate-to-high fracture risk should be treated with additional medication for osteoporosis. All patients continuing GC therapy should undergo annual BMD testing, vertebral X-ray, and fracture risk assessment using FRAX. When treatment failure is suspected, switching to another drug should be considered. Conclusions: This guideline is intended to guide clinicians in the prevention and treatment of GIOP.