• Nuclear Engineering and Technology
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• v.55 no.1
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• pp.254-260
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• 2023

Skeletal metastases are common in patients suffering from various primary cancers. Radiopharmaceuticals are an effective option for bone pain palliation. In this work, the radiation absorbed dose of ¹⁷⁷Lu-EDTMP radiopharmaceutical was estimated for adult man based on biodistribution data in Wistar rats. The MIRD dose calculation method and the Sparks and Aydogan methodology were applied. The results shows that about 46% of injected activity is cumulated on the surface of the trabecular and cortical bones. Radiation absorbed doses of red bone marrow and osteogenic cells were estimated to about 1.1 and 6.2 mGy/MBq, respectively. The maximum administrated activity was obtained 27 MBq/kg of body weight with an effective dose of 0.23 mSv/MBq. The results were compared with other available data from literature. This study indicated that ¹⁷⁷Lu-EDTMP provides therapeutic efficacy for achieving bone pain palliation with low undesired dose to other normal organs.

• Physical Therapy Korea
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• v.9 no.1
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• pp.81-96
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• 2002

The purpose of this research was to determine the effects on the healing of fibular fractures in rabbits of low-intensity pulsed ultrasound (50 $mW/cm^2$ and 500 $mW/cm^2$) applied for periods of 4, 14 and 24 days following fibular osteotomy. Thirty-six male Japanese white rabbits were randomly divided into three groups of twelve for three treatment protocols: (1) ultrasound treatment at intensities of 50 $mW/cm^2$ and 500 $mW/cm^2$ until the 4th day following fibular osteotomy, (2) ultrasound treatment at intensities of 50 $mW/cm^2$ and 500 $mW/cm^2$ until the 14th day following fibular osteotomy, and (3) ultrasound treatment at intensities of 50 $mW/cm^2$ and 500 $mW/cm^2$ until the 24th day following fibular osteotomy. The low-intensity pulsed ultrasound was applied to only one fibula of each rabbit (these served as the experimental group). The other fibula of each rabbit served as the control group. The selection of which fibula was to be treated was made randomly. The animals were sacrificed on the 4th, 14th and 24th day after the start of ultrasound treatments. Percent of trabecular bone area and fibular radiography were carried out to compare the degree of fibular bone healing. A microscope was also used to determine any histologic changes. For statistical differences in radiological changes due to length of treatment period (4, 14 and 24 days respectively), the Wilcoxon signed-ranks test was used to compare the experimental and control groups. For statistical differences in fracture healing due to differences in ultrasound intensity, radiological studies were compared using the Mann-Whitney Test. And, to compute percentage differences in areas of trabecular bone, Two-way analysis of variance (ultrasound intensity x each group) was used. Experiment results were as follows: 1. In animals sacrificed on the 4th day, no difference was found in the radiological studies of the fibulae in the experimental and control groups (p>.05). However, experimental groups showed more rapid bone repair than control group. 2. Both radiographic and percent of trabecular bone area studies showed significant differences in rabbits sacrificed after 14 days. Fracture healing was significantly increased in the experimental group (p<.05) 3. In the animals sacrificed on the 24th day, histologic study showed rapid bone repair but fibular radiologic studies did not show statistical differences between the two groups (p>.05). 4. On the 14th day, bone union on radiograph was significantly more rapid in the treatment group with pulsed ultrasound of 50 $mW/cm^2$ than the group with 500 $mW/cm^2$ (p<.05). Histologic studies showed that both the 14 and 24 days groups had more rapid bone repair in animals treated with 50 $mW/cm^2$ ultrasound intensity than those treated with 500 $mW/cm^2$ intensity. In conclusion, it has been shown that the low-intensity pulsed ultrasound has a positive effect on bone fracture healing in the early stage and the range of pulse ultrasound from 50 $mW/cm^2$ to 500 $mW/cm^2$ is effective for fracture healing. Further study is needed to investigate the influence of pulsed ultrasound on delayed union and non-union in bone fractures and also for the clinical use of low-intensity pulsed ultrasound for bone healing in humans.

• Journal of Radiation Protection and Research
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• v.40 no.1
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• pp.10-16
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• 2015

Bone changes are common sequela of irradiation in growing animal. The purpose of this study was to establish an experimental model of radiation-induced bone loss in growing mice using micro-computed tomography (${\mu}CT$). The extent of changes following 2 Gy gamma irradiation ($2Gy{\cdot}min^{-1}$) was studied at 4, 8 or 12 weeks after exposure. Mice that received 0.5, 1.0, 2.0 or 4.0 Gy of gamma-rays were examined 8 weeks after irradiation. Tibiae were analyzed using ${\mu}CT$. Serum alkaline phosphatase (ALP) and biomechanical properties were measured and the osteoclast surface was examined. A significant loss of trabecular bone in tibiae was evident 8 weeks after exposure. Measurements performed after irradiation showed a dose-related decrease in trabecular bone volume fraction (BV/TV) and bone mineral density (BMD), respectively. The best-fitting dose-response curves were linear-quadratic. Taking the controls into accounts, the lines of best fit were as follows: BV/TV (%) = $0.9584D^2-6.0168D+20.377$ ($r^2$ = 0.946, D = dose in Gy) and BMD ($mg{\cdot}cm^{-3}$) = $8.8115D^2-56.197D+194.41$ ($r^2$ = 0.999, D = dose in Gy). Body weight did not differ among the groups. No dose-dependent differences were apparent among the groups with regard to mechanical and anatomical properties of tibia, serum ALP and osteoclast activity. The findings provide the basis required for better understanding of the results that will be obtained in any further studies of radiation-induced bone responses.

• The Journal of Korean Academy of Prosthodontics
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• v.52 no.4
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• pp.298-304
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• 2014

Purpose: This preliminary rabbit study was conducted to evaluate the effect of recombinant human transforming growth factor-${\beta}2$ (rhTGF-${\beta}2$)/poly lactic-co-glycolic acid (PLGA) coating on osseointegration of the titanium (Ti) implant. Materials and methods: Eight Ti implants were anodized with 300 voltages for three minutes. Four of those were coated with rhTGF-${\beta}2$/PLGA by an electrospray method as the experimental group. The implants were placed into tibiae of four New Zealand rabbits, two implants per a tibia, one implant per each group. After 3 and 6 weeks, every two rabbits were sacrificed and micro-computed tomography (microCT) was taken for histomorphometric analysis. Results: In scanning electron microscope (SEM) image, the surface of rhTGF-${\beta}2$/PLGA coated Ti implant showed well distributed particles. Although statistically insignificant, microCT analysis showed that experimental group has higher bone volume / total volume (BV/TV) and trabecular thickness (Tb.Th) values relatively. Cross sectional view also showed more newly formed bone in the experimental group. Conclusion: In the limitation of this study, rhTGF-${\beta}2$/PLGA particles coating on the Ti implant show the possibility of more favorable quantity of newly formed bone after implant installation.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.21 no.3
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• pp.240-248
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• 1999

To investigate the expression pattern of noncollagenous bone matrix proteins such as osteonectin(OSN), osteopontin(OPN) and osteocalcin(OSC) mRNA during bony healing procedure induced by guided bone regeneration method, we made artificial defects on bilateral femur of rats. Then induced bony healing by application of a nonabsorbable PTFE membrane in experimental sites and without its application in control sites for 3 weeks. The mRNA expression pattern at specimens obtained at 1, 2 and 3 weeks after operation was detected by in situ hybridization method using its antisense mRNA probes. The experimental sites revealed more rapid and favorable bony healing than control sites and new bone formation was limited within defected area by inhibitory activity of bone marrow cells. In experimental sites, the OSN and OSC mRNA were expressed strongly on osteoblasts of regenerating cortical bone at 1st week and on osteoblasts lining the trabecular bone in marrow space at 3rd week, whereas, in control sites, their expression were noted on osteoblasts lining the reactively formed sponge bones at 2nd and 3rd week. In addition, the OPN mRNA was expressed on osteoblasts and osteoclasts at sites of remodeling and osteocytes of remained trabecular bone of defected area in experimental sites and on macrophages at 1st week and osteoclasts at sites of remolding at 2nd and 3rd week in control sites. The above findings suggest that the more rapid and favorable bony healing might be induced by blocking of invading fibrous connective tissue into bony defects. And the earlier expression of OSN and OSC mRNA on osteoblasts of experimental sites suggest that the formation and resorption of regenerating bone was more rapidly progressed in confined spaces made by applicate membranes.

• International Journal of Oral Biology
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• v.44 no.4
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• pp.173-181
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• 2019

The CC chemokine receptor 5 (CCR5) is a G protein-coupled receptor that regulates chemotaxis and effector functions of immune cells. It also serves as the major co-receptor for the entry of human immunodeficiency virus (HIV). Recently, CCR5 inhibitors have been developed and used for the treatment or prevention of HIV infections. Additionally, it has been identified that CCR5 controls bone homeostasis by regulating osteoclastogenesis and the communication between osteoblasts and osteoclasts. However, the effects of CCR5 inhibition on bone tissue in elderly patients are unknown. This study aimed to examine the bone phenotype of aged CCR5 knockout (KO) mice. Femoral and tibial bones were isolated from 12-month and 18-month old wild-type (WT) and CCR5 KO mice, and microcomputed tomography and histology analyses were performed. Twelve-month-old CCR5 KO mice exhibited a decreased trabecular bone mass and cortical bone thickness in both femoral and tibial bones compared with age-matched WT mice. Eighteen-month-old mice also showed a decreased trabecular bone mass in femurs compared with control WT mice, but not in tibial bones. Unlike in 12-month-old mice, the cortical margin of femurs and tibias in 18-month-old mice were rough, likely because they were aggravated by the deficiency of CCR5. Overall, our data suggest that the deficiency of CCR5 with aging can cause severe bone loss. When CCR5 inhibitors or CCR5 inactivating technologies are used in elderly patients, a preventive strategy for bone loss should be considered.

• Journal of Korean Dental Science
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• v.8 no.2
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• pp.65-73
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• 2015

Purpose: Parathyroid hormone (PTH) therapy has drawn attention, as an alternative to anti-resorptive drugs since PTH accelerates bone density by anabolic action. The purpose of this study was to identify the effect of intermittent PTH administration on jaw bones of rat undergone bilateral ovariectomy. Materials and Methods: Nine female Sprague-Dawley rats were divided into three groups. PTH group was ovariectomized (OVX) to induce osteoporosis and PTH $30{\mu}g/kg$ was administered 1 week after the surgery. In OVX group, ovariectomy was performed and only vehicle was administered by subcutaneous injection 3 times per week. Control group was subjected to sham surgery. The animals were sacrificed 8 weeks after the surgery and specimens were obtained from ilium and upper and lower jaw bones. Histological investigation was carried out by using an optical microscope and micro-computed tomography was taken to examine structural property changes in each bone sample. Result: In the ilium, the bone volume ratio (bone volume/total volume, BV/TV) of PTH, OVX and control groups was $53.75%{\pm}7.57%$, $50.61%{\pm}12.89%$, $76.20%{\pm}5.92%$ (P=0.061) and bone mineral density (BMD) was $1.12{\pm}0.09$, $0.88{\pm}0.48$, $1.38{\pm}0.07g/cm^3$ (P=0.061). In the mandible, BV/TV of PTH, OVX and control groups was $64.60%{\pm}12.17%$, $58.26%{\pm}9.63%$, $67.54%{\pm}14.74%$(P=0.670) and BMD was $1.21{\pm}0.17$, $1.19{\pm}0.13$, $1.27{\pm}0.18g/cm^3$ (P=0.587). In the maxilla, BV/TV of PTH, OVX and control groups was $61.19%{\pm}8.92%$, $52.50%{\pm}11.22%$, $64.60%{\pm}12.17%$ (P=0.430) and BMD was $1.20{\pm}0.11$, $1.11{\pm}0.16$, $1.21{\pm}0.17g/cm^3$ (P=0.561). No statistically significant difference was found in any variables in all groups. Histological observation revealed that the ilium in OVX group demonstrated sparsely formed trabecular bones compared with other groups. However, upper and lower trabecular bones did not present significant differences. Conclusion: Intermittent administration of PTH appears to affect the microstructure of rat jaw bones, but statistical significance was not found. However, the measurements in this study partly implicated the possible anabolic effect of PTH in vivo.

• Journal of Periodontal and Implant Science
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• v.24 no.3
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• pp.671-689
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• 1994

The purpose of this study was to compare effects of various bone grafts on periodontal regeneration of alveolar bone defects in dogs. Seven adult dogs aged 12 to 18 months were used in this study. Experimental alveolar bone defects were created surgically with a #1/2 round bur at the furcation area of the buccal surface of the mandibular 3rd, 4th premolars and 1st molar. Each experimental alveolar bone defects were grafted with dense hydroxyapatite, natural coral, and decalcified freeze-dried bone, and respectively divided into DHA, NC, DFDB group. An area without bone graft was divided into control group. At 1,2,4,6, and 12 weeks, dogs were serially sacrificed and specimens were prepared with Hematoxylin-Eosin stain and Mallory stain for light microscopic evaluation. The results of this study were as follows : 1. In control group, the matrix change of granulation tissue was observed at 1 week. And in experimental groups, the appearance of connective tissue around graft materials was loosely formed at 1 week, but densely formed at 2 weeks. 2. In every group, the slight formation of new trabecular bone was seen from remaining bone at 1 week. 3. The DHA and NC particles were gradually encapsulated by new trabecular bone from remaining bone, and the osteoid tissue was directly induced from DFDB particles. 4. The presence of osteoblasts was first observed at 1 week in control group and at 2 weeks in NC group, but at 6 weeks in DHA group. 5. In DHA group, the resorption of particles was not observed until 12 weeks. But in NC and DFDB group, the particles were resorbed at 6 weeks and replaced by new bone. And the amount and size of particles were reduced, and their border represented irregular form. In summary, in three experimental groups the inflammatory or foreign body reaction were slight, but the regeneration of new osteoid tissue and the matrix change of dense connective tissue fiber were observed. Especially, NC and DFDB materials were considered as the biocompatible graft materials which were effective in the regenertion of new bone.

• Journal of Periodontal and Implant Science
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• v.25 no.3
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• pp.703-719
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• 1995

The purpose of this study was to observe the effects of the periodontal ligament on the healing and the formation of alveolar bone in the extraction socket, when this ligament had artificially remained in the socket during the tooth removal. Twenty rats aged 4 weeks were used and devided into the control groups (10) and the experimental groups (10) in this study. The maxillary right and left first molars were extracted in both groups. In the experimental groups the periodontal ligament was remained in the extraction sockets using 0.4% ${\beta}-aminopropionitrile$, and in the control the periodontal ligament was completely removed by curettage. At 1, 3, 5, 7 and 14 days after the tooth extraction, rats in both groups were serially sacrificed. And the specimens were prepared with Hematoxylin-Eosin stain for the light microscopic evaluation. The results of this study were as follows ; 1. On 1 day, the periodontal ligament was only found in the extraction socket walls of the experimental groups, and there was not the distinguishable difference between the control and the experimental groups. 2. On 3 days, there were more collagen fibers and the appearance of higher cellular density in the experimental groups than in the control. And the cells and collagen of the periodontal ligament were so actively proliferated and synthesized that invaded into the connective tissue of the extraction sockets in the experimental groups. 3. In the experimental groups, the trabecular bone was formed on the basal and lateral bone surface on 5 days. However, there was not the new bone forming appearance in the control groups at this time. 4. On 7 days, the trabecular bone was formed in the control groups. 5. On 14 days, the extraction sockets were almost entirely filled with the bony trabeculae in both groups. But, compared to the control group, the experimental groups showed the prominent differences in the amount & the density of the new bone formed. In conclusion, it was suggested that the residual periodontal ligament tissue in the extraction socket will play a major role as the important cell source in the healing and the new bone formation of the extraction socket.

• 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.