• Journal of Periodontal and Implant Science
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• 제50권2호
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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.

• 생약학회지
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• 제46권2호
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• pp.167-172
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• 2015

Aleurone layer of Black rice (Oryza sativa L.) is enriched with anthocyanin that could increase bone density. This study was conducted to investigate the osteoporosis-preventing effects of the aleurone layer extract (BRE) on bone loss of ovariectomized (OVX) rats. OVX (or sham-operated) rats were assigned to three groups (n=8 per group): sham operated group (Sham); OVX control group (OVX); OVX-BRE group, OVX rats treated with BRE at 90 mg/kg B.W. The deionized water alone or deionized water with BRE was orally administrated to Sham, OVX or OVX-BRE groups, respectively for 12 weeks. High fat diet with 45 kcal% fat and water were fed to all rats ad libitum. Body weight was significantly decreased in the OVXBRE group compared to the OVX group (p<0.05). The bone mineral density and bone length of tibia were significantly higher in the OVX-BRE group compared to the OVX group and breaking force was significantly higher for the both tibia and femur bones. Serum estradiol concentration and calcium concentration of femur were higher in the OVX-BRE group than those of OVX group. However, serum alkaline phosphatase activity and parathyroid hormone concentration were decreased in the OVXBRE group compared to the OVX group. The results suggest that aleurone layer of Black rice is a potentially useful ingredient to protect against estrogen deficiency or menopause related osteoporosis.

• International Journal of Industrial Entomology and Biomaterials
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• 제32권2호
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• pp.80-89
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• 2016

The effects of Cudrania tricuspidata (CT) extract on markers of osteoporosis were examined in ovariectomized rats. We classified 26 rats into five groups and provided a pellet chow diet and tap water throughout the 27-wk experimental period. During the last 15 wk, we added oral injections to each group as follows: sham-operated (SHAM, n=4) and ovariectomized-control (OVX, n=5) with distilled water, alendronate with 10 mg/kg/d of alendronate sodium (ALEN, n=5), CT (CT100, n=6) with 100 mg/kg/d of CT, and CT (CT300, n=6) with 300 mg/kg/d of CT. After the experimental period, blood, urine, and micro-CT images were assessed. The CT100 and OVX groups did not show any significant differences in urinary n-terminal telopeptide (NTx) (p<0.05 ), but with increases in CT concentration, the NTx level was slightly reduced. Serum osteocalcin was significantly higher in the CT groups than in all other groups (p<0.05 ). Notably, the serum calcium levels of all groups were within the normal range, but urinary calcium levels in the CT groups were significantly lower than the OVX group (p<0.05 ). In addition, the CT groups exhibited higher trabecular BMD than the OVX groups while showing similar BMD to the ALEN group (p<0.05 ). The Tb.Th of the ALEN group was lower than all other groups. Based on the overall analysis of results, CT prevented bone loss by inhibiting bone resorption and enhancing bone formation. Although alendronate showed a similar effect in preventing bone loss, it did so by solely inhibiting bone resorption, and its long-term use reportedly causes paradoxical effects such as hip fractures. Thus, for osteoporosis induced by ovariectomy, we conclude that CT extract is an effective natural treatment without severe side effects.

• 한국임상수의학회지
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• 제19권1호
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• pp.49-54
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• 2002

Korean safflower (Carthami Flos) seed has been known to have healing effects on both bone fracture and osteoporosis. On the base of such a notice, this experiment was carried out to explore the effects of safflower seed on bone formation and bone repair. In addition, the healing mechanism was evaluated by analysing serum after feeding the seed to experimental. animals. The effect of Korean safflower seed were evaluated with 40 rats,3-month old. Forty Sprague-Dawley rats composed of 20 male and 20 female were underwent unilateral tibial defect and then fastened with unilateral fixators. The operated rats were divided into two groups depending on the composition of diet, such as positive control group fed normal diet (C-OP group) and safflower seed group fed 30% of safflower seed diet and 70% of normal diet (S-OP group). Postoperative radiographys were taken once in 2 weeks to evaluate callus formation for operated groups. In addition, a possible protein spots involved in bone recovery were examined using 2-Dimensional Gel Electrophoresis (2-DE). The comparison of the radiography between C-OP and S-OP group were showed that the safflower seed diet appeared to stimulate the formation of callus in the rat. On the images of 2-BE, it was able to identify possible five protein spots, having pl from 4 to 5 and molecular weight range from 24 to 26 kDa, involved in bone formation and repair, since no differing protein spots were found the two between groups except the five spots. No differences were observed between two groups before operation, but clear and bigger protein spots were observed from the S-OP group compared with C-OP group on 6 and 9 weeks post operation. These protein spots were, however, showed similar sizes and densities between two groups in 12 weeks later. The transformation of protein spots was suggested that these protein spots were involved in bone formation and recovery, in addition safflower seed might induce the formation of factors and activate these factors. In conclusion, this study suggest that safflower seed influence a variety of factors in the course of bone formation or the periods of remedy.

• Nutrition Research and Practice
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• 제8권5호
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• pp.539-543
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• 2014

BACKGROUND/OBJECTIVES: Soy isoflavones are structurally similar to estrogen and bind to estrogen receptors, suggesting that they exhibit estrogenic activities; therefore, they are referred to as phytoestrogens. Fermentation may affect the bioavailability of isoflavones altering soy isoflavone glycosides in the form of aglycones. Thus, this study investigated the effects of fermented soybeans by Rhizopus oligosporus on bone metabolism in both young rats as a pilot test and in ovariectomized (ovx) old rats as a model of menopause. MATERIALS/METHODS: In the pilot test, a total of 24 seven-week-old female Sprague-Dawley (SD) rats were fed one of three diets for a period of four weeks: casein, unfermented soybean product, or fermented soybean product by R. oligosporus. In the ovx rat model, 20-week-old SD rats weighing 260-290 g underwent either sham-operation (n = 10) or bilateral ovariectomy (n = 30) and were then fed the AIN-93M diet for one week. Thereafter, rats were fed sham-casein, ovx-casein, ovx-soybean, or ovx-fermented soybean diet for five weeks. After decapitation, femoral bones were isolated and preserved in 9% formalin for assessment of bone mineral density (BMD), bone mineral content (BMC), and bone-breaking strength (BBS). RESULTS: Ovx rats showed significantly increased weight gain and decreased uterine wet weight. Of particular interest, ovx rats fed fermented soybeans showed increased uterine wet weights compared to control rats. Fermented soybean diet caused a significant increase in plasma 17-${\beta}$ estradiol concentrations in young rats, and 17-${\beta}$ estradiol levels were enhanced in ovx rats to match those of sham-operated ones. Significantly lower femoral BMD and BMC were observed in ovx rats compared to sham-operated controls, whereas bone areas did not differ statistically among the groups. In addition, BBS tended to be increased in ovx rats fed soybeans and fermented soybeans. CONCLUSIONS: Supplementation of fermented soybeans could have preventive and therapeutic effects against osteoporosis in postmenopausal women.

• Journal of Nutrition and Health
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• 제42권4호
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• pp.309-317
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• 2009

As far as we know, there were no studies of the effect of L-arginine on bone metabolism in post-menopausal women or ovariectomized rats. The primary objective of the current study was to determine whether arginine supplementation was associated with alterations in femoral and spinal bone mineral density (BMD) and bone markers in ovariectomized (Ovx) rats. Forty female Sprague-Dawley rats were divided into two groups, Ovx and sham groups, which were each randomly divided into two subgroups that were fed control and arginine supplemented diet. All rats were fed on experimental diet and deionized water ad libitum for 9 weeks. Bone formation was measured by serum osteocalcin and alkaline phosphatase (ALP) concentrations. Bone resorption was measured by deoxypyridinoline (DPD) crosslinks immunoassay and corrected for creatinine. Serum osteocalcin, growth hormone, insulin-like growth factor-1 (IGF-1), parathyroid hormone (PTH) and calcitonin were analyzed using radioimmunoassay kits. Bone mineral density (BMD) and bone mineral content (BMC) were measured using PIXImus (GE Lunar Co, Wisconsin, USA) in spine and femur. The serum and urine concentrations of Ca and P were determined. The plasma was analyzed for arginine. Diet did not affect weight gain, mean food intake, and plasma arginine concentration. Urinary Ca excretion was decreased by arginine supplementation in Ovx rats, but statistically not significant. The Ovx rats fed arginine-supplemented diet were not significantly different in ALP, osteocalcin, crosslinks value, PTH, calcitonin and IGF-1 compared to those fed control diet. The arginine-supplemented group had significantly higher serum Ca and growth hormone than control group. Spine and femur BMD were significantly increased by arginine supplementation on 5th and 9th weeks after feeding. Our findings indicate that dietary L-arginine supplementation decreased bone mineral density loss in Ovx rats. Therefore, dietary arginine supplementation may represent a potentially useful strategy for the management of osteoporosis.

• 한국한의학연구원논문집
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• 제8권2호통권9호
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• pp.95-107
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• 2002

Yukmijihwang-tang(YM) is a noted herbal prescription in Chinese and Korean traditional medicines, and it has been known to reinforce the vital essence and has been widely used for a variety of disease such as stroke, osteoporosis, anti-tumor, and hypothyrodism. Regarding its traditional use, YM has been known to reinforce the Yin (vital essence) of liver and kidney. Also it has been known to reinforce nutrition and biological function in brain. Recently, studies suggested that YM increase antioxidant activities and exert the protective effect against oxidant-induced liver cell injury. We investigated the high-throughput gene expression analysis on the Yukmijihwang-tang administrated in SD rats. Microarray data were validated on a limited number of genes by semiquantitative RT-PCR and Western blot analyses. The recent availability of microarrays provides an attractive strategy for elaborating an unbiased molecular profile of large number of genes in drug discovery This experimental approach offers the potential to identify molecules or cellular pathways not previously associated with herbal medicine. Total RNA from normal control brain and Yukmijihwang-tang administrated brain were hybridized to microarrays containing 10,000 rat genes. The 52 genes were found to be up-regulated(twice or more) excluding EST gene. The nine genes were found to be down-regulated(twice or more) excluding EST gene. Gene array technology was used to identify for the first time many genes expression pathway analysis that arecell cycle pathway, apoptosis pathway, electron transport chain pathway, cytoplasmic ribosomal protein pathway, fatty acid degradation pathway, and TGF-beta signaling pathway. These differentially expressed genes pathway analysis have not previously been iavestigated in the context of herbal medicine efficacy and represent novel factors for further study of the mechanism of herbal medicine efficacy.

• 동아시아식생활학회지
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• 제6권3호
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• pp.295-305
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• 1996

This study was done to evaluate the effectiveness of dietary calcium level(a diet which met 100% or twice the calcium level in AIN-76 diet) on preventing bone loss in ovariectomized rats. Forty female Sprauge-Dawley rats(body weight 200$\pm$5g) were divided into two groups. One group were ovariectomized(Ovx) while the others received sham operation(Sham). Thereafter, each rat group was further divided into normal calcium diet(NCD, 0.52%) and high calcium diet(HCD, 1.04%) sub-groups. All rats were fed on experimental diet and deionized water ad libitum for 8 weeks. Urinary pyridinoline & creatinine and serum estradiol, luteinizing hormone, calcium, phosphate, total protein, albumin, alkaline phosphatase and osteocalcin were determined. There were no significant differences in serum calcium. total protein and albumin in the two groups(Ovx vs Sham) of rats. Ovariectomized rats had significantly lower estradiol than sham operated rats. There was a highly significant correlation between total bone mineral density(TBMD) and overall level of esteradiol(r=0.59, p<0.05). Total bone mineral density did not correlate significantly with ALP or osteocalcin, although a negative trend was evident. However, the rats fed high calcium diet had a lower crosslinks value and osteocalcine than the rats fed normal calcium diet. An increased rate of bone turnover is usually associated with a decrease in bone mass bexause bone formation at each remodeling site is never as great as resorption. Ovariectomized rats fed high calcium diet had a lower crosslink value and osteocalcin; it means high cacium diet decreased bone turnover rate. The findings from the present study demonstrated that bone loss due to ovarian hormonal deficiency can be partially prevented by a high calcium diet. Futhermore, these findings support the strategy of the use of a high calcium diet in the prevention of estrogen depletion bone loss (postmenopausal osteoporosis).

• Archives of Pharmacal Research
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• 제26권11호
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• pp.917-924
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• 2003

This research aims to test a new drug candidate based on a traditional medicinal herb, F1, an herbal extract obtained from Astragalus membranaceus and its main ingredient, 1-monolinolein that may have fewer side effects and less uterine hypertrophy. In vitro experiments, human osteoblast-like cell lines, MG-63 and Saos-2, were analyzed by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) and an alkaline phosphatase (ALP) assays. Mouse osteoclasts were induced through a calcium-deficient diet and inhibition effects were measured. In vivo experiments were done using ovariectomized (OVX) rats for 9 weeks. At necropsy, uterus weights were measured, trabecular bone area (TBA) of tibia and lumbar vertebra were measured bone histomorphology. In results, cell proliferation and ALP activity in Saos-2 by ether F1 or 1-monolinolein did not increased significantly compared to the control. The F1 inhibited osteoclast development ($IC_{25}=3.37{\times}10^{-5}$mg/mL) less than 17$\beta$-estradiol. The OVX rats administered F1 (2 mg/kg/day and 10 mg/kg/day) showed an increase in TBA of the tibia significantly (136.3${\pm}4.2% and 138.5{\pm}$10.3% of control). In conclusions, the herbal extract, F1 inhibited tibia and lumbar bone loss and did not cause uterine hypertrophy. However, 1-monolinolein, the main ingredient of the herbal extract, did not inhibit bone loss.

• Journal of Nutrition and Health
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• 제34권5호
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• pp.532-540
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• 2001

This study explored the effect of calcium levels and/or ovariectomy on bone composition and its related factors using the female Sprague-Dawley rats which achieved peak bone mass in normal(0.5%) calcium intake during growth period. The rats were randomly divided into six groups and fed 0.1%, 0.5% and 1.5% calcium diets for 8 weeks after ovariectomized and sham operation. The results indicated that body weight gain was higher in ovariectomized groups than sham groups, regardless of dietary calcium levels and food intakes. Serum Ca and P concentrations were normal level regardless of dietary calcium levels and operation. Estrogen concentration was decreased in ovariectomized rat groups. Serum alkaline phosphatase activity and urinary hydroxyproline were increased in ovariectomized groups. When rats were fed normal Ca diet during growing period, weight, length and breaking force of femur were not significantly different in all groups but increased the same level. Generally, lipid contents in lumbar and femur were lower in low calcium groups and this effect was more pronounced in femur. In case of femur, the significant decrease in Ca contents of bone was observed in a relatively short period of feeding low Ca diet, even though it appeared th desirable peak bone mass had achieved through the growing period by supplementing the adequate amount of calcium. The marked decrease of estrogen levels after ovariectomy did not seem to influence greatly bone parameters measured except bone wet weight. Therefore, this study indicated that lower intake of Ca might be more important determinating factor against osteoporosis than postmenopausal state stimulated by ovariectomy in female rats. With normal or high intake of Ca it appears possible to prevent bone loss in postmenopausal period, and this might apply only in case of achieving peak bone mass in the growing with the adequate intake of calcium. (Korean J Nutrition 34(5) : 532∼540, 2001)