• 셀메드
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• 제8권3호
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• pp.13.1-13.8
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• 2018

In the field of osteoporosis, there has been growing interest in anabolic agents that enhance bone formation. The purpose of this study was to examine the effects of NNMBS 246 osteoblastic differentiation with associated signaling pathways. NNMBS 246 markedly increased alkaline phosphatase (ALP) activity and calcium nodule formation. Stimulation with NNMBS 246 not only increased the differentiation markers (ALP, OPN, OCN) level and transcription markers (RUNX2, Osterix) mRNA expression but also upregulated the ECM molecules and OPG mRNA expression. Treatments of NNMBS 246 downregulated MMPs (MMP-1, MMP-2, MMP-9), but RANKL mRNA expression. Furthermore, NNMBS 246 activated osteoblastic differentiation markers and formed calcium nodules in human periodontal ligament cells (hPDLCs) and cementoblast cells. NNMBS 246 induced phosphorylation of MAPKs, Akt, nuclear p65 and IkB-${\alpha}$. BMP-2/Smad and ${\beta}$-catenin signaling pathways were activated by NNMBS 246. Sirtinol (SIRT1 inhibitor) inhibited NNMBS 246-induced osteoblastic differentiation markers mRNA expression. These results suggested that NNMBS 246 has the potential to enhance osteoblastogenesis probably through the activation of BMP/Smad and ${\beta}$-catenin signal pathways, and SIRT1 plays as critical mediator in bone anabolic effect of NNMBS 246.

• Asian Pacific Journal of Cancer Prevention
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• 제13권9호
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• pp.4331-4334
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• 2012

Aim and Background: The aim of the present study was to evaluate correlations between serum osteocalcin, osteoprotegerin and NTX (Cross-linked N-telopeptides of Type I Collagen) and urinary NTX in breast and lung cancer patients with bone metastases. These four markers are considered to have important roles in bone formation, resorption and metastases. Methods: Four markers were determined in the sera of 60 breast cancer and 21 lung cancer patients and healthy controls (n=30). Serum levels were studied using ELISA and EIA. Results: The median levels of serum osteoprotegerin (p<0.001) and osteocalcin (p=0.003) were higher in patients. Significant correlations were observed between the serum NTX-osteocalcin (r=0.431; p<0.001), serum NTX-osteoprotegerin (r=0.42; p=0.003) and serum NTX - urine NTX (r=0.255; p=0.022). Conclusion: We conclude that osteocalcin, osteoprotegerin and NTX are independent diagnostic tools. Due to the ease of urine collection, urine NTX may be applied routinely to allow early detection of bone metastases and indicate progression of the disease.

• Journal of Korean Neurosurgical Society
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• 제51권6호
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• pp.323-327
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• 2012

Objective : The purpose of this study was to verify the appropriateness of ovariectomized rats as the osteoporosis animal model. Methods : Twelve female Sprague-Dawley rats underwent a sham operation (the sham group) or bilateral ovariectomy [the ovariectomy (OVX) group]. Eight weeks after operations, serum biochemical markers of bone turnover were analyzed; osteocalcin and alkaline phosphatase, which are sensitive biochemical markers of bone formation, and C-terminal telopeptide fragment of type I collagen C-terminus (CTX), which is a sensitive biochemical marker of bone resorption. Bone histomorphometric parameters and microarchitectural properties of 4th lumbar vertebrae were determined by micro-computed tomographic (CT) scan. Results : The OVX group showed on average 75.4% higher osteocalcin and 72.5% higher CTX levels than the sham group, indicating increased bone turnover. Micro-CT analysis showed significantly lower bone mineral density (BMD) (p=0.005) and cortical BMD (p=0.021) in the OVX group. Furthermore, the OVX group was found to have a significantly lower trabecular bone volume fraction (p=0.002). Conclusion : Our results showed that bone turnover was significantly increased and bone mass was significantly decreased 8 weeks after ovariectomy in rats. Thus, we propose that the ovariectomized rat model be considered a reproducible and reliable model of osteoporosis.

• Nutrition Research and Practice
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• 제4권6호
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• pp.507-514
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• 2010

Vitamin K intake has been reported as an essential factor for bone formation. The current study was conducted under the hypothesis that insufficient vitamin K intake would affect inflammatory markers and bone mineral density in young adult women. The study was a cross-sectional design that included 75 women in their 20s. Physical assessments, bone mineral density measurements, 24-hr dietary recalls, and biochemical assessments for high sensitivity C-reactive protein (hs-CRP) and percentages of undercarboxylated osteocalcin (%ucOC) were performed. An analysis of vitamin K nutritional status was performed comparing first, second, and third tertiles of intake based on %ucOC in plasma. Vitamin K intake levels in the first, second, and third tertiles were $94.88{\pm}51.48\;{\mu}g$, $73.85{\pm}45.15\;{\mu}g$, and $62.58{\pm}39.92\;{\mu}g$, respectively (P < 0.05). The T-scores of the first and third tertiles were 1.06 and -0.03, respectively, indicating that bone mineral density was significantly lower in the group with lower vitamin K intake (P < 0.05). There was a tendency for different serum hs-CRP concentrations between the first ($0.04{\pm}0.02$) and third tertiles ($0.11{\pm}0.18$), however this was not statistically significant. Regression analysis was performed to identify the correlations between vitamin K nutritional status, inflammatory markers, and bone mineral density after adjusting for age and BMI. Serum hs-CRP concentrations were positively correlated with vitamin K deficiency status (P < 0.05). And bone mineral density, which was represented by speed, was negatively correlated with vitamin K deficiency status (P < 0.05). In conclusion, status of vitamin K affects inflammatory status and bone formation. Therefore, sufficient intake of vitamin K is required to secure peak bone mass in young adult 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.

• Journal of Nutrition and Health
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• 제44권3호
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• pp.189-195
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• 2011

Vitamin K has been suggested to plays a role in bone metabolism. The objective of this study was to determine whether vitamin K2 supplementation is related to bone mineral density, bone formation markers, and bone resorption in ovariectomized (OVX) rats. Forty Sprague-Dawley female rats (body weight, $200{\pm}10$ g) were divided into four groups: a sham group fed a control diet, a sham group fed a vitamin K2 supplemented diet, OVX fed a control diet, and OVX fed a vitamin $K_2$ supplemented diet (3.5 mg vitamin $K_2$/kg diet). All rats were fed the experimental diets for 6 weeks, and deionized water was provided ad libitum. Serum alkaline phosphatase activity (ALP), osteocalcin, and urinary deoxypyridinoline crosslink values were measured as markers of bone formation and resorption. Bone mineral density (BMD) and bone mineral content were measured in the spine and femur using PIXImus (GE Lunar Co., Madison, WI, USA). No significant differences in body weight gain, food intake, or food efficiency ratio were observed between the control and experimental groups. Serum ALP, osteocalcin, and urinary crosslink values were not significantly different between the vitamin $K_2$ supplemented groups. No significant differences were observed for any of the variables in the sham group. Spine BMD values were significantly lower in the OVX than those in the sham groups. Spine and femur BMD per weight of vitamin $K_2$ tended to be higher than the control diet group within the OVX group, but no significant differences were observed. In conclusion, dietary vitamin $K_2$ supplementation may have a beneficial effect on spine and femur BMD in OVX rats. Further research is needed to understand the potential benefits of vitamin $K_2$ on bone loss in OVX rats.

• 한국산학기술학회논문지
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• 제10권12호
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• pp.3943-3952
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• 2009

본 연구는 청년기 여대생을 대상으로 신체 각 부위의 골밀도와 생화학적 골대사지표를 측정한 후 1년 뒤의 변화를 추적 조사하였다. 각 신체부위별 주요 골격의 1년 후 평균 골밀도변화에서 전완부 골밀도는 유의하게 변화한 반면 요추골, 대퇴골 근위부(경부, 전자부, 워드 삼각부) 및 전신골밀도에서는 변화가 없었다. 골대사지표 중 골형성지 표인 혈청 오스테오칼신과 골흡수지표인 요중 디옥시피리디놀린은 모두 유의하게 변화하였다. 초기 청년기 여성에서 골밀도의 뚜렷한 변화가 없어도 골대사는 여전히 활발히 이루어지고 있음을 알 수 있었다.

• 한국임상수의학회지
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• 제19권4호
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• pp.405-410
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• 2002

The purpose of this investigation was to examine the effects of osteocalcin (serum bone GLA-protein, BGP) and procollagen carboxy-terminal propeptide (PICP) on new bone formation of canine fracture models. Serum osteocalcin and PICP were measured by standard RIA. The values of osteocalcin and PICP in the non-union and delayed-union fracture models were measured biweekly for 20 weeks in 14 dogs. The unions were radiographed for fracture healing. In non-union fracture group, the activity of BGP was markedly increased at four to eight weeks and decreased at twelve to twenty weeks and the activity of PICP was markedly increased at two to six weeks and slightly decreased at sixteen to twenty weeks. In delayed-union fracture group, the activity of BGP was markedly increased at two to eight weeks after treatment and maintained for the level until twenty weeks and the activity of PICP was markedly increased at two to six weeks after treatment and maintained for the level until twenty weeks. Radiologically, non-union group was not achieved until twenty weeks after fracture, delayed-union group was successfully achieved in eighteen weeks after fracture. These results suggested that the. activities of osteocalcin and PICP are useful parameters for biochemical markers of bone formation in dogs.

• 대한치과교정학회지
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• 제31권3호
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• pp.357-367
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• 2001

당뇨병 흰쥐를 대상으로 치조골의 교체(turnover)와 치아 이동 중 치조골의 흡수와 형성의 활성을 비교 관찰하기 위하여 8주령의 웅성 Sprague-Dawley계 흰쥐를 정상대조군(N), 당뇨군(D), 정상-치아이동군(N-tm), 당뇨-치아이동군(D-tm)으로 나누고, 각 실험군은 치아이동 실험 1일, 3일, 7일, 14일의 소군으로 나누었다. 당뇨병은 치아이동 실험 18일전에 스트렙토조토신(50mg/체중 kg)을 꼬리정맥에 단 회 주사하여 유발하였다. 치아이동은 상악 제1대구치를 초기 교정력 40그램으로 근심 이동시켰다. 상악 제1대구치 주위 치조골을 대상으로 골형성 징후표지로서 치조골 alkaline phosphatase(ALP)와 osteocalcin(OC)을, 골흡수 징후표지로서 acid phosphatase (ACP)와 tartrate-resistant acid phophatase(TRAP)을 정량 분석하였으며, D군과 N군에서는 이들의 혈중 농도를 정량 분석하였다. 1. D군의 혈청 TRAP농도와 혈청 OC농도는 모든 실험 경과군에서 N군보다 감소하였고(p<0.05), 당뇨기간이 길어질수록 더 많이 감소한 것으로 나타났다. 또한 치조골 흡수 징후표지는 감소하는 경향이었으며 골형성 징후표지도 실험기간이 경과함에 따라 더 많이 감소하는 것으로 나타났다. 2. N-tm군의 치조골 ACP농토와 TRAP농도는 N군과 비교하여 1일과 3일군에서 가장 높았으며(p<0.01), 그 이후 감소경향을 나타냈고, 치조골 OC함량은 3일, 7일 14일군에서 N 군보다 높았다(p<0.001). 그러나 D-tm군에서 치조골 ACP와 TRAP농도는 정상 N군에 비하여 1일에는 낮으나 7일, 14일 경과군에서 가장 높았고(p<0.001), 실험 경과에 따라 계속 증가 하였으며(p<0.001), 치조골 ALP와 OC 함량은 3일 경과 후부터 증가하지만 정상 N군과 유의차가 없었다. 3. 당뇨-치아이동군의 치아이동량은 정상-치아이동군보다 많은 것으로 나타났다. 이러한 실험 결과는 당뇨병의 전신 골격과 치조골은 골 흡수 활성이 억제되어 있으며 골형성 활성은 당뇨 지속시간이 길어질수록 더 많이 억제되는 느린 골교체를 하며, 교정력에 의한 치조골 흡수활성이 처음 높아지는 시기는 정상치아이동시보다 늦고 더 오랬 동안 지속되며 치조골 형성활성은 낮고, 치아 이동량은 증가하며 이동중 치아동요도가 증가함을 시사한다.

• Journal of Trauma and Injury
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• 제18권2호
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• pp.87-93
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• 2005

Background: The most frequent fracture seen at the emergency department (ED) in the elderly is a femur fracture whereas they do not know the degree of osteoporosis. We analyzed the degree of osteoporosis in patients with femur fractures and compared patients with only femur fractures (FX) to patients with femur and vertebral fractures (VX) by examining the clinical features, the bone mineral density (BMD), and biochemical markers. Methods: From January 2004 to December 2004, we enrolled prospectively 30 femur fracture patients who visited the ED. The bone mineral densities of the lumbar spine and the femur were examined. Total calcium, phosphate, alkaline phosphatase, osteocalcin, and serum C-terminal telopeptide (s-CTx) were measured. The patients with femur fractures were divided into two subgroups according to the presence of vertebral fracture. Results: All BMDs of the FX group showed osteoporosis. The s-CTx levels were higher than normal. The patients in the FX with VX were older than those in the FX only group, and had lower BMDs. There were no significant differences in markers between the subgroups, but the incidence of trochanteric fractures was higher in FX with VX group than in the FX only group. Conclusion: Femur fractures in the elderly were associated with osteoporosis. In our study, despite a considerable difference in BMD between patients with femur fractures and those with femur fractures combined with vertebral fractures, there was no difference in biochemical markers on bone formation nor in the those of bone resorption. We will further investigate the biochemical markers and BMD in the population of osteoporotic fractures. So those indicators should be helpful for planning treatment and for prevention of FX in the elderly.