• The Korean Journal of Nuclear Medicine
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• v.33 no.4
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• pp.341-351
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• 1999

Biochemical markers of bone turnover has received increasing attention over the past few years, because of the need for sensitive and specific tool in the clinical investigation of osteoporosis. Bone markers should be unique to bone, reflect changes of bone loss, and should be correlated with radiocalcium kinetics, histomorphometry, or changes in bone mass. The markers also should be useful in monitoring treatment efficacy. Although no bone marker has been established to meet all these criteria, currently osteocalcin and pyridinium crosslinks are the most efficient markers to assess the level of bone turnover in the menopausal and senile osteoporosis. Recently, N-terminal telopeptide (NTX), C-terminal telopeptide (CTX) and bone specific alkaline phosphatase are considered as new valid markers of bone turnover. Recent data suggest that CTX and free deoxypyridinoline could predict the subsequent risk of hiP fracture of elderly women. Treatment of postmenopausal women with estrogen, calcitonin and bisphosphonates demonstrated rapid decrease of the levels of bone markers that correlated with the long-term increase of bone mass. Factors such as circadian rhythms, diet, age, sex, bone mass and renal function affect the results of biochemical markers and should be appropriately adjusted whenever possible. Each biochemical markers of bone turnover may have its own specific advantages and limitations. Recent advances in research will provide more sensitive and specific assays.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.37 no.1
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• pp.1-8
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• 2011

Introduction: The utility of the C-terminal cross-linking telopeptide test (CTX) as a method for staging Bisphosphonate-related osteonecrosis of the jaws (BRONJ) and its healing process was examined. Materials and Methods: A total 19 patients who were diagnosed with BRONJ underwent a fasted morning CTX test, were enrolled in this study. The serum CTX values ranged from 50 to 630 pg/mL (mean 60). The risk assessment was rated according to the CTX values of the individual patient (minimal risk, ${\geq}$ 150 pg/mL, moderate, 100 to 150 pg/mL, high, ${\leq}$100 pg/mL). The BRONJ scores were then calculated according to the number of BRONJ lesions and their stage. The operation was done as soon as possible, regardless of BORNJ stage. Results: The mean duration of bisphosphonate therapy was 4.1 years. Of the 19 patients, 15, 2 ans 2 received alendronate, risedronate and zoledronate, respecively. Of the 19 patients who underwent a sequestrectomy, saucerization and smoothing, 15 healed after the initial surgery, 1 patient healed after one more surgical procedure, 3 patients did not heal completely but showed improvement in symptoms. Therefore, 17 out of the 19 patients healed completely with complete mucosal coverage and the elimination of pain. The risk assessment using the CTX value and disease severity were not correlated (r=-0.264, P=0.275). In addition, the risk assessment using CTX value and healing after surgery were not correlated (r=-0.147, P=0.547). Conclusion: The serum CTX should be considered carefully by clinicians as part of overall management. Early surgical intervention is of benefit in the treatment of stage II BRONJ.

• Journal of Nutrition and Health
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• v.39 no.1
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• pp.11-17
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• 2006

The effect of the level of casein phosphopeptide (CPP) on mineral (Ca and P) bioavailabilties and bone biomarker of aged ovariectomized (OVX) Sprague-Dawley rats were studied as a model for postmenopausal bone loss. Forty five Spargue dawley rats, 220-230 g of body weight were fed a control diet (AIN 93M) or containing different level of CPP diet for 7 weeks: $0\%$ (sham control; SC, OVX control; OC), $1\%$ (OVX low CPP diet: OL), $2\%$ (OVX medium CPP diet; OM), $3\%$ (OVX high CPP diet; OH) Ca absorption was unaffected by increasing CPP content from 0 to $3\%$. Urinary Ca excretion was increased by OVX, and decreased by CPP significantly (p < 0.05) with no evident doserelationship. The urinary P excretion was increased by CPP intake in OVX rats. The fecal excretion of P given CPP decreased in OVX with dose dependent manner. Ca and P contents of femur significantly increased by adding 2 or $3\%$ of CPP when compared with OC group and OL group (p < 0.05). There were no significant differences in serum alkaline phosphatase activity and c-terminal telopeptide excretion in experimental groups. Although ovariectomy induced the increase in urinary c-terminal telopeptide excretion, 2 or $3\%$ of CPP in the diet decreased urinary c-terminal telopetide excretion significantly. These finding suggest the usefulness of CPP in the prevention of postmenopausal bone loss by decreasing urinary Ca excretion and bone resorption. Over 2 percent of CPP in the diet was effective to prevent postmenopausal bone loss.

• Korean Journal of Clinical Laboratory Science
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• v.49 no.4
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• pp.337-344
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• 2017

To date, no clear threshold that has been established for defining an adequate store of vitamin D for bone health. Therefore, this study aims to determine the required level of vitamin D to maintain a healthy skeleton based on bone remodelling process among healthy adult population. This was a cross sectional study, involving a healthy adult population in Kota Bharu, Malaysia, aged 18~50 years. We measured serum 25(OH)D (vitamin D), serum parathyroid hormone (PTH), serum C-terminal telopeptide of type 1 collagen (CTX), and Procollagen 1 Intact N-Terminal (P1NP) in 120 healthy adults selected via multi stage sampling (64 males, 56 females) from 6 subdistricts in Kota Bharu. The mean level of 25(OH)D was 23.50 (${\pm}8.74$) nmol/L. There was a significant difference of the vitamin D level between genders ($26.81{\pm}8.3nmol/L$ vs $19.72{\pm}7.68nmol/L$ in males and females respectively) (p value<0.001). More than 50% of female subjects had 25(OH)D less than 20 nmol/L, while only 20.3% of male subjects had 25(OH)D below 20 nmol/L. Based on the LOESS plot, the bone turnover markers showed a plateauing result, at the 25(OH)D level of 35 nmol/L for CTX and 20 nmol/L for P1NP. Contrastingly, PTH showed a step rise in the 25(OH)D level of 20 nmol/L. Based on the LOESS plot for CTX, P1NP and PTH versus 25(OH)D, level of vitamin D between 20 to 35 nmol/L is recommended to maintain healthy skeleton.

• Journal of the Korean Society of Food Science and Nutrition
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• v.45 no.5
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• pp.634-641
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• 2016

The objective of this research was to investigate the in vivo effects of treatment with mulberry extract complex (MEC) on cartilage degeneration and pain severity in an experimental model of rat degenerative arthritis. Monosodium iodoacetate ($2mg/50{\mu}L$) was injected into right knee joints of rats, followed by administration of MEC for 8 weeks at 400 mg/kg or 800 mg/kg of body weight. The experimental data show that treatment with MEC inhibited degradation of glycosaminoglycan and collagen in cartilage. On the other hand, concentrations of cartilage oligomeric matrix protein, C-terminal telopeptide-2, matrix metalloproteinase (MMP)-2, MMP-9, and MMP-13 in serum decreased in comparison with the control. The MEC at all dose levels could inhibit formation of xylene-induced ear edema. In this study, MEC demonstrated significant anti-arthritis activity, which is required for improvement of degenerative arthritis. Based on these results, MEC may be employed for the development of new health foods to ease symptoms of degenerative arthritis.

• Journal of Oral Medicine and Pain
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• v.32 no.1
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• pp.35-43
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• 2007

This study was conducted to investigate the preventing effects of OPB (water extracts of Rehmannia glutinosa Libosch and Eleutherococcus senticosus Max) on bone loss in ovariectomized rats. Twenty Sprague Dawley rats of 13 week-old were divided into two groups: control group (ovariectomized, OVX)) and experimental group (OVX + OPB). The preventing effects of OPB on bone loss, OPB were fed with 100 mg OPB/kg body weight from 3 days after ovariectomization. The duration of the treatment period was 8 weeks. All bone mineral density, bone mineral content indices and bone strength indices measured by peripheral quantitative computerized tomography (pQCT) and serum bone marker assessment were carried out at end of experiment. pQCT scanning showed that OVX induced a significant decrease in cancellous bone mineral density in the proximal tibia ($-29.8{\pm}3.0%$). These decreases were significantly prevented by the administration of OPB 100 mg/kg ($-21.4{\pm}2.3%$. p<0.05). Bone strength indices showed significant difference between OVX and OPB treated rats (anti-fracture, anti-twisting, p<0.05). These data suggested that administration of OPB inhibited the loss of bone in OVX rats. CTx level were lower than in the OPB-treated animals compared with OVX. However there was no significant difference between OVX and OPB treated OVX rat. Our results suggest that OPB is effective in preventing the development of bone loss induced by ovariectomy in rats.

• Journal of Physiology & Pathology in Korean Medicine
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• v.29 no.4
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• pp.330-336
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• 2015

Polycan originating from Aureobasidium pullulans is mostly composed of β-1, 3/1, 6 glucans and possesses an anti-osteoporotic effect. We conducted a randomized, double-blind, placebo-controlled trial to examine the efficacy and safety of the polycan on bone biochemical markers in healthy perimenopausal women. Sixty subjects were randomly allocated to 2 groups-group 1 received 400 mg of polycan and group 2 received placebo-these were administered once daily for 28 days. Fasting blood and urine samples were collected at baseline and 4 weeks after treatment. The primary outcome was change in osteocalcin (OSC) and bone-specific alkaline phosphatase (BALP). Changes in calcium (Ca), phosphorus (P), C-telopeptide of collagen cross-links (CTx), N-telopeptide of collagen cross-links (NTx), and deoxypyridinoline (DPYR) were the secondary outcomes. A safety assessment was performed using adverse event (AE) and laboratory data. After 4 weeks of polycan treatment, OSC, DPYR, and BALP levels changed (P < 0.05) significantly from baseline in both groups. However, no significant differences were observed in any markers between the 2 groups, except for P (P < 0.05). Interestingly, group 2 showed a significant increase in CTx (65.2%, P < 0.05), while CTx in group 1 slightly increased (17.2%). Both groups showed no significant differences in AE. Although 4 weeks of polycan treatment did not have a statistically significant effect on bone metabolism biomarkers, increases in CTx were modestly inhibited by polycan. Further studies in a large population and longer treatment periods are needed to confirm the effect of polycan on bone turnover.

• Nutrition Research and Practice
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• v.9 no.5
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• pp.459-465
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• 2015

BACKGROUND/OBJECFTIVES: The effect of St. John's Wort extract (SJW) on MG-63 cell proliferation and trabecular bone loss induced by ovariectomy was examined. MATERIALS/METHODS: Proliferation, expression of estrogen receptor (ER) ${\alpha}$ and ER ${\beta}$, and gene expressions of osteoprotegerin (OPG), osteocalcin (OC) and alkaline phosphatase (ALP) were examined in MG-63 cells treated with or without SJW. Ovariectomized rats were treated with SJW at the dose of 100 or 200 mg/kg/day, ${\beta}$-estradiol-3-benzoate (E2), or vehicle only (OVX-C), and sham operated rats were treated with vehicle only (Sham-C). Serum ALP and C-telopeptide (CTX), and femoral trabecular bone loss were examined. RESULTS: SJW increased MG-63 cell proliferation and expression of ER ${\alpha}$ and ER ${\beta}$, and positive effect was shown on gene expressions of ALP, OC and OPG. SJW also showed estrogen like effect on bone associated with slowing down in trabecular bone loss. Histopathology by H&E showed rats treated with SJW displayed denser structure in metaphyseal region of distal femur compared with rats in OVX-C. SJW was shown to reduce serum CTX in OVX rats. CONCLUSION: The present study provides new insight in preventing estrogen deficiency induced bone loss of SJW and possibility for its application in bone health supplement.

• Journal of Korean Neurosurgical Society
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• v.51 no.6
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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.

• Journal of Korean Neurosurgical Society
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• v.63 no.4
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• pp.433-443
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• 2020

Objective : Osteoporosis is a disease of unbalanced bone metabolism that results in low bone mineral density with increased bone fragility and propensity for fractures. The increased rate of bone fracture due to osteoporosis places a significant burden on public health care expenditures. Therefore, numerous studies have been designed and performed to identify the drugs or health foods that can improve the bone quality or quantity. This study was designed to evaluate and analyze the therapeutic effects of rutin on histomorphometric values of the spine and femur in an osteoporotic mouse model induced by bilateral ovariectomy. Methods : Thirty female ICR mice (8 weeks old) underwent either a sham operation (only abdominal incision, sham group, n=10) or bilateral ovariectomy (n=20). The ovariectomized (OVX) animals were randomly divided into two groups : untreated OVX group (OVX-C, n=10), or rutin-administered group (OVX-R, n=10). The OVX-C group received weight-adjusted doses of saline vehicle and the OVX-R group received 50 mg/kg of rutin intraperitoneally, starting 1 day after surgery. At 4 and 8 weeks after surgery, serum estrogen, osteocalcin, alkaline phosphatase (ALP), and the telopeptide fragment of type I collagen C-terminus (CTX-1) were analyzed. Interleukin (IL)-1β, IL-6, IL-10, and tumor necrosis factor (TNF)-α were also analyzed. Bone histomorphometric parameters of the 4th lumbar vertebra and femur were determined by micro-computed tomography. Results : In OVX-C group, ALP, osteocalcin, CTX-1, IL-1β, IL-6, and TNF-α levels were significantly increased at 4 and 8 weeks compared to sham operation group. Rutin administration after OVX statistically significantly reduced ALP, CTX-1, IL-1β, IL-6, and TNF-α levels at 4 and 8 weeks. Rutin administration also improves bone histomorphometric parameters including trabecular bone volume fraction, trabecular thickness, and trabecular number. Trabecular separation was also decreased in OVX-R group compared to OVX-C group. Conclusion : The present study demonstrated that rutin has therapeutic effects on improving bone histomorphometric values in an OVX mouse model. The improvement in histomorphometric values may be associated with the reduction of osteoclastic activity via inhibition of IL-1β, IL-6, and TNF-α. In future studies, the mechanism for the effect of rutin on osteoporosis should be demonstrated more clearly to use rutin in human osteoporosis.