• 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.

• 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.

• 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 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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.39 no.12
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• pp.1769-1775
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• 2010

Menopause is often associated with the incidence of several chronic diseases including osteoporosis, cardiovascular disease, and obesity. The purpose of this study was designed to evaluate the possibility of osteoporosis prevention in postmenopausal women. In this study, we investigated the effects of Ecklonia stolonifera (ES) extracts on bone turnover markers in ovariectomized rats. For this study, the following four groups of 9-week-old Sprague-Dawley rats were evaluated over 6 weeks: normal rats (SHAM), ovariectomized rats (OVX-CON) and ovariectomized rats that were treated with ES extracts. We measured the osteocalcin and C-telopeptide of collagen cross-links (CTx) content, enzyme ALP activity in serum and collagen content in the cartilage, bone, skin and lungs. We found that the levels of indicators of bone metabolism such as alkaline phosphatase (ALP), osteocalcin and CTx were lower in rats in the ES extract group than the OVX-CON group. In addition, the collagen contents in the bone, cartilage, skin and lungs decreased in response to ovariectomy, but the levels of collagen were greater in the bone of rats that were treated with ES extract than in the bone of rats in the OVX-CON group. These results suggest that the ES may be an effective functional food to prevent osteoporosis in postmenopausal women.

• Journal of Korean Neurosurgical Society
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• v.52 no.1
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• pp.1-6
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• 2012

Objective : The purpose of this study was to evaluate the different patterns of bone loss between the lumbar spine and the femur after ovariectomy in rats. Methods : Twenty-four female Sprague-Dawley rats underwent a sham operation (the sham group) or bilateral ovariectomy (the ovariectomized group). Four and eight weeks after operation, six rats from each of the two groups were euthanized. Serum biochemical markers of bone turnover including osteocalcin and alkaline phosphatase (ALP), which are sensitive biochemical markers of bone formation, and the telopeptide fragment of type I collagen C-terminus (CTX), which is a sensitive biochemical marker of bone resorption, were analyzed. Bone histomorphometric parameters of the 4th lumbar vertebrae and femur were determined by micro-computed tomography. Results : Ovariectomized rats were found to have higher osteocalcin, ALP and CTX levels than sham controls. Additionally, 8 weeks after ovariectomy in the OVX group, serum levels of osteocalcin, ALP and CTX were significantly higher than those of 4 weeks after ovariectomy. Bone loss after ovariectomy was more extensive in the 4th lumbar spine compared to the femur. Bone loss in the 4th lumbar spine was mainly caused by trabecular thinning, but in the femur, it was mainly caused by trabecular elimination. Conclusion : The present study demonstrates different patterns of bone loss between the 4th lumbar spine and the femur in ovariectomized rats. Therefore, when considering animal models of osteoporosis, it is important that bone sites should be taken into account.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• v.37 no.1
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• pp.54-61
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• 2011

Introduction: Bisphosphonates is used widely for the treatment of the Paget's disease, multiple myeloma, bone metastases of malignant tumors with the prevention of pain and their pathological fracture. However, it was recently suggested that bisphosphonates related osteonecrosis of the jaw (BRONJ) is a side effect of bisphosphonate use. Materials and Methods: Twenty-four individuals, who were referred to the Department of Oral and Maxillofacial surgery, Dankook University Dental Hospital, were selected from those who had exposed bone associated with bisphosphonates from January, 2005 to December, 2009 according to the criteria of American Association of Oral and Maxillofacial Surgeons (AAOMS) for BRONJ. The patients group consisted of 7 males and 17 females between the age of 46 to 78 years (average 61.8 years). Each patient had panoramic imaging, computed tomography (CT), whole body bone scanning performed for a diagnosis and biopsy sampling from the necrotizing tissue. C-terminal cross-linking telopeptide of type I collagen (CTX) level of patients who had undergone surgical intervention was measured 7 days before surgery. Results: The main cause of bone exposure was post-extraction (15), chronic periodontitis (4), persistent irritation of the denture (3). Twenty people had undergone BRONJ treatment for two to eight months except for 4 people who had to maintain the bisphosphonates treatment to prevent a metastasis and bone trabecular pain with medical treatment. When the bisphosphonate treatment was suspended at least for 3 months and followed up according to the AAOMS protocols, the exposed necrotizing bones were found to be covered by soft tissue. Conclusion: Prevention therapy, interruption of bisphophonates for at least 3 months and cooperation with the physician for conservative treatment are the essential for treating BRONJ patient with high risk factors. The CTX level of BRONJ patients should be checked before undergoing surgical intervention. Surgical treatments should be delayed in the case of a CTX level <150 pg/mL.

• Korean Journal of Clinical Pharmacy
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• v.33 no.2
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• pp.128-134
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• 2023

Background: This systematic review and meta-analysis aimed to evaluate the efficacy and cardiovascular safety of romosozumab compared with placebo. Methods: Randomized controlled trials (RCTs) were searched from Medline, EMBASE, Cochrane Central, and Web of Science until July 2022. Primary outcomes included the change in bone mineral density (BMD) from baseline at month 6. The secondary outcomes were the change of bone turnover markers (N-terminal propeptide of type 1 procollagen (P1NP); C-terminal telopeptide of type 1 collagen (CTX)) from baseline at month 3, and the incidence of cardiovascular adverse events for the total follow-up period. Results: A total of 7 RCTs on 8,370patients were included. Romosozumab showed better effects in improving BMD in both lumbar spine and femoral neck at month 6 (standardized mean difference, SMD 2.20 [95% CI: 1.89-2.52], SMD 0.63 [95% CI: 0.41-0.86]). In contrast to placebo, romosozumab significantly increased PINP levels and reduced CTX levels at month 3 (SMD 0.93 [95% CI: 0.65-1.22], SMD -1.03 [95% CI: -1.23~ -0.82]. However, there was no significant difference in the composite incidence of cardiovascular adverse events and major adverse cardiovascular events (OR 1.16 [95% CI: 0.82-1.65], OR 1.08 [95% CI: 0.75-1.56]). Conclusion: This analysis showed that romosozumab significantly improved BMD compared to placebo and was beneficial for change in bone turnover markers. There is no significant difference in the incidence of cardiovascular adverse events compared to placebo.

• Journal of Nutrition and Health
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• v.44 no.1
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• pp.29-40
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• 2011

The purpose of this study was to examine the association among bone mineral density (BMD), biochemical bone markers, nutrients, and salt intake in premenopausal and postmenopausal women. We evaluated 431 subjects who visited a health promotion center of a university hospital between January 2008 and July 2009. We excluded those who were taking medications or who had an endocrine disorder affecting osteoporosis. The subjects were divided into premenopausal (n = 283) and postmenopausal (n = 143) women. We evaluated the correlation among BMD of the lumbar spine, femoral neck, and total femoral, as well as biochemical bone markers, hormone, serum profiles, general characteristics, nutrient intakes, and food intake frequencies. From a stepwise multiple regression analysis, lumbar spine BMD was positively correlated with weight (p < 0.001) and negatively correlated with osteocalcin (OC)(p < 0.001), Femoral neck BMD was positively correlated with weight (p < 0.001) and negatively correlated with C-telopeptide (CTx) and alkaline phosphatase (ALP)(p < 0.001, p < 0.05). In premenopausal women, femoral total BMD was positively correlated with BMI (p < 0.001) and negatively correlated with CTx (p < 0.001). In postmenopausal women, lumbar spine BMD was positively correlated with calcium intake (p < 0.01) and negatively correlated with sodium intake (p < 0.01). Femoral neck and femoral total BMD were both positively correlated with weight (p < 0.001), and femoral neck BMD was negatively correlated with age and ALP (p < 0.001, p < 0.05). Femoral total BMD was negatively correlated with age and OC (p < 0.001, p < 0.01). These results suggest that reducing sodium intake may play an important role delaying bone resorption and preventing a decrease in BMD.