• Journal of the Korean Association of Oral and Maxillofacial Surgeons
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• 제37권1호
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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.

• 대한핵의학회지
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• 제33권4호
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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.

• 대한임상검사과학회지
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• 제49권4호
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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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• 제32권1호
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• pp.35-43
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• 2007

본 연구는 숙지황과 가시오가피 복합추출물 (OPB)이 난소절제 흰쥐의 골밀도 및 골대사 변화에 미치는 영향을 관찰하기 위하여 수행하였다. 13주된 20마리의 Sprague-Dawley 암컷 흰쥐를 대조군과 실험군으로 나누었고, OPB의 골밀도 및 골대사 변화에 대한 효과를 관찰하기 위하여 난소절제 후 3일 후부터 OPB를 100 mg/kg씩 8주 동안 경구투여 하였다. pQCT 방식으로 골밀도, 골함유량, 골강도를 측정하였고, 혈청 중 CTx (C-telopeptide of type I collagen)의 변화를 관찰하였다. 난소절제 후 대조군의 골밀도는 $-29.8{\pm}3.0%$로 현저히 감소하였으며, 이러한 감소는 OPB의 투여에 의해 $-21.4{\pm}2.3%$로 억제되었다. 골강도의 변화에서는 anti-fracture 값과 anti-twisting 값이 대조군에 비해 OPB 처리군에서 유의성 있는 차이를 나타냈다. 또한 혈청 중 골흡수 지표인 CTx 농도는 대조군에 비해 OPB 처리군에서 낮게 나타났다. 이상의 결과로 숙지황과 가시오가피의 복합 추출물인 OPB가 난소를 절제한 흰쥐에서 골 소실을 억제하므로 임상에서 난소절제 후 또는 폐경 후 골다공증의 개선제로 이용될 수 있으리라 여겨진다.

• 동의생리병리학회지
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• 제29권4호
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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.

• 한국식품영양과학회지
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• 제39권12호
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• pp.1769-1775
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• 2010

갱년기 여성에는 여러 폐경 증후들이 나타나는데, 특히 에스트로겐의 감소로 인한 혈중 지질 조성의 변화 등으로 심혈관계 질환의 발병율이 급격히 증가하는 경향을 보이고 있으며, 또한 급격한 골 소실로 인한 골다공증의 위험성이 높아 이에 대한 예방 및 치료에 대한 연구가 활발히 이루어지고 있다. 본 연구에서는 갈조류인 곰피 추출물을 시료로하여 in vivo 실험을 통하여 갱년기 장애 시 나타날 수 있는 골 손실 개선효과를 검토하기 위하여 골 형성 지표인 alkaline phosphatase(ALP) 활성 및 osteocalcin 농도와 골 용해 지표인 C-telopeptide of collagen cross-links(CTx) 및 결합조직 중의 collagen 함량을 측정하였다. ALP는 폐경 시 에스트로겐의 결핍으로 인하여 골 전환이 증가하므로 골 형성의 지표로써 널리 사용되고 있다. 난소절제 시 에스트로겐 결핍으로 bone turnover가 증가되어 비 난소절제군에 비해 혈장 중의 ALP 활성이 증가되었으나, 난소 절제 후 곰피 추출물을 투여한 군에서는 그 활성이 유의적으로 감소하는 경향이 나타났다. 이것은 난소절제 후 에스트로겐의 분비가 감소되는데 반해 곰피 추출물이 에스트로겐 대체 작용을 함으로써 난소절제로 인한 골 손실 정도를 완화시킨 것으로 추측되어진다. 혈중 osteocalcin은 난소를 절제한 OVX-CON군의 경우 난소를 절제하지 않은 SHAM군에 비해 높은 경향을 나타내어 상대적으로 골 중의 osteocalcin 함량은 줄어들었음을 나타내었다. 곰피 추출물을 투여한 경우 OVX-CON군보다 혈중 osteocalcin 농도가 농도 의존적으로 감소하는 경향을 나타내었으나, 유의적인 차이는 나타나지 않았다. 혈중 osteocalcin은 골 대사가 균형을 유지할 때에는 골 대사 표지자로서 작용하여 폐경 후 증가하는 것으로 나타나고 골 대사가 불균형 시에는 골 형성 표지자로서 작용하여 증가 또는 감소하는 것으로 나타나 폐경 후 혈중 osteocalcin의 증감에 대한 해석이 다르게 나타날 수 있으므로 보다 많은 연구가 추가적으로 이루어져야 할 것으로 생각된다. 한편, 골 용해 지표인 혈액 중의 CTx는 난소절제군이 비 절제군에 비해 높은 수준을 보여 난소절제군에 있어 골 용해가 증가되었음을 나타내었다. 반면 곰피 추출물의 투여로 인해 CTx 함량이 감소하였으며, ES200군의 경우 SHAM군보다 높은 수준으로 나타났다. 이는 난소절제로 인해 bone turnover가 증가된 상태에서 곰피 추출물의 투여로 인해 CTx 함량이 점진적으로 감소한 결과로써 곰피의 골 흡수 저해 효과에 의한 것으로 추정된다. 결합조직 중의 collagen 함량은 난소절제로 인하여 감소하였으나, 곰피 추출물의 투여에 의해 회복되는 경향을 나타내었다. 특히 연골 및 폐 조직에서는 난소 절제에 의해 감소한 collagen 함량이 난소 절제 후 곰피 추출물을 투여한 군에서 증가하였고, 곰피 추출물 200 mg/kg bw/day 투여군인 OVXEC200군에서 유의적으로 증가하는 결과가 나타났다. 한편 골 및 피부조직에서도 난소 절제에 의해 감소한 collagen 함량이 곰피 추출물 투여에 의해 증가하였고, 정상군인 SHAM군 수준 이상으로 증가하는 결과가 나타났다. 이상의 실험 결과는 estrogen 부족 시 일어날 수 있는 골 손실에 대한 예방 소재로써 곰피의 활용 가능성을 시사하고 있으며, 이를 활용한 기능성 소재 개발도 가능할 것으로 기대된다.

• Journal of Korean Neurosurgical Society
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• 제52권1호
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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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• 제37권1호
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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.

• 한국임상약학회지
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• 제33권2호
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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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• 제44권1호
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• pp.29-40
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• 2011

본 연구는 서울 소재 대학병원에서 건강검진을 한 폐경 전 (283명)과 폐경 후 (143명) 여성 총 431명을 대상으로 골밀도, 골대사지표, 여성호르몬 및 영양소와의 관련성에 대해 알아보고자 실시하였으며 그 결과를 요약하면 다음과 같다. 연구 대상자의 평균 나이는 48.4세였고, 폐경 후 여성의 평균 폐경 나이는 50.3세였으며, 폐경 후 경과기간은 5.17년 이었다. 대상자의 평균 신장 체중 허리둘레 체질량지수 체지 방률은 각각 159.2 cm, 55.6 kg, 74.4 cm, $21.9\;kg/m^2$, 29.1% 이었으며, 폐경 후 여성의 나이, 신장, 허리둘레, BMI, 체지방률이 폐경 전 여성보다 유의하게 높았다 (p < 0.001, p < 0.001, p < 0.001, p < 0.01, p < 0.001). 평균 수축기혈압과 이완기혈압은 각각 113.5 mmHg, 69.4 mmHg었으며 폐경 후 여성에서 유의적으로 높았다 (p < 0.001, p < 0.01). 연구 대상자의 골 밀도를 살펴본 결과 폐경 후 여성이 폐경 전 여성보다 요추, 대퇴경부, 대퇴전체 골 밀도가 유의하게 감소되어 있었고 (p < 0.001) OC, CTx, ALP 지표는 폐경 전 여성보다 폐경 후 여성이 유의하게 높은 것으로 나타났다 (p < 0.001). 평균 열량 섭취량은 폐경 전 여성 1,679.4 kcal, 폐경 후 여성 1,621 kcal로 권장량의 93.2%, 90.05%이었으며 탄수화물, 단백질, 지방 섭취량의 에너지 기여 비율은 각각 58 : 18 : 24, 61 : 18 : 21 이었다, 단백질, 지방, 콜레스테롤 섭취량이 폐경 전 여성보다 폐경 후 여성에서 유의하게 높았다 (p < 0.05, p < 0.001, p < 0.001). 일반 영양소 섭취량 중에서 특히 칼륨 섭취량 (폐경 전 후 여성의 칼륨 섭취량은 권장량의 66.69%, 71.54%)이 권장량에 많이 부족한 반면 나트륨 섭취량 (폐경 전 후 여성의 나트륨 섭취량은 권장량의 226.8%, 216.5%)은 권장량보다 훨씬 높았으며 섬유소, 칼륨의 섭취량은 폐경 전 여성이 폐경 후 여성보다 유의하게 높게 나타났다 (p < 0.05, p < 0.05). 폐경 전 여성은 요추 골 밀도와 칼륨 섭취량 사이에서 음의 상관관계를, 폐경 후 여성에서는 요추 골 밀도와 칼슘 섭취량사이에서 양의 상관관계를 나타냈고 CTx와 열량, 지방, 탄수화물, 철분, 칼륨, 비타민 A, 베타카로틴, 나이아신, 엽산, 섬유소 섭취량과 음의 상관관계를 나타냈으며 OC와 나이아신 섭취량 사이에서 음의 상관관계를 나타났다. 요추골 밀도는 단백질, 지방, 칼슘과 양의 상관관계를 나타냈고 FSH 또한 지방, 나이아신 섭취량 사이에서 양의 상관관계를 나타냈다. 이상의 결과를 종합해 볼 때 폐경 전과 폐경 후 여성에서 골 표지자인 OC, CTx, ALP 지표는 골 밀도와 여성 호르몬 농도와 연관되어, 체내의 골 대사에 관련된 중요한 중재자의 하나임을 재확인하였고, 골 밀도를 예측하는 인자는 다소 차이가 있었지만 폐경 전 여성에서 체중, BMI, 폐경 후 여성에서는 칼슘 섭취량, 나이 등이 다른 인자들보다 중요도 및 예측에 있어 상대적인 영향이 더 큰 것을 알 수 있었다. 또한, 영양 섭취 상태는 폐경 전과 폐경 후 여성에서 열량 섭취는 권장량과 비교하였을 때 양호한 편이었으나 그에 반해, 칼륨, 칼슘 섭취는 부족, 나트륨은 과잉 섭취를 하고 있었다. 따라서 폐경 후 골다공증을 예방하고 골 감소를 최소화하기 위해서는 골 밀도에 긍정적 영향을 미친다고 판단된 혈청 칼슘의 충분한 섭취와 적절한 체중유지가 중요하며 반대로 부정적 영향을 미친 나트륨 섭취 감소는 골밀도의 감소를 예방하는데 중요한 역할을 할 수도 있다고 제안한다.