Effect of phylloquinone supplementation on biochemical markers of vitamin K status and bone turnover in postmenopausal women

While current intakes of phylloquinone (vitamin K1) in many populations are believed to be sufficient to maintain normal blood coagulation, these may be insufficient to cover the requirements for optimal bone metabolism. Therefore, the objective of the present study was to investigate the effect of increasing phylloquinone intakes above the usual dietary intake for 6 weeks on biochemical markers of vitamin K status and bone turnover in postmenopausal women. Thirty-one postmenopausal women completed this 3 x 6-week randomised cross-over study, in which volunteers were supplemented with 0 (placebo), 200, and 500 microg phylloquinone/d. In addition, the volunteers were given 10 microg vitamin D3/d throughout the study period. With increasing phylloquinone intake, the concentration of serum gamma-carboxylated and under-gamma-carboxylated osteocalcin was significantly increased and decreased, respectively, in a dose-dependent manner (P < 0.001). Mean serum phylloquinone concentration was significantly (P < 0.001) higher with daily supplementation with 500 microg phylloquinone/d compared with that during either of the placebo or 200 microg phylloquinone/d supplementation periods, which did not differ (P = 0.15). Serum total osteocalcin was significantly (P < 0.001) increased in response to daily supplementation with 500 (but not 200) microg phylloquinone compared with placebo. Serum bone-specific alkaline phosphatase as well as the urinary markers of bone resorption (N-telopeptide cross-links of collagen, pyridinoline and deoxypyridinoline) and urinary gamma-carboxyglutamate were unaffected by phylloquinone supplementation. In conclusion, while daily supplementation with 200 and 500 microg phylloquinone/d for 6 weeks increased vitamin K status in postmenopausal women, it had no effect on bone turnover.     

阿法骨化醇对绝经后妇女骨密度及骨转换标志物的影响

目的探讨阿法骨化醇对绝经后妇女骨密度及骨转换标志物的影响。方法选择2009年9月至2011年12月在本院更年期门诊经骨密度（BDM）测量诊断为骨量减少或骨质疏松症,年龄在55～75岁之间的67例绝经后女性为观察对象,随机分为试验组36例,对照组31例。试验组口服氨基酸螯合钙1 000mg/d,阿法骨化醇0.25μg/次,一天两次;对照组口服氨基酸螯合钙1 000mg/d。两组均连续服药48周。两组治疗前、后采用双能X线吸收法测定股骨颈、大粗隆、Ward三角区及腰椎L2-4骨密度;同时采用酶联免疫法检测血清骨碱性磷酸酶（BALP）、抗酒石酸酸性磷酸酶（TRACP）、25羟维生素D3[25-（OH）D3]结果治疗前试验组与对照组间股骨颈、大粗隆、Ward三角区及L2-4骨密度差异均无统计学意义（P〉0.05）。试验组各部位BMD治疗后均有显著增加（P〈0.05）,而对照组治疗前后仅L2-4有显著增加（P〈0.05）。治疗后试验组与对照组各部位BMD差异均有统计学意义（P〈0.05）。血清BALP、TRACP及25-（OH）D3水平治疗前试验组与对照组间比较,差异均无统计学意义（P〉0.05）,治疗后组间比较差异均有统计学意义（P〈0.05）。试验组治疗前血清BALP、TRACP及25-（OH）D3水平分别为（26.52±6.07）μg/L、（2.84±0.97）U/L、（53.91±19.04）nmol/L,治疗后分别为（21.85±5.96）μg/L、（2.37±0.88）U/L、（57.87±19.24）nmol/L,BALP、TRACP均呈显著降低,25-（OH）D3有显著升高（P〈0.05）;对照组治疗前后各骨代谢指标改变差异无统计学意义（P〉0.05）。结论阿法骨化醇可用于绝经后骨质疏松症的治疗,可增加骨密度、降低骨转换,对治疗骨质疏松症有理论依据和临床意义。     

日照对早期糖尿病肾病患者血维生素D和尿微量蛋白的影响

目的评估增加日光照射能否提高2型糖尿病早期肾病患者血25羟维生素D₃(25(OH)D₃)水平以及改善微量白蛋白尿。方法以2018年1月至2019年5月我院内分泌住院及门诊2型糖尿病患者25(OH)D₃ < 15 mg/L早期糖尿病肾病患者为研究对象,共150例。所有研究对象分为3组：日照组、1, 25(OH)₂D₃组和对照组,每组50例。比较3月后3组血25(OH)D₃水平的变化以及尿白蛋白/肌酐(ACR)的变化。结果治疗前3组间25(OH)D₃水平、ACR及糖化血红蛋白差异均无统计学意义(P>0.05)。治疗3月后日照组血清25(OH)D₃水平较对照组及1, 25(OH)₂D₃组显著升高;ACR较对照组显著降低,与1, 25(OH)₂D₃组差异无统计学意义。结论日光照射能够有效提高2型糖尿病早期肾病患者血25(OH)D₃水平以及改善微量白蛋白尿。     

Impact of supplementary high calcium milk with additional magnesium on parathyroid hormone and biochemical markers of bone turnover in postmenopausal women

The aim of this study was to investigate the impact of magnesium-enriched, high-calcium milk on serum parathyroid hormone (PTH) and biochemical markers of bone turnover in postmenopausal women. We recruited 50 healthy postmenopausal women to take part in this randomised controlled study. Half of the women consumed two serves of high-calcium skim milk enriched with magnesium (milk group) and half consumed two serves apple drink per day (apple group), each for 4 weeks. The milk provided 1200 mg calcium and an additional 106 mg magnesium. We investigated the responses of serum PTH, as well as the serum and urinary calcium, magnesium and biochemical markers of bone turnover. There was no effect of time or drink on the clinical biochemistry, serum PTH or urine markers of bone resorption (free deoxypyridinoline and N-telopeptides). Serum C-telopeptides (CTX), another marker of bone resorption, did not change with time in the apple group. However, in the milk group, serum CTX deceased significantly from 0.43 +/- 0.04 ng/mL to 0.32 +/- 0.02 at 2 weeks (p < 0.0001) and 0.28 +/- 0.02 at 4 weeks (p < 0.0001). In the milk group, urinary calcium and magnesium each increased during the night but not during the day. Overall, these data suggest that milk has an antiresorptive effect on bone, but that this is not accompanied by measurable changes in serum PTH.     

绝经后女性骨标志物与骨质疏松症的相关性研究

目的:探讨绝经后女性骨代谢标志物与骨质疏松之间的关系.方法:双能X线骨密度仪测定患者股骨的骨密度(BMD),计算其BMD与正常年轻人的骨峰值比值(以t值表示),并按照骨密度值将120例患者分为63例非骨质疏松组和57例骨质疏松组.选用瑞士罗氏诊断公司COBAS6000全自动电化学发光免疫分析仪,测定骨代谢标志物总骨I型前胶原N端肽(PINP)、血清骨钙素(N-MID)和β胶原特殊序列(β-crosslaps)的水平.结果:PINP、N-MID和β-crosslaps水平骨质疏松组均高于非骨质疏松组;两组患者的BMD、PINP、N-MID和β-crosslaps水平之间均具有统计学差异(P＜0.05).结论:绝经后女性的骨代谢标志物与骨质疏松的发生关系密切,血清中P1NP、N-MID、B-Crosslaps可作为诊断绝经后妇女骨质疏松症的理想生化指标.     

植物异黄酮对更年期妇女骨密度和骨代谢血清生化指标的影响

目的:研究植物异黄酮(葛根异黄酮和大豆异黄酮)对更年期妇女骨密度和骨代谢生化指标的影响。方法:将96例身体健康的更年期女性随机分为5组,安慰剂组、钙儿奇-D组、葛根异黄酮组、大豆异黄酮组和钙儿奇-D+大豆异黄酮组。服药3个月后,比较各处理组用药前后血清钙(Ca)、血清碱性磷酸酶(ALP)、骨钙素(BGP)和骨密度(BMD)等指标的变化情况。结果:服药后血清Ca有升高的趋势,其中钙儿奇-D和葛根异黄酮组的血清Ca比服药前显著升高(P<0.05);服药后血清ALP葛根异黄酮和大豆异黄酮组有上升趋势;服药后血清BGP(除了安慰剂组)各组有增加的趋势,其中钙儿奇-D组的血清BGP明显增加。结论:植物异黄酮可以使更年期妇女血清Ca升高,使血清ALP和BGP处于较活跃的水平。     

Biochemical markers of bone remodeling: recent data of their applications in managing postmenopausal osteoporosis

The recent development of new biochemical markers has considerably improved the non invasive exploration of bone turnover. Currently, the most sensitive markers to access bone formation are osteocalcin, bone alkaline phosphatase and N-terminal propeptide of type I procollagen. Blood or urinary immunoassays of pyridinoline, deoxy-pyridinoline and terminal telopeptides type I of collagen are currently the best indices to evaluate the bone resorption. The principal application fields of biochemical markers in postmenopausal osteoporosis, in combination with the measurement of the bone mineral mass, are primarily the monitoring of anti-resorptive therapy response and prediction of bone loss and risk of fractures. In fact, treatment with anti-resorptive drugs is followed by rapid decrease of bone markers levels (3 months for the markers of resorption and 6 months for those of osteo-formation ), whereas the bone mineral density measurements requires at least two years to change significantly.     

藏族女性青少年血清钙磷及骨代谢生化标志物水平检测结果分析

目的了解藏族女性青少年血清钙、磷及骨代谢生化标志物水平,为藏族青少年生长发育研究提供相应资料。方法采用分层整群抽样方法,从拉萨市和那曲地区中小学生中抽取12～18岁藏族健康女性青少年336名,检测血清钙(Ca)、磷(P)、碱性磷酸酶(ALP)、骨性碱性磷酸酶(BAP)、骨钙素(BGP)水平。结果藏族女性青少年血清钙与年龄不相关(P>0.05),但拉萨地区明显高于那曲地区(P<0.05)。血清P,ALP,BAP,BGP水平与年龄均呈负相关(P值均<0.01),且各指标在多数年龄组表现为拉萨地区明显高于那曲地区(P值均<0.05)。除血清钙外,其他指标之间呈显著正相关(P值均<0.01)。结论藏族女性青少年血清钙、磷及骨代谢生化标志物水平随着年龄的增加、居住地海拔高度的增加,各指标水平逐渐降低。     

骨转化标志物在早产儿代谢性骨病诊疗中的意义

目的探讨骨转化标志物(BTM)[包括Ⅰ型胶原羧基端肽B特殊序列(CTX)、总Ⅰ型胶原氨基端前肽(P1NP)和N端骨钙素(OC)]在早产儿代谢性骨病(MBDP)诊疗中的意义,为临床诊治提供参考依据。方法收集所有于2016年3月-2017年3月在河北医科大学第二医院住院治疗的符合MBDP诊断标准的患儿作为研究对象,定期监测血磷(P),血钙(Ca),碱性磷酸酶ALP的数值,并均在治疗前后留取静脉血标本检测血清25羟基维生素D_3[25 (OH) VD_3]及BTM (CTX、P1NP、OC)。结果治疗前后两组间25 (OH) VD3及血清Ca差异无统计学意义(均P0. 05),治疗前后血清BTM (CTX、P1NP、OC)水平,差异有统计学意义(均P0. 05)。结论早期检测血清BTM (CTX、P1NP、OC)水平能够帮助诊断MBDP病情,监测BTM (CTX、P1NP、OC)可以帮助判断临床疗效。     

Follow-up study on effects of height velocity and puberty onset on biochemical markers of bone turnover

In order to clarify the factors which affect bone metabolism at a young age, we investigated the relationships among the change of biochemical markers of bone turnover, the height velocity (HV) and puberty onset in healthy Japanese children. One hundred and twelve children (61 boys and 51 girls) were recruited at the fourth grade level in the elementary school (9 years old) and followed for 6 years. Serum bone specific alkaline phosphatase (B-ALP), serum tartrate-resistant acid phosphatase (TR-ACP), urine hydroxyproline (Hyp) and urine calcium (Ca) were measured as the biochemical markers of bone turnover. Bone mineral density of calcaneus was also measured by ultrasound method at the first grade (12 years old) and the third grade (14 years old) of junior high school. Heights and weights of all subjects were measured every April and the HV were calculated between each year. Puberty onset was defined as the time when pubic hair appeared in boys and as the time when menarche started in girls by self-administered questionnaire. All the biochemical markers of bone metabolism except for urine Ca had a significant positive relationship with HV. The values of the markers were highest of the time when the HV was maximum. In girls, the values of the biochemical markers remained high before menarche and then decreased significantly within three years after menarche, suggesting that bone turnover changed rapidly from high turnover type to low turnover type after menarche. On the other hand, in boys, high turnover type remained for a few years after puberty onset. Bone mineral density of calcaneus by ultrasound method increased significantly in boys between the two years in junior high school, but the increase was unclear except for broadband ultrasound attenuation (BUA) in girls in the same period.     

Effect of supplementation with fortified olive oil on biochemical markers of bone turnover in healthy women

Osteocalcin (OC) is a bone Gla protein synthesized by osteoblasts which have a high affinity for calcium. To adequately carboxylate OC to form carboxylated OC (cOC), the osteoblasts require sufficient vitamin K. If vitamin K is deficient, under-carboxylated OC (ucOC) is produced. The ratio between ucOC and cOC (UCR) as well as the levels of circulating ucOC are used as indicators of the vitamin K status of bone. The aim of the present study was to compare the vitamin K status of bone by measuring the plasma levels of ucOC and UCR in healthy adult women before and after 3 weeks of oral supplementation with 20 ml/day Petrini Plus extra virgin olive oil. Petrini Plus is an organic olive oil enriched with vitamins D₃, K₁ and B₆. Enrolled in the study were 15 healthy female volunteers (aged 25–40 years). Plasma levels of ucOC and cOC were measured by ELISA. ucOC was found to be reduced and UCR was reduced by 44% after Petrini Plus olive oil supplementation. Petrini Plus extra virgin olive oil might therefore be useful for bone protection as it was able to counteract bone loss in healthy volunteers.     

Use of bone turnover markers in clinical osteoporosis assessment in women: current issues and future options

Monitoring bone turnover of the adult and aging skeleton is essential for optimal treatment of bone metabolic diseases, such as postmenopausal osteoporosis. Diagnosis of osteoporosis is based solely on dual-emission x-ray absorptiometry-based measurements of bone mineral density. However, within the last 20 years, biochemical markers of bone turnover have been implemented to a larger degree, and especially within the field of drug development. Numerous clinical studies have underscored that the markers have promise in terms of predicting patients at high risk of losing bone, future fracture events and importantly also the fracture efficacy of drugs in development. Furthermore, while classical methods often require years to monitor the changes, the bone turnover markers do so within a shorter time span. The aims of this article are to provide an update on the different biochemical markers of bone turnover, and to give an overview of their applications in epidemiological and clinical research especially in women. The main emphasis will be on their utility in clinical trials testing the efficacy of drugs for the treatment of osteoporosis, and their ability to supplement bone mass measurements. Finally, recent evidence suggests that biochemical markers may provide information on bone age that may indirectly relate to bone quality, and this is discussed together with future possibilities for measuring bone quality using bone turnover markers. In summary, a more targeted use of biomarkers could assist in the identification of high-risk patients, the process of drug discovery and monitoring of the efficacy of osteoporosis treatment in clinical settings.     

SPA method; monitoring of bone mass during the treatment of osteoporosis

Accuracy and precision are indispensable to evaluate bone mass by non-invasive bone mineral measurement. In this paper, the methodological problems, such as measuring site and positioning errors of bone are described. Furthermore, the methods of monitoring of bone mass during ADFR treatment and double blind study for osteoporosis are also discussed.     

Effects of oligofructose-enriched inulin on intestinal absorption of calcium and magnesium and bone turnover markers in postmenopausal women

Deficiency of oestrogen at menopause decreases intestinal Ca absorption, contributing to a negative Ca balance and bone loss. Mg deficiency has also been associated with bone loss. The purpose of the present investigation was to test the hypothesis that treatment with a spray-dried mixture of chicory oligofructose and long-chain inulin (Synergy1; SYN1) would increase the absorption of both Ca and Mg and alter markers of bone turnover. Fifteen postmenopausal women (72.2 (SD 6.4) years) were treated with SYN1 or placebo for 6 weeks using a double-blind, placebo-controlled, cross-over design. Fractional Ca and Mg absorption were measured using dual-tracer stable isotopes before and after treatment. Bone turnover markers were measured at baseline, 3 and 6 weeks. Fractional absorption of Ca and Mg increased following SYN1 compared with placebo (P < 0.05). Bone resorption (by urinary deoxypyridinoline cross-links) was greater than baseline at 6 weeks of active treatment (P < 0.05). Bone formation (by serum osteocalcin) showed an upward trend at 3 weeks and an increase following 6 weeks of SYN1 (P < 0.05). Closer examination revealed a variation in response, with two-thirds of the subjects showing increased absorption with SYN1. Post hoc analyses demonstrated that positive responders had significantly lower lumbar spine bone mineral density than non-responders (dual X-ray absorptiometry 0.887 +/- 0.102 v. 1.104 +/- 0.121 g/cm2; P < 0.01), and changes in bone turnover markers occurred only in responders. These results suggest that 6 weeks of SYN1 can improve mineral absorption and impact markers of bone turnover in postmenopausal women. Further research is needed to determine why a greater response was found in women with lower initial spine bone mineral density.     

Inhibition of bone turnover by milk intake in postmenopausal women

Increased postmenopausal bone turnover leads to bone loss and fragility fracture risk. In the absence of osteoporosis, risk preventive measures, particularly those modifying nutritional lifestyle, are appropriate. We tested the hypothesis that milk supplementation affects bone turnover related to biochemical markers in a direction that, in the long term, may be expected to reduce postmenopausal bone loss. Thirty healthy postmenopausal women aged 59.3 (SD 3.3) years were enrolled in a prospective crossover trial of 16 weeks. After a 4-week period of adaptation with diet providing 600 mg calcium plus 300 mg ingested as 250 ml semi-skimmed milk, participants were maintained during 6 weeks under the same 600 mg calcium diet and randomized to receive either 500 ml semi-skimmed milk, thus providing a total of 1200 mg calcium, or no milk supplement. In the next 6 weeks they were switched to the alternative regimen. At the end of the each period, i.e. after 4, 10 and 16 weeks, blood and urinary samples were collected. The changes in blood variables between the periods of 6 weeks without and with milk supplementation were: for parathyroid hormone, -3.2 pg/ml (P=0.0054); for crosslinked telopeptide of type I collagen, -624 pg/ml (P<0.0001); for propeptide of type I procollagen, -5.5 ng/ml (P=0.0092); for osteocalcin, -2.8 ng/ml (P=0.0014). In conclusion, a 6-week period of milk supplementation induced a decrease in several biochemical variables compatible with diminished bone turnover mediated by reduction in parathyroid hormone secretion. This nutritional approach to postmenopausal alteration in bone metabolism may be a valuable measure in the primary prevention of osteoporosis.     

Menatetrenone (vitamin K2) and bone quality in the treatment of postmenopausal osteoporosis

Menatetrenone (vitamin K2) reduces the incidence of vertebral fractures but has only modest effects on bone mineral density (BMD) in postmenopausal women with osteoporosis. Combined treatment with bisphosphonates and menatetrenone may be more effective than treatment with bisphosphonates alone in preventing vertebral fractures, despite the lack of an additive effect of menatetrenone on the BMD increase by bisphosphonates. Menatetrenone improves bone architecture in ovariectomized rats, and the mineral/ matrix ratio of the bone in terms of matrix volume and bone strength (without increasing bone mass) in rats with magnesium deficiency. Thus, available evidence supports an effect of menatetrenone on bone quality during osteoporosis treatment.