60万单位维生素D3单次口服治疗维生素D缺乏

目的寻找治疗维生素D缺乏有效且依从性良好的治疗方案,为寻找治疗维生素D缺乏症的理想治疗方案提供依据。方法采用前瞻性干预方法,给予62例维生素D缺乏症患者单次口服60万单位负荷剂量维生素D3,观察用药第4、30、60和90天血钙、磷、尿钙和血清25OHD和甲状旁腺素（PTH）水平。结果患者血清25OHD水平基线值为（8.9±2.9）ng/m L,用药第4天为（58.9±11.1）ng/m L,第90天为（30.3±9.6）ng/m L,差异均有统计学意义（均P〈0.001）;PTH基线值水平为（66.6±30.2）pg/m L,用药第4天降至（32.7±21.6）pg/m L,第90天为（38.8±18.3）pg/m L,差异均有统计学意义（均P〈0.001）;用药后不同时点血钙与和血磷均较基线水平升高,但在正常值范围内;尿钙水平在用药第4天显著升高,但高尿钙患者未见明显增多。所有受试者均未出现泌尿系结石。结论单次口服60万单位负荷剂量维生素D3,可快速纠正维生素D缺乏,维持血清25OHD理想水平并持续3个月,该治疗方案可有效逆转继发性甲状旁腺功能亢进,且未增加发生高钙血症和高尿钙的危险。     

口服维生素D_3对维生素D不足绝经后妇女血清25-羟维生素D、骨密度和下肢肌力的影响

目的给予不同年龄、维生素D不足的绝经后妇女口服1 325 U维生素D3,观察其对血清总25-羟维生素D(25OHD)水平、骨密度(BMD)和下肢肌力(行走八步计时)的影响。方法上海市某社区67名绝经后妇女纳入本研究,按年龄将受试者分成2组:70岁组[n=35,(63.6±5.1)岁],≥70岁组[n=32,(75.2±3.4)岁]。受试者口服1 200 U/d维生素D3制剂加1片钙尔奇D(每片含维生素D3125 U和钙600 mg),为期1年。在0、3、6、9和12个月检测血清25OHD,干预前和研究结束时测定BMD及下肢肌力。结果干预1年后,2组平均血清25OHD水平均较基线值显著升高:70岁组从(17.8±6.7)ng/mL升至(33.8±5.8)ng/mL(P0.001);≥70岁组从(18.3±6.7)ng/mL升至(34.1±5.7)ng/mL(P0.001),但2组间增幅差异无统计学意义。有25%受试者(70岁组9名,≥70岁组6名)平均血清25OHD仍低于30 ng/mL。70岁组血清甲状旁腺素(PTH)明显降低,从(46.0±14.7)pg/mL降至(37.9±10.0)pg/mL(P0.01),各部位BMD较基线值无统计学差异。≥70岁组腰椎BMD提高1.37%(P=0.005),全髋部位BMD提高1.28%(P=0.028)。2组干预后下肢肌力均较干预前改善(P0.05)。2组均未出现高钙血症及过高的血清25OHD浓度。结论 2组维生素D不足的绝经后妇女每日口服1 325 U维生素D3可将血清25OHD升至理想水平,可改善下肢肌力,≥70岁组腰椎及全髋部BMD均有上升。     

老年骨折患者25-羟基维生素D和甲状旁腺素与骨质疏松程度的相关性

目的了解老年骨折患者25-羟基维生素D[25OHD]和甲状旁腺激素的状况,分析其与骨质疏松程度的关系,为防治骨质疏松性骨折提供依据。方法 2011年8月至2012年6月在北京友谊医院治疗的老年骨折患者146例(男性36例,女性110例)纳入本研究,患者年龄60～90岁,平均年龄(72.4±9.2)岁。采用酶联免疫分析法测定血清25OHD和PTH水平,根据血清25OHD水平将患者分为维生素D严重缺乏组(10ng/mL)、缺乏组(≥l020ng/mL)、不足组(≥2030ng/mL)和充足组(≥30ng/mL);根据PTH水平将患者分为不足组(8.3pg/mL)、正常组(≥8.3≤68pg/mL)、增高组(68pg/mL)。同时应用双能X线骨密度仪测定腰1-4及股骨近端(全髋、股骨颈)的骨密度。腰1-4、全髋、股骨颈任意一个部位骨密度T值-1为正常组,骨密度T值为-1～-2.5为骨量减少组,≤-2.5为骨质疏松组。对男女患者间的年龄、体重指数、25OHD、PTH及以及骨密度的差异进行描述性统计分析和独立样本t检验。对不同组间25OHD、PTH水平及骨密度差异进行单因素方差分析;对25OHD及PTH与腰1-4、全髋、股骨颈骨密度进行相关性分析。结果 146名老年骨折患者中维生素D严重缺乏者41例(28.1%),缺乏者83例(56.8%),不足者18例(12.3%),充足者仅4例(2.7%)。PTH水平增高组44例(30.1%),正常组102例(69.9%),不足组0例(0%);骨密度正常组16例(11.0%),骨量减少组48例(32.8%),骨质疏松组82例(56.2%)。女性患者维生素D严重缺乏组股骨颈的骨密度显著低于维生素D缺乏组(P0.05)。不同骨密度组间的25OHD差异无统计学意义(P0.05);PTH差异有统计学意义(P0.05)。血清25OHD与PTH无明显相关性。老年骨折患者25OHD与腰1-4骨密度呈正相关,相关系数为0.394(P0.05)。女性患者25OHD与腰1-4和股骨颈呈正相关,相关系数分别为0.392(P0.05)和0.432(P0.05)。男性患者25OHD和PTH与腰1-4、全髋和股骨颈骨密度均无明显的相关性。结论老年骨折人群中存在严重维生素D缺乏状况,女性患者尤为严重;同时存在PTH增高现象。25OHD与骨密度间存在相关性。     

钙补充、年龄及性别对上海社区老年人血清25羟维生素D与甲状旁腺素关系的影响

目的探讨钙补充、年龄及性别对上海社区老年人血清25羟维生素D(25-hydroxyvitamin D,25OHD)与甲状旁腺素(parathyroid hormone,PTH)的影响。方法采用自行设计的调查问卷对上海社区自愿参加血清25OHD、PTH检测的4 402位老年人进行生活方式调查,并采用罗氏公司的Cobas诊断体系对其血清25OHD、PTH进行检测。结果本研究人群血清25OHD及PTH的均值分别为(55.8±21.43)nmol/L[(22.32±8.57)ng/m L]和(32.99±18.60)ng/L。血清25OHD与PTH呈负相关;随着年龄增加,血清PTH水平有上升趋势,但差异无统计学意义(P=0.135);老年女性较老年男性血清PTH水平高,差异有统计学意义(33.67 ng/L vs.32.13 ng/L,P0.05);补充钙剂者血清PTH水平明显低于不补充钙剂者(31.19 ng/L vs.34.71 ng/L,P0.05),服用乳制品者血清PTH水平明显低于不服用乳制品者,且差异有统计学意义(P0.05),与服用乳制品的量无明显相关性。年龄、钙补充参与调控血清25OHD与PTH的关系,而性别不参与调控两者间的关系。结论上海社区老年人血清25OHD与PTH呈负相关,年龄、钙补充参与调控血清25OHD与PTH的关系,未发现性别对两者关系有调控作用。可有效抑制血清PTH的血清25OHD定值(cut-off值)50 nmol/L(20 ng/m L)。     

中国北方健康人群血清25羟维生素D_3和25羟维生素D_2水平

目的分析中国北方人群血清25羟维生素D3(25OHD3)和25羟维生素D2(25OHD2)水平。方法采用同位素稀释超高压液相色谱-串联质谱法(ID-UPLC/MS/MS)对2013年在北京、大连、乌鲁木齐3个城市征集的1 540名表观健康志愿者[男性744人,女性796人,平均年龄(42.0±14.0岁)]进行血清25OHD3和25OHD2测定。同时分别应用偶氮Ⅲ砷法、磷钼酸紫外比色法、酶化学发光法检测志愿者血清钙(Ca)、磷(P)及全段甲状旁腺素(iPTH)水平。使用SPSS17.0进行统计学分析,P0.05表示差异有统计学意义。结果受试人群血清总25OHD平均值为(18.80±6.65)ng/mL。3个城市受试人群血清总25OHD含量差异有统计学意义(F=97.57,P0.01),大连市受试者血清总25OHD水平[(21.72±6.47)ng/mL]显著高于乌鲁木齐市和北京市受试者[(18.44±6.64)ng/mL、(16.34±6.12)ng/mL](均P0.01);男性血清25OHD水平[(20.57±6.63)ng/mL]显著高于女性[(17.14±6.24)ng/mL],(P0.01);30~39岁年龄组25OHD含量显著低于其他年龄组(均P0.05)。3省受试人群血清总25OHD缺乏率为60.06%,大连市受试者血清总25OHD缺乏率(41.51%)显著低于乌鲁木齐市(64.87%)和北京市(73.76%),(均P0.01)。3个城市57例受试者(3.70%)血清25OHD2检测均值为(6.25±3.76)ng/mL。在57例检测25OHD2受试者中,25OHD2显著提高了血清总25OHD水平,使该人群血清25OHD缺乏率降低43.85%。血清25OHD水平与iPTH相关系数为-0.283(P0.01)。结论 3个城市受试人群血清25OHD含量存在明显的地域、性别和年龄差异。健康人群中血清25OHD主要为25OHD3。北方地区人群血清25OHD水平普遍较低。     

中国北方健康人群血清25羟维生素D_3和25羟维生素D_2水平

目的分析中国北方人群血清25羟维生素D3(25OHD3)和25羟维生素D2(25OHD2)水平。方法采用同位素稀释超高压液相色谱-串联质谱法(ID-UPLC/MS/MS)对2013年在北京、大连、乌鲁木齐3个城市征集的1 540名表观健康志愿者[男性744人,女性796人,平均年龄(42.0±14.0岁)]进行血清25OHD3和25OHD2测定。同时分别应用偶氮Ⅲ砷法、磷钼酸紫外比色法、酶化学发光法检测志愿者血清钙(Ca)、磷(P)及全段甲状旁腺素(iPTH)水平。使用SPSS17.0进行统计学分析,P<0.05表示差异有统计学意义。结果受试人群血清总25OHD平均值为(18.80±6.65)ng/mL。3个城市受试人群血清总25OHD含量差异有统计学意义(F=97.57,P<0.01),大连市受试者血清总25OHD水平[(21.72±6.47)ng/mL]显著高于乌鲁木齐市和北京市受试者[(18.44±6.64)ng/mL、(16.34±6.12)ng/mL](均P<0.01);男性血清25OHD水平[(20.57±6.63)ng/mL]显著高于女性[(17.14±6.24)ng/mL],(P<0.01);30~39岁年龄组25OHD含量显著低于其他年龄组(均P<0.05)。3省受试人群血清总25OHD缺乏率为60.06%,大连市受试者血清总25OHD缺乏率(41.51%)显著低于乌鲁木齐市(64.87%)和北京市(73.76%),(均P<0.01)。3个城市57例受试者(3.70%)血清25OHD2检测均值为(6.25±3.76)ng/mL。在57例检测25OHD2受试者中,25OHD2显著提高了血清总25OHD水平,使该人群血清25OHD缺乏率降低43.85%。血清25OHD水平与iPTH相关系数为-0.283(P<0.01)。结论 3个城市受试人群血清25OHD含量存在明显的地域、性别和年龄差异。健康人群中血清25OHD主要为25OHD3。北方地区人群血清25OHD水平普遍较低。     

南京市城区部分居民血清维生素D水平评估

目的了解南京市居民血清维生素D水平,为骨质疏松防治提供依据。方法 2011年6月至11月招募南京市城区≥40岁居民2 786名,其中40~49岁490人(17.6%),50~59岁1 084人(38.9%),60~69岁912人(32.7%),70~78岁300人(10.8%)。采集受试者清晨空腹静脉血,应用酶联免疫法测定血清25-羟维生素D[25OHD]浓度。以血清25OHD≥50 nmol/L和≥75 nmol/L分别定义为维生素D正常及良好,以血清25OHD25 nmol/L定义为维生素D缺乏,评估南京城区居民血清维生素D水平。采用超声骨密度仪(QUS),用超声振幅衰减(BUA)值及超声声速(SOS)值推算骨密度(BMD)。结果南京城区部分居民血清25OHD平均水平为(44.71±14.68)nmol/L,维生素D正常及良好者分别占31.7%和2.5%。40~49岁组血清25OHD平均为(43.48±14.23)nmol/L,50~59岁组为(45.33±14.49)nmol/L,60~69岁组为(44.41±14.66)nmol/L,70~78岁组为(45.36±15.97)nmol/L,4组间比较差异无统计学意义。血清25OHD缺乏者男性占4.3%(45例),女性占6.7%(117例),差异有统计学意义(P0.05);受试者BMD水平平均为(0.491±0.112)g/cm2,BMD和血清25OHD浓度呈正相关,差异有统计学意义(r=0.038,P=0.047)。结论南京市部分居民普遍存在维生素D缺乏,女性维生素D水平低于男性。     

北京市部分老年男性25羟维生素D水平及其与骨代谢的关系

目的探讨北京市部分老年男性维生素D水平及其与骨代谢指标的关系。方法采用化学发光法测定血清25羟化维生素D3（25OHD₃）、甲状旁腺素（PTH）、β-Ⅰ型胶原C端肽（β-CTX）、骨钙素（osteocalcin）、1型原胶原分子N一端前肽（PINP）水平。根据血清25OHD3水平分为维生素D严重缺乏（<10ng/mL）、缺乏（≥10<20ng/mL）、不足（≥20<30ng/mL）和充足（≥30ng/mL）。结果 2010年5月至6月入选564名老年受试者,平均年龄（73.7±8.5）岁。≥60～70岁为老年1组、≥70～80岁为老年2组,≥8O岁为老年3组。老年男性总体25OHD3水平为（14.57±5.95）ng/mL,均为维生素D缺乏。各组受试者血清PTH平均水平为（34.85±12.23）ng/mL,骨钙素平均水平为（13.49±4.81）ng/mL,β-CTX平均水平为（0.30±0.15）ng/mL。K-S检验结果表明,上述骨代谢指标均呈正态分布。各年龄组25OHD3、PTH、骨钙素、PINP、β-CTX水平差异均无统计学意义（P>0.05）。老年男性维生素D严重缺乏、缺乏、不足、充足的比例分别为23.4%（132/564）,56.6%（319/564）,18.4%（104/564）,1.6%（9/564）。不同年龄组间低维生素D状态的比例差异无统计学意义（F=15.57,P=0.076）。相关分析结果表明,25OHD3水平与PTH呈负相关（r=-0.240,P=0.000）;与骨钙素呈负相关（r=-0.080,P=0.034）;与β-CTX无显著相关（r=-0.044,P=0.252）。LOESS回归分析显示,25OHD3水平为9.8～15.6ng/mL时,血清PTH出现平台期。25OHD3与骨钙素尽管有较弱的负相关,但未出现明显平台期。结论北京市部分老年男性人群存在严重维生素D缺乏和不足状况。老年男性的维生索D状态与PTH、骨形成指标骨钙素水平有一定关联,但与I型胶原蛋白的形成与吸收可能无直接关系,有必要进一步探讨维生素D与骨转换的关系。     

钙补充、年龄及性别对上海社区老年人血清25羟维生素D与甲状旁腺素关系的影响

目的 探讨钙补充、年龄及性别对上海社区老年人血清25羟维生素D（25-hydroxyvitamin D，25OHD）与甲状旁腺素（parathyroid hormone，PTH）的影响。方法 采用自行设计的调查问卷对上海社区自愿参加血清25OHD、PTH检测的4 402位老年人进行生活方式调查，并采用罗氏公司的Cobas诊断体系对其血清25OHD、PTH进行检测。结果 本研究人群血清25OHD及PTH的均值分别为（55.8±21.43）nmol/L[（22.32±8.57）ng/mL]和（32.99±18.60）ng/L。血清25OHD与PTH呈负相关；随着年龄增加，血清PTH水平有上升趋势，但差异无统计学意义（P=0.135）；老年女性较老年男性血清PTH水平高，差异有统计学意义（33.67 ng/L vs.32.13 ng/L，P<0.05）；补充钙剂者血清PTH水平明显低于不补充钙剂者（31.19 ng/L vs.34.71 ng/L，P<0.05），服用乳制品者血清PTH水平明显低于不服用乳制品者，且差异有统计学意义（P<0.05），与服用乳制品的量无明显相关性。年龄、钙补充参与调控血清25OHD与PTH的关系，而性别不参与调控两者间的关系。结论 上海社区老年人血清25OHD与PTH呈负相关，年龄、钙补充参与调控血清25OHD与PTH的关系，未发现性别对两者关系有调控作用。可有效抑制血清PTH的血清25OHD定值（cut-off值）50 nmol/L（20 ng/mL）。     

25羟维生素D及甲状旁腺激素与高血压的关系

目的目前血清25羟维生素D[25-(OH)D]、甲状旁腺激素(PTH)与高血压是否直接相关尚无定论,文章旨在探讨三者之间的关系。方法选取2014年3月至2015年7月就诊于盛京医院心血管内科的患者368例,其中男性202例。按照是否患高血压分为高血压组(198例)和非高血压组(170例)。收集研究对象一般资料并检测PTH以及25-(OH)D水平。分析25-(OH)D、PTH与高血压之间的关系。结果高血压组患者25-(OH)D水平低于非高血压组(37.67±18.23 nmol/L比42.45±20.41 nmol/L,P=0.018)。两组间PTH水平差异无统计学意义(50.08±28.80 ng/L比50.45±22.37 ng/L,P=0.892)。Pearson相关性分析显示,25-(OH)D与PTH呈负相关(r=-0.225,P0.05)。二元Logistic回归分析显示维生素D缺乏或不足是高血压的独立危险因素(OR=1.847,95%CI 1.138~2.996,P=0.013),PTH升高与高血压发病风险不存在相关。结论维生素D不足或缺乏与高血压相关,是高血压的危险因素。     

The role of the vitamin D receptor in regulating vitamin D metabolism: a study of vitamin D-dependent rickets, type II

In vitro studies and animal experiments suggest that the production of 1,25-dihydroxyvitamin D [1,25-(OH)(2)D] and 24,25-(OH)(2)D is reciprocally controlled by 1,25-(OH)(2)D. To investigate the role of the vitamin D receptor (VDR) in controlling vitamin D metabolism in humans, we studied 10 patients with vitamin D-dependent rickets type II due to a defective VDR. After a period of high dose calcium therapy, 7 of the patients had normal serum calcium, phosphorus, alkaline phosphatase, and plasma PTH levels (PTH-N), and 3 showed increased serum alkaline phosphatase and plasma PTH (PTH-H). Serum calcium, phosphorus, alkaline phosphatase, PTH, vitamin D metabolites, urinary calcium/creatinine, and renal phosphate threshold concentration were compared with unaffected family members that comprised the control group. Vitamin D metabolites were measured before and after an oral load of 50,000 U/m(2) cholecalciferol. Compared with the control group, 1,25-(OH)(2)D levels were significantly higher and 24,25-(OH)(2)D levels were lower in the PTH-N group and even more so in the PTH-H group. 1alpha-Hydroxylase (1-OHase) and 24-OHase activities were estimated by the product/substrate ratio. In the PTH-N group, 1-OHase activity was higher and 24-OHase activity was lower than in controls. In the PTH-H group, 1-OHase activity was even higher, probably due to an additive effect of PTH. Thus, 1,25-(OH)(2)D-liganded VDR is a major control mechanism for vitamin D metabolism, and PTH exerts an additive effect. Assessment of the influence of 1,25-(OH)(2)D shows reciprocal control of enzyme activity in man, suppressing 1-OHase and stimulating 24-OHase activity.     

Osteomalacia as a result of vitamin D deficiency

Osteomalacia is an end-stage bone disease of chronic and severe vitamin D or phosphate depletion of any cause. Its importance has increased because of the rising incidence of vitamin D deficiency. Yet, not all cases of osteomalacia are cured by vitamin D replacement, and furthermore, not all individuals with vitamin D deficiency develop osteomalacia. Although in the past osteomalacia was commonly caused by malabsorption, nutritional deficiency now is more common. In addition, recent literature suggests that nutritional vitamin D deficiency osteomalacia follows various bariatric surgeries for morbid obesity. Bone pain, tenderness, muscle weakness, and difficulty walking are all common clinical manifestations of osteomalacia. Diagnostic work-up involves biochemical assessment of vitamin D status and may also include a transiliac bone biopsy. Treatment is based on aggressive vitamin D repletion in most cases with follow-up biopsies if patients are started on antiresorptive or anabolic agents.     

Pulmonary accumulation of drugs in vitamin a deficiency

The effect of vitamin A deficiency on the uptake of several drug substrates in rat lung slices was determined. Vitamin A deficiency resulted in significant increases in the pulmonary accumulation of imipramine, chlorpromazine, 5-hydroxytryptamine and norepinephrine. The enhanced uptake of 5-hydroxytryptamine by deficient slices was probably due to a decrease in pulmonary monoamine oxidase (MAO) activity, since accumulation of this amine was similar in control and deficient slices that had been preincubated in pargyline, an inhibitor of MAO. In contrast, pulmonary uptake of methadone and paraquat was not affected in vitamin A deficiency. These results suggest that the enhanced susceptibility of the respiratory tract of vitamin A deficient animals to toxic chemicals may be due in part to an increase in the accumulation of the chemicals by the lung.     

Hepatic hydrothorax associated with vitamin a toxicity

We report the first case of an adult presenting with respiratory symptoms caused by hepatic hydrothorax secondary to vitamin A intoxication. The patient was a 52-year-old woman who presented to the hospital with progressive dyspnea. Evaluation demonstrated mild elevation of her liver function tests, ascites, and a right pleural effusion. The patient consumed a variety of vitamins, including vitamin A. Her estimated vitamin A intake was at least 162,300,000 international units (IU) during 18 years. She dramatically escalated her dose the year before admission for a total acute dose of 98,550,000 IU, with a daily intake of 270,000 IU. The recommended daily allowance is 4,000 IU. A transjugular liver biopsy revealed histopathologic changes consistent with vitamin A toxicity: hypertrophy and hyperplasia of hepatic stellate cells, focal pericellular fibrosis, mild perivenular fibrosis, and minimal, predominantly microvesicular steatosis. Despite the absence of cirrhosis, pressure readings demonstrated portal hypertension. During her hospitalization, the patient's symptoms and biochemical profile improved. As the large and generally unregulated United States dietary supplement industry continues to grow, it is increasingly likely that individuals will present with the signs and symptoms of vitamin excess rather than vitamin deficiency. Physicians need to remain alert to the varied presentations and toxic manifestations of excessive vitamin use.     

Decyanation of vitamin B12 by a trafficking chaperone

The mystery of how the cyanide group in vitamin B₁₂ or cyanocobalamin, discovered 60 years ago, is removed, has been solved by the demonstration that the trafficking chaperone, MMACHC, catalyzes a reductive decyanation reaction. Electrons transferred from NADPH via cytosolic flavoprotein oxidoreductases are used to cleave the cobalt–carbon bond with reductive elimination of the cyanide ligand. The product, cob(II)alamin, is a known substrate for assimilation into the active cofactor forms, methylcobalamin and 5′-deoxyadenosylcobalamin, and is bound in the “base-off” state that is needed by the two B₁₂-dependent target enzymes, methionine synthase and methylmalonyl-CoA mutase. Defects in MMACHC represent the most common cause of inborn errors of B₁₂ metabolism, and our results explain the observation that fibroblasts from these patients are poorly responsive to vitamin B₁₂ but show some metabolic correction with aquocobalamin, a cofactor form lacking the cyanide ligand, which is mirrored by patients showing poorer clinical responsiveness to cyano- versus aquocobalamin.     

The mode of action of vitamin K. Isolation of a peptide containing the vitamin K-dependent portion of prothrombin

Previous evidence has indicated that vitamin K functions in a metabolic step that specifically alters a precursor protein and converts it to biologically active prothrombin. This alteration appears to be related to the biosynthesis or attachment of a noncarbohydrate prosthetic group [Nelsestuen and Suttie (1972) J. Biol. Chem. 247, 8176]. We report the isolation of a peptide from bovine prothrombin that contains the vitamin K-dependent region of the molecule. The properties of the isolated peptide would appear to account for the major differences observed between prothrombin and its biologically inactive form produced by animals administered Dicumarol orally. These differences are quantitative absorption onto insoluble barium salts and the ability to bind calcium ions. The observed properties of this peptide provide direct evidence for the presence of a covalently bound noncarbohydrate prosthetic group(s) on the prothrombin molecule.