驱铜联合活性维生素D3治疗对Wilson’s病患者骨骼及代谢的影响

目的 观察Wilson＇s病患者骨骼X线摄片表现，及驱铜治疗联合活性维生素D3补充治疗对骨代谢的影响。方法 对35例入选Wilson＇s病患者入院时进行骨骼X线摄片，并分别于治疗前及二巯基丙磺酸钠驱铜辅以活性维生素D3治疗8疗程后，放射免疫法测定骨代谢相关激素：PTH、CT、及血清BGP水平；用生化法测定血钙、血磷，尿钙、尿磷等。并用单光子吸收法（SPA）测定尺桡骨中远端1/3处平均骨密度值。结果 Wilson＇s病患者手腕部X线检测异常率达60%。治疗后，血PTH、血钙均降低，骨密度（BMD）值升高，较治疗前差异有统计学意义（P〈0.05）；血磷、尿钙、磷及血清CT、BGP水平较治疗前差异无显著性。结论 Wilson＇s病患者常并发骨质疏松或骨质软化等代谢性骨病，驱铜治疗联合活性维生素D3补充治疗可更好改善骨骼代谢，更快改善其骨密度。     

维生素D缺乏对骨骼肌肉系统的影响

维生素D是人体不可缺少的一种脂溶性维生素,主要功能是促进肠道对钙、磷的吸收。维生 素D缺乏会引起继发性甲状旁腺功能亢进,骨转化加快,骨丢失增加,从而引起骨软化、骨质疏松、骨 折。另外维生素D缺乏与肌无力、活动能力下降相关,使患者跌倒发生率增加。科学有效的补充维 生素D,不但能够防止由于钙、磷吸收障碍所导致的骨质疏松及骨折的发生,还能有效防止多种骨骼 肌肉系统疾病。     

生命、骨骼、维生素D3

维生素D_3是自然存在的脂溶性维生素,属类固醇激素。在人类多种组织细胞中均有维生素D受体(VDR)的表达。维生素D_3对人体具有重要生理作用,参与免疫应答、细胞生长、分化、凋亡等生理和病理学过程。它的作用主要是对骨骼,是骨代谢重要的调节激素。对皮肤组织、骨骼肌、免疫系统、神经组织、心血管、生殖器官等也具有重要作用。深入研究维生素D_3与人类疾病发生的机制,研究维生素D_3缺乏导致的骨质疏松及其与维生素D_3代谢相关疾病的预防、治疗具有重要的、深远的意义。本文综述了维生素D_3的生理作用、流行病学研究、维生素D_3与骨质疏松的关系及临床研究前景。     

活性维生素D3与尼尔雌醇对去卵巢大鼠骨代谢的影响

4月龄雌性SD大鼠随机分为：卵巢切除组，假手术组，切除卵巢后给予活性维生素D5组或给予尼尔雌醇组。活性维生素D3剂量为0．0208μg／100gBW，隔天一次；尼尔雌醇为0．15mg／100gBW，每周一次。10周后处死动物并取右胫骨制备不脱钙骨切片进行骨计量学测定，并测定肱骨重量．无机质重量及骨钙、磷含量等。结果：卵巢切除组从骨小梁体积，骨小粱宽度，骨重量和无机质重量与体重之比及骨钙含量等方面显示绝经后骨质疏松模型建立，骨再建指标显示该模型为高转换型骨质疏松。活性维生素D3组各指标与假手术组，相似，但成骨细胞指数高于假手术组与去势组相似，表明活性维生素D3通过抑制雌激素缺乏状态下过高的骨吸收而达到防止骨丢失的作用而尼尔雌醇组各指标均与假手术组相似，提示尼尔雌醇通过抑制雌激素缺乏状态下过高的骨转换，恢复骨再建过程的平衡而防止切除卵巢大鼠的骨丢失。     

活性维生素D对骨量减少的强直性脊柱炎患者骨代谢指标及病情的影响

目的探讨补充活性维生素D对于骨量减少的强直性脊柱炎(AS)患者骨代谢标志物、骨密度及炎性指标的影响。方法选取骨量减少的AS患者60例为研究对象,同期健康体检者20例作为健康组,比较两组受试者血清骨特异性碱性磷酸酶(BALP)、抗酒石酸酸性磷酸酶异构体-5b(TRACP-5b)、25-(OH)D3的水平。将上述AS患者随机分为治疗组和对照组,每组30例,对照组口服美洛昔康、柳氮磺吡啶、碳酸钙,治疗组在此基础上加用骨化三醇口服。比较2组治疗前后BALP、TRACP-5b、25-(OH)D3,骨密度(BMD)以及红细胞沉降率(ESR)、C反应蛋白(CRP)等指标的变化水平。结果 AS组BALP、TRACP-5b高于健康组,25-(OH)D3低于健康组(P0.05)。治疗组和对照组治疗后血清BALP、25-(OH)D3水平均有升高(P0.05),TRACP-5b水平均有下降(P0.05);治疗组BALP及25-(OH)D3治疗前后差值高于对照组(P0.05)。6个月后治疗组复查腰椎、大转子、转子间BMD较对照组均有不同程度的提升(P0.05),5例骨量恢复正常;对照组6个月后BMD变化不明显;治疗组治疗前后腰椎、大转子、转子间BMD变化差值均高于对照组(P0.05);治疗组与对照组ESR、CRP及BASDAI评分较前均有所降低(P0.05),其中治疗组ESR下降水平较对照组差异具有统计学意义(P0.05)。结论活性维生素D可以改善骨量减少的强直性脊柱炎患者的骨代谢指标并降低疾病活动度。     

血清活性维生素D3与原发性骨质疏松症的关系

本文对１７例５０～７０岁原发性骨质疏松患者血清活性维生素Ｄ３的含量进行测定，结果发现血清活性维生素Ｄ３含量有１１例下降，占被测试人数的６４．７％。提示我们在防治原发性骨质疏松症时要补充适量的维生素Ｄ３     

活性维生素D3治疗对维持性血透患者左心室肥厚的影响

目的：研究活性维生素D3制剂罗钙全治疗对维持性血透（MHD）患左心室肥厚（LVH）的影响。方法：伴继发性甲状旁腺功能亢进的MHD患30例随机分成两组，治疗组16例接受罗钙全治疗（口服，2μg/次，2－3次／周）共12周，余14例作为对照组。其它治疗两组均相同。期间观察血甲状旁腺素（iPTH)水平及左室舒张末期内径（LVDd)、左室收缩末期内径（LVDs)、左房内径（LAD）、室间隔厚度（IVST）和左室后壁厚度（PWT）变化。结果：（1）治疗前两组血iPTH水平明显高于正常，存在继发性甲状旁腺功能亢进，但两组间无差异：两组间LVDd、LVDs、LAD、IVST、PWT值均无差异，但均明显高于正常值或处于正常值高限；（2）治疗组12周后血iPTH水平和LVDd、LVDs、LAD、IVST、PWT值均较治疗前明显降低，而对照组12周后上述参数均无明显改变。结论：活性D3治疗可明显改善维持性血透患的左心室肥厚，此作用与其改变继发性甲状旁腺功能亢进有关。     

维生素D3和维生素K3对实验性肾结石的影响

目的：探讨维生素C3和维生素K3与尿石症的关系。方法SD大鼠36只,随机分为对照组（A组）、成石组（B组）、维生D3组（C组）、成石＋维生素D3组（D组）、维生素K3组（E组）和成石＋维生素K3组（F组）,用免疫组化和原位杂交技术检测各组大鼠肾脏骨桥蛋白（OPN）及其mRNA的表达量,并测定尿晶体成分的浓度。结果：免疫组化结果显示,OPN主要表达于肾脏远曲小管和集合管,B、C、E组鼠肾和OPN的表达强度明显高于A组（P均＜0．05）;D、F组OPN的表达强度明显高于C、E组（P均＜0．05）,即维生素D3或维生素K3与诱石剂合用时呈相加效应。应用诱石剂后,D组尿钙排泄量明显增加,而F组草酸盐明显低于B组（P＜0．05）。维生素K3可减少尿划石剂后,D组尿排泄量明显增加,而组草酸盐明显低于B组（P＜0．05）。维生素K3可减少尿草酸盐的分泌和草酸钙晶体的沉积。结论：维生素D3可能通过多种机制种促进肾结石殂成,而维生素K3有抑制结石形成的作用。     

活性维生素D3对体外原代培养人骨关节炎软骨细胞的影响

目的探讨不同浓度的1α,25二羟基维生素D3[1,25-（OH）2D3]对体外培养的人骨关节炎患者关节软骨细胞的增殖及凋亡率的影响。方法酶二步消化法体外分离培养人软骨细胞,以碱性磷酸酶染色法鉴定。加入不同剂量的[1,25-（OH）2D3],通过噻唑蓝比色试验检测细胞存活和增殖情况,以及用流式细胞仪检测软骨细胞在不同药物浓度、不同作用时间的凋亡率。结论 [1,25-（OH）2D3]作用于人骨关节炎软骨细胞的最佳作用浓度为1×10-5umol/L,最佳作用时间点为48 h。高浓度的[1,25-（OH）2D3]能明显促进细胞坏死,极低浓度的[1,25-（OH）2D3]对软骨细胞增殖、凋亡无明显影响。     

口服维生素D3加钙剂治疗原发性骨质疏松骨痛

我们于１９９４年３月～１９９６年９月联合应用维生素Ｄ３加钙剂口服治疗原发性骨质疏松骨痛患者,获得满意疗效。１临床资料１１对象原发性骨质疏松骨痛患者７８例,均为内分泌专业门诊及住院病人。其中男２９例,女４９例。平均年龄５７３±６９岁,女性４６～７...     

A new active vitamin D3 analog, eldecalcitol, prevents the risk of osteoporotic fractures--a randomized, active comparator, double-blind study

Background

Eldecalcitol is an analog of 1,25-dihydroxyvitamin D₃ that improves bone mineral density; however, the effect of eldecalcitol on the risk of fractures is unclear. The objective of this study is to examine whether eldecalcitol is superior to alfacalcidol in preventing osteoporotic fractures. This trial is registered with ClinicalTrials.gov, number NCT00144456.

Methods and results

This 3 year randomized, double-blind, active comparator, superiority trial tested the efficacy of daily oral 0.75 μg eldecalcitol versus 1.0 μg alfacalcidol for prevention of osteoporotic fractures. 1054 osteoporotic patients 46 to 92 years old were randomly assigned 1:1 to receive eldecalcitol (n = 528) or alfacalcidol (n = 526). Patients were stratified by study site and serum 25-hydroxyvitamin D level. Patients with low serum 25-hydroxyvitamin D levels (< 50 nmol/L) were supplemented with 400 IU/day vitamin D₃. Primary end point was incident vertebral fractures. Secondary end points included any non-vertebral fractures and change in bone mineral density and bone turnover markers. Compared with the alfacalcidol group, the incidence of vertebral fractures was lower in eldecalcitol group after 36 months of treatment (13.4 vs. 17.5%; hazard ratio, 0.74; predefined 90% confidence interval [CI], 0.56–0.97). Eldecalcitol reduced turnover markers and increased bone mineral density more strongly than alfacalcidol. Eldecalcitol reduced the incidence of three major non-vertebral fractures, which was due to a marked reduction in wrist fractures by a post-hoc analysis (1.1 vs. 3.6%; hazard ratio, 0.29; 95% CI, 0.11–0.77). Among the adverse events, the incidence of increase in serum and urinary calcium was higher in the eldecalcitol group, without any difference in glomerular filtration rate between the two groups.

Conclusions

Eldecalcitol is more efficacious than alfacalcidol in preventing vertebral and wrist fractures in osteoporotic patients with vitamin D sufficiency, with a safety profile similar to alfacalcidol.     

活性维生素D3对2型糖尿病患者肾脏保护作用的Meta分析

目的系统评价活性维生素D3治疗2型糖尿病(type 2 diabetes,T2DM)的有效性和安全性以及其对肾脏的保护作用。方法计算机检索PubMed、EMBase、谷歌学术、中国知网、维普数据库、万方数据库和中国生物医学文献数据库,检索时间范围均从建库至2014年12月。收集以活性维生素D3为干预措施治疗T2DM的临床随机对照试验(randomized controlled trials,RCT),按照Cochrane系统评价方法,对纳入标准的RCT进行方法学质量评价和疗效指标合并分析。结果共纳入10个RCT。采用固定效应模型对尿白蛋白肌酐比值(urinary albumin creatinine ratio,UACR)进行比较,加权均数差(standardized mean difference,SMD)=-0.34(95%CI:-0.55,-0.12;P=0.002),治疗组较对照组明显降低;采用随机效应模型对血肌酐进行比较:SMD=-1.27(95%CI:-3.66,1.12;P=0.30),差异无统计学意义(P0.05);另外,治疗组在降低T2DM患者胰岛素抵抗、三酰甘油、总胆固醇、收缩压和升高高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)等方面效果与对照组比较[SMD或加权均数差(weighted mean difference,WMD)(95%CI)分别为-2.69(-3.42,-1.97);-0.37(-0.63,-0.11);-0.30(-0.56,-0.05);-5.94(-9.08,-2.80);0.33(0.03,0.63)],差异有统计学意义(P0.05);但对糖化血红蛋白(glycosylated hemoglobin,HbA1c)和舒张压无明显影响[WMD(95%CI)分别为0.06(-0.08,0.19),-1.77(-3.65,-0.12);P0.05]。结论活性维生素D3可以改善T2DM患者糖代谢,降低血脂、血压及蛋白尿,具有一定的肾脏保护作用。     

维生素D3及其代谢物对成骨细胞分化及生物矿化的实验研究

目的研究体外维生素D₃及其代谢物在不同浓度下对成骨细胞分化和生物矿化的影响。方法采用胶原酶消化法分离成骨细胞;设立对照组,不同浓度VD₃、25(OH)VD₃和1α,25(OH)2VD₃药物处理组。采用CCK-8法检测细胞增殖,采用PNPP法测定ALP活性,采用钙含量测定、ELISA法和实时定量聚合酶链反应来评估成骨细胞对VD₃及其代谢物的反应,并对成骨标志物进行分析,评价VD₃及其代谢物对成骨细胞分化和生物矿化能力的影响。结果VD₃及其代谢物对成骨细胞无细胞毒性,只有200 nmol/L的VD₃能显著促进成骨细胞增殖,而25(OH)VD₃和1α,25(OH)2VD₃对成骨细胞增殖的促进作用不明显。25(OH)VD₃和1α,25(OH)2VD₃可以上调成骨细胞CYP24A1基因的转录活性,但不能直接代谢VD₃和25(OH)VD₃。25(OH)VD₃和1α,25(OH)2VD₃以剂量依赖性增加的方式促进早期成骨标志物(Runx2,ALP等)的表达。只有25(OH)VD₃能促进成骨细胞OCN基因和蛋白的表达,提高成骨细胞的生物矿化水平。结论体外25(OH)VD₃可诱导成骨细胞的分化和生物矿化,为其在临床骨质疏松症和骨组织工程中的应用提供依据。     

健脾方对去势大鼠维生素D代谢的影响

目的采用放射免疫方法与分子生物学方法从VitD代谢的角度探讨健脾方防治原发性骨质疏松症的机制。方法建立卵巢切除致骨质疏松大鼠模型,运用骨组织病理学、血液生物化学等方法综合观察健脾方对模型大鼠骨密度、尿吡啶酚（PYD）和血清骨钙素（BGP）的影响;同时应用放射免疫方法与逆转录聚合酶链式反应观察健脾方对模型大鼠血清1,25（OH）2D3和小肠、肾脏组织维生素D受体基因（VDR mRNA）表达的影响。结果健脾方能升高模型大鼠的骨密度,降低模型大鼠血清1,25（OH）2D3的含量（P〈0.05）,同时能上调模型大鼠小肠、肾脏VDR mRNA的表达。结论健脾方能增强机体对血清1,25（OH）2D3反应敏感性,上调小肠与肾脏VDR mRNA的表达,调节VitD代谢。     

维生素D对肌少症的影响及其作用

肌少症作为一种在老年人中发病率较高的综合征,日益受到人们的广泛关注,但是目前它的发病机制及治疗措施尚未达成共识。本文围绕维生素D与肌少症的相关性入手,探讨维生素D对于肌肉系统的病理生理作用,维生素D与肌肉细胞生长与衰退的关系,维生素D对肌肉的信号调控及功能的影响。初步阐述了维生素D对于肌少症的影响和作用,对于肌少症的防治提供新的临床思路。     

Immobilization osteoporosis and active vitamin D: Effect of active vitamin D analogs on the development of immobilization osteoporosis in rats

Summary The therapeutic effects of vitamin D analogs, 1,24(R)-dihydroxycholecalciferol [1,24(R)(OH)₂D₃], 1,24(S)-dihydroxycholecalciferol [1,24(S)(OH)₂D₃], and 1,25-dihydroxycholecalciferol [1,25(OH)₂D₃] on immobilization osteoporosis were studied in rats. The right hind limb was immobilized through application of a plaster cast following the section of the sciatic nerve. The left hind limb was intact. Vitamin D analogs were orally administered for 6 weeks at dose levels of 0.02 and 0.10μg/kg/day, respectively. The mean lengths of the immobilized femurs were not significantly different from those of the intact femurs in all the experimental groups. In the immobilized femur of animals treated with 1,24(R)(OH)₂D₃, 0.10μg/kg, dry and ash weights were heavier and calcium and phosphorus contents greater than those in the nontreated group. Furthermore, the amount of calcified bone mass and the cortical thickness of the femurs of the immobilized limb in 1,24(R)(OH)₂D₃-treated animals were greater than those in the nontreated animals. Treatment with 1,25(OH)₂D₃ at 0.10μg/kg caused an increase of the bone mass in both immobilized and intact femurs when compared with those of the control group. It was concluded that the administration of 1,24(R)(OH)₂D₃ diminished the effect of immobilization in the development of osteoporosis without any side effects.     

Effects of vitamin D supplementation as an adjuvant therapy in coronary artery disease patients*

Objectives: Low vitamin D status has been shown to be associated with coronary artery disease. We planned to research the effects of vitamin D₃ supplementation on the severity of coronary artery disease. Design: We investigated the effect of 0.5 μg vitamin D₃ per day in a randomized, placebo-controlled, double-blind study in 90 stable coronary artery disease patients residing in Beijing. Coronary angiography was performed before and after 6 months of treatment that took place between January and June. 25-Hydroxyvitamin D was measured by chemiluminescence assay. Coronary artery disease severity was assessed by using the SYNTAX scores. Results: In vitamin D supplementation group, there was a significant increase in mean 25-hydroxyvitamin D levels from baseline (19.9?±?9.8 ng/ml) to 6 months (35.8?±?12.1 ng/ml; p?<?0.001). At 6 months, the primary end point, a difference in the fall of SYNTAX score between the groups was ?2.5 (95% CI ?5.1 to ?0.5; p?<?0.001) under intention to treat analysis. Compared with the control group, patients treated with vitamin D₃ also had greater decreases in high sensitivity C-reactive protein and renin-angiotensin system activity (p?<?0.05). Conclusions: Vitamin D supplementation has beneficial effects on coronary artery disease; it can be an adjuvant therapy for patients with coronary artery disease.     

维生素K联合骨化三醇、钙尔奇D治疗男性骨质疏松的疗效观察

目的研究维生素K联合骨化三醇、钙尔奇D对男性骨质疏松的治疗效果及对骨代谢的影响。方法采用美国Hologic公司生产的Discovery WA型双能X线骨密度仪检测患者腰椎L_(1～4)骨密度(bone mineral density,BMD)与股骨颈骨密度。对男性骨质疏松患者采用固力康联合骨化三醇、碳酸钙D3进行治疗,连续治疗1年,治疗期间监测患者骨代谢变化。采用美国Thermo公司全自动酶标免疫分析仪检测患者血清骨代谢指标BGP、CTX-1、细胞因子IL-6、IL-10水平。结果治疗6个月后患者腰椎(L_(1～4)) BMD、股骨颈BMD开始增加,治疗12个月后患者腰椎(L_(1～4)) BMD、股骨颈BMD较治疗前增加明显。治疗后,血清骨形成指标BGP水平升高、细胞因子IL-10水平升高;血清骨吸收指标CTX-1水平、细胞因子IL-6水平降低。结论维生素K可提高患者腰椎与股骨颈骨密度,升高血清骨形成指标BGP、细胞因子IL-10水平,降低血清骨吸收指标CTX-1、细胞因子IL-6水平,维生素K治疗男性骨质疏松效果显著,是临床上治疗骨质疏松的重要策略之一。     

钙剂对实验性骨质疏松大鼠多指标的影响

本实验给大鼠肌肉流向地塞米松（0.1mg/100g体重），分别喂食低钙饲料和高钙饲料，观察大鼠骨灰重，骨密度，骨组织学形态及体内雌二醇，PGE3、1，25-（OH）2-D2和cAMP的变化。结果表明，低钙组大鼠骨盐丢失明显，且血中雌二醇，1，25-（OH）2-D3下降，而PGE2和cAMP则升高，高钙组大鼠则无上述变化，接近正常大鼠水平，说明钙剂可对抗地塞米松对骨代谢的影响。     

Arterial and cardiac disease in young adults with childhood-onset end-stage renal disease-impact of calcium and vitamin D therapy.

BACKGROUND: Studies in patients with childhood-onset end-stage renal disease (ESRD) provide a diagnostic window to the evolution of cardiovascular disease (CVD) in this population. Hyperphosphataemia and renal osteodystrophy are particularly difficult to treat in paediatric patients, but there is only limited information regarding the effect of calcium-containing phosphate binders and vitamin D preparations on the development of CVD in the young. METHODS: We studied 40 adult patients (mean age 23.6 years) who developed ESRD at the age of 11.5 +/- 4 years and 40 matched healthy control subjects. Nine patients were on dialysis and 31 had a functioning kidney transplant. Measurements included intima-media thickness (IMT) of the common carotid artery, electron beam computed tomography (EBCT) for the detection of coronary artery calcifications (CAC), echocardiography and post-ischaemic arterial blood flow by venous occlusion plethysmography. Patient characteristics, atherosclerotic risk factors and a complete account of prescribed medications were analysed for correlations with arterial and cardiac changes. RESULTS: The IMT was not significantly different in patients and controls; four patients (10%) had coronary calcifications on EBCT. Twenty-five patients (62.5%) had left ventricular hypertrophy. Patients had a 40% reduction of post-ischaemic arterial flow. Morphological alterations of the heart and arteries were significantly correlated with the duration of ESRD and dialysis time, and with the cumulative intake of calcium-containing phosphate binders and active vitamin D preparations. Functional changes (vascular reactivity) were correlated with duration of ESRD and non-traditional risk factors. CONCLUSIONS: Young adults with ESRD since childhood have systemic CVD characterized by a decrease in arterial elasticity, the occurrence of CAC and changes in left ventricular morphology. Treatment with calcium-containing phosphate binders and active vitamin D preparations is independently associated in a dose-dependent manner with surrogate markers for CVD.