维生素D缺乏对骨和骨外作用研究进展

维生素D缺乏作为一种在人群中发病率较高的疾病,日益受到人们的广泛关注。维生素D缺乏的主要诊断指标是血清25-羟维生素D水平。大量研究表明,维生素D缺乏不仅可以引起体内钙磷代谢障碍、佝偻病、软骨病和骨质疏松性骨折等骨骼系统疾病,而且还可能引起癌症、免疫系统疾病、心血管疾病、代谢性疾病(2型糖尿病和肥胖症)、肌肉功能障碍和跌倒等其他骨外系统疾病。维生素D缺乏对骨骼系统的作用,目前学术界已形成共识,然而维生素D缺乏对骨外系统的作用,目前学术界存在较大争议。笔者就维生素D缺乏对骨和骨外作用的研究进展进行全面介绍,探讨维生素D具有广泛作用的可能机理。初步阐述维生素D缺乏对骨和骨外系统的作用,不仅为研究维生素D缺乏对骨和骨外作用及可能机理提供新的研究思路,而且为防治维生素D缺乏的相关疾病提供新的临床思路。尽管目前对维生素D缺乏的骨外作用观点不一,但有充分证据表明补充适量的维生素D有助于身体健康。     

维生素D免疫调节的研究进展

维生素 D是人体生命中不可缺少的营养素,由于免疫细胞同样表达1α-羟化酶和维生素D受体（vitamin D receptor，VDR），所以维生素D是一种重要的免疫调节剂，它可以调节固有免疫和适应性免疫。维生素D通过与维生素D受体结合，激活和调节多种细胞通路来发挥其生物学效应。尤其是免疫细胞（抗原递呈细胞、B细胞、T细胞）能够表达1α-羟化酶从而合成维生素D的活性代谢物,更进一步证明了维生素D的免疫调节特性。维生素D缺乏会导致诸如自身免疫性疾病等异常反应。一些观察研究表明补充维生素D有利于降低疾病的严重程度。但是，用于预防或治疗自身免疫性疾病所需补充的血浆25-羟维生素D浓度标准仍有争议。本文将对维生素D免疫调节研究进展以及维生素D在自身免疫性内分泌疾病（自身免疫性甲状腺疾病、1型糖尿病、Addison’s病）发病机制中的作用进行综述。     

孕期VD缺乏以及对胎儿的影响

维生素D缺乏是目前社会所面临的严重健康问题。维生素D的主要作用是增加肠钙的吸收,对维持各年龄段骨骼健康矿化都起着非常重要的作用。维生素D缺乏在儿童导致佝偻病;在成年人会发生软骨病和骨质疏松。近年来发现除了传统的骨骼系统的作用外,维生素D缺乏还与多种疾病的发生有关。VD缺乏累及的人群非常广泛,可以发生在各个年龄阶段,特别是孕妇。造成孕期维生素D缺乏的主要原因是多方面的,主要是由于各种原因导致的阳光照射不足以及孕期VD的需求量增加所致。孕妇VD缺乏可能与胎儿及新生儿的多种不良状况有关,如影响胎儿及新生儿骨骼系统和大脑的发育,还可能与心脏疾病和I型糖尿病等的发生有关。因此,合理补充维生素D,预防孕期VD缺乏对提高产科质量以及母婴保健是非常重要的。     

维生素D缺乏相关性疾病研究进展

维生素D是人体必需的一种脂溶性维生素,它通过维生素D受体发挥其主要作用。近10年人们对于维生素D的关注度越来越高。根据流行病学调查,目前全球近10亿人处于维生素D不足或缺乏状态,我国人群维生素D不足现象也较为普遍。由于1,25-羟维生素D半衰期非常短,最近维生素D水平已用血清25-羟维生素D水平来描述。多种证据表明,维生素D缺乏不仅造成骨骼疾病(包括营养性佝偻病、软骨病、骨质疏松),还与多种骨骼外疾病密切相关,包括全因死亡率、心血管疾病及心血管病死亡率、代谢综合征(肥胖、糖耐量减低/糖尿病、脂代谢紊乱、高血压)、恶性肿瘤、感染、过敏性疾病及哮喘、精神及神经疾病、自身免疫性疾病、慢性肾病等。虽然使用维生素D治疗骨骼疾病已经得到广泛认可,但是治疗骨骼外疾病的疗效及远期效果还不明确。维生素D缺乏已成为全世界的公共健康问题。本文综述了近年来对维生素D缺乏相关性疾病的研究进展。     

现代社会维生素D缺乏及其预防

维生素D缺乏是目前社会所面临的严重健康问题。维生素D(VD)是人体不可缺少的一种脂溶性维生素,其主要作用是增加肠钙的吸收利用,对维持各年龄段骨骼健康矿化都起着非常重要的作用。维生素D缺乏在儿童导致佝偻病;在成年人会发生软骨病和骨质疏松。此外近年来发现维生素D缺乏还与肿瘤、糖尿病、心血管疾病等多种疾病的发生有关,使其重新引起了人们的关注。造成现代社会维生素D缺乏的原因是多方面的,主要是由于各种原因导致的阳光照射不足。血中的25(OH)D的水平可以作为了解人体内VD状况的指标,多数学者认为25(OH)D的水平低于30ng/mL为维生素D不足,现代社会维生素D缺乏发生率非常高,推测全球可能有10亿人口患有维生素D缺乏。合理补充维生素D对预防维生素D缺乏是非常重要的。     

维生素D缺乏与Graves病相关性的研究进展

维生素D作为维持机体钙磷代谢平衡的重要激素,对机体骨与矿物质盐代谢起着重要的调节作用。近年来研究发现Graves病患者体内维生素D水平偏低,这可能预示着Graves病患者机体内将出现一系列骨代谢紊乱的发生,测量Graves病患者体内维生素D水平,有助于Graves病相关骨质疏松的治疗和预防。此外,还有研究者发现维生素D缺乏可能参与Graves病的发生发展,而补充维生素D可能有助于Graves病的预防和治疗。本文将对维生素D与Graves病相关性及其可能存在的机制的研究新进展进行综述。     

骨质疏松症营养干预研究进展

随着人口老龄化加剧,骨质疏松症及骨质疏松性骨折的发生率和死亡率明显升高,给家庭和社会带来沉重负担。如何有效干预骨质疏松症的发生,减少骨质疏松症及其并发症带来的不良后果,不仅是有效提高骨质疏松症患者生活质量的关键,还可以减轻家庭和社会的经济负担。目前研究发现,饮食营养及营养素补充与骨质疏松症密切相关,早期营养及营养素补充改变有助于避免骨质疏松症的发生发展。在本文中,我们阐述了蛋白质、钙、维生素D及其他维生素和矿物质等营养素补充在预防骨质疏松症、维持骨骼健康中的作用,重点关注以骨密度或骨折作为结果的营养干预研究,探讨了近期关注的营养干预预防骨质疏松症的可能机制,强调了营养补充对预防骨质疏松和维持骨骼健康的重要性。     

长链非编码RNA在肌少-骨质疏松症中调控作用的展望

随着人口老龄化程度的加剧，与增龄有关的肌肉骨骼系统疾病正在严重威胁老年人的身体健康和生活质量。其中，肌少-骨质疏松症是老年人中常见的肌骨协同退变疾病，易导致老年人跌倒、骨折、甚至不同程度的残疾。近年来，不断有证据表明长链非编码RNA（lncRNA）在骨骼和肌肉的基因表达中扮演了重要角色。因此，本文通过梳理lncRNAs在肌少-骨质疏松症中的调控作用和最新发现，探讨lncRNAs有望成为未来诊治肌少-骨质疏松症的新靶点和新途径。     

维生素D与成年人骨骼健康应用指南 (2014年 简化版)

维生素D对人体健康产生广泛作用,维生素D缺乏症(Vitamin D deficiency)可能会导致骨质疏松症进展、跌倒和骨折;同时,在西方国家出现了不一致的维生素D标准和实践方案。鉴于此,中国老年学会骨质疏松委员会相关专业人员,制定了《维生素D与成年人骨骼健康应用指南》。该《指南》分为《简化版》和《标准版》,主要证据来源于2013年英国骨质疏松学会指南、2011年美国健康研究院报告,以及国内文献。该指南适用于成年人骨骼疾病,或有骨病风险患者的维生素D缺乏症管理。需说明,该指南不针对儿童期、妊娠期、以及患有严重或终末期慢性肾脏病(4~5期)的人群。指南内容包括中国成年人群维生素D阈值设定、维生素D状况评价、25OHD测量值解释、维生素D缺乏症的详细治疗计划和预防战略等。     

骨质疏松症治疗中维生素D的最佳水平及补充剂量的研究进展

人们普遍认为维生素D(vitamin D,VD)是骨骼系统中的积极调节因子。近年来,骨质疏松症发病率的增加,VD不足及缺乏现象明显,国内外越来越多研究发现骨密度与VD状态之间存在不一致表现,高水平VD状态对提高骨密度及降低骨折风险并没有起到积极作用,VD最佳水平和在骨质疏松症治疗时如何补充VD仍有争议。笔者综述了近年来的研究成果,进一步探讨VD最佳水平、高水平VD的补充对骨密度及骨折的影响,并提出目标25-羟维生素D[25-hydroxyvitamin D,25(OH)D]浓度为20 ng/mL(50 nmol/L),每日VD补充剂量为400~800 IU,超过这一水平增加VD补充剂量是不必要的,甚至可能存在潜在危险。     

The role of vitamin D in left ventricular hypertrophy and cardiac function

The role of vitamin D in left ventricular hypertrophy and cardiac function. Cardiovascular disease is the leading cause of death among patients with end-stage renal disease (ESRD). Traditional cardiac risk factors, as well as other factors specific to the ESRD population such as hyperphosphatemia, elevated calcium and phosphate product, abnormal lipid metabolism, hyperhomocysteinemia, and chronic inflammation play a role in the excessive risk of cardiovascular death in this population. Left ventricular disorders are proven risk factors for cardiac mortality in hemodialysis patients. These disorders are present in incident ESRD patients at rates far above the general population. There is an accumulating body of evidence that suggests that vitamin D plays a role in cardiovascular disease. Abnormal vitamin metabolism, through deficiency of the active form of 1,25-dihydroxyvitamin D(3), and acquired vitamin D resistance through the uremic state, have been shown to be important in ESRD. Vitamin D deficiency has long been known to affect cardiac contractility, vascular tone, cardiac collagen content, and cardiac tissue maturation. Recent studies using vitamin D receptor deficient mice as a model demonstrate a crucial role of vitamin D in regulation of the renin-angiotensin system. Additionally, there is emerging evidence linking treatment with vitamin D to improved survival on hemodialysis and improvement in cardiac function. The emergence of this data is focusing attention on the previously underappreciated nonmineral homeostatic effects of vitamin D that very likely play an important role in the pathogenesis of cardiac disease in ESRD.     

The virtues of vitamin D—but how much is too much?

Vitamin D deficiency is common in healthy adults and children as well as in the chronic kidney disease (CKD) population. What was once a disease of malnourished children in the developing world has re-emerged and reached pandemic proportions. In parallel with this development, there is a growing awareness that vitamin D is not simply a ‘calcaemic hormone’ but plays an important role in the prevention of cardiovascular disease, infectious and auto-immune conditions, renoprotection, glycaemic control and prevention of some common cancers. Most tissues in the body have a vitamin D receptor and the enzymatic machinery to convert ‘nutritional’ 25-hydroxyvitamin D to the active form 1,25-dihydroxyvitamin D; it is estimated that 3% of the human genome is regulated by the vitamin D endocrine system. Although there are few well-conducted studies on the benefits of vitamin D therapy, an exuberant use of vitamin D is now seen in the general population and at all stages of CKD. There is emerging evidence that vitamin D may in fact have a therapeutic window, and at least from the effects on the cardiovascular system, more is not necessarily better. In this review, we discuss the role of nutritional vitamin D (ergocalciferol or cholecalciferol) supplementation in CKD patients, interpreting the clinical studies in the light of the vitamin D metabolic pathway and its pluripotent effects. While nutritional vitamin D compounds clearly have numerous beneficial effects, randomised controlled studies are required to determine the effectiveness and optimal dose at different stages of CKD, its concurrent use with activated vitamin D compounds and its safety profile.     

The Role of Vitamin D in Chronic Obstructive Pulmonary Disease,Asthma and Other Respiratory Diseases

There has been a growing interest in recent years in the extraosseous effects of vitamin D.In this article, we review the physiology of vitamin D, the physiopathological effects associated with vitamin D deficit and the available evidence on its etiopathogenic role in respiratory diseases. Given the pleiotropic actions of vitamin D, it is biologically plausible that the deficit of this vitamin could play a pathogenic role in the development of various respiratory diseases. However, the many epidemiological studies that have shown an association between low vitamin D levels and a higher risk of developing various respiratory diseases, or a poorer prognosis if they do appear, were unable to show causality. Post hoc analyses of some clinical trials, particularly in chronic obstructive pulmonary disease (COPD) and asthma, appear to suggest that some patient subtypes may benefit from correction of a vitamin D deficit. In this respect, it would be interesting to determine if the interindividual differences found in the effect of vitamin D deficit and responses to correcting this deficit could be explained by the genetic variants involved in vitamin D metabolism. Ultimately, only appropriately designed clinical trials will determine whether 25-OH D supplements can prevent or improve the course of the various respiratory diseases in which an epidemiological association between prognosis and vitamin D deficit has been described.     

Vitamin D and its analogues: do they protect against cardiovascular disease in patients with kidney disease?

BACKGROUND: Patients with chronic kidney disease (CKD) are at high risk for cardiovascular disease, and despite recent advances in hypertension control, anemia management, and dialysis adequacy, mortality remains high. Improved understanding of nontraditional risk factors, including those present at early phases in CKD, may lead to novel therapeutic strategies. CKD has been demonstrated to be an independent risk factor for cardiovascular disease in the general population, but data are lacking as to the associated potential abnormalities that occur in association with reduced glomerular filtration rate (GFR), which may contribute to this increased risk. Data are accumulating regarding the role of abnormalities of calcium, phosphorus, vitamin D, and parathyroid hormone (PTH) in cardiovascular disease. Vitamin D deficiency is present even in the early stages of CKD. Vitamin D plays a central role in calcium-phosphorus homeostasis, regulation of PTH, and formation and maintenance of bone. However, until recently, vitamin D has not been considered to have a biologic role in CKD beyond mineral regulation, or has been considered as a negative factor contributing to soft tissue and cardiovascular calcification. In light of recent observational studies showing an association of vitamin D therapy and survival benefit in hemodialysis patients, the effects of vitamin D on cardiovascular system have become a heavily debated issue. METHODS: A Medline search was performed to identify relevant literature describing the role of vitamin D in the pathogenesis of cardiovascular disease. Both the experimental and clinical literatures in English were reviewed. RESULTS: The accumulating published data demonstrate both associative relationships and mechanisms for biologic plausibility. The following three potential mechanisms may be important for the protective effects of vitamin D against cardiovascular disease mortality: vitamin D can inhibit various aspects of inflammation, which have been established as a key pathogenic mechanism in atherosclerosis; vitamin D exerts an antiproliferative effect on myocardial cell hypertrophy and proliferation, which underlies the pathogenesis of congestive heart failure; and vitamin D acts as a negative endocrine regulator for the renin-angiotensin system, which itself plays an important independent role in hypertension and cardiovascular health. CONCLUSION: Vitamin D deficiency might be an underestimated nonclassical risk factor for cardiovascular disease in CKD. Based on a review of the evidence, from both basic science and clinical studies, this article supports the possible protective role of vitamin D beyond its effect on mineral metabolism, and suggests the need for ongoing evaluation of the role of vitamin D in cardiovascular health in the CKD population.     

Níveis de vitamina D na espondilite anquilosante: a deficiência corresponde à atividade da doença?

Ankylosing spondylitis (AS) is an inflammatory disorder that presents with arthritis of the axial skeleton, including sacroiliac joints. Vitamin D is a secosteroid hormone with a long‐established role in calcium and phosphate homeostasis, and in the regulation of bone formation and resorption. It is now known that vitamin D plays an immunosuppressive role in the body, and there is interest of late in the role of vitamin D in autoimmune diseases. Inflammation may be responsible for some of the loss of bone mineral density seen in AS. We reviewed the literature for studies assessing vitamin D level as a marker of AS disease activity and those examining vitamin D levels in AS in comparison to healthy controls. Four of 7 studies found a significant negative correlation between vitamin D levels and Bath Ankylosing Spondylitis Index (BASDAI), erythrocyte sedimentation rate (ESR) and C‐reactive protein (CRP). In a review of 8 case‐control studies, the mean level of 25‐hydroxyvitamin D3 was 22.8 ± 14.1 ng/mL in 555 AS patients versus 26.6 ± 12.5 ng/mL in 557 healthy controls. When compared with a 2‐sample t test, vitamin D levels were significantly higher in healthy controls (p < 0.01). We conclude that patients with AS appear to have lower vitamin D levels versus healthy controls; however, the cause is unclear. Existing studies do not demonstrate a consistent link between vitamin D levels and disease activity in AS. Further studies are in need to determine if a causative link exists between vitamin D deficiency and AS.     

25(OH) Vitamin D3 in patients with chronic kidney disease and those on dialysis: rediscovering its importance

In terms of both exogenous sources (diet), and endogenous production (activation through exposure to ultraviolet light), vitamin D is unique. Few foods naturally contain vitamin D and only a few are fortified with vitamin D. Most people get more than 90% of their vitamin D requirements from exposure to sunlight. Those who protect their skin from ultraviolet-B radiation with clothing or sunscreen, the elderly, and dark-skinned individuals have limited capacity to produce vitamin D. Vitamin D deficiency is common in the general population and even more common in patients with chronic renal failure (CKD). Increased use of sun-blocking agents and decreased exposure to sunlight, to reduce the risk of skin cancer, attributed to exposure to UV radiation, may contribute to the increase in vitamin D deficiency in the population. These issues are particularly important in the dialysis population who are at particular risk because these, mostly elderly, individuals have an inactive life style and have reduced exposure to sunshine and UV light, thus limiting the actinic synthesis of vitamin D. The nephrology community seems to have overlooked the importance of vitamin D for overall health and well being in patients with CKD. Recently however, several authors have called attention to the role of plasma 25(OH)D₃ levels in mineral metabolism dysregulation in patients with chronic kidney diseases, and those on dialysis. Vitamin D not only contributes to skeletal health but also plays a major role in the health of a wide variety of other organ systems. It seems that vitamin D supplementation is the most effective way of preventing vitamin D deficiency.     

维生素D与动脉粥样硬化相关性研究进展

关于维生素D的生物学效应除了调节钙磷代谢、骨质钙化外,最新研究发现,维生素D对其他多种非骨代谢疾病也同样存在着密切关系。越来越多的基础及临床研究证实,维生素D可以通过多条途径参与及影响动脉粥样硬化的形成,如炎症反应、肾素-血管紧张素系统及胰岛素的分泌与抵抗等。因此,维生素D缺乏可能导致罹患动脉粥样硬化的风险增加。本文就维生素D可能参与动脉粥样硬化发病机制及相关临床研究作一综述。     

Association of vitamin D and magnesium with insulin sensitivity and their influence on glycemic control

Insulin resistance increases the risk of developing diabetes, and the degree of resistance influences the glycemic control of patients with diabetes. Numerous researchers have focused on improving insulin sensitivity in order to prevent diabetes-related complications and other chronic diseases. Several studies have also linked vitamin D levels to insulin secretion and resistance, given that both vitamin D and its receptor complex play important roles in regulating pancreatic β-cells. It has been suggested that vitamin D supplementation improves vitamin D levels, but further research is needed to confirm this as neither insulin function nor glycemic control improves when vitamin D levels increase. Magnesium is a cofactor for many enzymes. Although the role of magnesium in the management of diabetes has long been evaluated, it has not yet been determined whether magnesium supplements improve insulin function. However, several researchers have found that patients with good glycemic control have high magnesium levels. Magnesium is closely related to vitamin D and is necessary for the transport and activation of vitamin D in humans. Combined supplementation with vitamin D and magnesium improves glycemic control in patients with diabetes.     

Conundrum of vitamin D on glucose and fuel homeostasis

As an endocrine hormone, vitamin D plays an important role in bone health and calcium homeostasis. Over the past two decades, the non-calcemic effects of vitamin D were extensively examined. Although the effect of vitamin D on beta cell function were known for some time, the effect of vitamin D on glucose and fuel homeostasis has attracted new interest among researchers. Yet, to date,studies remain inconclusive and controversial, in part, due to a lack of understanding of the threshold effects of vitamin D. In this review, a critical examination of interventional trials of vitamin D in prevention of diabetes is provided. Like use of vitamin D for bone loss, the benefits of vitamin D supplementation in diabetes prevention were observed in vitamin D-deficient subjects with serum 25-hydroxyvitamin D 50 nmol/L(20 ng/mL). The beneficial effect from vitamin D supplementation was not apparent in subjects with serum 25-hydroxyvitamin D 75 nmol/L(30 ng/mL). Furthermore, no benefit was noted in subjects that achieved serum 25-hydroxyvitamin D 100 nmol/L(40 ng/mL).Further studies are required to confirm these observations.