维生素D的临床研究进展

近年来的研究发现维生素D不仅在骨骼疾病中发挥重要作用,在非骨骼系统疾病中的也起到十分重要的作用。基础研究证实维生素D受体广泛分布于体内各种组织细胞中,越来越多的临床研究发现补充维生素D在预防和治疗骨质疏松症、心脑血管病、肺部疾病、慢性代谢性及肿瘤性疾病中有重要作用。本文就维生素D与上述疾病关系的研究进展进行综述,主要着眼于当前的临床热点研究方面。结果显示观察性研究证据支持维生素D与上述非骨骼系统疾病有很强的相关性,但是尚缺乏大规模和长期的随机临床试验证据,因此,需要更多的研究来探讨补充维生素D在预防和治疗非骨骼系统疾病中的作用。     

Molecular epidemiological survey and phylogenetic analysis of bovine influenza D virus in Japan

The influenza D virus, a new member of the Orthomyxoviridae family, is predominantly found in cattle. Although viral pathology and clinical disease in cattle appear mild, this virus plays an important role as a trigger of bovine respiratory disease (BRD ). BRD is a costly illness worldwide. Thus, epidemiological surveys of the influenza D virus are necessary. Here, we conducted a molecular epidemiological survey for the influenza D virus in healthy and respiratory‐diseased cattle in Japan. We found that 2.1% (8/377) of the cattle were infected with influenza D. The cattle with and without respiratory symptoms had approximately equal amounts of the virus. A full‐genome sequence analysis revealed that the influenza D virus that was isolated in Japan formed an individual cluster that was distinct from the strains found in other countries. These results suggest that this virus might have evolved uniquely in Japan over a long period of time and that the viral pathology of Japanese strains might be different from the strains found in other countries. Continuous surveillance is required to determine the importance of this virus and to characterize its evolution.     

Vitamin D in Renal Transplantation – from Biological Mechanisms to Clinical Benefits

Recent developments in our understanding of vitamin D show that it plays a significant role in immunological health, uniquely occupying both an anti‐microbial and immunoregulatory niche. Vitamin D deficiency is widespread amongst renal transplant recipients (RTRs), thus providing one patho‐mechanism that may influence the achievement of a successful degree of immunosuppression. It may also influence the development of the infectious, cardiovascular and neoplastic complications seen in RTRs. This review examines the biological roles of vitamin D in the immune system of relevance to renal transplantation (RTx) and evaluates whether vitamin D repletion may be relevant in determining immunologically‐related clinical outcomes in RTRs, (including graft survival, cardiovascular disease and cancer). While there are plausible biological and epidemiological reasons to undertake vitamin D repletion in RTRs, there are few randomized‐controlled trials in this area. Based on the available literature, we cannot at present categorically make the case for routine measurement and repletion of vitamin D in clinical practice but we do suggest that this is an area in urgent need of further randomized controlled level evidence.     

Prostate cancer and vitamin D: what does the evidence really suggest?

The optimal approach to vitamin D supplementation for the average healthy person is debatable. In patients with cancer, the role of vitamin D supplementation, possibly in treatment, is even less clear. Vitamin D is shown to play a role in prostate cancer biology; however, the clinical data have not consistently demonstrated a link. Additional studies are needed to determine if higher doses of vitamin D supplements could benefit selected populations (ie, the elderly or patients with cancer) even if they may not be beneficial for the general population.     

Role of vitamin D in diabetes mellitus and chronic kidney disease

Approximately 30%-50% of people are recognized to have low levels of vitamin D,and insufficiency and deficiency of vitamin D are recognized as global health problems worldwide.Although the presence of hypovitamin D increases the risk of rickets and fractures,low vitamin D levels are also associated with hypertension,cancer,and cardiovascular disease.In addition,diabetes mellitus(DM) and chronic kidney disease(CKD) are also related to vitamin D levels.Vitamin D deficiency has been linked to onset and progression of DM.Although in patients with DM the relationship between vitamin D and insulin secretion,insulin resistance,and β-cell dysfunction are pointed out,evidence regarding vitamin D levels and DM is contradictory,and well controlled studies are needed.In addition,vitamin D influences the renin-angiotensin system,inflammation,and mineral bone disease,which may be associated with the cause and progression CKD.There is increasing evidence that vitamin D deficiency may be a risk factor for DM and CKD;however,it remains uncertain whether vitamin D deficiency also predisposes to death from DM and CKD.Although at this time,supplementation with vitamin D has not been shown to improve glycemic control or prevent incident DM,clinical trials with sufficient sample size,study periods,and optimal doses of vitamin D supplementation are still needed.This review focuses on the mechanism of vitamin D insufficiency and deficiency in DM or CKD,and discusses the current evidence regarding supplementation with vitamin D in patients with these diseases.     

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.     

Shining D' light on chronic kidney disease: mechanisms that may underpin the cardiovascular benefit of vitamin D

Hypovitaminosis D is a significant health-care burden worldwide, particularly in susceptible populations such as those with chronic kidney disease (CKD). Recent epidemiological studies have identified that both higher serum vitamin D concentrations and use of vitamin D supplements may confer a survival benefit both in terms of all-cause and cardiovascular mortality. There is potential to investigate this inexpensive therapy for the CKD population, which suffers excessive cardiovascular events, although the mechanisms explaining this link have yet to be fully elucidated. This review discusses potential mechanisms identified in the basic science literature that may provide important insights into how vitamin D may orchestrate a change in cardiovascular risk profile through such diverse mechanisms as inflammation, atherogenesis, glucose homeostasis, vascular calcification, renin-angiotensin regulation and alterations in cardiac physiology. Where available, the clinical translation of these concepts to intervention trials in the CKD population will be reviewed.     

Role of vitamin d receptor activators in cardio-renal syndromes

The involvement of vitamin D deficiency in cardiovascular morbidity and mortality is attracting great interest. In patients with chronic kidney disease this association is stronger because vitamin D levels decrease as a result of renal progressive impairment. In chronic kidney disease secondary hyperparathyroidism commonly occurs in response to persistent hypocalcemia and hyperphosphatemia; moreover, parathyroid gland volume increases, vascular calcification is accelerated, and structural and functional modifications of the left ventricle are observed. These alterations entail both cardiac and renal involvement, resulting in cardio-renal syndrome. Recent studies concluded that vitamin D administration seems to have cardioprotective and renoprotective effects and improve peripheral vascular disease, vascular calcification, cardiac outcome, and blood pressure control. In clinical practice, therefore, the use of this hormone may play an important role in cardio-renal syndrome prevention.     

Metabolic syndrome:A review of the role of vitamin D in mediating susceptibility and outcome

Despite the well-recognised role of vitamin D in a wide range of physiological processes,hypovitaminosis is common worldwide(prevalence 30%-50%) presumably arising from inadequate exposure to ultraviolet radiation and insufficient consumption.While generally not at the very low levels associated with rickets,hypovitaminosis D has been implicated in various very different,pathophysiological processes.These include putative effects on the pathogenesis of neoplastic change,inflammatory and demyelinating conditions,cardiovascular disease(CVD) and diabetes.This review focuses on the association between hypovitaminosis D and the metabolic syndrome as well as its component characteristics which are central obesity,glucose homeostasis,insulin resistance,hypertension and atherogenic dyslipidaemia.We also consider the effects of hypovitaminosis D on outcomes associated with the metabolic syndrome such as CVD,diabetes and non-alcoholic fatty liver disease.We structure this review into 3 distinct sections; the metabolic syndrome,vitamin D biochemistry and the putative association between hypovitaminosis D,the metabolic syndrome and cardiovascular risk.     

Recommendations for Fitness for Work Medical Evaluations in Chronic Respiratory Patients

Chronic respiratory diseases often cause impairment in the functions and/or structure of the respiratory system, and impose limitations on different activities in the lives of persons who suffer them. In younger patients with an active working life, these limitations can cause problems in carrying out their normal work. Article 41 of the Spanish Constitution states that “the public authorities shall maintain a public Social Security system for all citizens guaranteeing adequate social assistance and benefits in situations of hardship”. Within this framework is the assessment of fitness for work, as a dual-nature process (medico-legal) that aims to determine whether it is appropriate or not to recognize a person's right to receive benefits which replace the income that they no longer receive as they cannot carry out their work, due to loss of health.The role of the pulmonologist is essential in evaluating the diagnosis, treatment, prognosis, and functional capacity of respiratory patients. These recommendations seek to bring the complex setting of fitness for work evaluation to pulmonologists and thoracic surgeons, providing action guidelines that allow them to advise their own patients about their incorporation into working life.     

Vitamin D for skeletal and non-skeletal health: What we should know

Vitamin D plays an essential role in regulating calcium and phosphate metabolism and maintaining a healthy mineralized skeleton. Humans obtain vitamin D from sunlight exposure, dietary foods and supplements. There are two forms of vitamin D: vitamin D₃ and vitamin D₂. Vitamin D₃ is synthesized endogenously in the skin and found naturally in oily fish and cod liver oil. Vitamin D₂ is synthesized from ergosterol and found in yeast and mushrooms. Once vitamin D enters the circulation it is converted by 25-hydroxylase in the liver to 25-hydroxyvitamin D [25(OH)D], which is further converted by the 25-hydroxyvitamin D-1α-hydroxylase in the kidneys to the active form, 1,25-dihydroxyvitamin D [1,25(OH)₂D]. 1,25(OH)₂D binds to its nuclear vitamin D receptor to exert its physiologic functions. These functions include: promotion of intestinal calcium and phosphate absorption, renal tubular calcium reabsorption, and calcium mobilization from bone. The Endocrine Society's Clinical Practice Guideline defines vitamin D deficiency, insufficiency, and sufficiency as serum concentrations of 25(OH)D of <20 ng/mL, 21–29 ng/mL, and 30–100 ng/mL, respectively. Vitamin D deficiency is a major global public health problem in all age groups. It is estimated that 1 billion people worldwide have vitamin D deficiency or insufficiency. This pandemic of vitamin D deficiency and insufficiency is attributed to a modern lifestyle and environmental factors that restrict sunlight exposure, which is essential for endogenous synthesis of vitamin D in the skin. Vitamin D deficiency is the most common cause of rickets and osteomalacia, and can exacerbate osteoporosis. It is also associated with chronic musculoskeletal pain, muscle weakness, and an increased risk of falling. In addition, several observational studies observed the association between robust levels of serum 25(OH)D in the range of 40–60 ng/mL with decreased mortality and risk of development of several types of chronic diseases. Therefore, vitamin D-deficient patients should be treated with vitamin D₂ or vitamin D₃ supplementation to achieve an optimal level of serum 25(OH)D. Screening of vitamin D deficiency by measuring serum 25(OH)D is recommended in individuals at risk such as patients with diseases affecting vitamin D metabolism and absorption, osteoporosis, and older adults with a history of falls or nontraumatic fracture. It is important to know if a laboratory assay measures total 25(OH)D or only 25(OH)D₃. Using assays that measure only 25(OH)D₃ could underestimate total levels of 25(OH)D and may mislead physicians who treat patients with vitamin D₂ supplementation.     

Ethnicité et vitamine D

Cohort studies, mainly US, show that vitamin D deficiency is more common in African-American population. Social and environmental factors play a role but the difference in skin color is essential. Despite low 25-hydroxyvitamin D concentrations, a lower risk of fragility or fracture exists in these populations. Vitamin D deficiency is a contributing factor in many chronic diseases. There is a relationship between vitamin D deficiencies, progression of chronic kidney disease and increased relative risk of mortality. If the ethnicity of patients is now taken into account to estimate renal function, probably specific recommendations for vitamin D deficiency are needed.     

Differential Effects of D-Hormone Analogs and Native Vitamin D on the Risk of Falls: A Comparative Meta-Analysis

The aim of this meta-analysis was to compare the antifall efficacy of native vitamin D to that of its hydroxylated analogs alfacalcidol and calcitriol. Randomized clinical trials comparing oral native vitamin D and its analogs alfacalcidol and calcitriol to a placebo were included. Sources included the Cochrane Controlled Trials Register, EMBASE, MEDLINE, a hand search of abstracts, as well as reference lists. The time range was January 1995 to May 2007. Data were abstracted and scored by two investigators. The core analysis was based on double-blind trials, while open trials were included as a robustness analysis. Relative risks (RRs) for falls while allocated to D-hormone analogs or vitamin D were calculated. Publication bias and robustness were formally tested. Fourteen trials including 21,268 subjects were included. Using double-blind data only, vitamin D-hormone analogs provided a statistically significant lower level of risk for falling compared to native vitamin D: RR = 0.79 (95% confidence interval 0.64–0.96) vs. 0.94 (0.87–1.01) (intergroup difference P = 0.049). The dropout rates observed in the two sets of trials were comparable: 0.33% per month. Publication bias investigation did not report any significant trend for selective publication favoring active treatment arms. Upon current evidence, D-hormone analogs seem to prevent falls to a greater extent than their native compound. Long-term, prospective, head-to-head, confirmatory trials are required to address the exact role of vitamin D and D-hormone analogs in the prevention of falls and fractures.     

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。     

Is there a relationship between vitamin D with insulin resistance and diabetes mellitus?

Available data suggest a possible link between abnormal vitamin D level and abnormal glucose homeostasis, two of the most common chronic medical conditions. Both conditions are associated with inflammation, and the exact mechanism for role of either on the other is not well clear. Literature investigating the link between vitamin D and either pre-diabetic states or diabetes is reviewed. Vitamin D deficiency is detrimental to insulin synthesis and secretion in animal and human studies. In humans, it has been shown by majority of observational studies, that vitamin D is positively correlated with insulin sensitivity and its role is mediated both by direct mechanism through the availability of vitamin D receptors in several tissues and indirectly through the changes in calcium levels. Large number of, but not all, variable samples cross sectional human trials have demonstrated an inverse relation between vitamin D status and impaired glucose tolerance, insulin resistance or diabetes. To compliment this conclusively, evidence from intervention studies is critically warranted before we can frankly state that vitamin D plays a role in diabetes prevention or treatment. Absence of both sizable prospective observational trials utilizing 25(OH)D as the main variable and the non-availability of randomized studies specifically designed to assess the effects of vitamin D on pre-diabetes and diabetes states, are the main obstacles to draw solid and conclusive relationships.     

人群维生素D水平检测的必要性

维生素D是维持人体健康必不可少的营养素,其作为细胞核类固醇超家族激素成员具有调节钙磷代谢的经典作用和影响细胞增殖分化等非经典作用。流行病学研究表明维生素D缺乏除与骨代谢疾病、肿瘤、心衰等常见多发慢性疾病相关外,也是传染病和自发免疫性疾病易感的危险因素。针对目前中国人群维生素D水平偏低的现状,有必要在中国人群中普及维生素D水平检测以及对重点人群进行筛查。     

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。     

Insight into the impact of vitamin D on cardiovascular outcomes in chronic kidney disease

Patients with chronic kidney disease (CKD) experience excess cardiovascular morbidity and mortality that is unexplained by traditional cardiovascular risk factors. Vitamin D deficiency is highly prevalent in CKD and is associated with increased cardiovascular mortality in both the general population and in CKD patients. Vitamin D supplementation is a reasonably safe and simple intervention and meta‐analyses of observational studies have suggested that vitamin D supplementation in CKD improves cardiovascular mortality. However, randomized controlled trials examining the impact of vitamin D supplementation in improving surrogate markers of cardiovascular structure and function remain inconclusive. This review investigates the impact of vitamin D supplementation on surrogate end‐points and cardiovascular events from trials in CKD; and discusses why results have been heterogenous, particularly critiquing the effect of different dosing regimens and the failure to take into account the implications of vitamin D supplementation in study participants with differing vitamin D binding protein genotypes.     

The Women's Health Initiative: A Landmark Resource for Skeletal Research Since 1992

The Women's Health Initiative (WHI) is a large longitudinal study designed to investigate strategies for the prevention and control of common chronic diseases in postmenopausal women, including cardiovascular disease, cancer, and osteoporotic fractures. The WHI consisted of three overlapping clinical trials of hormone therapy, diet modification to reduce total dietary fat, and calcium/vitamin D supplementation. Women who were ineligible for the hormone therapy or diet modification trials or not interested were invited to participate in the observational study. Women were recruited into WHI from 1993 to 1998 at 40 US clinical centers. WHI enrolled 26,046 underrepresented minority women and 135,762 white women. Women could participate in each trial if eligible. The final enrollment included 27,347 women in the hormone trial; 48,835 women in the diet modification trial; 36,282 women in the calcium/vitamin D trial, and 93,676 in the observational study. After the main study ended in 2005, women were invited to continue follow-up for exposures and outcomes through two extensions to 2020. Proposals were recently submitted to continue follow-up through 2027. Information was collected on an extensive number of risk factors for fractures at baseline and over the follow-up, including fall and fracture history, weight patterns, comorbidities, diet, reproductive history, medications, anthropometry, and biomarkers. Bone mineral density was measured at three WHI clinical centers (n = 11,020) chosen to maximize race/ethnic diversity. WHI encourages outside investigators to make use of the publicly available WHI data and to access the biobank of specimens ( www.whi.org ). © 2020 American Society for Bone and Mineral Research.     

Questions and Answers on Smoking in Patients with Diffuse ILD. Use of PICO Methodology

IntroductionThe Smoking and the Diffuse Interstitial Lung Diseases (ILD) groups of ALAT and SEPAR collaborated in the preparation of this document.Materials and methodsThis document uses PICO methodology to answer various questions on the relationship between tobacco use and diffuse ILD.Results and conclusionsThe main recommendations are: (a) moderate level of evidence and strong recommendation to consider smoking as a risk factor for the development and/or modification of the progression of diffuse ILD; (b) moderate level of evidence to identify an increase in mortality in diffuse ILD, irrespective of histologic pattern. Low evidence for ascribing it to smoking and strong recommendation for the early identification of patients with diffuse ILD. Further studies are needed to evaluate the effect of smoking cessation in patients with diffuse ILD; (c) low level of evidence and weak recommendation for defining the impact of passive smoking in diffuse ILD; (d) low level of evidence to demonstrate that smoking cessation improves the outcomes of patients diagnosed with diffuse ILD and strong recommendation to advise smoking cessation in smokers with diffuse ILD, and (e) low level of evidence to support the clinical or epidemiological usefulness of active case finding for diffuse ILD in smoking cessation programs, and strong recommendation justifying the performance of spirometry in active case finding, based not on current smoking status, but on previous accumulated consumption, even in asymptomatic cases.