维生素D治疗慢性肾脏疾病继发性甲状旁腺功能亢进症的进展

继发性甲状旁腺功能亢进症(SHPT)是慢性肾脏疾病(CKD)最常见的并发症之一.维生素D及其类似物是治疗SHPT的常用药物,充分了解低维生素D状态对CKD患者的危害,维生素D制剂治疗SHPT的药理机制及治疗过程中应该注意的问题,有助于临床医师合理应用此类药物,延缓SHPT发展为三发性甲状旁腺功能亢进症.     

Vitamin D deficiency and secondary hyperparathyroidism: clinical and biochemical associations in older non-institutionalised Southern Tasmanians

Aim : To determine the prevalence and associations of vitamin D (25-OHD) deficiency in a sample of older Tasmanian subjects.
Methods : A cross-sectional survey of: 109 patients with a mean age of 79 years (range 60–101 years) consecutively admitted to a short stay geriatric rehabilitation ward; 52 community dwelling subjects with a mean age of 75 years (range 64–88 years). Subjects answered a questionnaire, had anthropometric measurements and underwent venepuncture.
Results : The main outcome measure was 25 hydroxy vitamin D (25-OHD) level with deficiency defined as < 28 nmol/L. Vitamin D deficiency was found in 67% and secondary hyperparathyroidism in 49% of the hospitalised group. Vitamin D deficiency was also found in 17% of the community group, in particular one in three residents of Independent Living Units was deficient. Subjects who were deficient were older (80 years vs 76 years [ p <0.001]), had lower body mass index (23.7 kg/m² vs 25.9 kg/m² [ p <0.001]) and had a lower serum albumin (35 gm/L vs 39 gm/L [ p <0.001]). Deficient subjects had poorer physical functional status ( p =0.02) and lower activity levels ( p <0.001) and reported less habitual sun exposure ( p <0.001). Biochemical measures such as parathyroid hormone, alkaline phosphatase and calcium were weakly predictive of vitamin D levels. By stepwise multiple regression analysis, the only significant predictors of vitamin D levels were the Frenchay Activity Index, albumin and calcium.
Conclusion : Vitamin D deficiency and secondary hyperparathyroidism is common in community living older people who are hospitalised in Southern Tasmania and is associated with increasing age, poor physical function and activity and low reported sun exposure.     

Vitamin D receptor activator reduces oxidative stress in hemodialysis patients with secondary hyperparathyroidism

Treatment with a vitamin D receptor activator (VDRA) has survival benefits probably related to its effects beyond the traditional role in mineral metabolism. We hypothesized that VDRA reduces oxidative stress in hemodialysis (HD) patients. To test this hypothesis, we investigated the effect of VDRA on the oxidative status of albumin in HD patients with secondary hyperparathyroidism. Eleven HD patients with secondary hyperparathyroidism were treated with calcitriol at an intravenous dose of 1.5 μg/week for four weeks. Serum intact parathyroid hormone, calcium and phosphorus were monitored and we measured the amount of oxidized albumin and albumin hydroperoxides form before and after calcitriol treatment. The ratio of oxidized to un-oxidized albumin was determined as a representative marker of oxidative stress. The radical scavenging activity of albumin was also evaluated. After four weeks of calcitriol therapy, there were no significant changes in serum intact parathyroid hormone, calcium, or phosphorus levels; however, the ratio of oxidized to un-oxidized albumin was markedly decreased and serum thiol content was significantly increased after calcitriol treatment. Furthermore, the radical scavenging activity of albumin was greater after calcitriol treatment compared with that of untreated albumin. Our data suggest that intravenous calcitriol treatment reduces oxidative stress and strengthens antioxidant defenses by inhibiting albumin oxidation in HD patients with secondary hyperparathyroidism.     

维生素D和肥胖

大量研究表明维生素D及维牛素D受体(VDR)与肥胖密切相关.血清25(OH)D及1,25(OH),D的浓度都与体重指数(BMI)呈负相关.潜在的原因可能是由于肥胖者活动少及着装习惯导致的日光照射少以及大量的维生素D储存于脂肪组织中所致.研究发现,补充维生素D有利于减轻体重.因此,肥胖者比非肥胖者更需要补充维生素D.只有增加安全、合适的日照时间,食用强化维生素D的食品或者补充高剂量的维牛素D才能保证体内充足的维生素D水平.     

维生素D和肥胖

大量研究表明维生素D及维牛素D受体（VDR）与肥胖密切相关.血清25（OH）D及1,25（OH）,D的浓度都与体重指数（BMI）呈负相关.潜在的原因可能是由于肥胖者活动少及着装习惯导致的日光照射少以及大量的维生素D储存于脂肪组织中所致.研究发现,补充维生素D有利于减轻体重.因此,肥胖者比非肥胖者更需要补充维生素D.只有增加安全、合适的日照时间,食用强化维生素D的食品或者补充高剂量的维牛素D才能保证体内充足的维生素D水平.     

High prevalence of hypovitaminosis D and secondary hyperparathyroidism in elders living in nonprofit homes in South Brazil

Objectives Hypovitaminosis D (HD) and secondary hyperparathyroidism (SHP) are common in elders, and many factors could contribute to them. The objectives of this study were to estimate the prevalence of HD, SHP, and its associated factors, in individuals living in nonprofit homes for elders in south Brazil. Design Cross-sectional study. Methods Serum 25-hydroxyvitamin D 25(OH)D, intact parathyroid hormone (PTH), total calcium, phosphorus, alkaline phosphatase, magnesium, creatinine, and albumin levels were measured in late spring, November, 2005. The presence of factors potentially related with HD and SHP—age, sex, weight, height, skin phototype, sun exposure, exercise, smoking, use of ≤5 medications or diuretics or alcohol, and daily calcium ingestion. Results 102 subjects age 77.8 ± 9.0 were included in the study. HD was found in 85.7% and SHP in 53% of the subjects. The estimated daily calcium ingestion was 720 mg. There was no association between serum 25(OH)D levels and any of the risk factors evaluated. Serum 25(OH)D levels were correlated with serum PTH (r = −0.358, P = 0.000), calcium (r = 0.306, P = 0.002), and albumin (r = 0.253, P = 0.011) levels. In univariate analysis, SHP was positively associated with age (P = 0.006), and female sex (0.007); and negatively associated with sunlight exposure (P = 0.020), GFR (P = 0.000), Ln25(OH)D (P = 0.002), and total serum calcium (P = 0.024). After multivariate model adjustment, age [OR 1.09 (CI 1.01–1.18); P = 0.024], Ln25(OH)D [OR 0.92 (CI 0.08–0.74); P = 0.013], GFR [OR 0.96 (CI 0.92–0.99); P = 0.013], and hydrochlorothiazide treatment [OR 7.63 (CI 1.67–34.9); P = 0.008] were independently associated with SHP. Conclusions HD and SHP are highly prevalent in elders living in old-age homes. No associations were established between common risk factors and low serum levels of 25(OH)D levels; however, SHP was independently related with age, 25(OH)D, GFR, and hydrochlorothiazide use.     

Interpreting Vitamin D Assay Results: Proceed with Caution

Vitamin D deficiency and insufficiency are common in patients with CKD. Association studies suggest that low 25-hydroxyvitamin D₃ (25-OH-D₃) is a harbinger of poor outcomes in these patients. Serum 25-OH-D represents the best biomarker of vitamin D status, but there is much debate surrounding the performance of some of the assay methods. Programs such as the Vitamin D Standardization Program and Vitamin D External Quality Assessment Scheme (DEQAS) in the United Kingdom have allowed us to assess the accuracy and reproducibility of the available methods. Liquid chromatography–tandem mass spectrometry–based methods for serum 25-OH-D measurement are emerging as more accurate and reliable alternatives to the immunoassay-based methods that have dominated over the past 2 decades. There is a renewed optimism that serum 25-OH-D is a useful biomarker to be used in patients with CKD, in particular to diagnose vitamin D deficiency and monitor vitamin D therapy. This commentary discusses some of the methodologic problems associated with serum 25-OH-D assays and their resolution, and looks forward to the future of vitamin D testing.     

维生素D与高血压关系的研究进展

维生素D缺乏在世界范围内非常普遍,目前研究显示维生素D同多种疾病密切相关。维生素D通过作用于维生素D受体发挥作用。近年来,国内外大量研究显示维生素D缺乏同高血压病、冠状动脉疾病、心衰以及心血管不良事件相关,其中维生素D与高血压的研究涉及多个方面,但其具体机制尚不十分清楚。本文将对维生素D与高血压的关系进行综述。     

Vitamin D in Fracture Prevention and Muscle Function and Fall Prevention

This chapter reviews the potential of vitamin D for the prevention of falls and fractures. Evidence from randomized-controlled trials will be reviewed for both endpoints, as well as epidemiologic data that links higher 25-hydroxyvitamin D (25(OH)D) status to better bone and muscle health. The chapter addresses the evidence of fracture and fall prevention by dose of vitamin D, by type of dwelling and treatment duration. All data considered, this chapter summarizes the compelling dual benefit of vitamin D on fracture reduction by its bone and muscle target, a concept that is reviewed at the onset of the chapter.     

成都市区髋部骨折发病率及其分布特点的研究

为了解成都市髋部骨折发病率,并研究其发病特点及规律,作者采用专访和与信访相结合的方法对成都市东、西城区33所医院确诊的髋部骨折445例资料构成分布情况进行了分析研究。成都市东、西城区1989年髋部骨折发病率至少为30.38/10万,男性发病率较高(30.54/10万),女性较低(30.22/10万)。骨折发病率随增龄而上升,尤其在45岁以上的中老年人,其发病率高达130.53/10万,骨折患者平均年龄为63岁。跌伤为主要伤因,自行车损伤也不可忽视。骨折发生月份在统计学上无显著差异,骨折部位以左股骨颈居多,男性股骨颈骨折与股骨转子部骨折之比值为1.36,女性为2.79,男、女骨折部位有显著差异。     

维生素D、维生素D受体与支气管哮喘

越来越多证据表明,维生素D与支气管哮喘(简称哮喘)发病有关,主要机制包括维生素D和环境危险因素等共同作用导致免疫系统的失衡.以及维生素D影响胚胎肺发育等.本文主要综述维生素D、维生素D受体和免疫系统之间的关系,以及维生素D如何通过免疫学机制影响哮喘发病方面的研究进展.深入研究维生素D、维生素D受体在哮喘发病中所起的作用及作用机制,有助于进一步阐明哮喘的发病机制.从而为哮喘的预防和治疗提供新的途径.     

Lack of secondary hyperparathyroidism in sub-group of vitamin D deficient postmenopausal women: Is VDR gene polymorphism behind this mystery?

Background and aimsWe aimed to determine the cause of non-secondary hyperparathyroidism (Non-SHPT) in Indian postmenopausal women.Materials & methods334 apparently healthy postmenopausal women were assessed for bone mineral homeostaisis including Vitamin D, PTH and VDR polymorphism.Results83% of the subjects had vitamin D deficiency further associated with VDR gene polymorphism (P 0.000). A sizable number of subjects (N = 83) did evoke SHPT despite low vitamin D levels. We observe that VDR gene polymorphism was strongly associated in the sub-group of non-SHPT.Conclusion: lack of SHPT warrants researchers to study the pathophysiology of non-SHPT in detail to substantiate our findings.     

维生素D与糖尿病并发症

近年来,关于维生素D与糖尿病并发症的研究逐渐增多.其中,维生素D与糖尿病大血管病变的相关性尚有争议.而维生素D缺乏是糖尿病肾病的独立危险因素,补充维生素D能够延缓糖尿病肾病的进展.同时,多数研究提示维生素D缺乏也很可能是糖尿病视网膜病变和糖尿病周围神经病变的独立危险因素.探讨其作用机制,可能为糖尿病并发症的治疗提供新的思路.     

Vitamin D and Innate Immunity

This chapter will examine the role of vitamin D in the innate immune system as a mediator of human host defense mechanisms microbial disease, focusing on tuberculosis. The first section will examine tuberculosis and the innate immune response to the intracellular pathogen, Mycobacterium tuberculosis (M. tuberculosis), the causative agent of tuberculosis. This is followed by a discussion of the known associations, genetic and mechanistic, between the vitamin D pathway and tuberculosis susceptibility. Finally, the chapter will conclude with a discussion on the potential for adjuvant treatment of tuberculosis with vitamin D.     

Handgrip Strength Predicts Persistent Walking Recovery After Hip Fracture Surgery

Background

In older people, hip fractures often lead to disability and death. We evaluated handgrip strength, an objective measure of physical function for bedridden patients, as a predictor of walking recovery in the year after fracture surgery.

Methods

This multicenter prospective cohort study included 504 patients, aged 70 years or more, who were admitted to the hospital for hip fracture surgery and were formerly able to walk independently. A multidimensional geriatric evaluation that included a physical examination, Short Portable Mental Status Questionnaire, Geriatric Depression Scale, Charlson Index, Basic Activities of Daily Living, and grip strength was administered at the time of admission. Follow-ups were performed every 3 months for 1 year after surgery to assess functional status and survival. The walking recovery probability was evaluated using multivariable logistic regression models.

Results

The mean age of the participants was 85.3 ± 5.5 years, and 76.1% of the participants were women. The mean grip strength was greater in men (β: 6.6 ± 0.62, P < .001) and was directly related to the Short Portable Mental Status Questionnaire results (P < .001), Basic Activities of Daily Living results (P < .001), serum vitamin D levels (P = .03), and time before surgery (P < .001), whereas it was inversely related to age (P < .001), Geriatric Depression Scale score (P < .001), and Charlson Index (P < .001). After adjusting for confounders, the grip strength was directly associated with the probability of both incident and persistent walking recovery (odds ratio highest tertile vs lowest tertile, 2.84, confidence interval, 1.76-4.59 and 2.79, confidence interval, 1.35-5.79, respectively).

Conclusions

In older patients with hip fractures, early grip strength evaluation might provide important prognostic information regarding the patient's future functional trajectory.     

Early Intervention With Intravenous or Pulse Oral Vitamin D Therapy Is More Effective in the Treatment of Secondary Hyperparathyroidism

The K/DOQI clinical practice guidelines recommend vitamin D therapy should be started when the intact parathyroid hormone (iPTH) exceeds 300 pg/mL in patients with secondary hyperparathyroidism. To examine whether the effect of vitamin D therapy on mineral metabolism and parathyroid gland growth varies according to the stage of secondary hyperparathyroidism and iPTH level, 47 patients with secondary hyperparathyroidism received either intravenous or pulse oral vitamin D therapy. The patients were divided into two groups based on the iPTH level at the start of vitamin D therapy: the P_<300 group (N = 23) with iPTH <300 pg/mL; and the P^≥300 group (N = 24) with iPTH ≥300 pg/mL. We examined serial changes in several serum mineral parameters and parathyroid gland volume and the cumulative incidence of parathyroidectomy in the first two years. Serum calcium, phosphorus, calcium–phosphorus product, and iPTH levels of the P^≥300 group were significantly higher than those of the P_<300 group, and could not be maintained within the target ranges set by the K/DOQI guidelines. In contrast, the serum levels of phosphorus, calcium–phosphorus product, and iPTH were maintained within the target ranges and the parathyroid gland did not enlarge in the P_<300 group. The cumulative incidence of parathyroidectomy in the P^≥300 group was significantly higher than in the P_<300 group. Early intervention with intravenous or pulse oral vitamin D therapy at serum iPTH <300 pg/mL can control serum phosphorus, calcium–phosphorus product, and PTH levels to the target ranges and slow the progression of secondary hyperparathyroidism.     

维生素D与脑梗死

维生素D是一组类固醇激素.近年来的研究显示,维生素D与脑梗死的发病率、梗死严重程度和功能转归有关.除通过间接影响血管危险因素外,维生素D还可通过抑制脑梗死后的炎症和氧化应激起到直接的保护作用.     

维生素D与自身免疫性甲状腺疾病

维生素D能通过其活性形式参与免疫调节过程,它能抑制树突状细胞的成熟和分化,也能通过细胞因子,促进调节性T淋巴细胞的增殖.多项研究提示维生素D与自身免疫性疾病相关,其中包括自身免疫性甲状腺疾病.维生素D与甲状腺相关抗体,如甲状腺过氧化物酶抗体(TPOAb)及异常的甲状腺功能相关,其可能的作用机制包括对甲状腺功能、细胞因子及细胞凋亡的直接或间接影响;另外,维生素D受体(VDR)基因多态性与自身免疫性甲状腺疾病间的相关性可能与基因的连锁不平衡以及显性或隐性的表达有关(如BsmⅠ、Apa Ⅰ和TaqⅠ),但该影响存在一定的种族、地域、遗传差异.