Circulating vitamin D3 and 25-hydroxyvitamin D in humans: An important tool to define adequate nutritional vitamin D status

Circulating 25-hydroxyvitamin D [25(OH)D] is generally considered the means by which we define nutritional vitamin D status. There is much debate, however, with respect to what a healthy minimum level of circulation 25(OH)D should be. Recent data using various biomarkers such as intact parathyroid hormone (PTH), intestinal calcium absorption, and skeletal density measurements suggest this minimum level to be 80 nmol (32 ng/mL). Surprisingly, the relationship between circulating vitamin D₃ and its metabolic product—25(OH)D₃ has not been studied. We investigated this relationship in two separate populations: the first, individuals from Hawaii who received significant sun exposure; the second, subjects from a lactation study who received up to 6400 IU vitamin D₃/day for 6 months.

Results (1) the relationship between circulating vitamin D₃ and 25(OH)D in both groups was not linear, but appeared saturable and controlled; (2) optimal nutritional vitamin D status appeared to occur when molar ratios of circulating vitamin D₃ and 25(OH)D exceeded 0.3; at this point, the V_max of the 25-hydroxylase appeared to be achieved. This was achieved when circulating 25(OH)D exceeded 100 nmol.

We hypothesize that as humans live today, the 25-hydroxylase operates well below its V_max because of chronic substrate deficiency, namely vitamin D₃. When humans are sun (or dietary) replete, the vitamin D endocrine system will function in a fashion as do these other steroid synthetic pathways, not limited by substrate. Thus, the relationship between circulating vitamin D and 25(OH)D may represent what “normal” vitamin D status should be.     

Circulating vitamin D3 and 25-hydroxyvitamin D in humans: An important tool to define adequate nutritional vitamin D status

Circulating 25-hydroxyvitamin D [25(OH)D] is generally considered the means by which we define nutritional vitamin D status. There is much debate, however, with respect to what a healthy minimum level of circulation 25(OH)D should be. Recent data using various biomarkers such as intact parathyroid hormone (PTH), intestinal calcium absorption, and skeletal density measurements suggest this minimum level to be 80 nmol (32 ng/mL). Surprisingly, the relationship between circulating vitamin D₃ and its metabolic product—25(OH)D₃ has not been studied. We investigated this relationship in two separate populations: the first, individuals from Hawaii who received significant sun exposure; the second, subjects from a lactation study who received up to 6400 IU vitamin D₃/day for 6 months.Results (1) the relationship between circulating vitamin D₃ and 25(OH)D in both groups was not linear, but appeared saturable and controlled; (2) optimal nutritional vitamin D status appeared to occur when molar ratios of circulating vitamin D₃ and 25(OH)D exceeded 0.3; at this point, the V_max of the 25-hydroxylase appeared to be achieved. This was achieved when circulating 25(OH)D exceeded 100 nmol.We hypothesize that as humans live today, the 25-hydroxylase operates well below its V_max because of chronic substrate deficiency, namely vitamin D₃. When humans are sun (or dietary) replete, the vitamin D endocrine system will function in a fashion as do these other steroid synthetic pathways, not limited by substrate. Thus, the relationship between circulating vitamin D and 25(OH)D may represent what “normal” vitamin D status should be.     

Rapid and sensitive high-performance liquid chromatographic method for simultaneous determination of retinol, α-tocopherol, 25-hydroxyvitamin D3 and 25-hydroxyvitamin D2 in human plasma with photodiode-array ultraviolet detection

A new rapid and sensitive high-performance liquid chromatographic method using 0.5 ml of plasma has been developed for the simultaneous determination of retinol (vitamin A), α-tocopherol (vitamin E), 25-hydroxyvitamin D₂ and 25-hydroxyvitamin D₃. The eluate was monitored with a photodiode-array detector with two fixed wavelengths (267 nm for vitamin D, 292 nm for α-tocopherol and retinol). For all compounds, including internal standards, the method provides extraction recoveries greater than 81%. Detection limits were equal to or lower than 1.5 μg/l for the 4 vitamins. Linearity of standards was excellent (r>0.999 in all cases). Intra-day and inter-day precision were generally acceptable; the intra-day-assay C.V. was 7.7 for all compounds and the inter-day-assay C.V. was <9.2% except for the lower concentrations of 25-hydroxyvitamin D₃, 25-hydroxyvitamin D₂ and α-tocopherol (10.8, 11.8 and 11.9, respectively). The important properties of the present method are its ease of use, its rapidity, since sample preparation was achieved in 15 min and all the compounds were eluted in less than 15 min, and its small sample volume required (=0.5 ml), which enables it to be used in pediatric practice.     

Serum 25-hydroxyvitamin D levels are not associated with impaired postural sway in community-dwelling older women: a 6-year follow-up study

Objectives:A positive association between levels of blood 25-hydroxyvitamin D (25[OH]D), an index of vitamin D status, and physical balance has been reported from cross-sectional studies, but longitudinal studies are rare. The present study aimed to test the hypothesis that low serum 25(OH)D levels are longitudinally associated with impaired postural sway over a 6-year follow-up period in older women.Methods:The present cohort consisted of 392 community-dwelling Japanese women aged ≥69 years. Baseline examinations included serum 25(OH)D and physical performance tests, including postural sway velocity. Standing postural sway was evaluated by measuring gravity-center sway velocity. Follow-up physical performance tests were conducted 6 years later.Results:Mean subject age and serum 25(OH)D levels were 73.3 years (SD 3.7) and 61.0 nmol/L (SD 16.9), respectively. No significant association was found between 25(OH)D levels and changes in postural sway velocity (adjusted P for trend=0.72). Women with 25(OH)D <30 nmol/L tended to have lower Δpostural sway velocity than those with 25(OH)D ≥30 nmol/L (mean, -0.59 vs 0.37 cm/s, respectively; adjusted P=0.13).Conclusions:Vitamin D levels are not longitudinally associated with impaired postural sway in older women. Further longitudinal studies are needed to corroborate the results of this study.     

儿童运动发育迟缓与血碱性磷酸酶、血25-羟维生素D3表达水平的相关性

摘要 目的：探讨儿童运动发育迟缓与血碱性磷酸酶(Alkaline phosphatase,ALP)、血25-羟维生素D3[25(OH)D3]表达水平的相关性。方法：2016年10月到2018年6月选择在本院儿保科门诊就诊500例(6~12月龄)的儿童作为研究对象,诊断儿童发育迟缓的发生率,检测发育迟缓患儿血清ALP与25(OH)D3水平,Gesell测评评定小儿的运动发育状况,所有患儿每天均给予了维生素D3 400 IU,对于发育迟缓患儿每天给予维生素D 800 IU~1200 IU补充,治疗3个月,再做Gesell测评评估其运动发育水平,对比治疗后运动发育情况,并分析影响儿童运动发育的相关因素。结果：在500例小儿中,判断为运动发育迟缓120例(迟缓组),占比24.0 %。两组小儿的性别、胎龄、分娩方式、出生体重、头围、身长等对比差异无统计学意义(P>0.05)。迟缓组的血清ALP水平高于非迟缓组(P<0.05),25(OH)D3水平低于非迟缓组(P<0.05)。迟缓组的大动作、精细运动、适应性行为、语言、个人社交评分都低于非迟缓组(P<0.05),迟缓组治疗后,大动作、精细运动、适应性行为、语言、个人社交评分均显著升高(P<0.05)。在120例发育迟缓中,Pearson分析显示ALP、25(OH)D3与小儿运动迟缓发育具有相关性(P<0.05);二分类多因素条件Logistic分析结果显示ALP、25(OH)D3都影响儿童运动发育迟缓的主要因素(P<0.05)。结论：儿童运动发育迟缓与血清ALP、25(OH)D3水平存在相关性,两者的联合检测可为儿童发育迟缓的早期诊断提供实验依据,经过维生素D治疗后,能显著的改善其患儿的运动发育,有很好的应用价值。     

Determination of 25-hydroxyvitamin D3 in human plasma by reversed-phase high-performance liquid chromatography with ultraviolet detection

A method for the determination of 25-hydroxyvitamin D₃, the major metabolite of vitamin D₃ in human plasma, using a non-radioactive internal standard and reversed-phase high-performance liquid chromatography with UV detection (265 nm) has been developed. The method was applied to the determination of the metabolite in plasma from healthy subjects (n=25) and from patients with chronic renal failure (n=12). 25-Hydroxyvitamin D₃ 3-sulfate, a major conjugated metabolite of 25-hyroxyvitamin D₃, was also determined and the correlation between the concentrations of these metabolites was examined. The study showed that almost equal amounts of both compounds were detected in the plasma of healthy subjects, however, in two subjects, the amount of sulfate in the free form was found to be about twice as high as normally detected. In contrast, the free form was predominant in the plasma of patients with chronic renal failure and the sulfate was not detected in four patients.     

Measurement of 25-hydroxyvitamin D in the clinical laboratory: Current procedures, performance characteristics and limitations

In this review we describe procedures, performance characteristics and limitations of methods available for the measurement of 25-hydroxyvitamin (25OHD) since the year 2000. The two main types of methods are competitive immunoassay and those based on chromatographic separation followed by non-immunological direct detection (HPLC, LC-MS/MS). Lack of a reference standard for 25OHD has, until recently, been a major issue resulting in poor between-method comparability. Fortunately this should soon improve due to the recent introduction of a standard reference material in human serum (SRM 972) from the National Institute of Standards and Technology (NIST). For immunoassay, specificity can be an issue especially in relation to the proportion of 25OHD2 that is quantified whereas HPLC and LC-MS/MS methods are able to measure the two major vitamin D metabolites 25OHD2 and 25OHD3 independently. HPLC and LC-MS/MS require more expensive equipment and expert staff but this can be offset against lower reagent costs. Increasingly procedures are being developed to semi-automate or automate HPLC and LC-MS/MS but run times remain considerably longer than for immunoassays especially if performed on automated platforms. For most HPLC and LC-MS/MS methods extraction and procedural losses are corrected for by the inclusion of an internal standard which, in part, may account for higher results compared to immunoassay. In general precision of immunoassay, HPLC and LC-MS/MS are comparable and all have the required sensitivity to identify severe vitamin D deficiency. Looking to the future it is hoped that the imminent introduction of a standard reference method (or methods) for 25OHD will further accelerate improvements in between method comparability.     

Real-life use of vitamin D3-fortified bread and milk during a winter season: the effects of CYP2R1 and GC genes on 25-hydroxyvitamin D concentrations in Danish families,the VitmaD study

Common genetic variants rs10741657 and rs10766197 in CYP2R1 and rs4588 and rs842999 in GC and a combined genetic risk score (GRS) of these four variants influence late summer 25-hydroxyvitamin D (25(OH)D) concentrations. The objectives were to identify those who are most at risk of developing low vitamin D status during winter and to assess whether vitamin D₃-fortified bread and milk will increase 25(OH)D concentrations in those with genetically determined low 25(OH)D concentrations at late summer. We used data from the VitmaD study. Participants were allocated to either vitamin D₃-fortified bread and milk or non-fortified bread and milk during winter. In the fortification group, CYP2R1 (rs10741657) and GC (rs4588 and rs842999) were statistically significantly associated with winter 25(OH)D concentrations and CYP2R1 (rs10766197) was borderline significant. There was a negative linear trend between 25(OH)D concentrations and carriage of 0–8 risk alleles (p < 0.0001). No association was found for the control group (p = 0.1428). There was a significant positive linear relationship between different quintiles of total vitamin D intake and the increase in 25(OH)D concentrations among carriers of 0–2 (p = 0.0012), 3 (p = 0.0001), 4 (p = 0.0118) or 5 (p = 0.0029) risk alleles, but not among carriers of 6–8 risk alleles (p = 0.1051). Carriers of a high GRS were more prone to be vitamin D deficient compared to carriers of a low GRS. Furthermore, rs4588-AA carriers have a low but very stable 25(OH)D concentration, and interestingly, also low PTH level.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-014-0413-7) contains supplementary material, which is available to authorized users.     

Absence of regulatory effects of 1alpha25-dihydroxyvitamin D3 on 25-hydroxyvitamin D metabolism in rats constantly infused with parathyroid hormone

The regulatory role of 1alpha,25-dihydroxyvitamin D3 [1alpha,25-(OH)2-D3] in metabolism of 25-hydroxyvitamin D was studied in sham-operated (sham) or thyroparathyroidectomized (TPTX) vitamin D-deficient rats into which calcium and parathyroid hormone (PTH) were constantly infused. A single dose of 325 or 650 pmol of 1alpha,25-(OH)2-D3 caused significant inhibition of 1alpha,25-(OH)2-D3 synthesis in D-deficient sham rats. This inhibition by 1alpha,25-(OH)2-D3, however, was not observed in D-deficient TPTX rats into which PTH was constantly infused. These results can be explained by supposing that the major regulatory effect of 1alpha,25-(OH) 2-D3 on 1alpha,25-(OH)2-D3 synthesis is realized mostly, if not all, by suppressing endogenous secretion of PTH.     

Development of free 25-hydroxyvitamin D3 assay method using liquid chromatography-tandem mass spectrometry

The free hormone hypothesis has triggered controversies regarding the measurement of free vitamin D metabolites, such as free 25-hydroxyvitamin D (25(OH)D), as a suitable indicator for total vitamin D for clinical use. This issue can be addressed by developing a precise and accurate method for free 25(OH)D measurement. In the present study, a novel assay method for free 25(OH)D₃ based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed. Sample preparation first involved ultrafiltration to remove vitamin D-binding protein-bound and albumin-bound 25(OH)D, followed by extraction with a column, derivatization, evaporation, dissolution, and injection into the LC-MS/MS system. The coefficient of variation of repeatability and reproducibility obtained were 3.8–4.5% and 4.8–5.9%, respectively. Satisfactory linearity (r=0.999) was obtained up to 80 pg/ml. The lower quantification limit was 0.97 pg/ml and the S/N ratio on the peak of 1.0 pg/ml sample was 24.8 (which is more than the acceptable value of 10). The recovery rate was between 84.5 and 92.4% with a negligible matrix effect (94.5–104.9%). Levels of free 25(OH)D₃, but not total 25(OH)D₃, in the serum of the patients with chronic kidney disease (CKD) and hepatic cirrhosis (HC) were substantially lower than those in healthy subjects. The correlation coefficient between total and free 25(OH)D₃ was 0.738 in all samples, while the linear regression equations were different between the patients with CKD and HC. In conclusion, LC-MS/MS assay for free 25(OH)D₃ might be useful to evaluate high-throughput methods, including ELISA.     

血清25-羟维生素D水平与儿童骨密度的相关性研究

目的:研究血清25-羟维生素D[25-(OH)D]水平与儿童骨密度(BMD)的相关性。方法:选择2017年1月到2017年12月在亳州市人民医院接受健康体检的儿童100例作为研究对象。根据血清25-(OH)D水平对维生素D(Vit D)营养状况进行分组,其中严重缺乏组9例,缺乏组28例,不足组42例和充足组21例。对比不同年龄段和不同性别儿童血清25-(OH)D、BMD水平以及不同Vit D营养状况儿童对应的BMD水平,并采用Spearman相关性分析法分析血清25-(OH)D水平与儿童BMD、年龄的相关性。结果:5-9岁和10-14岁儿童的血清25-(OH)D及BMD水平均分别低于1-4岁儿童,而10-14岁儿童又低于5-9岁儿童(P0.05)。男童的血清25-(OH)D及BMD水平均分别高于女童,差异有统计学意义(P0.05)。不足组、缺乏组、严重缺乏组儿童的BMD水平均分别低于充足组,且缺乏组和严重缺乏组低于不足组,严重缺乏组又低于缺乏组(P0.05)。根据Spearman相关性分析结果显示,血清25-(OH)D水平与儿童BMD呈正相关,而与年龄呈负相关(P0.05),年龄与儿童BMD呈负相关(P0.05)。结论:血清25-(OH)D水平与儿童BMD呈正相关,但与年龄则呈负相关,及时补充适量的Vit D以满足儿童的机体所需,有利于儿童健康成长。     

Characterization of monoglucuronides of vitamin D2 and 25-hydroxyvitamin D2 in rat bile using high-performance liquid chromatography-atmospheric pressure chemical ionization mass spectrometry

The characterization of vitamin D₂ 3-glucuronide, 25-hydroxyvitamin D₂ 3-glucuronide and 25-hydroxyvitamin D₂ 25-glucuronide, biliary metabolites obtained from rats dosed with vitamin D₂ and 25-hydroxyvitamin D₂ per os, was carried out using HPLC-atmospheric pressure chemical ionization (APCI)-MS. The glucuronide obtained from bile specimens was identified by comparison of its chromatographic behaviour with an authentic sample using HPLC—APCI-MS operating in the negative-ion mode. Methylation of the respective fraction with diazomethane gave the methyl ester, which was also confirmed by HPLC—APCI-MS operating in the positive-ion mode. The (M-M)⁻ and (M+NH₄)⁺ ions were monitored in the selected-ion monitoring mode.     

Stereochemistry of naturally-occurring 25-hydroxyvitamin D3-26,23 lactone as determined by radioligand binding analysis and high-performance liquid chromatography

The four stereoisomers of 25-hydroxyvitamin D₃-26,23 lactone (25-OHD₃-26,23 lactone) were tested against in vivo 25-OHD₃-26,23 lactone to determine their relative competition in the radioligand binding assays for 25-OHD₃ and 1,25-(OH)₂D₃. The 25R-OHD₃-26,23S lactone and in vivo 25-OHD₃-26,23 lactone behaved identically in the radioligand binding assay for 25-OHD₃ and were ～5-fold more potent than 25-OHD₃ at displacing 25-OH[³H]D₃. The 25S-OHD₃-26,23S lactone was the poorest competitor in this assay, requiring a 10-fold excess relative to 25-OHD₃ to displace 50% of the 25-OH[³H]D₃. The order of competition in the 25-OHD₃ radioligand binding assay was 25R-OHD₃-26,23S lactone = in vivo 25-OHD₃-26,23 lactone ? 25S-OHD₃-26,23R lactone > 25-OHD₃ ? 25R-OHD₃-26,23R lactone > 25S-OHD₃-26,23S lactone. The order of competition in the 1,25-(OH)₂D₃ cytosol receptor assay was essentially reversed from the competition in the 25-OHD₃ assay and was 25S-OHD₃-26,23S lactone > 25-OHD₃ ? 25S-OHD₃-26,23R lactone > 25R-OHD₃-26,23S lactone = in vivo 25-OHD₃-26,23 lactone. When tested in a high-performance liquid chromatographic system which separates all four stereoisomers, the in vivo 25-OHD₃-26,23 lactone comigrated with synthetic 25R-OHD₃-26,23S lactone. These data firmly establish that the naturally-occurring 25-OHD₃-26,23 lactone has the 25R, 23S stereochemistry. In addition, these data are the first to demonstrate that the four stereoisomers of 25-OHD₃-26,23 lactone have different affinities for the plasma vitamin D binding protein and the 1,25-(OH)₂D cytosol receptor.     

Oral temperatures of the elderly in nursing homes in summer and winter in relation to activities of daily living

 This study was conducted to clarify the seasonal difference in body temperature in summer and winter, and to document the thermal environment of the elderly living in nursing homes. The subjects were 57 healthy elderly people aged ≥63 years living in two nursing homes in Japan. One of the homes was characterized by subjects with low levels of activities of daily living (ADL). Oral temperatures were measured in the morning and afternoon, with simultaneous recording of ambient temperature and relative humidity. Oral temperatures in summer were higher than in winter, with statistically significant differences (P<0.05) of 0.25 (SD 0.61) °C in the morning and 0.24 (SD 0.50) °C in the afternoon. Differences between oral temperatures in summer and winter tended to be greater in subjects with low ADL scores, even when their room temperature was well-controlled. In conclusion, the oral temperatures of the elderly are lower in winter than summer, particularly in physically inactive people. It appears that those with low levels of ADL are more vulnerable to large changes in ambient temperature. Received: 28 March 1996 / Accepted: 12 November 1996     

Cross-talk among structural domains of human DBP upon binding 25-hydroxyvitamin D

Serum vitamin D-binding protein (DBP) is structurally very similar to serum albumin (ALB); both have three distinct structural domains and high cysteine-content. Yet, functionally they are very different. DBP possesses high affinity for vitamin D metabolites and G-actin, but ALB does not. It has been suggested that there may be cross-talk among the domains so that binding of one ligand may influence the binding of others. In this study we have employed 2-p-toluidinyl-6-sulfonate (TNS), a reporter molecule that fluoresces upon binding to hydrophobic pockets of DBP. We observed that recombinant domain III possesses strong binding for TNS, which is not influenced by 25-hydroxyvitamin D₃ (25-OH-D₃), yet TNS fluorescence of the whole protein is quenched by 25-OH-D₃. These results provide a direct evidence of cross-talk among the structural domains of DBP.     

Synthesis of two carboxylic haptens for raising antibodies to 25-hydroxyvitamin D3 and 1α,25-dihydroxyvitamin D3

Hapten derivatives of 25-hydroxyvitamin D₃ and 1α,25-dihydroxyvitamin D₃ were synthesized using the Wittig–Horner approach. Both haptens bearing a carboxylic group at the side chain that can be linked to a protein for raising antibodies of potential utility for the determination of 25-hydroxyvitamin D₃, 1α,25-dihydroxyvitamin D₃ and 1α-hydroxylated vitamin D₃ analogues.     

RNAi-mediated silencing of CYP27B1 abolishes 1,25(OH)2D3 synthesis and reduces osteocalcin and CYP24 mRNA expression in human osteosarcoma (HOS) cells

Although local synthesis of 1,25D has been postulated to regulate parameters of cell growth and differentiation in non-renal cells, the physiological role of 1,25D production in bone cells remains unclear. We used the technique of RNA interference to inhibit the mRNA encoding the enzyme responsible for 1,25D synthesis, 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1). Human osteosarcoma (HOS) cells were transfected with siRNA for CYP27B1 or non-silencing RNA before being treated with 25D for 48 h under normal growth conditions. De novo synthesis of 1,25D was measured in the media as well as mRNA levels for CYP27B1, osteocalcin (OCN) and 25-hydroxyvitamin D 24-hydroxylase (CYP24). We demonstrated that HOS cells express CYP27B1 mRNA, metabolize 25D and secrete detectable levels of de novo synthesized 1,25D. CYP27B1 mRNA silencing by RNAi, resulted in the suppression of 1,25D production and subsequent reduction of OCN and CYP24 mRNA expression. Our findings suggest that local 1,25D synthesis has paracrine effects in the bone microenvironment implying that vitamin D metabolism in human osteoblasts represents a physiologically important pathway, possibly regulating the maturation of osteoblasts.     

Isolation and identification of 1alpha-hydroxy-3-epi-vitamin D3, a potent suppressor of parathyroid hormone secretion

Since our original demonstration of the metabolism of 1alpha,25(OH)2D3 into 1alpha,25(OH)2-3-epi-D3 in human keratinocytes, there have been several reports indicating that epimerization of the 3 hydroxyl group of vitamin D compounds is a common metabolic process. Recent studies reported the metabolism of 25OHD3 and 24(R),25(OH)2D3 into their respective C-3 epimers, indicating that the presence of 1alpha hydroxyl group is not necessary for the 3-epimerization of vitamin D compounds. To determine whether the presence of a 25 hydroxyl group is required for 3-epimerization of vitamin D compounds, we investigated the metabolism of 1alphaOHD3, a non-25 hydroxylated vitamin D compound, in rat osteosarcoma cells (ROS 17/2.8). We noted metabolism of 1alphaOHD3 into a less polar metabolite which was unequivocally identified as 1alphaOH-3-epi-D3 using the techniques of HPLC, GC/MS, and 1H-NMR analysis. We also identified 1alphaOH-3-epi-D3 as a circulating metabolite in rats treated with pharmacological concentrations of 1alphaOHD3. Thus, these results indicated that the presence of a 25 hydroxyl group is not required for 3-epimerization of vitamin D compounds. Furthermore, the results from the same studies also provided evidence to indicate that 1alphaOH-3-epi-D3, like 1alphaOHD3, is hydroxylated at C-25. We then evaluated the biological activities of 1alphaOH-3-epi-D3. Treatment of normal rats every other day for 7 days with 2.5 nmol/kg of 1alphaOH-3-epi-D3 did not raise serum calcium, while the same dose of 1alphaOHD3 increased serum calcium by 3.39 +/- 0.52 mg/dl. Interestingly, in the same rats which received 1alphaOH-3-epi-D3 we also noted a reduction in circulating PTH levels by 65 +/- 7%. This ability of 1alphaOH-3-epi-D3 to suppress PTH levels in normal rats without altering serum calcium was further tested in rats with reduced renal function. The results indicated that the ED50 of 1alphaOH-3-epi-D3 for suppression of PTH was only slightly higher than that of 1alpha,25(OH)2D3, but that the threshold dose of the development of hypercalcemia (total serum Ca > 10.5 mg/dl) was nearly 80 times higher. These findings indicate that 1alphaOH-3-epi-D3 is a highly selective vitamin D analog with tremendous potential for treatment of secondary hyperparathyroidism in chronic renal failure patients.     

血清25-羟维生素D水平与脓毒症患儿凝血功能、炎性因子及预后的关系*

目的:探讨血清25-羟维生素D(25-OH-VitD)水平与脓毒症患儿凝血功能、炎性因子及预后的相关性。方法:选取2016年5月-2017年12月期间山东省立医院收治的脓毒症患儿68例为研究组,根据研究组患儿血清25-OH-VitD水平将其分为三组:缺乏组(20 ng/mL)6例、不足组(20-29.9 ng/mL)19例、充足组(≥30 ng/mL)43例,再根据研究组患儿28d后转归情况分为好转组56例与恶化组12例。另选取同时期在山东省立医院进行体检的健康儿童46例为对照组,检测并比较各组实验室指标,并分析血清25-OH-VitD与C反应蛋白(CRP)、白介素-2R(IL-2R)、白介素-6(IL-6)、降钙素原(PCT)、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)的相关性,对脓毒症患儿预后的独立影响因素进行Logistic回归分析。结果:缺乏组、不足组、充足组患儿CRP、IL-2R、IL-6、PCT、PT、APTT水平均明显高于对照组(P0.05),其中CRP、IL-2R、IL-6、PCT随着25-OH-VitD水平的降低而升高(P0.05)。与恶化组对比,好转组患儿血清25-OH-VitD水平明显升高,CRP、IL-2R、IL-6、PCT水平明显降低(P0.05)。经Pearson相关性分析显示,脓毒症患儿血清25-OH-VitD均与CRP、IL-2R、IL-6、PCT呈负相关(P0.05),与PT、APTT无关(P0.05)。经Logistic回归分析显示,血清25-OH-VitD是脓毒症患儿预后的独立影响因素(P0.05)。结论:血清25-OH-VitD与脓毒症患儿炎性因子密切相关,与凝血功能指标无关,且血清25-OH-VitD是其预后的独立影响因素。