Parathyroid hormone and 25-hydroxyvitamin D concentrations in sick and normal elderly people.

Serum 25-hydroxyvitamin D and immunoreactive parathyroid hormone concentrations were measured in normal elderly subjects living at home and in sick elderly patients in hospital. Normal old people tended to have high 25-hydroxyvitamin D and low parathyroid hormone concentrations; in the sick elderly this pattern was reversed. The raised serum parathyroid hormone concentrations in the sick elderly were not due to poor renal function and may have been a response to vitamin D deficiency. A high serum parathyroid hormone concentration in an elderly patient must be interpreted in the light of the patient''s general health and nutritional state. Caution is needed in diagnosing primary hyperparathyroidism in this age group.     

Summer/winter differences in the serum 25-hydroxyvitamin D3 and parathyroid hormone levels of Japanese women

Serum 25-hydroxyvitamin D₃ [25(OH)D₃] is produced in the skin in response to exposure to ultraviolet radiation, and is a good indicator of vitamin D nutritional status. The aim of this study was to determine summer/winter differences in serum 25(OH)D₃ and parathyroid hormone (PTH) in Japanese women and how the summer and winter values are related. The subjects were 122 healthy Japanese women aged 45–81 years (average age: 65.7 years). They were medically examined twice, in September 1997 and February 1999. Serum 25(OH)D₃ and intact PTH were determined by high-performance liquid chromatography and a two-site immunoradiometric assay respectively. Lifestyle information was obtained through an interview. The seasonal differences (winter minus summer) in 25(OH)D₃ [Δ25(OH)D₃] and intact PTH concentrations were –18.8 nmol/l (SD 19.2, P<0.0001) and 0.98pmol/l (SD 1.02, P<0.0001) respectively. The correlation coefficient between summer (x) and winter (y) 25(OH)D₃ levels was 0.462 (P<0.0001), with a linearly fitted line of y=0.42x+26.4. This relationship was interpreted as subjects with higher summer 25(OH)D₃ values having greater reductions in winter 25(OH)D₃ concentrations. There were inter-individual differences in Δ25(OH)D₃, although the summer and winter 25(OH)D₃ concentrations were well-correlated. Since Δ25(OH)D₃ was not associated with any of the lifestyle factors, seasonal differences in the 25(OH)D₃ concentrations of an individual appeared to reflect her ability to produce 25(OH)D₃ photochemically in the skin. Sun bathing would be a less effective means of attaining adequate vitamin D nutritional status in a person with a small seasonal difference in 25(OH)D₃, i.e., one with a low 25(OH)D₃ level. Received: 17 December 1999 / Revised: 24 April 2000 / Accepted: 10 May 2000     

Control of kidney 25-hydroxyvitamin D3 metabolism. Strontium and the involvement of parathyroid hormone.

The action of parathyroid extract (PTE) on the renal metabolism of 25-hydroxyvitamin D₃ (25-OHD₃) was evaluated in rat models for strontium rickets and hypoparathyroidism. PTE elevated the production of 1α,25-(OH)₂D₃ and suppressed the synthesis of 24,25-(OH)₂D₃ in both animal models. Part of strontium's action in suppressing 1α,25-(OH)₂D₃ and stimulating 24,25-(OH)₂D₃ synthesis in strontium rickets appears to involve a decrease in parathyroid hormone (PTH) secretion and/or action. Calcitonin (CT) was not implicated in the cation's action. Thyroparathyroidectomized rats showed a low level of 1α,25-(OH)₂D₃ production which increased four- to eightfold following chronic PTE treatment. PTH appears to be the major calcium regulatory hormone involved in modulation of renal 25-OHD₃ metabolism.     

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.     

The role of 1,25-dihydroxyvitamin D3 and parathyroid hormone in the regulation of chick renal 25-hydroxyvitamin D3-24-hydroxylase.

A single 325-pmol dose of 1,25-dihydroxyvitamin D₃ given to chicks fed a vitamin D-deficient diet containing 3% calcium and 0.6% phosphorus suppresses renal mitochondrial 25-hydroxyvitamin D₃-1α-hydroxylase and stimulates the 25-hydroxyvitamin D₃-24-hydroxylase as measured by in vitro assay. This alteration in the enzymatic activity takes place over a period of hours. The administration of parathyroid hormone rapidly suppresses the 25-hydroxyvitamin D₃-24-hydroxylase. The alterations in the hydroxylases by parathyroid hormone or 1,25-dihydroxyvitamin D₃ are not related to changes in serum clacium or phosphate but could be related to changes in intracellular levels of these ions. Actinomycin D or cycloheximide given in vivo reduces the 25-hydroxyvitamin D₃-24-hydroxylase activity rapidly which suggests that the turnover of the enzyme and its messenger RNA is rapid (1- and 5-h half-life, respectively). The half-lives of the hydroxylases are sufficiently short to permit a consideration that the regulation by 1,25-dihydroxyvitamin D₃ and parathyroid hormone may involve enzyme synthesis and degradation.     

Bone mineral density is inversely related to parathyroid hormone in adolescent girls.

Preventive programs aimed at maximizing peak bone mass as a way of reducing the risk of osteoporotic fractures later in life should take into account the contribution of nutritional factors to bone mass accumulation in young age. The role of calcium and energy intakes on radial mineral density was investigated in 200 healthy girls (aged 11-15 yr) simultaneously evaluating serum changes of insulin-like growth factor-I (IGF-I), parathyroid hormone (PTH) and osteocalcin (OC). Dietary calcium and energy intakes were assessed by a 3-day food record method, bone mineral density (BMD) was performed at ultradistal (ud) and proximal (pr) radial sites using dual energy X-ray absorptiometry. Calcium consumption below the levels suggested by Dietary Reference Intakes in more than 80% of population studied was not related to BMD, which in turn markedly increased in post-compared to premenarcheal girls. Interestingly, in a multiple regression analysis PTH was inversely related to BMD after adjustment for calcium intake, bone age and menarche. Serum IGF-I was positively associated to energy intakes and bone age in girls before menarche, who exhibited the highest values of OC. Our data highlighted the role of food habits in modulating some hormonal response that might influence bone mineral apposition during adolescent age. Low calcium consumption associated to enhanced PTH values, if persisting, could be responsible for reduced rate of gain in bone mineral density. Thus, to optimize bone mineralization during the critical period of rapid body growth adequate intakes of calcium and energy should be recommended.     

Milk consumption and bone mineral density in middle aged and elderly women.

OBJECTIVES--To study the effects of historical milk consumption on current bone mineral density at the hip and spine. DESIGN--Cross sectional study. SUBJECTS--284 community based women aged 44-74 years recruited from four general practice age-sex registers in Cambridge. Subjects categorised their average milk consumption up to age 25, from age 25-44, and from age 44 to the present time as > or = 1 glass/day, < 1 glass/day but > 1 glass/week, or < 1 glass/week. MAIN OUTCOME MEASURES--Bone mineral density at the hip and spine measured by dual energy x ray absorptiometry. RESULTS--Data on milk consumption up to age 25 years were available for 252 women. There was a consistent upward trend in bone mineral density at all sites with increasing historical milk consumption (total hip, femoral neck, trochanter, intertrochanter, P < 0.05; Ward''s triangle, P = 0.005). Adjustment for age and body size did not alter these trends. Milk consumption up to age 25 was a significant independent predictor of bone mineral density at all sites in multiple linear regression analyses controlling for age, body mass index, menopausal status, smoking, ever use of hormone replacement therapy or oral contraceptives, physical activity, and alcohol intake. The effects of milk consumption from age 25-44 and from age 44 to the present were similar in direction though not statistically significant. CONCLUSION--Frequent milk consumption before age 25 favourably influences hip bone mass in middle aged and older women.     

24,24-Difluoro-25-hydroxyvitamin D3-enhanced bone mineralization in rats. Comparison with 25-hydroxyvitamin3 and vitamin D3

The biological activity of 24,24-difluoro-25-hydroxyvitamin D₃ was assessed using elevation of serum phosphorus and healing of rickets of vitamin D-deficient rats. Various levels of 24,24-difluoro-25-hydroxyvitamin D₃ and 25-hydroxyvitamin D₃ were administered daily for 2 weeks in the dose range of 6.5 to 3250 pmol after feeding rats a low phosphorus, vitamin D-deficient diet for 3 weeks. Vitamin D₃ was concurrently tested at dose levels of 650 and 3250 pmol. 24,24-Difluoro-25-hydroxyvitamin D₃ is approximately equipotent with 25-hydroxyvitamin D₃ in stimulation of growth, mineralization of rachitic bone, and elevation of serum inorganic phosphorus. Radiological manifestations of rickets were also equally improved by 24,24-difluoro-25-hydroxyvitamin D₃ and 25-hydroxyvitamin D₃. Compared with vitamin D₃, these compounds were approximately 5 to 10 times more active in mineralization using rats on a low phosphorus, vitamin D-deficient diet. The functional role, if any, for 24-hydroxylated vitamin D compounds, such as 24,25-dihydroxyvitamin D₃, therefore remains obscure. It appears that vitamin D compounds that cannot be 24-hydroxylated evoke no disorder in bone mineralization.     

Pathways for kidney-specific uptake of the steroid hormone 25-hydroxyvitamin D3

Steroid hormones are believed to enter cells solely by free diffusion through the plasma membrane. However, recent work on the uptake of 25-hydroxyvitamin D3 into the kidney has identified an endocytic pathway that is responsible for the delivery of this steroid to renal tissues. This finding led to a new perception that endocytosis may play an important role in the cell-type-specific targeting and uptake of steroid hormones. In the present review, we describe the molecular components (e.g. steroid carriers, endocytic receptors and intracellular transport proteins) that constitute this novel pathway for tissue-specific uptake of vitamin D metabolites.     

Pre-diagnostic plasma 25-hydroxyvitamin D levels and risk of non-melanoma skin cancer in women

Background

Recent reports have shown that vitamin D status was inversely associated with the risk of various cancers. However, few studies examined the association between vitamin D levels and risk of skin cancer.

Methods

We prospectively evaluated the association between baseline plasma 25(OH)D levels and the risk of incident squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) among 4,641 women from the Nurses’ Health Study (NHS) and the NHS II with 510 incident BCC cases and 75 incident SCC cases. We used multivariate logistic regression models to calculate odds ratios (ORs) and 95% confidence intervals (CIs).

Results

Plasma 25(OH)D levels were positively associated with risk of BCC after adjusting for age at blood draw, season of blood draw, lab batch, hair color, burning tendency, the number of sunburns, and ultra-violet B flux of residence at blood collection. Women in the highest quartile of 25(OH)D had more than 2-fold increased risk of BCC compared with women in the lowest quartile (OR = 2.07, 95% CI = 1.52–2.80, P for trend <0.0001). We also found a significantly positive association between plasma 25(OH)D levels and SCC risk after adjusting for the same covariates (OR, highest vs. lowest quartile  = 3.77, 95% CI = 1.70–8.36, P for trend  = 0.0002).

Conclusion

In this prospective study of women, plasma vitamin D levels were positively associated with non-melanoma skin cancer risk. Considering that most circulating vitamin D is due to sun exposure, the positive association between plasma vitamin D and non-melanoma skin cancer is confounded by sun exposure. Our data suggest that one-time measurement of plasma vitamin D levels may reasonably reflect long-term sun exposure and predict the risk of non-melanoma skin cancer.     

Hepatic accumulation of vitamin D3 and 25-hydroxyvitamin D3.

Concomitant intravenous administration of 25-hydroxycholecalciferol and [3H] vitamin D3 to vitamin D-depleted rats did not affect the conversion of [3H] vitamin D3 to 25-OH-[3H] vitamin D3 as indicated by a serum 25-OH-[3H] vitamin D3 to content at 3 and 24 h identical to those observed in animals receiving [3H] vitamin D3 alone. Similarly, pre-dosing with 25-OH vitamin D3 24 h earlier did not affect the conversion. Co-administration to vitamin D depleted rats of vitamin D2 or D3, at 200-fold higher doses than a control group receiving tracer [3H] vitamin D3 alone, resulted in serum 25-OH vitamin D levels that were 15-20 fold higher than the control, indicating a similar metabolic fate for synthetic and natural vitamin D in rats and the ability of increased substrate to overwhelm hepatic constraints on 25-OH vitamin D production. Following intravenous administration of 25-OH-[3H] vitamin D3 to vitamin D depleted rats, hepatic 3H content decreased in parallel with serum radioactivity. Hepatic accumulation of intravenously administered vitamin D3 ([14C] vitamin D3) alone or with 25-OH-[3H] vitamin D3, by vitamin D-depleted rats revealed a marked preference for vitamin D3; the hepatic accumulation of [14C] vitamin D3 increased to 35% of the dose by 45 min, at which time 25-OH-[3H] vitamin D3 hepatic content was 7-fold less, and decreasing. Chromatography of extracts of hepatic subcellular fractions revealed more [14C] vitamin D3 than 25-OH-[3H] vitamin D3 in the microsomes, the reported site of calciferol 25-hydroxylase. Circulating 25-OH vitamin D, therefore, has comparatively minimal potential for hepatic accumulation. Product inhibition of the calciferol 25-hydroxylase must, therefore, result from recently synthesized hepatic 25-OH vitamin D, and is not affected by exogenous 25-OH vitamin D3.     

Parathyroid hormone is not involved in 1,25-dihydroxyvitamin D regulation of 25-hydroxyvitamin D metabolism in vivo

1,25-Dihydroxyvitamin D₃ administration to vitamin D-deficient rats suppresses accumulation of 1,25-dihydroxy-[3α-³H]vitamin D₃ and stimulates accumulation of 24,25-dihydroxy-[3α-³3H]vitamin D₃ from 25-hydroxy-[3α-³H]vitamin D₃ equally well in the presence and absence of parathyroid glands. These results demonstrate that this regulatory action is not mediated by the parathyroid glands and support conclusions from $\text{in}\text{vitro}$ studies that this represents a direct action of 1,25-dihydroxyvitamin D₃.     

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。     

Individual quantitation of vitamin D2, vitamin D3, 25-hydroxyvitamin D2, and 25-hydroxyvitamin D3 in human milk

Extraction, lipid-reduction, and chromatographic methods suitable for the resolution and subsequent quantitation of vitamin D2, vitamin D3, 25-hydroxyvitamin D2, and 25-hydroxy-vitamin D3 from human milk are described. This procedure utilizes a methanol:methylene chloride extraction, precipitation of unwanted lipids with cold methanol and ether, backwash with alkaline buffer, silica Sep-Pak preparative chromatography, normal- and reverse-phase high-performance liquid chromatography with final quantitation of the antirachitic sterols by competitive protein binding assay. The described assay was used to determine these antirachitic sterols in milk from women receiving various supplements of vitamin D or undergoing ultraviolet phototherapy.     

Fluorometric assay of 25-hydroxyvitamin D3 and 24R,25-dihydroxyvitamin D3 in plasma.

The first practical fluorometric assay of plasma 25-hydroxyvitamin D3 (25-OH-D3) and 24R,25-dihydroxyvitamin D3 (24,25-(OH)2D3) is described. The method uses a highly fluorescent dienophile, 4-[2-(6,7-dimethoxy-4-methyl-3-oxo-3,4-dihydroquinoxalyl)ethyl]-1, 2,4- triazoline-3,5-dione (DMEQ-TAD), to fluorescence-label vitamin D. Vitamin D metabolites were roughly purified with a short cartridge column followed by HPLC, labeled with DMEQ-TAD, and the product was analyzed on HPLC. In the assay of 25-OH-D3 the new fluorometric method was compared with the HPLC-uv method and was confirmed to be as accurate and reliable (CV, 4-5%) as the HPLC-uv method. Plasma 24,25-(OH)2D3 was accurately assayed by the HPLC-FL method, where the standard addition method was successfully used to calculate the overall recovery.