Influence of the Vitamin D-binding Protein on the Serum Concentration of 1,25-Dihydroxyvitamin D3: SIGNIFICANCE OF THE FREE 1,25-DIHYDROXYVITAMIN D3 CONCENTRATION
01 Mar 1981-Journal of Clinical Investigation (American Society for Clinical Investigation)-Vol. 67, Iss: 3, pp 589-596
TL;DR: The influence of the serum binding protein (DBP) for vitamin D and its metabolites on the concentration of its main ligands, 25-hydroxyvitamin D (3) (25-OHD(3)) and 1,25-dihydroxyv vitamin D(3)(1,25]-OH](2)D(3), was studied in this article.
Abstract: The influence of the serum binding protein (DBP) for vitamin D and its metabolites on the concentration of its main ligands, 25-hydroxyvitamin D(3) (25-OHD(3)) and 1,25-dihydroxyvitamin D(3) (1,25-[OH](2)D(3)) was studied. The concentration of both 1,25-(OH)(2)D(3) and DBP in normal female subjects (45+/-14 ng/liter and 333+/-58 mg/liter, mean+/-SD, respectively; n = 58) increased during the intake of estro-progestogens (69+/-27 ng/liter and 488+/-90 mg/liter, respectively; n = 29), whereas the 25-OHD(3) concentration remained unchanged. A positive correlation was found between the concentrations of 1,25-(OH)(2)D(3) and DBP in these women. At the end of pregnancy, the total concentrations of 1,25-(OH)(2)D(3) (97+/-26 ng/liter, n = 40) and DBP (616+/-84 mg/liter) are both significantly higher than in nonpregnant females and paired cord serum samples (48+/-11 ng/liter and 266+/-41 mg/liter, respectively). A marked seasonal variation of 25-OHD(3) was observed in pregnant females and their infants, whereas in the same samples the concentrations of both DBP and 1,25-(OH)(2)D(3) remained constant throughout the year. The free 1,25-(OH)(2)D(3) index, calculated as the molar ratio of this steroid and DBP, remains normal in women taking estro-progestogens, however, and this might explain their normal intestinal calcium absorption despite a high total 1,25-(OH)(2)D(3) concentration. In pregnancy the free 1,25-(OH)(2)D(3) index remains normal up to 35 wk of gestation, but during the last weeks of gestation, the free 1,25-(OH)(2)D(3) index increases in both circulations. A highly significant correlation exists between the (total and free) 25-OHD(3) and 1,25-(OH)(2)D(3) concentrations in maternal and cord serum both at 35 and 40 wk of gestation.
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TL;DR: Vitamin D3 is recommended in housebound elderly, and it may be cost-effective in hip fracture prevention in selected risk groups, and vitamin D3 supplementation may decrease the incidence of hip and other peripheral fractures in nursing home residents.
Abstract: Vitamin D deficiency is common in the elderly, especially in the housebound and in geriatric patients. The establishment of strict diagnostic criteria is hampered by differences in assay methods for 25-hydroxyvitamin D. The synthesis of vitamin D3 in the skin under influence of UV light decreases with aging due to insufficient sunlight exposure, and a decreased functional capacity of the skin. The diet contains a minor part of the vitamin D requirement. Vitamin D deficiency in the elderly is less common in the United States than elsewhere due to the fortification of milk and use of supplements. Deficiency in vitamin D causes secondary hyperparathyroidism, high bone turnover, bone loss, mineralization defects, and hip and other fractures. Less certain consequences include myopathy and falls. A diet low in calcium may cause an increased turnover of vitamin D metabolites and thereby aggravate vitamin D deficiency. Prevention is feasible by UV light exposure, food fortification, and supplements. Vitamin D3 supplementation causes a decrease of the serum PTH concentration, a decrease of bone turnover, and an increase of bone mineral density. Vitamin D3 and calcium may decrease the incidence of hip and other peripheral fractures in nursing home residents. Vitamin D3 is recommended in housebound elderly, and it may be cost-effective in hip fracture prevention in selected risk groups. (Endocrine Reviews 22: 477–501, 2001)
2,004 citations
TL;DR: These revised guidelines for vitamin D intake for healthy infants, children, and adolescents are based on evidence from new clinical trials and the historical precedence of safely giving 400 IU of vitamin D per day in the pediatric and adolescent population.
Abstract: Rickets in infants attributable to inadequate vitamin D intake and decreased exposure to sunlight continues to be reported in the United States. There are also concerns for vitamin D deficiency in older children and adolescents. Because there are limited natural dietary sources of vitamin D and adequate sunshine exposure for the cutaneous synthesis of vitamin D is not easily determined for a given individual and may increase the risk of skin cancer, the recommendations to ensure adequate vitamin D status have been revised to include all infants, including those who are exclusively breastfed and older children and adolescents. It is now recommended that all infants and children, including adolescents, have a minimum daily intake of 400 IU of vitamin D beginning soon after birth. The current recommendation replaces the previous recommendation of a minimum daily intake of 200 IU/day of vitamin D supplementation beginning in the first 2 months after birth and continuing through adolescence. These revised guidelines for vitamin D intake for healthy infants, children, and adolescents are based on evidence from new clinical trials and the historical precedence of safely giving 400 IU of vitamin D per day in the pediatric and adolescent population. New evidence supports a potential role for vitamin D in maintaining innate immunity and preventing diseases such as diabetes and cancer. The new data may eventually refine what constitutes vitamin D sufficiency or deficiency.
1,382 citations
TL;DR: A new unitary model for the pathophysiology of involutional osteoporosis is proposed that identifies estrogen (E) deficiency as the cause of both the early, accelerated and the late, slow phases of bone loss in postmenopausal women and as a contributing cause of the continuous phase ofBone loss in aging men.
Abstract: We propose here a new unitary model for the pathophysiology of involutional osteoporosis that identifies estrogen (E) deficiency as the cause of both the early, accelerated and the late, slow phases of bone loss in postmenopausal women and as a contributing cause of the continuous phase of bone loss in aging men. The accelerated phase in women is most apparent during the first decade after menopause, involves disproportionate loss of cancellous bone, and is mediated mainly by loss of the direct restraining effects of E on bone cell function. The ensuing slow phase continues throughout life in women, involves proportionate losses of cancellous and cortical bone, and is associated with progressive secondary hyperparathyroidism. This phase is mediated mainly by loss of E action on extraskeletal calcium homeostasis which results in net calcium wasting and increases in the level of dietary calcium intake required to maintain bone balance. Because elderly men have low circulating levels of both bioavailable E and bioavailable testosterone (T) and because recent data suggest that E is at least as important as T in determining bone mass in aging men, E deficiency may also contribute substantially to the continuous bone loss of aging men. In both genders, E deficiency increases bone resorption and may also impair a compensatory increase in bone formation. For the most part, this unitary model is well supported by observational and experimental data and provides plausible explanations to traditional objections to a unitary hypothesis.
1,104 citations
TL;DR: Adequate vitamin D supplementation and sensible sunlight exposure to reach optimal vitamin D status are among the front line factors of prophylaxis for the spectrum of disorders.
704 citations
References
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TL;DR: The data suggest that inadequate metabolism of 25-OH-D to 1,25(OH)(2)D contributes significantly to decreased calcium absorption and adaptation in both osteoporotic patients and elderly normal subjects.
Abstract: Intestinal calcium absorption assessed by a double-isotope method, decreased significantly with aging in 94 normal subjects (r = -0.22, P < 0.025). In 52 untreated patients with postmenopausal osteoporosis, calcium absorption was significantly lower than normal when either age or habitual calcium intake was used as a covariable (P < 0.001). Serum 25-hydroxyvitamin D (25-OH-D) and 1,25-dihydroxyvitamin D (1,25(OH)(2)D) were measured in 44 normal subjects and 27 osteoporotic patients. For all normals, calcium absorption and serum 1,25(OH)(2)D were positively correlated (r = 0.50, P < 0.001). In nonelderly normal subjects (ages 30-65 yr), dietary calcium intake correlated inversely with both calcium absorption (r = -0.39, P < 0.01) and with serum 1,25(OH)(2)D (r = -0.50, P < 0.01). Both osteoporotic patients and elderly normal subjects (ages 65-90 yr) differed from nonelderly normals in that these correlations were not present. In addition although serum 25-OH-D was normal, serum 1,25(OH)(2)D was significantly decreased in both osteoporotic patients and elderly normals (P < 0.001). In osteoporotic patients, calcium absorption increased significantly (P < 0.001) after 7 d administration of a small dose (0.4 mug/d) of synthetic 1,25(OH)(2)D(3). In osteoporotics mean serum immunoreactive parathyroid hormone was either normal (COOH-terminal assay) or low (NH(2)-terminal assay) relative to age-matched controls, and mean serum phosphate was increased. The data suggest that inadequate metabolism of 25-OH-D to 1,25(OH)(2)D contributes significantly to decreased calcium absorption and adaptation in both osteoporotics and elderly normal subjects. In patients with osteoporosis this abnormality could result from a decrease in factors that normally stimulate 1,25(OH)(2)D production, such as the decreased parathyroid hormone secretion and increased serum phosphate demonstrated in this group. In elderly subjects a primary abnormality in metabolism of 25-OH-D to 1,25(OH)(2)D, analagous to that seen in aging rats, cannot be excluded.
800 citations
TL;DR: It is concluded that postmenopausal sex-hormone replacement measurably decreases age-related bone loss by suppressing bone turnover, resorption more than accretion, and calcium supplements produce the same effect but at the dose the authors used were slightly less effective.
Abstract: Sixty postmenopausal women were placed in three groups--control, sex hormone-treated, and CaCO3-treated--and followed for 2 years. Skeletal mass decreased by 1.18%/year in the control group, 0.15%/year in the hormone group, and 0.22%/year in the CaCO3 group by radiogrammetry; and 2.88%/year in the control group, 0.73%/year in the hormone group, and 1.83%/year in the CaCO3 group by photon absorptiometry. The treatment groups differed significantly from the control group except for photon absorptiometry in the CaCO3 group. Bone accretion and resorption decreased in the treatment groups as measured by calcium tracer kinetics, resorption more so than accretion. We conclude that [1] these techniques are sufficiently sensitive to detect age-related bone loss; [2] postmenopausal sex-hormone replacement measurably decreases age-related bone loss by suppressing bone turnover, resorption more than accretion; and [3] calcium supplements produce the same effect but at the dose we used were slightly less effective.
525 citations
Journal Article•
TL;DR: In this article, the authors found a statistically significant positive correlation between calcium balance and both calcium intake and calcium absorption, and concluded that there is a specific, estrogen-related shift in calcium performance across menopause and that the reason for the positive effect of estrogen on balance and intake requirement is a combination of enhancement of intestinal absorption efficiency and improved renal calcium conservation.
488 citations
TL;DR: Intestinal calcium absorption was twice usual normal levels from the earliest period studied and remained high throughout pregnancy, and there was a 20% increase in miscible calcium pool by term, and an approximate doubling of both pool turnover and bone mineral accretion rates.
Abstract: Fifteen normal pregnant women and 9 female controls of similar age underwent mineral balance and calcium kinetic studies during and after pregnancy 48Ca, a stable isotope, was employed in the pregnant women and specimens were measured by neutron activation analysis Results were related to stage of pregnancy and demonstrated the expected and well documented retention of nitrogen, phosphorus, and calcium associated with fetal development In addition, there was a 20% increase in miscible calcium pool by term, and an approximate doubling of both pool turnover and bone mineral accretion rates, both rising progressively with duration of pregnancy Intestinal calcium absorption was twice usual normal levels from the earliest period studied and remained high throughout pregnancy Virtually all these changes reverted to normal non-pregnant levels by 3 months after delivery The importance of maternal adjustments as a component in these changes was emphasized by the presence of significant changes in ac
349 citations
TL;DR: In vitro synthesis of 24,25(OH)2D3 by human placenta and of 1α,25 (OH) 2D3 and 24, 25(OH), 2D and 3 by human decidua is reported, suggesting that there may be independent vitamin D metabolism in the fetoplacental unit.
Abstract: The biologically active metabolite of vitamin D, 1α, 25-dihydroxyvitamin D (1α, 25(OH)2D), is synthesised by successive hydroxylation of vitamin D in the liver and kidney1. The latter organ is the only known site of 1α-hydroxylation of 25-hydroxyvitamin D (25-OH-D)2 and is also a major site of production of 24,25-dihydroxyvitamin D (24,25(OH)2D), a metabolite involved in bone ossification3. However, 24-hydroxylation of 25-OH-D may also occur in rat intestinal homogenates and in cartilage cells4,5. Accumulating data show that, during pregnancy, 1α, 25(OH)2D increases in the maternal circulation6 but is absent or present only in small amounts in the fetus7,8. In comparison, 24,25(OH)2D accumulates in fetal tissues, particularly in the skeleton8. Little is known, however, about the independent metabolism of vitamin D in the fetoplacental unit. It has been reported9 that the nephrectomised pregnant rat can synthesise 1α, 25(OH)2D3 and 24,25(OH)2D3 and that the fetoplacental unit is the most likely site of production of such metabolites. Those data suggested that there may be independent vitamin D metabolism in the fetoplacental unit. We now report in vitro synthesis of 24,25(OH)2D3 by human placenta and of 1α,25(OH)2D3 and 24,25(OH)2D3 by human decidua. The human decidua is a development of the endometrium that is unique to pregnancy, originating from both epithelial and stromal cells and intimately attached to fetal structures, that is, the placenta and chorion.
339 citations