admission. This proportion could already be greater in some parts of the country and may increase if referrals of cases of self-poisoning increase faster than the facilities for their assessment and management. The provision of social work and psychiatric expertise in casualty departments may be one means of preventing unnecessary medical admissions without risk to the patients. Dr Blake's and Dr Bramble's figures do not demonstrate, however, that any advantage would attach to medical teams taking over assessment from psychiatrists except that, by implication, assessments would be completed sooner by staff working on the ward full time. What the figures actually suggest is that if assessment of overdoses were left to house doctors there would be an increase in admissions to psychiatric units (by 19°U), outpatients (by 5O°'), and referrals to social services (by 140o). So for house doctors to assess overdoses would provide no economy for the psychiatric or social services. The study does not tell us what the consequences would have been for the six patients who the psychiatrists would have admitted but to whom the house doctors would have offered outpatient appointments. E J SALTER

Vitamin D deficiency.

METHODS In the Healthy Aging in Neighborhoods of Diversity across the Life Span cohort of blacks and whites (2085 participants), we measured levels of total 25-hydroxyvitamin D, vitamin D–binding protein, and parathyroid hormone as well as bone mineral density (BMD). We genotyped study participants for two common polymorphisms in the vitamin D–binding protein gene (rs7041 and rs4588). We estimated levels of bioavailable 25-hydroxyvitamin D in homozygous participants. RESULTS Mean (±SE) levels of both total 25-hydroxyvitamin D and vitamin D–binding protein were lower in blacks than in whites (total 25-hydroxyvitamin D, 15.6±0.2 ng per milliliter vs. 25.8±0.4 ng per milliliter, P<0.001; vitamin D–binding protein, 168±3 µg per milliliter vs. 337±5 µg per milliliter, P<0.001). Genetic polymorphisms independently appeared to explain 79.4% and 9.9% of the variation in levels of vitamin D–binding protein and total 25-hydroxyvitamin D, respectively. BMD was higher in blacks than in whites (1.05±0.01 g per square centimeter vs. 0.94±0.01 g per square centimeter, P<0.001). Levels of parathyroid hormone increased with decreasing levels of total or bioavailable 25-hydroxyvitamin D (P<0.001 for both relationships), yet within each quintile of parathyroid hormone concentration, blacks had significantly lower levels of total 25-hydroxyvitamin D than whites. Among homozygous participants, blacks and whites had similar levels of bioavailable 25-hydroxy vitamin D overall (2.9±0.1 ng per milliliter and 3.1±0.1 ng per milliliter, respectively; P = 0.71) and within quintiles of parathyroid hormone concentration. CONCLUSIONS Community-dwelling black Americans, as compared with whites, had low levels of total 25-hydroxyvitamin D and vitamin D–binding protein, resulting in similar concentrations of estimated bioavailable 25-hydroxyvitamin D. Racial differences in the prevalence of common genetic polymorphisms provide a likely explanation for this observation. (Funded by the National Institute on Aging and others.)

https://handls.nih.gov/pubs/2013-Powe-NEJM-1991-2000.pdf

Vitamin D–Binding Protein and Vitamin D Status of Black Americans and White Americans

BACKGROUND
Hypovitaminosis D and a low calcium intake contribute to increased parathyroid function in elderly persons. Calcium and vitamin D supplements reduce this secondary hyperparathyroidism, but whether such supplements reduce the risk of hip fractures among elderly people is not known.


METHODS
We studied the effects of supplementation with vitamin D3 (cholecalciferol) and calcium on the frequency of hip fractures and other nonvertebral fractures, identified radiologically, in 3270 healthy ambulatory women (mean [+/- SD] age, 84 +/- 6 years). Each day for 18 months, 1634 women received tricalcium phosphate (containing 1.2 g of elemental calcium) and 20 micrograms (800 IU) of vitamin D3, and 1636 women received a double placebo. We measured serial serum parathyroid hormone and 25-hydroxyvitamin D (25(OH)D) concentrations in 142 women and determined the femoral bone mineral density at base line and after 18 months in 56 women.


RESULTS
Among the women who completed the 18-month study, the number of hip fractures was 43 percent lower (P = 0.043) and the total number of nonvertebral fractures was 32 percent lower (P = 0.015) among the women treated with vitamin D3 and calcium than among those who received placebo. The results of analyses according to active treatment and according to intention to treat were similar. In the vitamin D3-calcium group, the mean serum parathyroid hormone concentration had decreased by 44 percent from the base-line value at 18 months (P < 0.001) and the serum 25(OH)D concentration had increased by 162 percent over the base-line value (P < 0.001). The bone density of the proximal femur increased 2.7 percent in the vitamin D3-calcium group and decreased 4.6 percent in the placebo group (P < 0.001).


CONCLUSIONS
Supplementation with vitamin D3 and calcium reduces the risk of hip fractures and other nonvertebral fractures among elderly women.

Vitamin D and Calcium to Prevent Hip Fractures in Elderly Women

In the last 5 years, there has been a remarkable change in our understanding of the health benefits of vitamin D. The classical actions of vitamin D as a determinant of mineral metabolism and rachitic bone disease have been expanded to include a broader role in skeletal homoeostasis and prevalent bone disorders such as osteoporosis. However, it is the nonskeletal function of vitamin D that has attracted most attention. Although pluripotent responses to vitamin D have been recognized for many years, our new perspective on nonclassical vitamin D function stems from two more recent concepts. The first is that impaired, vitamin D status is common to many populations across the globe. This has prompted studies to explore the health impact of suboptimal circulating levels of vitamin D, with association studies linking vitamin D 'insufficiency' to several chronic health problems including autoimmune and cardiovascular disease, hypertension and common cancers. In support of a broader role for vitamin D in human health, studies in vitro and using animal models have highlighted immunomodulatory and anticancer effects of vitamin D that appear to depend on localized activation of vitamin D. The conclusion from these reports is that many nonclassical actions of vitamin D are independent of conventional vitamin D endocrinology and are therefore more sensitive to variations in vitamin D status. The current review summarizes these developments, with specific reference to the newly identified effects of vitamin D on the immune system, but also highlights the challenges in translating these observations to clinical practice.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1365-2265.2011.04261.x

An update on vitamin D and human immunity.

Vitamin D and DBP: the free hormone hypothesis revisited.

Studies examining the relationship between total circulating 25-hydroxyvitamin D [25(OH)D] levels and bone mineral density (BMD) have yielded mixed results. Vitamin D-binding protein (DBP), the major carrier protein for 25(OH)D, may alter the biologic activity of circulating vitamin D. We hypothesized that free and bioavailable 25(OH)D, calculated from total 25(OH)D, DBP, and serum albumin levels, would be more strongly associated with BMD than levels of total 25(OH)D. We measured total 25(OH)D, DBP, and serum albumin levels in 49 healthy young adults enrolled in the Metabolic Abnormalities in College-Aged Students (MACS) study. Lumbar spine BMD was measured in all subjects using dual-energy X-ray absorptiometry. Clinical, diet, and laboratory information also was gathered at this time. We determined free and bioavailable (free + albumin-bound) 25(OH)D using previously validated formulas and examined their associations with BMD. BMD was not associated with total 25(OH)D levels (r = 0.172, p = .236). In contrast, free and bioavailable 25(OH)D levels were positively correlated with BMD (r = 0.413, p = .003 for free, r = 0.441, p = .002 for bioavailable). Bioavailable 25(OH)D levels remained independently associated with BMD in multivariate regression models adjusting for age, sex, body mass index, and race (p = .03). It is concluded that free and bioavailable 25(OH)D are more strongly correlated with BMD than total 25(OH)D. These findings have important implications for vitamin D supplementation in vitamin D-deficient states. Future studies should continue to explore the relationship between free and bioavailable 25(OH)D and health outcomes.

Delger Erdenesanaa

Papers

Vitamin D–binding protein modifies the vitamin D–bone mineral density relationship