FGF23 is correlated with iron status but not with inflammation and decreases after iron supplementation: a supplementation study.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: Recent studies have described relationships between iron status and fibroblast growth factor-23 (FGF23) but the possible confounding effects of inflammation on iron status have not been considered. The aims of this study were a) to consider a relationship between FGF23 and inflammation b) to identify relationships between iron status and FGF23 whilst correcting for inflammation and c) to assess the relationship between changes in FGF23 and iron status after supplementation. STUDY DESIGN AND METHODOLOGY: Blood samples from an iron supplementation study in children (n=79) were collected at baseline and after 3 months supplementation with iron sulphate. The children were from a rural Gambian population where rates of iron deficiency and infection/inflammation are high. This study identified cross-sectional and longitudinal relationships between FGF23, inflammation (C-reactive protein (CRP)) and iron status (ferritin, haemoglobin, and zinc protoporphyrin). CRP ≥ 5 mg/dL was used to indicate inflammation and FGF23 ≥ 125 RU/mL was considered elevated. RESULTS: FGF23 was not significantly correlated with CRP. At baseline, all markers of iron status were significantly correlated with FGF23. Ferritin was the strongest independent inverse predictor of FGF23 in subjects with and without elevated CRP (coefficient (SE)): All subjects=-0.57 (0.12), R2=22.3%, P≤0.0001; subjects with CRP < 5 mg/dL=-0.89 (0.14), R2=38.9%, P≤0.0001. FGF23 was elevated in 28% of children at baseline and 16% post supplementation (P=0.1). Improved iron status was associated with a decrease in FGF23 concentration in univariate (ferritin =-0.41 (0.11), R2=14.1%, P=0.0004; haemoglobin=-2.22 (0.64), R2=12.5%, P=0.0008; zinc protoporphyrin=1.12 (0.26), R2=18.6%, P≤0.0001) and multivariate analysis (R2=33.1%; ferritin=-0.36 (0.10), P=0.0007, haemoglobin = -1.83 (0.61), P=0.004, zinc protoporphyrin=0.62 (0.26), P=0.02). CONCLUSIONS: Iron status rather than inflammation is a negative predictor of plasma FGF23 concentration. Improvements in iron status following iron supplementation are associated with a significant decrease in FGF23 concentration

"Living on Paper:" Georgia O'Keeffe and the Culture of Drawing and Watercolor in the Stieglitz Circle

Drawing and watercolor were important in shaping the modernism of artist Georgia O'Keeffe and photographer Alfred Stieglitz. In his gallery 291 and journal Camera Work, Stieglitz introduced European avant-garde art to early twentieth-century America and promoted American modernists including O'Keeffe. Stieglitz as a child collected drawings and watercolors and learned traditional drawing connoisseurship that valued revelation of the artist's character through the marks he made on paper. Stieglitz's journals Camera Notes and Camera Work asserted connections between photography and other graphic media. Stieglitz and Edward Steichen founded 291 as a pictorial photography gallery but later exhibited modern paintings and many drawings and watercolors. O'Keeffe studied academic art at the Art Institute of Chicago and the Art Students League in New York, but she wanted more creative freedom. Art educator Arthur Wesley Dow introduced O'Keeffe to abstract design principles and prepared her to appreciate modern art. While O'Keeffe was training as an art teacher at Columbia University Teachers College in New York in 1914 and 1915, she visited 291 and became interested in modern art. The modern art O'Keeffe had seen was mainly in form of drawings and watercolor at 291 and reproductions in modernist journals, so her original conception of modernism was graphic. Her first modern art works, made in South Carolina in 1915, were abstract charcoal drawings that combined academic drawing techniques with modernist approaches from charcoal drawings by Pablo Picasso and Marius de Zayas. Stieglitz interpreted O'Keeffe's drawings as naïve expressions of female sexuality and showed them at 291 in 1916. O'Keeffe taught art in Texas and made modernist watercolors of the Texas sky and landscape. Stieglitz showed her new works at 291 in 1917. In 1918 O'Keeffe returned to New York and moved in with Stieglitz. She concentrated on painting in oils for the rest of her career. Stieglitz photographed O'Keeffe with her drawings and watercolors, connecting the marks on paper with the artist's body, hands, and sexuality. While exhibiting O'Keeffe's oil paintings, Stieglitz continued for decades to show O'Keeffe's early drawings to critics and to stress her origins as a simple graphic artist

The adolescent transition under energetic stress: Body composition tradeoffs among adolescent women in The Gambia

Background and objectives: Life history theory predicts a shift in energy allocation from growth to reproductive function as a consequence of puberty. During adolescence, linear growth tapers off and, in females, ovarian steroid production increases. In this model, acquisition of lean mass is associated with growth while investment in adiposity is associated with reproduction. This study examines the chronological and developmental predictors of energy allocation patterns among adolescent women under conditions of energy constraint. Methodology: Fifty post-menarcheal adolescent women between 14 and 20 years old were sampled for weight and body composition at the beginning and end of 1 month in an energy-adequate season and 1 month in the subsequent energy-constrained season in a rural province of The Gambia. Results: Chronologically and developmentally younger adolescent girls gain weight in the form of lean mass in both energy-adequate and energy-constrained seasons, whereas older adolescents lose lean mass under conditions of energetic stress (generalized estimating equation (GEE) Wald chi-square comparing youngest tertile with older two tertiles 9.750, P = 0.002; GEE Wald chi-square comparing fast- with slow-growing individuals for growth rate 19.806, P < 0.001). When energy is limited, younger adolescents lose and older adolescents maintain fat (GEE Wald chi-square for interaction of age and season 6.568, P = 0.010; GEE Wald chi-square comparing fast- with slow-growing individuals for interaction of growth rate and season 7.807, P = 0.005). Conclusions and implications: When energy is constrained, the physiology of younger adolescents invests in growth while that of older adolescent females privileges reproductively valuable adipose tissue

Predictors of intact and C-terminal fibroblast growth factor 23 in Gambian children

Elevated C-terminal fibroblast growth factor 23 (C-FGF23) concentrations have been reported in Gambian children with and without putative Ca-deficiency rickets. The aims of this study were to investigate whether i) elevated C-FGF23 concentrations in Gambian children persist long term; ii) they are associated with higher intact FGF23 concentrations (I-FGF23), poor iron status and shorter 25-hydroxyvitamin D half-life (25OHD-t1/2); and iii) the persistence and predictors of elevated FGF23 concentrations differ between children with and without a history of rickets. Children (8-16 years, n=64) with a history of rickets and a C-FGF23 concentration >125 RU/ml (bone deformity (BD), n=20) and local community children with a previously measured elevated C-FGF23 concentration (LC+, n=20) or a previously measured C-FGF23 concentration within the normal range (LC-, n=24) participated. BD children had no remaining signs of bone deformities. C-FGF23 concentration had normalised in BD children, but remained elevated in LC+ children. All the children had I-FGF23 concentration within the normal range, but I-FGF23 concentration was higher and iron status poorer in LC+ children. 1,25-dihydroxyvitamin D was the strongest negative predictor of I-FGF23 concentration (R(2)=18%; P=0.0006) and soluble transferrin receptor was the strongest positive predictor of C-FGF23 concentration (R(2)=33%; P≤0.0001). C-FGF23 and I-FGF23 concentrations were poorly correlated with each other (R(2)=5.3%; P=0.07). 25OHD-t1/2 was shorter in BD children than in LC- children (mean (s.d.): 24.5 (6.1) and 31.5 (11.5) days respectively; P=0.05). This study demonstrated that elevated C-FGF23 concentrations normalised over time in Gambian children with a history of rickets but not in local children, suggesting a different aetiology; that children with resolved rickets had a shorter 25OHD-t1/2, suggesting a long-standing increased expenditure of 25OHD, and that iron deficiency is a predictor of elevated C-FGF23 concentrations in both groups of Gambian children

Life course dietary patterns and bone health in later life in a British birth cohort study

Evidence for the contribution of individual foods and nutrients to bone health is weak. Few studies have considered hypothesis-based dietary patterns and bone health. We investigated whether a protein, calcium and potassium-rich (PrCaK-rich) dietary pattern over the adult life course, was positively associated with bone outcomes at 60-64 years of age. Diet diaries were collected at ages 36, 46, 53 and 60-64 years in 1263 participants (661 women) from the MRC National Survey of Health and Development. DXA and pQCT measurements were obtained at 60-64y, including size-adjusted bone mineral content (SA-BMC) and volumetric bone mineral density (vBMD). A food-based dietary pattern best explaining dietary calcium, potassium and protein intakes (g/1000?kcal) was identified using reduced rank regression. Dietary pattern z-scores were calculated for each individual, at each time point. Individual trajectories in dietary pattern z-scores were modelled to summarise changes in z-scores over the study period. Regression models examined associations between these trajectories and bone outcomes at 60-64y, adjusting for baseline dietary pattern z-score and other confounders. A consistent PrCaK-rich dietary pattern was identified within the population, over time. Mean [SD] dietary pattern z-scores at age 36 and 60-64 years were -0.32[0.97], 2.2[1.5] (women) and -0.35[0.98], 1.7[1.6] (men). Mean trajectory in dietary pattern z-scores [SD] was 0.07[0.02]SD units/year. Among women, a 0.02 SD unit/year higher trajectory in dietary pattern z-score over time was associated with higher SA-BMC (spine 1.40% [95% CI: 0.30,2.51]; hip 1.35% [95% CI: 0.48,2.23]) and vBMD (radius 1.81% [95% CI: 0.13,3.50]) at 60-64 y. No statistically significant associations were found in men. During adulthood, an increasing score for a dietary pattern rich in protein, calcium and potassium was associated with greater SA-BMC at fracture-prone sites in women. This study emphasises the importance of these nutrients, within the context of the whole diet, to bone healt

Plasma appearance and disappearance of an oral dose of 25-hydroxyvitamin D2 in healthy adults

25-Hydroxyvitamin D (25(OH)D) half-life is a potential biomarker for investigating vitamin D metabolism and requirements. We performed a pilot study to assess the approach and practical feasibility of measuring 25(OH)D half-life after an oral dose. A total of twelve healthy Gambian men aged 18–23 years were divided into two groups to investigate the rate and timing of (1) absorption and (2) plasma disappearance after an 80 nmol oral dose of 25(OH)D2. Fasting blood samples were collected at baseline and, in the first group, every 2 h post-dose for 12 h, at 24 h, 48 h and on day 15. In the second group, fasting blood samples were collected on days 3, 4, 5, 6, 9, 12, 15, 18 and 21. Urine was collected for 2 h after the first morning void at baseline and on day 15. 25(OH)D2 plasma concentration was measured by ultra-performance liquid chromatography-tandem MS/MS and corrected for baseline. Biomarkers of vitamin D, Ca and P metabolism were measured at baseline and on day 15. The peak plasma concentration of 25(OH)D2 was 9·6 (sd 0·9) nmol/l at 4·4 (sd 1·8) h. The terminal slope of 25(OH)D2 disappearance was identified to commence from day 6. The terminal half-life of plasma 25(OH)D2 was 13·4 (sd 2·7) d. There were no significant differences in plasma 25(OH)D3, total 1,25(OH)2D, parathyroid hormone, P, Ca and ionised Ca and urinary Ca and P between baseline and day 15 and between the two groups. The present study provides data on the plasma response to oral 25(OH)D2 that will underpin and contribute to the further development of studies to investigate 25(OH)D half-life

Prevalence of rickets-like bone deformities in rural Gambian children.

The aim of this study was to estimate the burden of childhood rickets-like bone deformity in a rural region of West Africa where rickets has been reported in association with a low calcium intake. A population-based survey of children aged 0.5-17.9 years living in the province of West Kiang, The Gambia was conducted in 2007. 6221 children, 92% of those recorded in a recent census, were screened for physical signs of rickets by a trained survey team with clinical referral of suspected cases. Several objective measures were tested as potential screening tools. The prevalence of bone deformity in children <18.0 years was 3.3%. The prevalence was greater in males (M = 4.3%, F = 2.3%, p < 0.001) and in children <5.0 years (5.7%, M = 8.3%, F = 2.9%). Knock-knee was more common (58%) than bow-leg (31%) or windswept deformity (9%). Of the 196 examined clinically, 36 were confirmed to have a deformity outside normal variation (47% knock-knee, 53% bow-leg), resulting in more conservative prevalence estimates of bone deformity: 0.6% for children <18.0 years (M = 0.9%, F = 0.2%), 1.5% for children < 5.0 years (M = 2.3%, F = 0.6%). Three of these children (9% of those with clinically-confirmed deformity, 0.05% of those screened) had active rickets on X-ray at the time of medical examination. This emphasises the difficulties in comparing prevalence estimates of rickets-like bone deformities from population surveys and clinic-based studies. Interpopliteal distance showed promise as an objective screening measure for bow-leg deformity. In conclusion, this population survey in a rural region of West Africa with a low calcium diet has demonstrated a significant burden of rickets-like bone deformity, whether based on physical signs under survey conditions or after clinical examination, especially in boys < 5.0 years

Changes in Bone Mineral Density During and After Lactation in Ugandan Women With HIV on Tenofovir-Based Antiretroviral Therapy.

Antiretroviral therapy (ART) in people living with human immunodeficiency virus (HIV) is associated with bone loss, but data are limited in lactation, when physiological bone mineral mobilization is occurring. This research charted changes in areal bone mineral density (aBMD) during and after lactation in Ugandan women with HIV (WWH) initiated onto ART in pregnancy, compared to women without HIV (REF). One-hundred WWH on tenofovir-based ART and 100 REF were enrolled in pregnancy. Lumbar spine (LS), total hip (TH), and whole-body-less-head (WBLH) aBMD were measured by dual-energy X-ray absorptiometry (DXA) at 2, 14, and 26 weeks of lactation, and at 3 months postlactation. The primary outcome was the difference between groups in mean percent change in LS aBMD between 2 and 14 weeks. Statistical analysis was performed in hierarchical repeated measures ANOVA models that corrected for multiple testing. Median age was 23.4 (IQR, 21.0 to 26.8) years. WWH had lower body weight. aBMD decreased in both groups during lactation, but WWH had greater decreases at TH (2-to-26 weeks: WWH [n = 63] -5.9% [95% CI, -6.4 to -5.4] versus REF [n = 64] -4.3% [95% CI, -4.8 to -3.8]; group*time point interaction p = .008). Decreases in LS aBMD were similar in WWH and REF (2-to-26 weeks: -2.0% [95% CI, -2.5 to -1.5]), although there was a tendency toward a smaller decrease in WWH between 2 and 14 weeks (WWH [n = 77] -1.8% [95% CI, -2.2 to -1.4] versus REF [n = 69] -2.9% [95% CI, -3.3 to -2.5]; group*time point interaction p = .08). Postlactation, LS aBMD was higher relative to week 2 in both groups. TH and WBLH aBMD did not return to week 2 values in WWH but did in REF (TH postlactation versus week 2: WWH [n = 61] -3.1% [95% CI, -3.6 to -2.6]; REF [n = 29] +0.1% [95% CI, -0.9 to +1.1]). These data show accentuated bone loss during lactation and only partial skeletal recovery by 3 months postlactation in Ugandan WWH on tenofovir-based ART. Studies are ongoing to understand longer-term consequences for bone health. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research

Iron bioavailability: UK Food Standards Agency workshop report

The UK Food Standards Agency convened a group of expert scientists to review current research investigating factors affecting iron status and the bioavailability of dietary iron. Results presented at the workshop show menstrual blood loss to be the major determinant of body iron stores in premenopausal women. In the presence of abundant and varied food supplies, the health consequences of lower iron bioavailability are unclear and require further investigatio

Vitamin D expenditure is not altered in pregnancy and lactation despite changes in vitamin D metabolite concentrations.

Pregnancy and lactation are associated with changes in vitamin D and calcium metabolism but the impact of these changes on vitamin D expenditure is unknown. We measured plasma 25(OH)D3 half-life with a stable-isotope tracer and investigated relationships with vitamin D metabolites in pregnant, lactating and 'non-pregnant, non-lactating' (NPNL) women. Vitamin D metabolites, vitamin D binding protein (DBP), PTH and 25(OH)D3 half-life were measured in third-trimester pregnant women (n22) and repeated during lactation 12 weeks post-partum (n14) and twice in NPNL women (n23 and n10, respectively) in rural Gambia where calcium intakes are low with little seasonality in UVB-exposure. 25(OH)D3 half-life was not significantly different between groups (mean(SD): 20.6(6.8), 22.6(7.7), 18.0(4.7) and 17.7(9.5) days in pregnant, lactating and NPNL women, respectively). Plasma 25(OH)D3, 1,25(OH)2D, and DBP were higher in pregnancy, and calculated free-25(OH)D3 and PTH were lower (P < 0.05). In lactation, 25(OH)D3 and 24,25(OH)2D3 were lower compared to pregnant (P < 0.001, P = 0.02) and NPNL women (P = 0.04, P = 0.07). Significant associations were observed between half-life and 25(OH)D3 (+ve) in pregnancy, and in all groups between 25(OH)D3 and free-25(OH)D3 (+ve) and PTH and 25(OH)D3 (-ve) (P < 0.0001). These data suggest that adaptive changes in pregnancy and lactation occur that prevent pronounced changes in vitamin D expenditure