Maternal diet but not gestational weight gain predicts central adiposity accretion in utero among pregnant adolescents.

BACKGROUND: Modifiable risk factors during pregnancy, such as diet and weight gain, are associated with fetal birth weight but little is known about how these factors influence fetal fat acquisition in utero among pregnant adolescents. OBJECTIVE: To determine whether maternal pre-pregnancy BMI (ppBMI), gestational weight gain (GWG) and dietary intake during pregnancy influence fetal fat accretion in utero. METHODS: Longitudinal data were obtained from 121 pregnant adolescents enrolled in a study designed to identify determinants of maternal and fetal bone changes across gestation. Adolescents (ages 13-18 years) completed up to three study visits during early, mid- and late gestation. Maternal anthropometrics, 24 h dietary recalls and measures of fetal biometry were obtained at each visit. Fetal abdominal wall thickness (abdominal subcutaneous fat thickness, AbFat), a measure of fetal subcutaneous fat, was calculated by sonography at each visit. Statistical determinants of AbFat during late pregnancy were explored using simple and multiple regression. RESULTS: During late pregnancy (34.8±2.0 weeks; range 31.0-40.6 weeks of gestation), the median (inter-quartile range) fetal AbFat and GWG were 0.44 (0.39, 0.55) cm and 14.6 (9.5, 18.3) kg, respectively. After adjusting for infant birth weight, variables significantly associated with fetal AbFat included gestational age (P<0.0001, 95% confidence interval, CI: 0.01, 0.03), maternal race (P=0.029, 95% CI: -0.04, -0.002) and dietary intake of added sugar (P=0.025, 95% CI: 1.42e-6, 2.06e-5). Fetal AbFat had a significant positive quadratic relationship with total maternal dietary sugar intake such that both low and high extremes of sugar consumption were associated with significantly higher fetal AbFat. Birth weight was not significantly associated with maternal intake of added sugars. CONCLUSION: Extreme sugar intakes among pregnant adolescents may lead to increased accumulation of fetal abdominal fat with little net effect on birth weight. This finding suggests that increased sugar consumption during pregnancy promotes shifts in fetal body composition.

Fifty years of human space travel: implications for bone and calcium research.

Calcium and bone metabolism remain key concerns for space travelers, and ground-based models of space flight have provided a vast literature to complement the smaller set of reports from flight studies. Increased bone resorption and largely unchanged bone formation result in the loss of calcium and bone mineral during space flight, which alters the endocrine regulation of calcium metabolism. Physical, pharmacologic, and nutritional means have been used to counteract these changes. In 2012, heavy resistance exercise plus good nutritional and vitamin D status were demonstrated to reduce loss of bone mineral density on long-duration International Space Station missions. Uncertainty continues to exist, however, as to whether the bone is as strong after flight as it was before flight and whether nutritional and exercise prescriptions can be optimized during space flight. Findings from these studies not only will help future space explorers but also will broaden our understanding of the regulation of bone and calcium homeostasis on Earth.

Calcium kinetics during bed rest with artificial gravity and exercise countermeasures.

UNLABELLED: We assessed the potential for countermeasures to lessen the loss of bone calcium during bed rest. Subjects ingested less calcium during bed rest, and with artificial gravity, they also absorbed less calcium. With exercise, they excreted less calcium. To retain bone during bed rest, calcium intake needs to be maintained. INTRODUCTION: This study aims to assess the potential for artificial gravity (AG) and exercise (EX) to mitigate loss of bone calcium during space flight. METHODS: We performed two studies: (1) a 21-day bed rest (BR) study with subjects receiving 1 h/day AG (n = 8) or no AG (n = 7) and (2) a 28-day BR study with 1 h/day resistance EX (n = 10) or no EX (n = 3). In both studies, stable isotopes of Ca were administered orally and intravenously, at baseline and after 10 days of BR, and blood, urine, and feces were sampled for up to 14 days post dosing. Tracers were measured using thermal ionization mass spectrometry. Data were analyzed by compartmental modeling. RESULTS: Less Ca was absorbed during BR, resulting in lower Ca balance in BR+AG (-6.04 ± 3.38 mmol/day, P = 0.023). However, Ca balance did not change with BR+EX, even though absorbed Ca decreased and urinary Ca excretion increased, because endogenous excretion decreased, and there was a trend for increased bone deposition (P = 0.06). Urinary N-telopeptide excretion increased in controls during BR, but not in the EX group. Markers of bone formation were not different between treatment groups for either study. Ca intake decreased during BR (by 5.4 mmol/day in the AG study and 2.8 mmol/day in the EX study), resulting in lower absorbed Ca. CONCLUSIONS: During BR (or space flight), Ca intake needs to be maintained or even increased with countermeasures such as exercise, to enable maintenance of bone Ca.

Profound hypogonadism has significant negative effects on calcium balance in males: a calcium kinetic study.

The impact of estrogen deficiency on bone has been extensively studied in the female; however, the effects of androgen deficiency on calcium fluxes in males have been less well characterized. We investigated the effect of short-term, severe androgen deficiency on measures of calcium absorption and kinetics as well as on markers of bone turnover in males. To accomplish this, 11 healthy male volunteers were recruited (mean age 23.3 +/- 0.5 years [SEM], body mass index 25.3 +/- 0.8 kg/m2). They consumed a weight maintenance diet for at least 3 days prior to admission to our Research Unit, with a calcium intake of approximately 1200 mg/day. At baseline (D1), subjects received 42Ca intravenously as well as 44Ca PO mixed with milk or juice. A 29-h urine collection was begun and blood samples collected at frequent intervals for the measurement of the isotopic enrichment of 42Ca and 44Ca using thermal ionization mass spectrometry. Twice daily urine samples were collected for 5 days after the administration of the isotopes. A gonadotropin-releasing hormone agonist (Lupron) was given after D1, again 3 weeks later, and studies repeated identically 4 weeks (D2, n = 6) and 10 weeks from baseline (D3, n = 7) (two subjects completed three studies). Testosterone concentrations were markedly suppressed on both D2 and D3 (-95%, p < 0.006), whereas there were no detectable changes in growth hormone and insulin-like growth factor-1 concentrations. Urinary calcium excretion increased significantly after 4 weeks (43%, p = 0.0007) and 10 weeks (73%, p = 0.003) of sustained hypogonadism. Using a multicompartmental kinetic model, the contribution of oral calcium to the urinary losses was decreased by D3 (-41%, p = 0.01), yet the contribution of bone calcium to urine losses increased by 10 weeks (+11%, p = 0.01). There was a 21% decrease in bone calcium deposition (Vo+) by D3 (p < 0.05) with no significant change in bone resorption rates (Vo-). There was a significant correlation between the decrease in testosterone concentration and the increase in urinary calcium excretion, especially at 10 weeks (R2 = 0.84, p = 0.004). These kinetic changes were accompanied by a decrease in osteocalcin concentrations on D2, with improvements by D3. Urinary N telopeptide, a measure of bone resorption, also increased during the studies. In summary, profound hypogonadism in young males is associated with marked increases in urinary calcium losses, with a greater contribution of bone calcium to those losses and decreased kinetic markers of bone calcium deposition. We conclude that even short-term, severe deficiency in gonadal steroids can have profound negative effects on calcium and bone metabolism in males.

Differences in calcium absorption and kinetics between black and white girls aged 5-16 years.

To assess racial differences in calcium (Ca) metabolism, we measured Ca absorption and kinetics in 89 girls (38 black and 51 white) aged 4.9-16.7 years using a dual-tracer stable isotope technique. We found significantly greater rates of fractional (0.44 +/- 0.13 vs. 0.25 +/- 0.08, p < 0.0001) and total calcium absorption (406 +/- 142 vs. 234 +/- 82 mg/day, p < 0.0003) in black than in white postmenarcheal girls. Fractional absorption of Ca was also greater in black than in white premenarcheal girls (0.39 +/- 0.14 vs. 0.30 +/- 0.10, p = 0.01). Fractional absorption of Ca was more closely correlated to Ca intake in white (r = -0.42, p = 0.002) than in black girls (r = -0.25, p = 0.14). Urinary Ca excretion was significantly lower in pre- but not postmenarcheal black girls than in white girls. Calcium kinetic values associated with bone calcium deposition were greater in black girls, indicating a greater rate of bone Ca deposition in both pre- and postmenarcheal black girls. These results suggest that the greater bone mass accumulated during childhood and adolescence in black than in white females is due, in part, to greater rates of Ca absorption in black girls.

Bone turnover response to changes in calcium intake is altered in girls and adult women in families with histories of osteoporosis.

Heredity and environmental factors contribute to the development of osteoporosis. Because calcium is the major mineral in bone and adolescence is a key period in bone acquisition, we hypothesized that bone turnover would be less responsive to alterations in dietary calcium intake in both girls and adult women from families with histories of osteoporosis. To address this issue, we studied calcium kinetics in the maternal grandmother (age range 56-81 years), mother (age range 32-47 years), and granddaughter (age range 8-15 years) in 10 multigenerational families. In five families, the mother and/or grandmother had osteoporosis (bone mineral density > or = 2 SD below the age-specific mean). To examine both active and passive calcium absorption, families consumed low- (279 +/- 64 mg/day) and high- (1580 +/- 385) calcium diets for 10 days prior to administration of oral (46Ca) and intravenous (42Ca) stable isotopes. Using repeated measures analysis of variance, fractional calcium absorption, true calcium absorption, bone calcium deposition, and the balance in bone calcium turnover were all significantly affected by diet (p < 0.01). Females from nonosteoporotic families had decreased bone calcium resorption with little change in bone calcium deposition during the high-calcium study. In contrast, girls and adult women from osteoporotic families had increased both bone calcium deposition and resorption during the high-calcium period, leading to a less positive balance in bone calcium turnover. A significant interaction between bone status and diet was found for bone calcium resorption (p < 0.05) and approached significance for bone calcium deposition (p < 0.07), effects which were independent of generation. We conclude that girls and women from osteoporotic families have a significantly altered bone turnover response to acute changes in calcium intake.

Changes in calcium kinetics associated with menarche.

To evaluate the consequences of puberty on calcium (Ca) metabolism, we measured Ca kinetic parameters in 43 healthy girls 1-60 months post menarche. There was a close relationship between the logarithmic transform of the number of months post menarche and the bone Ca deposition rate (Vo +) (r = -0.90, P < 0.001). Using multiple regression analysis with the logarithmic transforms of chronological age and months post menarche as independent parameters, we found that the number of months post menarche was more significantly correlated with Vo + (t = -7.4, P < 0.0001) than with chronological age (t = -3.1, P = 0.003). A longitudinal study of 17 girls demonstrated a peak Vo + approximately 8 months before menarche, with a decrease in Vo + after menarche. These studies indicate that the peak time for bone Ca deposition is in the premenarcheal and perimenarcheal time period. The close correlation between Vo + and months post menarche demonstrates the importance of puberty in consideration of bone Ca metabolism in girls.

Estrogen suppression in males: metabolic effects.

We have shown that testosterone (T) deficiency per se is associated with marked catabolic effects on protein, calcium metabolism, and body composition in men independent of changes in GH or insulin-like growth factor I production. It is not clear,,however, whether estrogens have a major role in whole body anabolism in males. We investigated the metabolic effects of selective estrogen suppression in the male using a potent aromatase inhibitor, Arimidex (Anastrozole). First, a dose-response study of 12 males (mean age, 16.1 +/- 0.3 yr) was conducted, and blood withdrawn at baseline and after 10 days of oral Arimidex given as two different doses (either 0.5 or 1 mg) in random order with a 14-day washout in between. A sensitive estradiol (E2) assay showed an approximately 50% decrease in E2 concentrations with either of the two doses; hence, a 1-mg dose was selected for other studies. Subsequently, eight males (aged 15-22 yr; four adults and four late pubertal) had isotopic infusions of [(13)C]leucine and (42)Ca/(44)Ca, indirect calorimetry, dual energy x-ray absorptiometry, isokinetic dynamometry, and growth factors measurements performed before and after 10 weeks of daily doses of Arimidex. Contrary to the effects of T withdrawal, there were no significant changes in body composition (body mass index, fat mass, and fat-free mass) after estrogen suppression or in rates of protein synthesis or degradation; carbohydrate, lipid, or protein oxidation; muscle strength; calcium kinetics; or bone growth factors concentrations. However, E2 concentrations decreased 48% (P = 0.006), with no significant change in mean and peak GH concentrations, but with an 18% decrease in plasma insulin-like growth factor I concentrations. There was a 58% increase in serum T (P = 0.0001), sex hormone-binding globulin did not change, whereas LH and FSH concentrations increased (P < 0.02, both). Serum bone markers, osteocalcin and bone alkaline phosphatase concentrations, and rates of bone calcium deposition and resorption did not change. In conclusion, these data suggest that in the male 1) estrogens do not contribute significantly to the changes in body composition and protein synthesis observed with changing androgen levels; 2) estrogen is a main regulator of the gonadal-pituitary feedback for the gonadotropin axis; and 3) this level of aromatase inhibition does not negatively impact either kinetically measured rates of bone calcium turnover or indirect markers of bone calcium turnover, at least in the short term. Further studies will provide valuable information on whether timed aromatase inhibition can be useful in increasing the height potential of pubertal boys with profound growth retardation without the confounding negative effects of gonadal androgen suppression.

Insulin-like growth factor I and growth hormone (GH) treatment in GH-deficient humans: differential effects on protein, glucose, lipid, and calcium metabolism.

We examined the effects of recombinant human (rh) insulin-like growth factor I (IGF-I) vs. rhGH in a variety of metabolic paths in a group of eight severely GH-deficient young adults using an array of contemporary tools. Protein, glucose, and calcium metabolism were studied using stable labeled tracer infusions of L-[1-13C]leucine, [6,6-2H2]glucose, and 42Ca and 44Ca; substrate oxidation rates were assessed using indirect calorimetry; muscle strength was determined by isokinetic and isometric dynamometry of the anterior quadriceps, as well as growth factors, hormones, glucose, and lipid concentrations in plasma before and after 8 weeks of rhIGF-I (60 microg/kg, sc, twice daily), followed by 4 weeks of washout, then 8 weeks ofrhGH (12.5 microg/kg-day, sc); the treatment order was randomized. In the doses administered, rhIGF-I and rhGH both increased fat-free mass and decreased the percent fat mass, with a more robust decrease in the percent fat mass after rhGH; both were associated with an increase in whole body protein synthesis rates and a decrease in protein oxidation. Neither hormone affected isokinetic or isometric measures of skeletal muscle strength. However, rhGH was more potent than rhIGF-I at increasing lipid oxidation rates and improving plasma lipid profiles. Both hormones increased hepatic glucose output, but rhGH treatment was also associated with decreased carbohydrate oxidation and increased glucose and insulin concentrations, indicating subtle insulin resistance. Neither hormone significantly affected bone calcium fluxes, supporting the concept that these hormones, by themselves, are not pivotal in bone calcium metabolism. In conclusion, rhIGF-I and rhGH share common effects on protein, muscle, and calcium metabolism, yet have divergent effects on lipid and carbohydrate metabolism in the GH-deficient state. These differences may allow for better selection of treatment modalities depending on the choice of desired effects in hypopituitarism.

Dietary protein affects intestinal calcium absorption.

BACKGROUND: Changes in dietary protein in adults are associated with changes in urinary calcium excretion. The mechanisms underlying this effect are not completely understood, but alterations in intestinal absorption of calcium are not thought to be involved. OBJECTIVE: We reexamined this mechanism by evaluating the effect of 2 amounts of dietary protein (low: 0.7 g/kg; and high: 2.1 g/kg) on fractional calcium absorption in 7 healthy, young women. DESIGN: The experiment consisted of 2 wk of a well-balanced diet containing moderate amounts of calcium, sodium, and protein followed by 5 d of an experimental diet that contained 1 of 2 amounts of protein and constant amounts of other nutrients known to influence calcium metabolism. Seven subjects received both amounts of dietary protein in random order. Blood and urine were sampled at baseline and on day 4. Fractional calcium absorption was measured by dual-stable calcium isotopes on day 5. In a second study of 5 additional women, we evaluated the effects of dietary fiber on calcitropic hormones. RESULTS: Subjects developed hypocalciuria and secondary hyperparathyroidism on day 4 of the low-protein diet. Urinary calcium excretion and the glomerular filtration rate were elevated significantly by day 4 of the high-protein compared with the low-protein diet. Fractional calcium absorption after the low-protein diet was 0.19+/-0.03, which was significantly lower than that after the high-protein diet (0.26+/-0.03, P=0.05). CONCLUSION: These data provide evidence that depressed intestinal calcium absorption explains, in part, low-protein-induced secondary hyperparathyroidism.

Calcium and magnesium balance in 9-14-y-old children.

Few data are available regarding calcium and magnesium absorption and endogenous fecal excretion in children. We used a multitracer stable isotope technique to assess calcium and magnesium balance in 12 boys and 13 girls aged 9-14 y (mean weight: 42 kg) maintained on relatively high calcium intakes (mean: 1310 +/- 82 mg/d). There were no significant differences in absorption of calcium or magnesium from milk between boys and girls. Calcium retention (balance) correlated positively with calcidiol (25-hydroxyvitamin D) concentration (r = 0.48, P = 0.02) and serum alkaline phosphatase activity (r = 0.44, P = 0.03). There was no significant relation between magnesium balance and concentration. When data from this study were combined with our previously reported data, an increase in total calcium absorption was seen for pubertal (Tanner stages 2-4) but not prepubertal (Tanner stage 1) white children over the range of intakes from approximately 750 to 1350 mg/d. Despite intakes similar to the 1989 recommended dietary allowance for magnesium (mean intake: 6.4 +/- 1.2 mg.kg-1.d-1), 11 of the 25 subjects (6 girls and 5 boys) were in negative magnesium balance. We conclude that benefits from higher calcium intakes, < or = 1350 mg/d, were most apparent in pubertal children. In addiction, higher magnesium intakes should be considered for children.

Bone mineral content in girls perinatally infected with HIV.

BACKGROUND: Early diagnostic efforts and advances in multidrug therapy have considerably prolonged the survival time of children infected perinatally with HIV. Despite these advances, few studies have addressed calcium status and bone growth in HIV-infected children. OBJECTIVE: Our objective was to examine the effect of HIV infection on calcium status and bone growth in children. DESIGN: We measured calcitropic hormones, urinary calcium excretion, bone mineral content, and body composition in 19 young girls aged 9.2 +/- 2.6 y (range: 5.9-15.2 y) who were infected perinatally with HIV. RESULTS: Serum concentrations of 1,25-dihydroxyvitamin D [1,25(OH)(2)D] and parathyroid hormone concentrations were elevated above normal ranges in 25% and 12% of these girls, respectively. Urinary calcium excretion normalized for creatinine excretion was also elevated (Ca/Cr >0.18) in 17% of these children despite suboptimal calcium intakes (679 +/- 437 mg/d). Total-body bone mineral content, measured with the use of dual-energy X-ray absorptiometry, averaged 845.1 +/- 279.0 g and was on average 2.7 z scores below age- and race-matched values reported in non-HIV-infected healthy girls. Significant positive correlations were found between an indirect marker of bone resorption in urine (N:-telopeptide) and 1,25(OH)2D (P < 0.02, r2 = 0.586, n = 9), and between serum N-telopeptide and total alkaline phosphatase (P < 0.001, r2 = 0.541, n = 17), suggesting that calcium insufficiency may be increasing bone resorption in this group. CONCLUSIONS: Young girls with HIV infection had low bone mass and evidence of calcium insufficiency. Nutritional counseling of children with HIV infection should emphasize adequate calcium intakes because of the importance of this age period in bone mineral acquisition.

Increased efficiency of calcium absorption during short periods of inadequate calcium intake in girls.

Adequate calcium intake is essential for skeletal integrity, particularly during the period of peak bone mass acquisition from 9 to 17 y of age. Currently, the calcium intake of many adolescent girls is below the recommended dietary allowance. The purpose of this study was to evaluate the ability of girls to respond to acute periods of inadequate dietary calcium intake. Calcium absorption was evaluated in 11 girls aged 11.6 +/- 2.4 y after 10 d on both a low-calcium (7.05 +/- 2.03 mmol/d) and a high-calcium (35.30 +/- 2.28 mmol/d) diet. Fractional calcium absorption was determined by using oral (46Ca) and intravenous (42Ca) stable isotopes of calcium. During a low calcium intake, fractional calcium absorption was significantly greater (0.582 +/- 0.087 compared with 0.260 +/- 0.068, P < 0.0001) and urinary calcium excretion was significantly lower (1.30 +/- 0.83 compared with 3.08 +/- 1.98 mmol/d, P < 0.004) than values obtained during a high calcium intake. Concentrations of 1,25-dihydroxyvitamin D (combination of cholecalciferol and ergocalciferol) were greater during the low calcium intake, although the difference was not significant (108.7 +/- 30.6 compared with 90.0 +/- 25.1 pmol/L, P < 0.1; n = 9). Excretion of N-telopeptide was significantly greater during the low calcium intake (761 +/- 508 compared with 413 +/- 341 nmol bone collagen equivalent (BCM)/mmol creatinine, P < 0.02; n = 9), indicating that bone resorption was increased. These results suggest that during short periods of inadequate calcium intake, girls are able to significantly increase the efficiency of calcium absorption and decrease urinary calcium losses to conserve calcium required for bone mineral acquisition.

Influence of prenatal iron and zinc supplements on supplemental iron absorption, red blood cell iron incorporation, and iron status in pregnant Peruvian women.

BACKGROUND: It is estimated that 60% of pregnant women worldwide are anemic. OBJECTIVE: We aimed to examine the influence of iron status on iron absorption during pregnancy by measuring supplemental iron absorption, red blood cell iron incorporation, and iron status in pregnant women. DESIGN: Subjects were 45 pregnant Peruvian women (33+/-1 wk gestation), of whom 28 received daily prenatal supplements containing 60 mg Fe and 250 microg folate without (Fe group, n = 14) or with (Fe+Zn group, n = 14) 15 mg Zn, which were were consumed from week 10 to 24 of gestation until delivery. The remaining 17 women (control) received no prenatal supplementation. Iron status indicators and isotopes were measured in maternal blood collected 2 wk postdosing with oral (57Fe) and intravenous (58Fe) stable iron isotopes. RESULTS: Maternal serum ferritin and folate concentrations were significantly influenced by supplementation (P < 0.05). Serum iron was also significantly higher in the Fe than in the Fe+Zn (P < 0.03) or control (P < 0.001) groups. However, the supplemented groups had significantly lower serum zinc concentrations than the control group (8.4+/-2.3 and 10.9+/-1.8 micromol/L, respectively, P < 0.01). Although percentage iron absorption was inversely related to maternal serum ferritin concentrations (P = 0.036), this effect was limited and percentage iron absorption did not differ significantly between groups. CONCLUSIONS: Because absorption of nonheme iron was not substantially greater in pregnant women with depleted iron reserves, prenatal iron supplementation is important for meeting iron requirements during pregnancy.

PIP: The influence of iron status on iron absorption during pregnancy was examined among pregnant Peruvian women. This was done by measuring supplemental iron absorption, red blood cell iron incorporation and iron status. The subjects were 45 pregnant Peruvian women (33 +or- 1 week gestation) who were divided into 2 groups. The first group of 28 pregnant women received daily prenatal supplements containing 60 mg of iron and 250 mcg of folate with or without 15 mg of zinc, from week 10 to 24 of gestation until delivery. The second group of 17 women served as the control group. The control group was not given prenatal supplementation. The iron status indicators and isotopes were measured in maternal blood collected 2 weeks postdosing with oral iron-57 and intravenous iron-58 stable isotopes. The results showed that supplementation significantly influenced the maternal serum ferritin and folate concentrations (P 0.05). The serum iron of the iron group was significantly higher than that of the iron + zinc group (P 0.03) or control group (P 0.001). However, the serum zinc concentrations were lower in the supplemented group than in the control group. Even though the percentage of iron absorption was inversely related to maternal serum ferritin concentration, the effect was limited and the percentage of iron absorption did not differ significantly between the two groups. Considering that the absorption of nonheme iron was not substantially greater in pregnant women with depleted iron reserves, it was concluded that prenatal iron supplementation is essential for meeting iron requirements, especially during pregnancy.

Calcium kinetics in lactating women with low and high calcium intakes.

Absorption of calcium and its mobilization from bone during lactation are important for delivery of calcium to breast-feeding infants; whether calcium intake offsets bone resorption is not known. We hypothesized that calcium absorption is increased in lactation and greater in women on low calcium diets, resulting in similar rates of bone resorption and accretion. Calcium absorption and kinetic indexes were calculated by using two stable isotopic tracers in 8 women; 6 were studied both during lactation and nonlactation. Women consumed low calcium diets, with half receiving supplemental calcium. Intestinal absorption was related to serum 1,25-dihydroxyvitamin D and did not increase during lactation. Despite decreased urinary calcium excretion during lactation, especially in women with low calcium intake, net balance tended to be lower during lactation. Mean residence time decreased and bone resorption exceeded accretion in almost all lactating women. Calcium need for milk production appears to be met by decreased urinary excretion and increased bone resorption, and not by increased intestinal absorption.

Combined calcium and vitamin D supplementation reduces bone loss and fracture incidence in older men and women.

A recent supplementation study of 389 men and women, over the age of 65 years was conducted to address the impact of combined calcium and vitamin D supplementation on nonvertebral fracture incidence and maintenance of bone mass. Daily supplementation with 500 mg calcium and 700 IU vitamin D for 3 years moderately reduced bone loss at several sites and significantly decreased the rate of nonvertebral fractures, compared with a placebo group. Optimal intake of both calcium and vitamin D may be an easily implemented strategy to maintain existing bone mass and reduce the risk of fracture in older men and women.

Estrogen treatment and estrogen suppression: metabolic effects in adolescence.

The metabolic consequences of reaching full reproductive maturity in humans involve not only growth hormone (GH) and insulin-like growth factor-I, but also the collaborative interaction of the gonadal sex steroids. Estrogen is critical for completing linear growth. It also inhibits bone resorption, decreases plasma lipid levels and serves as an antiatherosclerotic agent. Our studies show that, in low doses, estrogen increases GH production, increases calcium absorption and decreases bone turnover; however, unlike testosterone, estrogen has no effects as a protein-anabolic agent, at least at the whole body level. Studies of selective estrogen suppression, achieved using a potent aromatase inhibitor, show that estrogen is the main regulator of the gonadotropin axis. In boys, selective aromatase blockade may have a role in delaying epiphyseal fusion. Large placebo-controlled trials will be required to study this effect further.

Regulation of mineral metabolism from fetus to infant: metabolic studies.

Optimal mineral intake is crucial, especially during the period of rapid growth that occurs during infancy and childhood. Two minerals that have been found to play key roles during this period are iron and zinc. Supplementation studies have shown that these minerals have significant effects on birth weight as well as on weight and height increase during childhood. However, because a myriad of nutritional factors influence growth, it has often been difficult to characterize the role of any given mineral on fetal and early childhood growth. Stable iron and zinc isotopes can be used to study how the mineral status of iron- and zinc-deficient pregnant women affects their ability to absorb and transfer iron to the fetus. Furthermore, these isotopic tracers can be employed to examine the ability of infants to modify mineral absorption over time as the mineral stores of birth are depleted. Further studies using stable mineral isotopes during gestation, infancy and childhood will provide additional information on the regulation of mineral absorption and transport during these key periods of growth.

Impact of maternal and neonatal iron status on placental transferrin receptor expression in pregnant adolescents.

OBJECTIVE: To elucidate the role of maternal and neonatal iron status on placental transferrin receptor (TfR) expression. STUDY DESIGN AND OUTCOMES: Ninety-two healthy pregnant adolescents (ages 14-18 years) were followed across pregnancy. Maternal iron status (hemoglobin, hematocrit, serum ferritin, TfR, and total body iron) was assessed in mid-gestation (21-25 wks) and at delivery in the mother and neonate. Placental TfR protein expression was assessed by western blot in placental tissue collected at delivery. RESULTS: Placental TfR expression was inversely associated with maternal iron status at mid-gestation (hemoglobin p = 0.046, R(2) = 0.1 and hematocrit p = 0.005, R(2) = 0.24) and at delivery (serum ferritin p = 0.02, R(2) = 0.08 and total body iron p = 0.02, R(2) = 0.07). Mothers with depleted body iron stores had significantly greater placental expression of TfR than mothers with body iron stores greater than zero (p = 0.003). Neonatal iron stores were also inversely associated with the expression of placental TfR (p = 0.04, R(2) = 0.06). Neonates with serum ferritin values ≤ 34 µg/L had significantly greater protein expression of placental TfR compared to neonates with cord serum ferritin values >34 µg/L (p = 0.01). CONCLUSIONS: Expression of placental TfR is associated with both maternal and neonatal iron demands. Increased expression of placental TfR may be an important compensatory mechanism in response to iron deficiency in otherwise healthy pregnant women.

Calcium acquisition rates do not support age-appropriate gains in total body bone mineral content in prepuberty and late puberty in girls with cystic fibrosis.

Few longitudinal data are available characterizing bone development in adolescents with cystic fibrosis (CF) although this is a critical time for bone mineralization. Dual energy X-ray absorptiometry (DXA) scans were obtained at 1- to 4-year intervals in 18 prepubertal and pubertal girls (age 7-18 years) with CF to determine calcium (Ca) accretion rates and changes (Delta) in total body bone mineral content (TBBMC) and lumbar spine bone mineral density (LS BMD) Z-scores. Daily Ca acquisition rates were calculated assuming TBBMC was composed of 32.2% Ca. Bone Ca accretion averaged 82 mg/day (2.05 mmol/day) [(range:-38 to +197 mg/day (-0.95 to 4.9 mmol/day)] on approximately 1,200 mg/day (30 mmol/day) Ca intakes. Estimated mean peak Ca accretion was 160 mg/day (4 mmol/day) at age 13 years; losses of bone Ca occurred in late puberty. Gains in insulin-like growth factor 1 (IGF-1) predicted Ca accretion (p<0.06). Body mass index (BMI) Z-score predicted LS BMD and TBBMC Z-score cross-sectionally but did not predict DeltaTBBMC Z-score. Changes in TBBMC Z-score paralleled Ca accretion rates with age. Bone Ca accretion in girls with CF fell below rates in healthy girls during prepuberty and late puberty despite Ca intakes approaching recommendations. IGF-1 and BMI Z-scores may identify children with CF at risk of compromised bone accretion, and more data are required to elucidate roles of lung function and glucocorticoid use in compromised bone health.