Cystic fibrosis (CF) is the most common genetic disease within the Caucasian population and leads to premature respiratory failure. Approximately 60,000 individuals are currently living with CF in North America and Europe, 40% of whom are adults. The life span of these patients has increased from approximately 2 to 32 yr of age over the last three decades. Bone disease has emerged as a common complication in long-term survivors of CF. Some studies have observed that 50-75% of adults have low bone density and increased rates of fractures. Prevention and treatment of CF-related bone disease must address the myriad risk factors (decreased absorption of fat-soluble vitamins due to pancreatic insufficiency, altered sex hormone production, chronic lung infection with increased levels of bone-active cytokines, physical inactivity, and glucocorticoid therapy) for poor bone health. This review is a condensed and updated summary of the Guide to Bone Health and Disease in Cystic Fibrosis: A Consensus Conference, a statement that evolved from a meeting convened by the Cystic Fibrosis Foundation in May 2002 to address the pathogenesis, diagnosis, and treatment of bone disease in CF. The goal of this conference was to develop practice guidelines for optimizing bone health in patients with CF.

It has been nearly 15 years since the first review on pregnancy and iron deficiency was published in Nutrition Reviews. Many unresolved issues raised in that seminal review have been addressed. New proteins involved in nonheme and heme iron transport have been identified in the enterocyte, and information on the roles of these proteins in the placenta is evolving. The systemic iron regulatory hormone, hepcidin, has since been identified as a key regulator of iron homeostasis. Additional data on the efficacy and consequences of prenatal iron supplementation are available. Emerging data on developmental changes in iron absorption across early infancy have further emphasized the need to ensure that the iron endowment of the neonate at birth is optimal. This is especially important, given growing evidence linking neonatal iron status with subsequent cognitive and neurobehavioral outcomes. Along with the many advances, new questions and gaps in knowledge have been identified. This review summarizes new data on maternal iron utilization across pregnancy as it impacts the pregnant woman and the iron status of the neonate at birth.

Bone loss is a current limitation for long-term space exploration. Bone markers, calcitropic hormones, and calcium kinetics of crew members on space missions of 4-6 months were evaluated. Spaceflight-induced bone loss was associated with increased bone resorption and decreased calcium absorption.Introduction: Bone loss is a significant concern for the health of astronauts on long-duration missions. Defining the time course and mechanism of these changes will aid in developing means to counteract these losses during space flight and will have relevance for other clinical situations that impair weight-bearing activity. Materials and Methods: We report here results from two studies conducted during the Shuttle-Mir Science Program. Study 1 was an evaluation of bone and calcium biochemical markers of 13 subjects before and after long-duration (4-6 months) space missions. In study 2, stable calcium isotopes were used to evaluate calcium metabolism in six subjects before, during, and after flight. Relationships between measures of bone turnover, biochemical markers, and calcium kinetics were examined. Results: Pre-and postflight study results confirmed that, after landing, bone resorption was increased, as indicated by increases in urinary calcium (p < 0.05) and collagen cross-links (N-telopeptide, pyridinoline, and deoxypyridinoline were all increased >55% above preflight levels, p < 0.001). Parathyroid hormone and vitamin D metabolites were unchanged at landing. Biochemical markers of bone formation were unchanged at landing, but 2-3 weeks later, both bone-specific alkaline phosphatase and osteocalcin were significantly (p < 0.01) increased above preflight levels. In studies conducted during flight, bone resorption markers were also significantly higher than before flight. The calcium kinetic data also validated that bone resorption was increased during flight compared with preflight values (668 ± 130 versus 427 ± 153 mg/day; p < 0.001) and clearly documented that true intestinal calcium absorption was significantly lower during flight compared with preflight values (233 ± 87 versus 460 ± 47 mg/day; p < 0.01). Weightlessness had a detrimental effect on the balance in bone turnover such that the daily difference in calcium retention during flight compared with preflight values approached 300 mg/day (−234 ± 102 versus 63 ± 75 mg/day; p < 0.01). Conclusions: These bone marker and calcium kinetic studies indicated that the bone loss that occurs during space flight is a consequence of increased bone resorption and decreased intestinal calcium absorption.

Although high-protein diets induce hypercalciuria in humans, the source of the additional urinary calcium remains unclear. One hypothesis is that the high endogenous acid load of a high-protein diet is partially buffered by bone, leading to increased skeletal resorption and hypercalciuria. We used dual stable calcium isotopes to quantify the effect of a high-protein diet on calcium kinetics in women. The study consisted of 2 wk of a lead-in, well-balanced diet followed by 10 d of an experimental diet containing either moderate (1.0 g/kg) or high (2.1 g/kg) protein. Thirteen healthy women received both levels of protein in random order. Intestinal calcium absorption increased during the high-protein diet in comparison with the moderate (26.2 +/- 1.9% vs. 18.5 +/- 1.6%, P < 0.0001, mean +/- sem) as did urinary calcium (5.23 +/- 0.37 vs. 3.57 +/- 0.35 mmol/d, P < 0.0001, mean +/- sem). The high-protein diet caused a significant reduction in the fraction of urinary calcium of bone origin and a nonsignificant trend toward a reduction in the rate of bone turnover. There were no protein-induced effects on net bone balance. These data directly demonstrate that, at least in the short term, high-protein diets are not detrimental to bone.

Although overt vitamin D deficiency is no longer common in US children, lesser degrees of vitamin D insufficiency are widespread.

Increasing dietary protein results in an increase in urinary calcium. Despite over 80 y of research, the source of the additional urinary calcium remains unclear. Because most calcium balance studies found little effect of dietary protein on intestinal calcium absorption, it was assumed that the skeleton was the source of the calcium. The hypothesis was that the high endogenous acid load generated by a protein-rich diet would increase bone resorption and skeletal fracture. However, there are no definitive nutrition intervention studies that show a detrimental effect of a high protein diet on the skeleton and the hypothesis remains unproven. Recent studies from our laboratory demonstrate that dietary protein affects intestinal calcium absorption. We conducted a series of short-term nutrition intervention trials in healthy adults where dietary protein was adjusted to either low, medium or high. The highest protein diet resulted in hypercalciuria with no change in serum parathyroid hormone. Surprisingly, within 4 d, the low protein diet induced secondary hyperparathyroidism that persisted for 2 wk. The secondary hyperparathyroidism induced by the low protein diet was attributed to a reduction in intestinal calcium absorption (as assessed by dual stable calcium isotopes). The long-term consequences of these low protein-induced changes in calcium metabolism are not known, but they could be detrimental to skeletal health. Several recent epidemiological studies demonstrate reduced bone density and increased rates of bone loss in individuals habitually consuming low protein diets. Therefore, studies are needed to determine whether low protein intakes directly affect rates of bone resorption, bone formation or both.

Relationships between hemoglobin concentrations and birth outcomes have not been well characterized in African-American adolescents despite the fact that this group is at a higher risk of early childbearing. To address this issue, we characterized the prevalence of anemia and maternal factors associated with anemia in pregnant African-American adolescents. A retrospective medical chart review was undertaken of 918 adolescents who had received prenatal care at an inner-city maternity clinic between 1990 and 2000. Multiple log-linear regression analyses were used to address relationships between hemoglobin and adverse birth outcomes. The prevalence of anemia during the third trimester averaged 57-66% and was substantially higher than typically reported in adolescent and adult women. Multiparity, inadequate prenatal care, low prepregnancy BMI, history of self-reported cigarette use and infection with sexually transmitted diseases were significantly associated with lower hemoglobin during pregnancy. Adolescents with pre-eclampsia had higher hemoglobin (P < 0.01). Compared with the reference group (106-120 g/L), high hemoglobin (>120 g/L) during the second and third trimester significantly increased the risk of low birth weight (risk ratio (RR) = 3.11; [CI] 1.35, 7.13), and in the second-trimester cohort only, high hemoglobin concentrations increased the risk of preterm delivery (RR = 2.33; [CI] 1.07, 5.05). A U-shaped distribution between hemoglobin concentration and adverse birth outcomes was found in the third-trimester cohort when the reference range was decreased to 96-105 g/L to adjust for potentially lower hemoglobin concentrations among the African-American population. Our results suggest that additional medical attention may be warranted in pregnant African-American adolescents with hemoglobin concentrations of 120 g/L.

High dietary protein intakes are known to increase urinary calcium excretion and, if maintained, will result in sustained hypercalciuria. To date, the majority of calcium balance studies in humans have not detected an effect of dietary protein on intestinal calcium absorption or serum parathyroid hormone. Therefore, it is commonly concluded that the source of the excess urinary calcium is increased bone resorption. Recent studies from our laboratory indicate that alterations in dietary protein can, in fact, profoundly affect intestinal calcium absorption. In short-term dietary trials in healthy adults, we fixed calcium intake at 20 mmol/d while dietary protein was increased from 0.7 to 2.1 g/kg. Increasing dietary protein induced hypercalciuria in 20 women [from 3.4 ± 0.3 (x -± SE) during the low-protein to 5.4 ± 0.4 mmol/d during the high-protein diet]. The increased dietary protein was accompanied by a significant increase in intestinal calcium absorption from 18.4 ± 1.3% to 26.3 ± 1.5% (as determined by dual stable isotopic methodology). Dietary protein intakes at and below 0.8 g/kg were associated with a probable reduction in intestinal calcium absorption sufficient to cause secondary hyperparathyroidism. The long-term consequences of these low-protein diet-induced changes in mineral metabolism are not known, but the diet could be detrimental to skeletal health. Of concern are several recent epidemiologic studies that demonstrate reduced bone density and increased rates of bone loss in individuals habitually consuming low-protein diets. Studies are needed to determine whether low protein intakes directly affect rates of bone resorption, bone formation, or both.Am J Clin Nutr 2003;78(suppl):584S-92S. KEY WORDSDietary protein, urinary calcium, parathyroid hormone, vitamin D, hypercalciuria, bone, soy INTRODUCTIONAlmost 30 million Americans are affected by osteoporosis, and women are 4 times more likely to suffer from this disease than men (1). The health problem is reaching near-epidemic proportions in the United States and worldwide. Nutrition plays an important role in both the prevention and the pathogenesis of many chronic diseases, including osteoporosis. Numerous studies have established that dietary calcium and vitamin D are critical nutrients for both accruing and maintaining skeletal mass. In contrast, our understanding of how other dietary components, such as protein, affect calcium homeostasis and skeletal metabolism is limited.