Zinc Supplementation Trial in Pediatric Chronic Kidney Disease: Effects on Circulating FGF-23 and Klotho.

Background: Zinc status, its role in bone metabolism and efficacy of deficiency correction has not been well studied in children with chronic kidney disease (CKD). Objectives: The primary objective was to investigate whether 3 months of oral zinc supplementation corrects zinc deficiency in children with CKD who have native or transplanted kidneys. The secondary objective was to compare circulating intact FGF-23 (iFGF-23), c-terminal FGF-23 (cFGF-23), and Klotho between zinc-sufficient and zinc-deficient children with CKD and to assess the relationship between circulating zinc, iFGF-23, cFGF-23, Klotho, bone biomarkers, copper, and phosphate excretion pre-supplementation and post-supplementation of zinc. Methods: Forty-one children (25 male and 16 female, age 12.94 ± 4.13 years) with CKD in native or transplanted kidneys were recruited through 2 pediatric nephrology divisions in Ontario, Canada. Of those, 14 patients (9 native CKD, 5 transplant CKD) with identified zinc deficiency (64% enrollment rate) received zinc citrate supplement for 3 months: 10 mg orally once (4-8 years) or twice (9-18 years) daily. Results: Zinc deficiency (plasma concentration < 11.5 µmol/L) was found in 22 patients (53.7%). A linear regression model suggested that zinc concentration reduced by 0.026 µmol/L (P = .04) for every 1-unit of estimated glomerular filtration rate (eGFR) drop. Zinc deficiency status was associated with higher serum iFGF-23; however, this was predominantly determined by the falling GFR. Zinc deficient and sufficient children had similar circulating c-FGF-23 and alpha-Klotho. Normalization of plasma zinc concentration was achieved in 8 (5 native CKD and 3 transplant CKD) out of 14 treated patients rising from 10.04 ± 1.42 to 12.29 ± 3.77 µmol/L (P = .0038). There were no significant changes in other biochemical measures in all treated patients. A statistically significant (P = .0078) rise in c-FGF-23 was observed only in a subgroup of 11 children treated with zinc but not receiving calcitriol. Conclusions: Zinc status is related to kidney function and possibly connected to bone metabolism in patients with CKD. However, it plays a minor role in fine-tuning various metabolic processes. In this exploratory non-randomized study, 3 months supplementation with zinc corrected deficiency in just over half of patients and only modestly affected bone metabolism in asymptomatic CKD patients.

Contexte: Le statut du zinc, son rôle dans le métabolisme osseux et l'efficacité de la correction d'une carence n'ont pas encore été bien étudiés chez les enfants atteints d'insuffisance rénale chronique (IRC). Objectifs: L'objectif principal était d'examiner si une supplémentation orale en zinc pendant trois mois pouvait corriger une carence chez les enfants atteints d'IRC avec des reins natifs ou transplantés. Les objectifs secondaires étaient de comparer les taux circulants de FGF-23 intact (iFGF-23), de FGF-23 c-terminal (cFGF-23) et de Klotho d'enfants atteints d'IRC et ayant des niveaux corrects ou déficients en zinc, puis d'évaluer la relation entre le zinc circulant, l'iFGF-23, le cFGF-23, le Klotho, les biomarqueurs osseux et l'excrétion de cuivre et de phosphate avant et après la supplémentation en zinc. Méthodologie: Un total de 41 enfants (25 garçons et 16 filles, âgés de 12,94 ±4,13 ans) atteints d'IRC avec reins natifs ou transplantés ont été recrutés par deux divisions de néphrologie pédiatrique en Ontario, au Canada. De ceux-ci, 14 patients (9 avec reins natifs; 5 avec reins transplantés) qui présentaient une carence en zinc (taux d'inclusion de 64 %) ont reçu un supplément de citrate de zinc pendant trois mois à raison de 10 mg par voie orale une fois (4 à 8 ans) ou deux fois (9 à 18 ans) par jour. Résultats: Une carence en zinc (concentration plasmatique < 11,5 µmol/L) a été constatée chez 22 patients (53,7 %). Un modèle de régression linéaire a suggéré que la concentration de zinc diminue de 0,026 µmol/L (P = 0,04) pour chaque chute d'une unité de DFGe. Le statut de carence en zinc était associé à un taux sérique d'iFGF-23 plus élevé; cependant, cela était principalement déterminé par la baisse du DFG. Tous les enfants, avec ou sans carence en zinc, avaient des taux circulants similaires de c-FGF-23 et d'alpha-Klotho. La normalisation de la concentration plasmatique de zinc a été obtenue chez 8 patients (5 avec reins natifs; 3 avec reins transplantés) sur les 14 qui ont été traités, passant de 10,04 ±1,42 à 12,29 ±3,77 µmol/L (P = 0,003 8). Aucun changement significatif n'a été observé dans les autres mesures biochimiques chez les patients traités. Une augmentation statistiquement significative (P = 0,007 8) du taux de c-FGF-23 a été observée uniquement dans un sous-groupe de 11 enfants traités avec du zinc, mais ne recevant pas de calcitriol. Conclusion: Le statut du zinc est lié à la fonction rénale et peut être lié au métabolisme osseux chez les patients atteints d'IRC. Il joue toutefois un rôle mineur dans le réglage fin de divers processus métaboliques. Dans cet essai exploratoire non randomisé, une supplémentation en zinc pendant trois mois a permis de corriger la carence chez un peu plus de la moitié des patients et n'a eu qu'un effet modeste sur le métabolisme osseux chez les patients asymptomatiques atteints d'IRC.

Alendronate for steroid-induced osteopenia in children with acute lymphoblastic leukaemia or non-Hodgkin's lymphoma: results of a pilot study.

BACKGROUND/OBJECTIVES: Osteopenia is a significant morbidity in children undergoing therapy for acute lymphoblastic leukaemia (ALL) or non-Hodgkin's lymphoma (NHL). We conducted a pilot study to assess the impact of alendronate on whole body bone mineral content (WB-BMC), lumbar spine bone mineral density (LS-BMD), biochemical measures of bone mineral metabolism, as well as gross motor function and health-related quality of life (HRQL) in children undergoing therapy for ALL or NHL. METHODS: Ten children (nine boys) between the ages of 3.6 and 14.6 years, on identical maintenance chemotherapy for ALL or NHL were treated with oral alendronate once weekly, and daily calcium supplementation, for a period of six months. Outcome measures were WB-BMC and LS-BMD; biochemical measures of bone mineral metabolism including plasma osteocalcin, C-terminal telopeptide of type I collagen (CTx), serum calcium, 25-hydroxy-vitamin D (25-OHD), and parathyroid hormone (PTH); as well as assessments of motor function and HRQL. RESULTS: A gain in Z score was observed in 7/9 evaluable patients for WB-BMC (mean increase of 0.49) and LS-BMD (0.51). Plasma osteocalcin and CTx showed a change in bone turnover favouring formation over resorption. Serum calcium and 25-OHD remained normal throughout treatment. After an initial spike, serum PTH returned to baseline values at week 4. Measures of motor function showed some improvement and there were modest gains in HRQL. CONCLUSIONS: Alendronate therapy was tolerated well. Further study in a larger sample of children with ALL or NHL is warranted, in the context of a randomized clinical trial.

Special nutritional needs of infants for prevention of and recovery from bronchopulmonary dysplasia.

Extremely low birth weight infants who develop severe respiratory disease may have special nutrient requirements imposed by a combination of enhanced utilization of nutrients or the need for epithelial cell repair resulting from the disease process, as well as to support catch-up growth. Inositol, free fatty acids, vitamin E and vitamin A are proposed as nutrients for which infants at risk of chronic pulmonary insufficiency may have special requirements. Of these nutrients, only for vitamin A does suggestive evidence exist that high doses when given intramuscularly may reduce the incidence of death or chronic lung disease. Exogenous steroid therapy (dexamethasone), which is often used to improve pulmonary compliance in ventilated premature infants, may compromise vitamin A status and induce restricted somatic and bone mineral growth. Supplemental nutrition by means of enriched infant formulas has provided benefits in growth and bone mass accretion to infants recovering from bronchopulmonary dysplasia up to 3-mo corrected age. This growth advantage was not sustained over the subsequent 9 mo, suggesting that prolonged nutritional support is required until catch-up growth is complete. Further studies are required to delineate the needs for specific nutrients such as antioxidant vitamins and minerals or vitamin A that may play a role in preventing severe chronic lung disease in premature infants. As well, the role of supplemental nutrition (beyond the requirements of term infants) to support catch-up growth and maintenance during the critical stages of early development requires further investigation before evidence-based nutrient recommendations can be developed for this special population of infants.

Calcium does not inhibit iron absorption or alter iron status in infant piglets adapted to a high calcium diet.

The purpose of this study was to investigate whether a dietary calcium:iron ratio similar to that often consumed by premature human infants inhibits iron absorption in infant piglets adapted to a high calcium diet. Male Yorkshire piglets were randomized at 3 to 4 d of age to a high calcium diet (4.67 g/L = HC) or a normal calcium diet (2.0 g/L = NC) and fed for 2 to 2.5 wk. An iron dextran injection was administered in amounts to achieve a marginal state of iron repletion to simulate iron status of premature infants. In vivo iron absorption from the diet was determined using the radiotracers 55Fe and 59Fe and whole body counting. Calcium:iron interactions at absorption sites in piglets fed HC and NC were investigated by measurements of time-dependent 59Fe uptake in response to different calcium:iron ratios in vitro in brush border membrane vesicles (BBMV). In vivo iron absorption from the diet did not differ between NC and HC diet groups [57 +/- 8% versus 55 +/- 17% (mean +/- SD), respectively]. Iron status and iron contencentrations in spleen, liver, intestine, kidney and heart did not differ between diet groups. Iron uptake in BBMV was significantly reduced by calcium in both HC and NC (P < 0.001); but there were no significant differences in iron uptake in response to different calcium:iron ratios between HC and NC. With feeding a HC diet for 2 wk there may be an adaptive response to counteract the inhibitory effects of calcium on iron absorption, thus resulting in similar in vivo iron absorption and iron status irrespective of the 1.3-fold difference in dietary calcium:iron ratio between piglet groups. However, future studies are needed to determine the specific sites of calcium:iron interactions and adaptation mechanisms. Since the calcium:iron ratios used in this study reflect the usual calcium:iron ratios in diets for premature infants, it is unlikely that interactive effects of calcium with iron will compromise iron status in this infant population when diets are supplemented with calcium.

Growth and body composition in infants with bronchopulmonary dysplasia up to 3 months corrected age: a randomized trial of a high-energy nutrient-enriched formula fed after hospital discharge.

OBJECTIVES: (1) To determine whether nutrient malabsorption or inadequate nutrient intake were involved in the cause of growth delay in patients with bronchopulmonary dysplasia, and (2) to determine whether a nutrient-enriched formula given to infants with bronchopulmonary dysplasia to 3 months corrected age improves the rate of growth with greater lean and bone mass accretion when compared with infants fed an isoenergetic standard infant formula. STUDY DESIGN: A blinded, nutrition intervention trial of 60 preterm infants with bronchopulmonary dysplasia (birth weight, 866 +/- 169 g, gestational age, 26 +/- 1.5 weeks) randomized to either nutrient-enriched formula or standard formula. Growth, body composition, and nutrient retention were compared between groups by Student's t tests and analysis of covariance. RESULTS: Infants fed the enriched formula had significantly greater nitrogen and mineral retention at 38 weeks' postmenstrual age, and only the infants fed enriched formula had zinc retention similar to the intrauterine accretion. At 3 months corrected age infants fed enriched formula attained greater length (P < .05), greater radial bone mineral content (P < .01), and greater lean mass (P < .01). The male infants in the enriched formula group had greater whole body bone mineral content than did male infants in the standard formula group (P = .02). CONCLUSIONS: Greater linear growth and lean and bone mass in the enriched formula group suggests that infants with bronchopulmonary dysplasia attain faster "catch-up" growth when fed higher intakes of protein, calcium, phosphorus, and zinc than provided in standard proprietary formulas.

Growth and body composition of preterm infants: influence of nutrient fortification of mother's milk in hospital and breastfeeding post-hospital discharge.

We examined the influence of multi-nutrient fortification of mother's milk (MM + MNF) compared to supplementation with calcium and phosphorus (MM + CaGP) alone in hospital (in a randomized trial), and of breastfeeding (post-MM) compared to formula feeding (post-FF ) after hospital discharge with a descriptive analysis of growth and body composition to 1 y corrected age in preterm infants. Anthropometry, nutrient intakes and whole body bone mineral content, lean and fat mass were determined at four time points in the first year after term corrected age. Body composition was determined with dual energy X-ray absorptiometry. MM + MNF compared to MM + CaGP for preterm infants in the early neonatal period did not appear to influence growth or body composition in the first year. Growth in post-MM and post-FF groups was within the normal range of growth references derived from term infants fed mother's milk. Post-MM infants had lower whole body bone mineral content (132.3 +/- 10.4 g) at 6 months corrected age when compared to post-FF infants (159.4 +/- 14.1 g) and greater percent fat mass to 12 months corrected age. These differences may result from the lower calcium, phosphorus and protein intakes in post-MM compared to post-FF infants. Our findings demonstrate that dietary practices after hospital discharge likely have a greater impact on body composition in prematurely born infants than dietary practices in hospital. Whether the observed differences in body composition between breastfed and formula-fed preterm infants have any long-term consequences requires further investigation.

Moderate nutrient supplementation of mother's milk for preterm infants supports adequate bone mass and short-term growth: a randomized, controlled trial.

Our objectives were 1) to determine whether moderate nutrient supplementation of mother's milk (MM) for preterm infants, in the form of a new multinutrient fortifier (MNF), would improve short-term growth and bone mineral content (BMC) when compared with supplementation with calcium and phosphorus alone; and 2) to investigate whether moderate calcium and phosphorus intakes, in the form of calcium glycerophosphate (CaGP), resulted in a BMC similar to that of term corrected infants. Twenty-five preterm infants fed MM were randomly assigned to receive either MM+MNF or MM+CaGP. A third group of infants fed preterm formula (PTF) served as a comparison group. Whole-body BMC and lean and fat mass were determined by dual-energy X-ray absorptiometry (DXA) at full-term age. Nitrogen retention and calcium, phosphorus, and zinc intakes were determined by using mass balance techniques. Nitrogen retention was significantly lower in the MM+CaGP group than in the PTF group as were both weight and length gain (weight gain: 16.6 +/- 1.6, 14.2 +/- 2.0, and 16.1 +/- 2.9 g x kg(-1) x d(-1); length gain: 1.1 +/- 0.2, 0.9 +/- 0.2, and 1.1 +/- 0.3 cm/wk for the MM+MNF, MM+CaGP, and PTF groups, respectively). Biochemical indexes of mineral status and bone turnover were normal. Conservative amounts of calcium and phosphorus, as CaGP, resulted in adequate BMC. Moderate amounts of protein, calcium, and phosphorus plus trace elements added to MM in the form of an MNF resulted in improved linear growth but did not provide any advantages to BMC when compared with supplementation with calcium and phosphorus alone.

Bone and mineral abnormalities in childhood acute lymphoblastic leukemia: influence of disease, drugs and nutrition.

In children with acute lymphoblastic leukemia (ALL), abnormalities in mineral homeostasis and bone mass were first reported by our group in the late 1980s. Prospective longitudinal cohort studies in 40 consecutive patients receiving treatment according to the Dana-Farber Cancer Institute (DFCI) protocol 87-001 and 16 children receiving DFCI protocol 91-001 afforded us the opportunity to explore various etiologies of the observed abnormalities in mineral and bone metabolism, specifically the leukemic disease process and chemotherapeutic drugs such as steroids and aminoglycoside antibiotics. At diagnosis of ALL, > 70% of children had abnormally low plasma 1,25-dihydroxyvitamin D, 73% had low osteocalcin and 64% had hypercalciuria, indicating an effect of the leukemic process on vitamin D metabolism and bone turnover. During remission induction, treatment with high-dose steroid (prednisone or dexamethasone) resulted in further reduction in plasma osteocalcin and elevated parathyroid hormone levels. During 24 months of chemotherapy-maintained remission, reduction in bone mineral content (BMC), as measured by Z-scores, occurred in 64% of children, most severely affecting those > 11 years of age. A reduction in BMC during the first 6 months had a positive predictive value of 64% for subsequent fracture. By the end of 2 years of therapy, fractures occurred in 39% of children and radiographic evidence of osteopenia was found in 83% of the entire study group. Investigations of the biochemical basis of the bone abnormalities revealed that by 6 months hypomagnesemia developed in 84% of children (of whom 52% were hypermagnesuric) and plasma 1,25-dihydroxyvitamin D remained abnormally low in 70%. Altered magnesium status was attributed to renal wastage of magnesium following cyclical prednisone therapy and treatment with aminoglycoside antibiotics such as amikacin for fever accompanying neutropenia. Dietary intake and absorption of magnesium were normal. In 10 children treated for hypomagnesemia with supplemental magnesium for up to 16-20 weeks, plasma magnesium normalized in only 50% of subjects.

Longitudinal assessment of growth and bone mineral accretion in prematurely born infants treated for chronic lung disease with dexamethasone.

The objective of this study in premature infants was to assess the relationship between dexamethasone, growth and bone mineral accretion. Nine appropriate size for gestational age premature infants treated for chronic lung disease with tapering doses of dexamethasone (0.5-0.1 mg/kg/day over 37 +/- 7 days) were individually matched to a comparison infant by sex, gestational age, birth-weight, and type of feed. Infant growth and bone mineral accretion were measured at equivalent gestational ages from recruitment until 6 months corrected age. During hospitalization, mean rate of weight, length and head circumference growth and bone mineral accretion in the distal radius were significantly lower in the dexamethasone-treated infants in spite of similar nutrient intakes. Dexamethasone infants had significantly lower plasma phosphorus, and urinary calcium, pyridinoline and N-telopeptide excretion. Dexamethasone affected absolute length, but not weight, throughout the study. No significant differences were observed in body composition or absolute radial and whole body bone mineral content. The results indicate that dexamethasone therapy compromises growth and bone mineral accretion in small premature infants. 'Catch-up' linear growth was not evident at 6 months of age and reflects the importance of early nutrition interventions.

Mixed carbohydrate supplementation increases carbohydrate oxidation and endurance exercise performance and attenuates potassium accumulation.

We studied the effects of different CHO supplements on exercise metabolism (1 hr at 75% VO2max) and performance (fatigue time at 85% VO2max) in 8 male endurance athletes (VO2max = 68.8 +/- 3.8 ml.kg-1.min-1. Four treatments were administered in a randomized, double-blind fashion: Trial A = 3-day pretest, postexercise supplementation (177 kcal [81% carbohydrate, 19% protein] consumed < 10 min after exercise) + 600 ml 8% glucose polymers/ fructose 1 hr pretesting + 600 ml 8% glucose polymers/glucose during testing; Trial B = placebo during 3-day pretest + remainder same as Trial A; Trial C = placebo at all time points; and Trial D = same as Trial B with 8% glucose 1 hr before the test as well as during the test. Time to fatigue at 85% VO2max (increases 24%) and total CHO oxidation were greater for A versus C (p < .05). Plasma glucose concentration was higher for A and B versus C, while increases in plasma potassium concentration were attenuated for A versus C (both p < .05). None of the supplements had differential effects upon hematocrit, plasma sodium [Na+] and lactate, VO2, or rating of perceived exertion during exercise. Three-day preexercise protein + carbohydrate supplements followed by 1-hr pre- and during-exercise mixed carbohydrate supplements increased time to fatigue and carbohydrate oxidation and attenuated rises in plasma [K+] compared to placebo.

Calcium and phosphorus needs of premature infants.

Interpretation of the available studies for the purpose of predicting the recommended Ca and P needs of LBW infants is difficult because of the number of confounding variables that can affect Ca and P metabolism. Clinically, the most important measure of Ca/P "adequacy" must also be determined. Clearly, the predicted recommended intakes for dietary Ca and P would be different if normalization of serum and urine Ca and P levels is chosen rather than achievement of intrauterine retention of mineral or bone mineral content as the index of adequacy of mineral intake. The factorial approach to the estimation of Ca/P requirements was previously proposed by Ziegler et al. A reevaluation of their estimation is warranted in the light of recent data on estimates of fetal accretion of minerals in the third trimester (2.9 used by Zeigler et al.) vs. 3.7 estimated by Widdowson et al. and reported efficiencies of absorption of various sources of Ca and P in feedings for LBW infants. Based on the observed differences in bioavailability of Ca and P from different salts and combined with various milks, it may be appropriate to recommend intakes of Ca and possibly P that are specific for premature formulas separate from that recommended for supplements to preterm mother's milk.

Efficacy of calcium glycerophosphate vs conventional mineral salts for total parenteral nutrition in low-birth-weight infants: a randomized clinical trial.

To test the efficacy of calcium glycerophosphate (CaGlyP) vs the conventional mineral salts, calcium gluconate plus KH2PO4 + K2HPO4 (CaGluc + P), in promoting mineral retention, 72-h mineral balance, biochemical status, net acid excretion, and growth were assessed in 16 low-birth-weight infants receiving total parenteral nutrition (TPN) containing approximately 1.5 mmol Ca and P.kg-1.d-1 for 5 d. Net retentions of calcium (1.2 +/- 0.2 vs 1.0 +/- 0.2 mmol.kg-1.d-1, means +/- SD) and phosphorus (1.1 +/- 0.3 vs 0.8 +/- 0.3 mmol.kg-1.d-1) from CaGluc + P vs CaGlyP, respectively, were similar, as were retentions of magnesium and sodium, urinary pH, and net acid excretion. Plasma ionized calcium, inorganic phosphorus, alkaline phosphatase, and osteocalcin were normal and not different between groups. CaGlyP is as effective as CaGluc + P in promoting mineral retention and normal mineral homeostasis. However, at intakes of less than or equal to 1.5 mmol Ca and P.kg-1.d-1 from either mineral salt, retention represented only 60% and 45%, respectively, of the predicted intrauterine accretion for calcium and phosphorus. Larger intakes permitted by the more-soluble CaGlyP may be desirable for infants receiving TPN.

Contribution of sulfate and sulfoesters to total sulfur intake in infants fed human milk.

Colostrum (d 2-4) and mature human milk samples (d 23-30) collected from eight mothers giving birth at 31 +/- 7 wk of gestation were analyzed for total sulfur, free inorganic sulfate and acid labile sulfoesters. The data presented are representative of complete 24-h expressions. Total sulfur was measured using a wet digestion procedure in which all forms of sulfur were converted to inorganic sulfate. The sulfate was quantified by a radiometric barium precipitation assay. Total sulfur showed no marked diurnal variation, but the mean concentration in 19 colostrum samples (10.2 +/- 4.2 mmol/L) was significantly higher than in 14 mature milk samples (4.3 +/- 0.8 mmol/L) (P less than 0.001). The range of predicted 24-h intakes of sulfur by infants fed colostrum (0.78-3.22 mmol/kg body weight) was slightly higher than those fed mature milk (0.54-1.06 mmol/kg), but it was not significantly different. The combined fractions of free inorganic sulfate and acid-labile sulfoester fractions contribute less than 5% to the total sulfur content of either colostrum or mature milk. However, the physiological significance of these milk components remains to be determined.

In vitro solubility of calcium glycerophosphate versus conventional mineral salts in pediatric parenteral nutrition solutions.

Low-birth-weight infants requiring total parenteral nutrition receive inadequate intakes of calcium (Ca) and phosphorus (P) due to poor solubility of available mineral salts. To optimize Ca/P delivery, we tested the effects on in vitro solubility of mineral salt:calcium glycerophosphate (CaGP) versus calcium gluconate and K2HPO4 (CG + P); Ca:P ratios of 1:1 (at 12.5 and 25 mmol/L of Ca and P) and 2:1 (25:12.5 mmol/L); amino acid (AA) formulation: Aminosyn (A), Aminosyn-PF (A-PF), TrophAmine (T) or Vaminolac (V); and AA concentration (25 versus 8.3 g/L). Parenteral nutrition solutions contained 10% dextrose and vitamins and minerals typical of a neonatal prescription. Solutions were sampled at preparation, after 24 h in the neonatal unit (25 degrees C), and from before and after a 0.22-micron filter in extension tubing through which solutions were pumped at 5 ml/h within an incubator at 37 degrees C. Samples were analyzed for Ca and pH, and precipitation by spectrophotometry at 600 nm and light microscopy at x 100 magnification. The Ca concentration was unaffected by filtration. While spectrophotometry detected only gross precipitation, with light microscopy crystal formation was evident with 25 mmol/L of Ca and P as CG + P in A and T at 25 g of AA/L and in A, V, T, and A-PF at 8.3 g of AA/L. Precipitation did not occur with CaGP or CG + P at 12.5 mmol/L of Ca and P. Under in vitro conditions mimicking the neonatal unit, CaGP versus CG + P resulted in greater mineral solubility even at low AA concentrations.

Mineral homeostasis and bone mass in children treated for acute lymphoblastic leukemia.

Clinical observations of bone pain, abnormal gait, and unusual fractures during remission of leukemia led us to assess mineral status in a cohort of 16 children with acute lymphoblastic leukemia treated with intensive chemotherapy. During maintenance and 6 months after the completion of therapy, blood and urine were analyzed for calcium and magnesium and blood for osteocalcin, vitamin D, and parathyroid hormone. Bone mineral content and bone width of the distal one third of the radius of the nondominant arm was measured by single-photon absorptiometry. During therapy, mild ionic hypocalcemia (less than 1.19 mmol/L) and hypomagnesemia (less than 0.77 mmol/L) were demonstrated in 9 and 8 of 16 children, respectively; hypercalciuria (8/16) and hypomagnesiuria (12/16) were also observed. Plasma osteocalcin values correlated with plasma magnesium levels (r = 0.54; p less than 0.05). Oral magnesium supplements normalized plasma magnesium, calcium, and osteocalcin levels, all of which were normal at the postchemotherapy study. Plasma 1,25-dihydroxyvitamin D levels were nondetectable (less than 8 ng/ml) in 12 of 13 patients receiving therapy and in 7 of 14 patients not receiving therapy; alkaline phosphatase activity increased significantly after therapy (179 +/- 86 to 340 +/- 101 units/L), and parathyroid hormone levels were normal in both studies. Bone mineral content/bone width ratio was less than 1 SD below the mean for age- and sex-related population standards in 70% of patients. These data indicate that alterations in magnesium, calcium, and vitamin D metabolism in children treated for acute lymphoblastic leukemia may be instrumental in inducing or sustaining altered bone turnover during chemotherapy.

Macromineral balances in premature infants fed their own mothers' milk or formula.

The premature infant's own mother's milk (preterm milk) and modified infant formula (SMA, 67 and 80 kcal/dl) were fed to paired groups of seven infants, all of whom were of very low birth weight (VLBW) (less than 1.3 kg) and were studied during the first month of life. Sodium, potassium, magnesium, calcium, and phosphorus status was compared. The apparent retention of sodium from their mother's milk paralleled intrauterine retention rates and was greater than retention from SMA formula (P less than 0.01) during the first two weeks of life. However, when the formula was supplemented with NaHCO3 to intakes of 2.7 mmol Na/kg/24 hr after week 2, the infants retained adequate amounts of sodium. Potassium retention was similar to intrauterine retention rates in both groups throughout the four postnatal weeks. Magnesium intake, but not retention, was consistently higher in the group fed SMA (P less than 0.01), and intrauterine retention rates were achieved only in the group given formula. Calcium and phosphorus intakes from SMA were also higher (P less than 0.01) than from human milk. However, retention of calcium and phosphorus in both groups did not meet intrauterine retention rates, and hypophosphatemia developed in infants who received their mothers' milk. Growth in length and head circumference in both groups approximated intrauterine growth rates. If it is assumed that body composition of the growing VLBW infants should be similar to the composition of the fetus at corresponding gestational ages, then their nutrient requirements should be based on knowledge of intrauterine nutrient accretion rates. Based on this premise, we conclude that, for the growing VLBW infant, early maternal milk provided for sufficient retention of sodium, chloride, and potassium during the first four postnatal weeks. Neither human preterm milk nor SMA supplied adequate calcium and phosphorus for the growing VLBW infant.