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      Calcium Supplementation Increases Bone Mass in GH-Deficient Prepubertal Children during GH Replacement

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          Abstract

          Background/aims: Since GH plays an important role in bone mineralization, and several studies demonstrated the positive influence of a higher calcium intake on bone mass, we studied the effect of calcium supplementation in GHD children during GH therapy. Methods: 28 prepubertal GHD children, 5.0–9.9 years old, were assigned to two groups: group A (n = 14; 7 females) treated with GH, and group B (n = 14; 7 females) treated with GH + calcium gluconolactate and carbonate (1 g calcium/day per os). Auxological parameters, total bone mineral content (TBMC) and density (TBMD), leg BMC and BMD, lumbar BMD, fat mass (FM) and lean tissue mass (LTM), blood 25-hydroxyvitamin D (25-OHD), parathyroid hormone (PTH), osteocalcin (OC) and urinary N-terminal telopeptide of type I collagen (NTx) were determined at the start of therapy and after 1 and 2 years of treatment. Results: During the 2 years of the study, TBMC, TBMD, leg BMC and BMD (but not lumbar BMD) increased in both groups of patients, however after 2 years of treatment they were significantly higher in the calcium-supplemented group B than in group A (p < 0.05, for all parameters). At the start of therapy, in both groups of patients percentage FM was higher and total and leg LTM lower than in controls (p < 0.05 for each parameter). Thereafter, FM decreased and LTM increased and after 2 years they were both different from baseline (p < 0.05). After 2 years of treatment, leg BMC and BMD were more positively correlated with regional leg LTM in patients of group B (r = 0.834 and r = 0.827, respectively; p < 0.001) than in patients of group A (r = 0.617 and r = 0.637, respectively; p < 0.05). 25-OHD and PTH levels were in the normal range in all patients at the start and during treatment. OC levels were lower and urinary NTx levels higher in patients than in controls (p < 0.05 for both parameters), either at the start and after 1 year of treatment. After 2 years of treatment, OC levels were significantly higher than at the start of the study (p < 0.05) in both groups of patients, but they were higher in group B than in group A (p < 0.05); on the contrary, urinary Ntx levels were lower in group B than in group A (p < 0.05). Conclusion: In GHD children, treated with GH, calcium supplementation improved bone mass; it may aid in reaching better peak bone mass and in protecting weight-bearing bones, usually completed in childhood to maximum levels, from risk of osteoporosis and fractures later in life.

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          Most cited references 23

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          Calcium supplementation and increases in bone mineral density in children.

          Increased dietary intake of calcium during childhood, usually as calcium in milk, is associated with increased bone mass in adulthood; the increase in mass is important in modifying the later risk of fracture. Whether the increase is due to the calcium content of milk, however, is not certain. We conducted a three-year, double-blind, placebo-controlled trial of the effect of calcium supplementation (1000 mg of calcium citrate malate per day) on bone mineral density in 70 pairs of identical twins (mean [+/- SD] age, 10 +/- 2 years; range, 6 to 14). In each pair, one twin served as a control for the other; 45 pairs completed the study. Bone mineral density was measured by photon absorptiometry at two sites in the radius (at base line, six months, and one, two, and three years) and at three sites in the hip and in the spine (at base line and three years). The mean daily calcium intake of the twins given placebo was 908 mg, and that of the twins given calcium supplements was 1612 mg (894 mg from the diet and 718 mg from the supplement). Among the 22 twin pairs who were prepubertal throughout the study, the twins given supplements had significantly greater increases in bone mineral density at both radial sites (mean difference in the increase in bone mineral density: midshaft radius, 5.1 percent [95 percent confidence interval, 1.5 to 8.7 percent]; distal radius, 3.8 percent [95 percent confidence interval, 1.4 to 6.2 percent]) and in the lumbar spine (increase, 2.8 percent [95 percent confidence interval, 1.1 to 4.5 percent]) after three years; the differences in the increases at two of three femoral sites approached significance (Ward's triangle in the femoral neck, 2.9 percent; greater trochanter, 3.5 percent). Among the 23 pairs who went through puberty or were postpubertal, the twins given supplements received no benefit. In prepubertal children whose average dietary intake of calcium approximated the recommended dietary allowance, calcium supplementation increased the rate of increase in bone mineral density. If the gain persists, peak bone density should be increased and the risk of fracture reduced.
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            Endocrine control of body composition in infancy, childhood, and puberty.

            Body composition exhibits marked variations across the early human lifetime. The precise physiological mechanisms that drive such developmental adaptations are difficult to establish. This clinical challenge reflects an array of potentially confounding factors, such as marked intersubject differences in tissue compartments; the incremental nature of longitudinal intrasubject variations in body composition; technical limitations in quantitating the unobserved mass of mineral, fat, water, and muscle ad seriatim; and the multifold contributions of genetic, dietary, environmental, hormonal, nutritional, and behavioral signals to physical and sexual maturation. From an endocrine perspective (reviewed here), gonadal sex steroids and GH/IGF-I constitute prime determinants of evolving body composition. The present critical review examines hormonal regulation of body composition in infancy, childhood, and puberty.
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              Calcium-enriched foods and bone mass growth in prepubertal girls: a randomized, double-blind, placebo-controlled trial.

              High calcium intake during childhood has been suggested to increase bone mass accrual, potentially resulting in a greater peak bone mass. Whether the effects of calcium supplementation on bone mass accrual vary from one skeletal region to another, and to what extent the level of spontaneous calcium intake may affect the magnitude of the response has, however, not yet been clearly established. In a double-blind, placebo-controlled study, 149 healthy prepubertal girls aged 7.9+/-0.1 yr (mean+/-SEM) were either allocated two food products containing 850 mg of calcium (Ca-suppl.) or not (placebo) on a daily basis for 1 yr. Areal bone mineral density (BMD), bone mineral content (BMC), and bone size were determined at six sites by dual-energy x-ray absorptiometry. The difference in BMD gain between calcium-supplemented (Ca-suppl.) and placebo was greater at radial (metaphysis and diaphysis) and femoral (neck, trochanter, and diaphyses) sites (7-12 mg/cm2 per yr) than in the lumbar spine (2 mg/cm2 per yr). The difference in BMD gains between Ca-suppl. and placebo was greatest in girls with a spontaneous calcium intake below the median of 880 mg/d. The increase in mean BMD of the 6 sites in the low-calcium consumers was accompanied by increased gains in mean BMC, bone size, and statural height. These results suggest a possible positive effect of calcium supplementation on skeletal growth at that age. In conclusion, calcium-enriched foods significantly increased bone mass accrual in prepubertal girls, with a preferential effect in the appendicular skeleton, and greater benefit at lower spontaneous calcium intake.
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                Author and article information

                Journal
                HRE
                Horm Res Paediatr
                10.1159/issn.1663-2818
                Hormone Research in Paediatrics
                S. Karger AG
                1663-2818
                1663-2826
                2006
                April 2006
                22 May 2006
                : 65
                : 5
                : 223-230
                Affiliations
                aPediatric Clinic and bDepartment of Internal Medicine, University of Verona, Verona, Italy
                Article
                92403 Horm Res 2006;65:223–230
                10.1159/000092403
                16569932
                © 2006 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 2, Tables: 3, References: 36, Pages: 8
                Categories
                Original Paper

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