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      Effects of Reduced Dialysate Calcium on Calcium-Phosphorus Product and Bone Metabolism in Hemodialysis Patients

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          Abstract

          Background: The safety of using reduced calcium dialysate (RDC) in hemodialysis (HD) patients is controversial due to related changes in bone metabolism. In the present study we investigated whether an 18-month treatment period with RDC may induce significant changes in calcium-phosphorus product (CaxP), bone metabolism, and components of the insulin-like growth factor (IGF) system in HD patients. Study Design: In this prospective study, 13 HD patients with biochemical signs of diminished or low-normal bone turnover and high CaxP due to high serum calcium level were treated by lowering dialysate calcium from 3.5 to 2.5 mEq/l for 18 months. By specific immunometric assays, serum levels of intact parathyroid hormone (PTH), bone alkaline phosphatase (B-ALP), pyridinoline (PYR), desoxypyridinoline (D-PYR), 25-OH-vitamin D<sub>3</sub> (25-vit D<sub>3</sub>), 1,25-(OH)<sub>2</sub>-vitamin D<sub>3</sub> (1,25-vit D<sub>3</sub>), free IGF-I, IGF-II, and IGF-binding protein (IGFBP)-1 to -6 were measured. Results: CaxP decreased significantly from 5.62 (baseline) to 3.95 mmol<sup>2</sup>/l<sup>2</sup> (at 18 months), whereas PTH increased from 81 ± 57 pg/ml at baseline to 236 ± 188 at 12 months (p < 0.01), remaining in this range thereafter. Parameters of bone resorption (PYR) as well as formation (B-ALP) significantly increased during RDC, with peak levels after 12 months. Despite increasing doses of oral alfacalcidol, levels of 25-vit D<sub>3</sub> and 1,25-vit D<sub>3</sub> subsequently declined during RDC. In parallel with the changes in bone markers, free IGF-I levels decreased (baseline: 1.9 ± 0.9 ng/ml, after 18 months: 1.1 ± 0.7; p < 0.01). The decline of free IGF-I correlated with decreasing levels of IGFBP-3 and increasing levels of IGFBP-1/-4. Conclusion: The treatment with RDC effectively lowered CaxP and stimulated bone formation and resorption. The different changes in bone markers and IGF system components mirror the complex effects on bone metabolism.

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          Most cited references 10

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          Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis.

          Once-daily injections of parathyroid hormone or its amino-terminal fragments increase bone formation and bone mass without causing hypercalcemia, but their effects on fractures are unknown. We randomly assigned 1637 postmenopausal women with prior vertebral fractures to receive 20 or 40 microg of parathyroid hormone (1-34) or placebo, administered subcutaneously by the women daily. We obtained vertebral radiographs at base line and at the end of the study (median duration of observation, 21 months) and performed serial measurements of bone mass by dual-energy x-ray absorptiometry. New vertebral fractures occurred in 14 percent of the women in the placebo group and in 5 percent and 4 percent, respectively, of the women in the 20-microg and 40-microg parathyroid hormone groups; the respective relative risks of fracture in the 20-microg and 40-microg groups, as compared with the placebo group, were 0.35 and 0.31 (95 percent confidence intervals, 0.22 to 0.55 and 0.19 to 0.50). New nonvertebral fragility fractures occurred in 6 percent of the women in the placebo group and in 3 percent of those in each parathyroid hormone group (relative risk, 0.47 and 0.46, respectively [95 percent confidence intervals, 0.25 to 0.88 and 0.25 to 0.861). As compared with placebo, the 20-microg and 40-microg doses of parathyroid hormone increased bone mineral density by 9 and 13 more percentage points in the lumbar spine and by 3 and 6 more percentage points in the femoral neck; the 40-microg dose decreased bone mineral density at the shaft of the radius by 2 more percentage points. Both doses increased total-body bone mineral by 2 to 4 more percentage points than did placebo. Parathyroid hormone had only minor side effects (occasional nausea and headache). Treatment of postmenopausal osteoporosis with parathyroid hormone (1-34) decreases the risk of vertebral and nonvertebral fractures; increases vertebral, femoral, and total-body bone mineral density; and is well tolerated. The 40-microg dose increased bone mineral density more than the 20-microg dose but had similar effects on the risk of fracture and was more likely to have side effects.
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            Intrauterine growth retardation and postnatal growth failure associated with deletion of the insulin-like growth factor I gene.

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              Insulin-like growth factors and their binding proteins: biological actions

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                Author and article information

                Journal
                NEC
                Nephron Clin Pract
                10.1159/issn.1660-2110
                Nephron Clinical Practice
                S. Karger AG
                1660-2110
                2004
                January 2004
                17 November 2004
                : 96
                : 1
                : c3-c9
                Affiliations
                aDepartment of Nephrology, Martin Luther University Halle-Wittenberg, Halle, bKfH Dialysis Center, Zirndorf, cDepartment of Internal Medicine I, St. Elisabeth Hospital, Halle, Germany; dMusculoskeletal Diseases Center (151), Jerry L. Pettis VA Medical Center, Loma Linda, Calif., USA, and eInternal Medicine, Hospital of the Paul Gerhardt Foundation, Lutherstadt Wittenberg, Germany
                Article
                75565 Nephron Clin Pract 2004;96:c3–c9
                10.1159/000075565
                14752247
                © 2004 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: 1, Tables: 3, References: 47, Pages: 1
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/75565
                Categories
                Original Paper

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