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      Pamidronate Therapy for Preventing Steroid-Induced Osteoporosis in Children with Nephropathy

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          Abstract

          Background: Steroid-induced osteoporosis (SIO) is a serious complication of long-term steroid therapy and is of particular concern in growing children. Recently bisphosphonates have been applied in the treatment or prevention of SIO. We investigated the efficacy of pamidronate on SIO in childhood nephropathy patients receiving long-term corticosteroid therapy. Methods: Forty-four children receiving high doses of steroids were enrolled in the study. There was no history of bone, liver, or endocrine disease. Patients were randomly classified into two groups, the control group and the study group. All patients received corticosteroids for 3 months. Control group took oral calcium supplements (500 mg/day) only, and the study group oral calcium and pamidronate (125 mg) for 3 months. Biochemical tests, long bone radiography, and bone mineral density (BMD) were performed in the first month and 3 months later in all patients. Results: The differences in the results of biochemical tests such as serum calcium, BUN, and cre atinine level obtained in the first month and three months later were not of statistical significance in both the control and the study groups. However, the mean BMD of the lumbar spine decreased from 0.654 ± 0.069 (g/cm<sup>2</sup>) to 0.631 ± 0.070 (g/cm<sup>2</sup>) in the control group (p = 0.0017), while it did not in the study group from 0.644 ± 0.189 (g/cm<sup>2</sup>) to 0.647 ± 0.214 (g/cm<sup>2</sup>). Conclusions: Pamidronate appears to be effective in preventing SIO in children with nephropathy requiring long-term steroid therapy. Further long-term follow-up studies regarding the efficacy and side effects appear to be necessary to set a more solid basis for such pediatric uses of bisphosphonates such as pamidronate.

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          Most cited references 19

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          Cyclic administration of pamidronate in children with severe osteogenesis imperfecta.

          Severe osteogenesis imperfecta is a disorder characterized by osteopenia, frequent fractures, progressive deformity, loss of mobility, and chronic bone pain. There is no effective therapy for the disorder. We assessed the effects of treatment with a bisphosphonate on bone resorption. In an uncontrolled observational study involving 30 children who were 3 to 16 years old and had severe osteogenesis imperfecta, we administered pamidronate intravenously (mean [+/-SD] dose, 6.8+/-1.1 mg per kilogram of body weight per year) at 4-to-6-month intervals for 1.3 to 5.0 years. Clinical status, biochemical characteristics reflecting bone turnover, the bone mineral density of the lumbar spine, and radiologic changes were assessed regularly during treatment. Administration of pamidronate resulted in sustained reductions in serum alkaline phosphatase concentrations and in the urinary excretion of calcium and type I collagen N-telopeptide. There was a mean annualized increase of 41.9+/-29.0 percent in bone mineral density, and the deviation of bone mineral density from normal, as indicated by the z score, improved from -5.3+/-1.2 to -3.4+/-1.5. The cortical width of the metacarpals increased by 27+/-20.2 percent per year. The increases in the size of the vertebral bodies suggested that new bone had formed. The mean incidence of radiologically confirmed fractures decreased by 1.7 per year (P<0.001). Treatment with pamidronate did not alter the rate of fracture healing, the growth rate, or the appearance of the growth plates. Mobility and ambulation improved in 16 children and remained unchanged in the other 14. All the children reported substantial relief of chronic pain and fatigue. In children with severe osteogenesis imperfecta, cyclic administration of intravenous pamidronate improved clinical outcomes, reduced bone resorption, and increased bone density.
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            Molecular mechanisms of action of bisphosphonates.

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              Long-term effects of bisphosphonates on the growing skeleton. Studies of young patients with severe osteoporosis.

              Osteoporosis in children and adolescents is relatively uncommon and usually secondary to identifiable causal factors. There are no generally accepted therapies for patients with no treatable underlying cause of disease. Any treatment of young patients with bone-acting compounds should be not only effective but also devoid of adverse effects on bone growth and remodeling. For many years we have been studying the effects of bisphosphonates-an effective treatment of postmenopausal osteoporosis-on the growing skeleton. We review here our experience in the treatment of young patients with osteoporosis with special emphasis on issues of skeletal safety and effectiveness, and we discuss the available literature data. We studied 12 patients aged between 10.7 and 17.2 years with symptomatic osteoporosis and multiple fractures treated with the bisphosphonates pamidronate or olpadronate for periods between 2 and 8 years continuously. Linear growth continued normally on treatment; there was even a catch-up growth in prepubertal patients, and there was no excessive suppression of bone remodeling, assessed biochemically. Bone biopsies obtained at various stages during treatment showed bone of normal lamellar structure without mineralization defects. There was an increase in calcium balance, already evident within 10 days, the level of which was maintained for at least 3 years of treatment. This was associated with progressive increases in bone mineral density along a different slope from that of healthy peers as well as correction of vertebral deformities on X-rays in patients given bisphosphonates before puberty. Treatment was well tolerated and clinical improvement was remarkable. Our studies, supported by literature data, strongly suggest that bisphosphonate therapy can be beneficial to young patients with osteoporosis for whom no other options are currently available, and justify planning controlled studies in more common conditions for which no treatment is currently available, such as osteogenesis imperfecta.
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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
                2006
                February 2006
                11 November 2005
                : 102
                : 3-4
                : c81-c87
                Affiliations
                East-West Kidney Disease Research Institute and Department of Pediatrics, Kyung Hee University Hospital, Hoegi-dong, Dongdaemun-gu,Seoul, Korea
                Article
                89664 Nephron Clin Pract 2006;102:c81–c87
                10.1159/000089664
                16282699
                © 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: 37, Pages: 1
                Product
                Self URI (application/pdf): https://www.karger.com/Article/Pdf/89664
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