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      Bone Mineral Density in Girls and Their Mothers with Idiopathic Hypercalciuria

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          Abstract

          Background/Aims: Idiopathic hypercalciuria (IH) is associated with a decreased bone mineral density (BMD) both in children and adults. It is being increasingly recognized that IH may be a contributing factor to osteopenia and/or osteoporosis in adults. We studied BMD in girls with IH and in their mothers, also affected with IH, in order to evaluate the influence of genetic background on bone mass in the setting of IH. Methods: BMD was evaluated in 40 girls with IH and in their premenopausal mothers from whom they had inherited this disease. Urinary creatinine and calcium were measured by standard laboratory methods. BMD was determined by dual X-ray absorptiometry scanning of the lumbar spine (LS) and the femoral neck (FN), and values are expressed as Z- and T-scores. Results: A Z-score of <–1 at the LS was found in 42.5% of the girls, whilst in the mothers, a Z score of <–1 at the LS and/or FN was observed in 47.5% and a T-score of <–1 at the LS and/or FN in 62.5%. The Z-score at the LS was significantly lower in girls and their mothers compared to controls, although this finding did not apply for the Z-score at the FN in the mothers. Z-scores in the girls of mothers with osteopenia were significantly lower or there was a trend for the score to be lower than in the girls of mothers with normal BMD. There was a significant relationship between the Z-score of the girls and the T-score at the LS in the mothers (r = 0.32, p < 0.05). Conclusion: We have observed a high prevalence of osteopenia in our population affected by IH, both in girls and in their mothers. We suggest that BMD should be measured during the third or fourth decades of life in those individuals with nephrolithiasis or with children diagnosed as having IH.

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          Bone mineral density in pediatric patients with idiopathic hypercalciuria.

          It is well known that some patients with renal lithiasis due to idiopathic hypercalciuria (IH) may exhibit decreased bone mineral density (BMD). We have studied a large group of children in IH and related their BMD values to several renal function parameters and calcium and bone metabolism markers. Children with IH had higher osteocalcin and calcitriol levels and higher urinary excretion of magnesium and prostaglandin E2, as well as lower tubular reabsorption of phosphate, urinary excretion of ammonium, maximum urinary PCO2, and BMD compared with control group of children. In children with IH we observed a negative correlation between BMD and age. We found osteopenia in 22 of 73 children with IH (30.1%); these children showed lower citraturia levels and higher fractional excretion of uric acid than children with normal BMD. In osteopenic children there was a negative correlation between BMD and calcitriol levels. Several possible pathogenetic factors have been proposed for the bone mass loss. Our results demonstrate that, at least in some cases, it may be related to high levels of calcitriol, which has a well-known resorption ability. Whether a certain degree of intracellular acidosis or a higher production of prostaglandin E2 could play a role in some cases is still an open question. In children with normal BMD we observed a direct correlation between osteocalcin and tartrate-resistant acid phosphatase levels; this correlation did not hold for children with osteopenia.
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            Effect of Etidronate Treatment on Bone Mass of Male Nephrolithiasis Patients with Idiopathic Hypercalciuria and Osteopenia

            Osteopenia is frequently found among calcium stone forming (CSF) patients with hypercalciuria. We investigated the effect of a 2-year therapeutic course of etidronate, a bone-sparing agent, in 7 young male CSF patients. The treatment consisted of a cyclic intermittent administration of phosphate followed by sodium etidronate and calcium supplementation every 74 days. Bone mineral density (BMD) measured at 12-month intervals and bone biopsies performed at baseline and after 2 years were the primary efficacy parameters. Mean lumbar spine BMD increased significantly after the 1st year by 2.6 ± 1.0% (mean ± SE, p < 0.05) and nonsignificantly after the 2nd year by 5.6 ± 2.6%. Nonsignificant changes were observed for femoral neck mean BMD after either the 1st or the 2nd year (decrease of 2.0 ± 1.0% and 2.0 ± 3.0%, respectively). Mean histomorphometric parameters showed that bone volume, osteoid volume, and eroded surfaces did not differ from baseline (13.9 ± 2.2 vs. 12.2 ± 1.1%, 1.2 ± 0.7 vs. 2.6 ± 0.7%, and 20.7 ± 6.2 vs. 13.7 ± 1.3%, respectively). Osteoid surface was significantly lower than baseline values (9.5 ± 5.2 vs. 18.8 ± 5.3%, p < 0.05). These data suggest that etidronate given to young male CSF patients presenting with hypercalciuria and osteopenia led to a significant amelioration of BMD, evident only in the lumbar spine after 1 year of treatment. There was no histological evidence of long-term improvement in bone remodeling.
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              Sodium transport and bone mineral density in hypercalciuria with thiazide treatment.

              Erythrocyte sodium-potassium (Na+/K+)-ATPase and sodium-lithium (Na+/Li+) countertransport activities were measured in 18 children (aged 9.6 years, range 6-16 years) with idiopathic hypercalciuria (IHU) to evaluate cellular Na handling. The effect of chronic thiazide administration on these parameters and on bone mineral density was also evaluated. Patients with IHU had significantly lower erythrocyte Na+/K+-ATPase activity than 23 age-matched healthy controls (mean +/- SEM 2,156 +/- 110 micromol P/l erythrocyte per hour vs. 3,165 +/- 175, P < 0.01). Thiazide treatment significantly lowered urinary calcium excretion; this was followed by a slight suppression of intact parathyroid hormone (iPTH). The urinary calcium/creatinine ratio before and during treatment was 0.90 +/- 0.07 mmol/mmol versus 0.51 +/- 0.06 respectively, P < 0.01. The corresponding iPTH levels were 5.9 +/- 0.6 pmol/l and 5.1 +/- 0.7, P < 0.05. The Na+/K+-ATPase activity increased significantly (2,769 +/- 169 micromol P/l erythrocyte per hour vs. 2,156 +/- 110 in the control period, P < 0.01) and the Na+/Li+ countertransport decreased (268 +/- 28 micromol Li/l erythrocyte per hour vs. 328+26 in the control period, P < 0.03). The bone mineral density Z score rose from -1.3 +/- 0.26 to -0.8 +/- 0.22 (P < 0.03). We conclude that IHU is accompanied by abnormalities of erythrocyte Na+/K+-ATPase and Na+/Li+ countertransport which are corrected by chronic hydrochlorothiazide administration. These changes could model alterations in renal tubular transport mechanisms still to be elucidated. Chronic thiazide treatment also has a positive effect on bone mineral density.
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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
                2003
                August 2003
                17 November 2004
                : 94
                : 4
                : c89-c93
                Affiliations
                aPediatric Nephrology Unit and bNephrology Service, Hospital Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Canary Islands, Spain
                Article
                72491 Nephron Clin Pract 2003;94:c89–c93
                10.1159/000072491
                12972718
                8dbd8834-186a-446c-b970-ab523075cccc
                © 2003 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.

                History
                : 24 April 2003
                Page count
                Tables: 2, References: 19, Pages: 1
                Categories
                Original Paper

                Cardiovascular Medicine,Nephrology
                Adults,Densitometry,Children,Idiopathic hypercalciuria,Osteoporosis,Osteopenia

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