Skip to main content
Top
Published in: Pediatric Nephrology 6/2014

01-06-2014 | Original Article

Calcium and vitamin D for osteoprotection in children with new-onset nephrotic syndrome treated with steroids: a prospective, randomized, controlled, interventional study

Authors: Surabhi Choudhary, Indira Agarwal, Mandalam S. Seshadri

Published in: Pediatric Nephrology | Issue 6/2014

Login to get access

Abstract

Background

There are no robust guidelines on strategies to prevent the adverse skeletal effects of glucocorticoids in children.

Objectives

To evaluate the role of prophylactic calcium and vitamin D on bone health in children with new-onset nephrotic syndrome (NS) treated with short-term (12 weeks), high-dose glucocorticoids.

Methods

Prospective, randomized, controlled, single blind, interventional study conducted on 41 steroid-naïve pre-pubertal children (29 boys, 12 girls). All children received prednisolone for 12 weeks (60 mg/m2/day daily for 6 weeks, followed by 40 mg/m2/day alternate days for 6 weeks). Recruited children were randomized into the intervention group (IG; vitamin D 1,000 IU/day and elemental calcium 500 mg/day) and the control group (CG). Bone mineral content (BMC) and bone mineral density (BMD) at the lumbar spine (L1–L4) were estimated at baseline and at 12 weeks. Mean percentage changes in BMC and BMD in IG and CG were compared.

Results

Children in the IG showed an increase of 11.2 % in BMC versus the CG, who showed an 8.9 % fall (p < 0.0001). Net intervention-attributable difference in BMC was 20.1 %. BMD increased in both groups (IG 2.8 % vs CG 0.74 %), but the difference was not statistically significant (p = 0.27).

Conclusions

Short-term, high-dose glucocorticoid therapy decreases the BMC of the lumbar spine in steroid-naïve children with NS. Vitamin D and calcium co-administration not only prevents this decline, but also enhances BMC of the lumbar spine.
Literature
1.
go back to reference Parfitt AM (1997) Prevention of osteoporosis is a paediatric responsibility. Osteologicky Bull 66-70 Parfitt AM (1997) Prevention of osteoporosis is a paediatric responsibility. Osteologicky Bull 66-70
3.
go back to reference Hegarty J, Mughal MZ, Adams J, Webb NJ (2005) Reduced bone mineral density in adults treated with high-dose corticosteroids for childhood nephrotic syndrome. Kidney Int 68:2304–2309PubMedCrossRef Hegarty J, Mughal MZ, Adams J, Webb NJ (2005) Reduced bone mineral density in adults treated with high-dose corticosteroids for childhood nephrotic syndrome. Kidney Int 68:2304–2309PubMedCrossRef
4.
go back to reference Van Staa TP, Cooper C, Leufkens HG, Bishop N (2003) Children and the risk of fractures caused by oral corticosteroids. J Bone Miner Res 18:913–918PubMedCrossRef Van Staa TP, Cooper C, Leufkens HG, Bishop N (2003) Children and the risk of fractures caused by oral corticosteroids. J Bone Miner Res 18:913–918PubMedCrossRef
5.
6.
go back to reference Blodgett FM, Burgin L, Iezzoni D, Gribetz D, Talbot NB (1956) Effects of prolonged cortisone therapy on the statural growth, skeletal maturation and metabolic status of children. N Engl J Med 254:636–641PubMedCrossRef Blodgett FM, Burgin L, Iezzoni D, Gribetz D, Talbot NB (1956) Effects of prolonged cortisone therapy on the statural growth, skeletal maturation and metabolic status of children. N Engl J Med 254:636–641PubMedCrossRef
7.
go back to reference Kano K, Hoshi M, Nishikura K, Yamada Y, Arisaka O (2001) Skeletal effects of short-term prednisolone therapy in children with steroid-responsive nephrotic syndrome. Clin Exp Nephrol 5:40–43CrossRef Kano K, Hoshi M, Nishikura K, Yamada Y, Arisaka O (2001) Skeletal effects of short-term prednisolone therapy in children with steroid-responsive nephrotic syndrome. Clin Exp Nephrol 5:40–43CrossRef
8.
go back to reference Grossman JM, Gordon R, Ranganath VK, Deal C, Caplan L, Chen W, Curtis JR, Furst DE, McMahon M, Patkar NM, Volkmann E, Saag KG (2010) American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res (Hoboken) 62:1515–1526CrossRef Grossman JM, Gordon R, Ranganath VK, Deal C, Caplan L, Chen W, Curtis JR, Furst DE, McMahon M, Patkar NM, Volkmann E, Saag KG (2010) American College of Rheumatology 2010 recommendations for the prevention and treatment of glucocorticoid-induced osteoporosis. Arthritis Care Res (Hoboken) 62:1515–1526CrossRef
9.
go back to reference Ward L, Tricco AC, Phuong P, Cranney A, Barrowman N, Gaboury I, Rauch F, Tugwell P, Moher D (2007) Bisphosphonate therapy for children and adolescents with secondary osteoporosis. Cochrane Database Syst Rev CD005324. Ward L, Tricco AC, Phuong P, Cranney A, Barrowman N, Gaboury I, Rauch F, Tugwell P, Moher D (2007) Bisphosphonate therapy for children and adolescents with secondary osteoporosis. Cochrane Database Syst Rev CD005324.
10.
go back to reference Bachrach LK (2007) Consensus and controversy regarding osteoporosis in the pediatric population. Endocr Pract 13:513–520PubMedCrossRef Bachrach LK (2007) Consensus and controversy regarding osteoporosis in the pediatric population. Endocr Pract 13:513–520PubMedCrossRef
11.
go back to reference Leonard MB (2007) Glucocorticoid-induced osteoporosis in children: impact of the underlying disease. Pediatrics 119 [Suppl 2]:S166–S174PubMedCrossRef Leonard MB (2007) Glucocorticoid-induced osteoporosis in children: impact of the underlying disease. Pediatrics 119 [Suppl 2]:S166–S174PubMedCrossRef
12.
go back to reference Bak M, Serdaroglu E, Guclu R (2006) Prophylactic calcium and vitamin D treatments in steroid-treated children with nephrotic syndrome. Pediatr Nephrol 21:350–354PubMedCrossRef Bak M, Serdaroglu E, Guclu R (2006) Prophylactic calcium and vitamin D treatments in steroid-treated children with nephrotic syndrome. Pediatr Nephrol 21:350–354PubMedCrossRef
13.
go back to reference Gulati S, Sharma RK, Gulati K, Singh U, Srivastava A (2005) Longitudinal follow-up of bone mineral density in children with nephrotic syndrome and the role of calcium and vitamin D supplements. Nephrol Dial Transplant 20:1598–1603PubMedCrossRef Gulati S, Sharma RK, Gulati K, Singh U, Srivastava A (2005) Longitudinal follow-up of bone mineral density in children with nephrotic syndrome and the role of calcium and vitamin D supplements. Nephrol Dial Transplant 20:1598–1603PubMedCrossRef
14.
go back to reference Heaney RP (2003) Bone mineral content, not bone mineral density, is the correct bone measure for growth studies. Am J Clin Nutr 78:350–351, author reply 351–352PubMed Heaney RP (2003) Bone mineral content, not bone mineral density, is the correct bone measure for growth studies. Am J Clin Nutr 78:350–351, author reply 351–352PubMed
15.
go back to reference Heaney RP (2001) Design considerations for clinical investigations of osteoporosis. In: Marcus R, Kelsey J, Feldman D (eds) Osteoporosis. Academic Press, San Diego, pp 513–532CrossRef Heaney RP (2001) Design considerations for clinical investigations of osteoporosis. In: Marcus R, Kelsey J, Feldman D (eds) Osteoporosis. Academic Press, San Diego, pp 513–532CrossRef
16.
go back to reference Prentice A, Parsons TJ, Cole TJ (1994) Uncritical use of bone mineral density in absorptiometry may lead to size-related artifacts in the identification of bone mineral determinants. Am J Clin Nutr 60:837–842PubMed Prentice A, Parsons TJ, Cole TJ (1994) Uncritical use of bone mineral density in absorptiometry may lead to size-related artifacts in the identification of bone mineral determinants. Am J Clin Nutr 60:837–842PubMed
17.
go back to reference Pais P, Avner E (2011) Nephrotic syndrome. In: Kliegman RM, Stanton BF, Schor NF, St Geme JW, Behrman RE (eds) Nelson textbook of pediatrics. Elsevier Saunders, Philadelphia, pp 1801–1807CrossRef Pais P, Avner E (2011) Nephrotic syndrome. In: Kliegman RM, Stanton BF, Schor NF, St Geme JW, Behrman RE (eds) Nelson textbook of pediatrics. Elsevier Saunders, Philadelphia, pp 1801–1807CrossRef
18.
go back to reference Brodehl J (1991) The treatment of minimal change nephrotic syndrome: lessons learned from multicentre co-operative studies. Eur J Pediatr 150:380–387PubMedCrossRef Brodehl J (1991) The treatment of minimal change nephrotic syndrome: lessons learned from multicentre co-operative studies. Eur J Pediatr 150:380–387PubMedCrossRef
19.
go back to reference Gafni RI, Baron J (2004) Overdiagnosis of osteoporosis in children due to misinterpretation of dual-energy x-ray absorptiometry (DEXA). J Pediatr 144:253–257PubMedCrossRef Gafni RI, Baron J (2004) Overdiagnosis of osteoporosis in children due to misinterpretation of dual-energy x-ray absorptiometry (DEXA). J Pediatr 144:253–257PubMedCrossRef
20.
go back to reference Ward LM (2005) Osteoporosis due to glucocorticoid use in children with chronic illness. Horm Res 64:209–221PubMedCrossRef Ward LM (2005) Osteoporosis due to glucocorticoid use in children with chronic illness. Horm Res 64:209–221PubMedCrossRef
21.
go back to reference Mølgaard C, Thomsen BL, Prentice A, Cole TJ, Michaelsen KF (1997) Whole body bone mineral content in healthy children and adolescents. Arch Dis Child 76:9–15PubMedCentralPubMedCrossRef Mølgaard C, Thomsen BL, Prentice A, Cole TJ, Michaelsen KF (1997) Whole body bone mineral content in healthy children and adolescents. Arch Dis Child 76:9–15PubMedCentralPubMedCrossRef
22.
go back to reference Bachrach LK (2000) Dual energy X-ray absorptiometry (DEXA) measurements of bone density and body composition: promise and pitfalls. J Pediatr Endocrinol Metab 13 [Suppl 2]:983–988PubMed Bachrach LK (2000) Dual energy X-ray absorptiometry (DEXA) measurements of bone density and body composition: promise and pitfalls. J Pediatr Endocrinol Metab 13 [Suppl 2]:983–988PubMed
23.
go back to reference Reid IR, Evans MC, Stapleton J (1992) Lateral spine densitometry is a more sensitive indicator of glucocorticoid-induced bone loss. J Bone Miner Res 7:1221–1225PubMedCrossRef Reid IR, Evans MC, Stapleton J (1992) Lateral spine densitometry is a more sensitive indicator of glucocorticoid-induced bone loss. J Bone Miner Res 7:1221–1225PubMedCrossRef
24.
go back to reference Leonard MB, Zemel BS (2002) Current concepts in pediatric bone disease. Pediatr Clin North Am 49:143–173PubMedCrossRef Leonard MB, Zemel BS (2002) Current concepts in pediatric bone disease. Pediatr Clin North Am 49:143–173PubMedCrossRef
25.
go back to reference Leonard MB, Feldman HI, Shults J, Zemel BS, Foster BJ, Stallings VA (2004) Long-term, high-dose glucocorticoids and bone mineral content in childhood glucocorticoid-sensitive nephrotic syndrome. N Engl J Med 351:868–875PubMedCrossRef Leonard MB, Feldman HI, Shults J, Zemel BS, Foster BJ, Stallings VA (2004) Long-term, high-dose glucocorticoids and bone mineral content in childhood glucocorticoid-sensitive nephrotic syndrome. N Engl J Med 351:868–875PubMedCrossRef
26.
go back to reference Gulati S, Godbole M, Singh U, Gulati K, Srivastava A (2003) Are children with idiopathic nephrotic syndrome at risk for metabolic bone disease? Am J Kidney Dis 41:1163–1169PubMedCrossRef Gulati S, Godbole M, Singh U, Gulati K, Srivastava A (2003) Are children with idiopathic nephrotic syndrome at risk for metabolic bone disease? Am J Kidney Dis 41:1163–1169PubMedCrossRef
27.
go back to reference Basiratnia M, Fallahzadeh M, Derakhshan A, Hosseini-Al-Hashemi G (2006) Bone mineral density in children with relapsing nephrotic syndrome. Iran J Med Sci 31:82–86 Basiratnia M, Fallahzadeh M, Derakhshan A, Hosseini-Al-Hashemi G (2006) Bone mineral density in children with relapsing nephrotic syndrome. Iran J Med Sci 31:82–86
28.
go back to reference Del Rio L, Carrascosa A, Pons F, Gusinyé M, Yeste D, Domenech FM (1994) Bone mineral density of the lumbar spine in white Mediterranean Spanish children and adolescents: changes related to age, sex, and puberty. Pediatr Res 35:362–366PubMedCrossRef Del Rio L, Carrascosa A, Pons F, Gusinyé M, Yeste D, Domenech FM (1994) Bone mineral density of the lumbar spine in white Mediterranean Spanish children and adolescents: changes related to age, sex, and puberty. Pediatr Res 35:362–366PubMedCrossRef
29.
go back to reference Van der Sluis IM, van den Heuvel-Eibrink MM, Hählen K, Krenning EP, de Muinck Keizer-Schrama SM (2002) Altered bone mineral density and body composition, and increased fracture risk in childhood acute lymphoblastic leukemia. J Pediatr 141:204–210PubMedCrossRef Van der Sluis IM, van den Heuvel-Eibrink MM, Hählen K, Krenning EP, de Muinck Keizer-Schrama SM (2002) Altered bone mineral density and body composition, and increased fracture risk in childhood acute lymphoblastic leukemia. J Pediatr 141:204–210PubMedCrossRef
30.
go back to reference Ahmed SF, Wallace WH, Crofton PM, Wardhaugh B, Magowan R, Kelnar CJ (1999) Short-term changes in lower leg length in children treated for acute lymphoblastic leukaemia. J Pediatr Endocrinol Metab 12:75–80PubMed Ahmed SF, Wallace WH, Crofton PM, Wardhaugh B, Magowan R, Kelnar CJ (1999) Short-term changes in lower leg length in children treated for acute lymphoblastic leukaemia. J Pediatr Endocrinol Metab 12:75–80PubMed
31.
go back to reference Barragry JM, France MW, Carter ND, Auton JA, Beer M, Boucher BJ, Cohen RD (1977) Vitamin-D metabolism in nephrotic syndrome. Lancet 2:629–632PubMedCrossRef Barragry JM, France MW, Carter ND, Auton JA, Beer M, Boucher BJ, Cohen RD (1977) Vitamin-D metabolism in nephrotic syndrome. Lancet 2:629–632PubMedCrossRef
32.
go back to reference Koenig KG, Lindberg JS, Zerwekh JE, Padalino PK, Cushner HM, Copley JB (1992) Free and total 1,25-dihydroxyvitamin D levels in subjects with renal disease. Kidney Int 41:161–165PubMedCrossRef Koenig KG, Lindberg JS, Zerwekh JE, Padalino PK, Cushner HM, Copley JB (1992) Free and total 1,25-dihydroxyvitamin D levels in subjects with renal disease. Kidney Int 41:161–165PubMedCrossRef
34.
go back to reference Trivedi DP, Doll R, Khaw KT (2003) Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ 326:469PubMedCentralPubMedCrossRef Trivedi DP, Doll R, Khaw KT (2003) Effect of four monthly oral vitamin D3 (cholecalciferol) supplementation on fractures and mortality in men and women living in the community: randomised double blind controlled trial. BMJ 326:469PubMedCentralPubMedCrossRef
35.
go back to reference Gopalan C, Ramasastri BV, Balasubramanyam SC (2007) Recommended dietary allowances for Indians (Indian Council of Medical Research ICMR 1990). Nutritive value of Indian food. National Institute of Nutrition, Hyderabad, p 98 Gopalan C, Ramasastri BV, Balasubramanyam SC (2007) Recommended dietary allowances for Indians (Indian Council of Medical Research ICMR 1990). Nutritive value of Indian food. National Institute of Nutrition, Hyderabad, p 98
36.
go back to reference Marwaha RK, Tandon N, Reddy DR, Aggarwal R, Singh R, Sawhney RC, Saluja B, Ganie MA, Singh S (2005) Vitamin D and bone mineral density status of healthy schoolchildren in northern India. Am J Clin Nutr 82:477–482PubMed Marwaha RK, Tandon N, Reddy DR, Aggarwal R, Singh R, Sawhney RC, Saluja B, Ganie MA, Singh S (2005) Vitamin D and bone mineral density status of healthy schoolchildren in northern India. Am J Clin Nutr 82:477–482PubMed
37.
go back to reference Sachan A, Gupta R, Das V, Agarwal A, Awasthi PK, Bhatia V (2005) High prevalence of vitamin D deficiency among pregnant women and their newborns in northern India. Am J Clin Nutr 81:1060–1064PubMed Sachan A, Gupta R, Das V, Agarwal A, Awasthi PK, Bhatia V (2005) High prevalence of vitamin D deficiency among pregnant women and their newborns in northern India. Am J Clin Nutr 81:1060–1064PubMed
Metadata
Title
Calcium and vitamin D for osteoprotection in children with new-onset nephrotic syndrome treated with steroids: a prospective, randomized, controlled, interventional study
Authors
Surabhi Choudhary
Indira Agarwal
Mandalam S. Seshadri
Publication date
01-06-2014
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 6/2014
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-013-2720-4

Other articles of this Issue 6/2014

Pediatric Nephrology 6/2014 Go to the issue