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Published in: Pediatric Nephrology 11/2014

01-11-2014 | Original Article

Bone health in children and adolescents with steroid-sensitive nephrotic syndrome assessed by DXA and QUS

Authors: Gabriella Aceto, Olinda D’Addato, Giovanni Messina, Vincenza Carbone, Luciano Cavallo, Giacomina Brunetti, Maria Felicia Faienza

Published in: Pediatric Nephrology | Issue 11/2014

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Abstract

Background

The management of steroid-sensitive nephrotic syndrome (SSNS) requires treatment with high-dose glucocorticoids (GCs), but GC usage causes the most frequent form of drug-induced osteoporosis. The aim of our study was to evaluate the impact of GCs on bone mineralization in patients with SSNS using two diagnostic tools, dual-energy X-ray densitometry (DXA) and quantitative ultrasound (QUS), and to compare the diagnostic efficacy of these two imaging tools.

Methods

A total of 30 children with SSNS (age 5.20 ± 2.20 years) were evaluated at the start (T0) and after 1 (T1), 2.44 ± 0.75 (T2, 18 patients) and 5.96 ± 2.33 years (T4, 12 patients) of GC treatment. Patients who stopped at T2 were also evaluated at the 1-year timepoint after ceasing GC treatment (T3).

Results

Of the patients assessed at T2, 11 had bone mineralization at the lower limit of normal versus those at T0 and T1, with bone mineralization rescue at the 1-year timepoint after GC discontinuation. At T4, 6/12 patients had densitometric parameters at the lower limit of normal values, and 3/12 patients showed reduced bone mineralization. The parameters derived from measurements of DXA and QUS were significantly related to each timepoint.

Conclusions

Patients with SSNS receiving GC therapy undergo bone status alteration related to the dosage and duration of the therapy. In terms of diagnostic efficacy, DXA and QUS were comparable, indicating that QUS is a reliable tool to evaluate bone health in children with SSNS.
Literature
1.
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
2.
go back to reference Canalis E, Mazziotti G, Giustina A, Bilezikian JP (2007) Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporos Int 10:1319–1328CrossRef Canalis E, Mazziotti G, Giustina A, Bilezikian JP (2007) Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporos Int 10:1319–1328CrossRef
3.
go back to reference Ventura A, Brunetti G, Colucci S, Oranger A, Ladisa F, Cavallo L, Grano M, Faienza MF (2013) Glucocorticoid-induced osteoporosis in children with 21-hydroxylase deficiency. Biomed Res Int 2013:250462PubMedCrossRefPubMedCentral Ventura A, Brunetti G, Colucci S, Oranger A, Ladisa F, Cavallo L, Grano M, Faienza MF (2013) Glucocorticoid-induced osteoporosis in children with 21-hydroxylase deficiency. Biomed Res Int 2013:250462PubMedCrossRefPubMedCentral
4.
go back to reference O’Brien CA, Jia D, Plotkin LI, Bellido T, Powers CC, Stewart SA, Manolagas SC, Weinstein RS (2004) Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. Endocrinology 145:1835–1841PubMedCrossRef O’Brien CA, Jia D, Plotkin LI, Bellido T, Powers CC, Stewart SA, Manolagas SC, Weinstein RS (2004) Glucocorticoids act directly on osteoblasts and osteocytes to induce their apoptosis and reduce bone formation and strength. Endocrinology 145:1835–1841PubMedCrossRef
5.
go back to reference Faienza MF, Brunetti G, Colucci S, Piacente L, Ciccarelli M, Giordani L, Del Vecchio GC, D’Amore M, Albanese L, Cavallo L, Grano M (2009) Osteoclastogenesis in children with 21-hydroxylase deficiency on long-term glucocorticoid therapy: the role of receptor activator of nuclear factor-kappaB ligand/osteoprotegerin imbalance. J Clin Endocrinol Metab 94:2269–2276PubMedCrossRef Faienza MF, Brunetti G, Colucci S, Piacente L, Ciccarelli M, Giordani L, Del Vecchio GC, D’Amore M, Albanese L, Cavallo L, Grano M (2009) Osteoclastogenesis in children with 21-hydroxylase deficiency on long-term glucocorticoid therapy: the role of receptor activator of nuclear factor-kappaB ligand/osteoprotegerin imbalance. J Clin Endocrinol Metab 94:2269–2276PubMedCrossRef
6.
go back to reference Brunetti G, Faienza MF, PiacenteL VA, Oranger A, Carbone C, Di Benedetto A, Colaianni G, Gigante M, Mori G, Gesualdo L, Colucci S, Cavallo L, Grano M (2013) High dickkopf-1 levels in sera and leukocytes from children with 21-hydroxylase deficiency on chronic glucocorticoid treatment. Am J Physiol Endocrinol Metab 304:E546–E554PubMedCrossRef Brunetti G, Faienza MF, PiacenteL VA, Oranger A, Carbone C, Di Benedetto A, Colaianni G, Gigante M, Mori G, Gesualdo L, Colucci S, Cavallo L, Grano M (2013) High dickkopf-1 levels in sera and leukocytes from children with 21-hydroxylase deficiency on chronic glucocorticoid treatment. Am J Physiol Endocrinol Metab 304:E546–E554PubMedCrossRef
8.
go back to reference Foster BJ, Shults J, Zemel BS, Leonard MB (2004) Interactions between growth and body composition in children treated with high-dose chronic glucocorticoids. Am J Clin Nutr 80:1334–1341PubMed Foster BJ, Shults J, Zemel BS, Leonard MB (2004) Interactions between growth and body composition in children treated with high-dose chronic glucocorticoids. Am J Clin Nutr 80:1334–1341PubMed
9.
go back to reference Phan V, Blydt-Hansen T, Feber J, Alos N, Arora S, Atkinson S, Bell L, Clarson C, Couch R, Cummings EA, Filler G, Grant RM, Grimmer J, Hebert D, Lentle B, Ma J, Matzinger M, Midgley J, Pinsk M, Rodd C, Shenouda N, Stein R, Stephure D, Taback S, Williams K, Rauch F, Siminoski K, Ward LM (2014) Skeletal findings in the first 12 months following initiation of glucocorticoid therapy for pediatric nephrotic syndrome. Osteoporos Int 25:627–637PubMedCrossRef Phan V, Blydt-Hansen T, Feber J, Alos N, Arora S, Atkinson S, Bell L, Clarson C, Couch R, Cummings EA, Filler G, Grant RM, Grimmer J, Hebert D, Lentle B, Ma J, Matzinger M, Midgley J, Pinsk M, Rodd C, Shenouda N, Stein R, Stephure D, Taback S, Williams K, Rauch F, Siminoski K, Ward LM (2014) Skeletal findings in the first 12 months following initiation of glucocorticoid therapy for pediatric nephrotic syndrome. Osteoporos Int 25:627–637PubMedCrossRef
10.
go back to reference Hogler W, Blimkie CJ, Cowell CT, Kemp AF, Briody J, Wiebe P, Farpour-Lambert N, Duncan CS, Woodhead HJ (2003) A comparison of bone geometry and cortical density at the mid-femur between prepuberty and young adulthood using magnetic resonance imaging. Bone 33:771–778PubMedCrossRef Hogler W, Blimkie CJ, Cowell CT, Kemp AF, Briody J, Wiebe P, Farpour-Lambert N, Duncan CS, Woodhead HJ (2003) A comparison of bone geometry and cortical density at the mid-femur between prepuberty and young adulthood using magnetic resonance imaging. Bone 33:771–778PubMedCrossRef
11.
go back to reference Bianchi ML (2002) Glucorticoids and bone: some general remarks and some special observations in pediatric patients. Calcif Tissue Int 70:384–390PubMedCrossRef Bianchi ML (2002) Glucorticoids and bone: some general remarks and some special observations in pediatric patients. Calcif Tissue Int 70:384–390PubMedCrossRef
12.
go back to reference Halton JM, Atkinson SA, Fraher L, Webber C, Gill GJ, Dawson S, Barr RD (1996) Altered mineral metabolism and bone mass in children during treatment for acute lymphoblastic leukemia. J Bone Miner Res 11:1774–1783PubMedCrossRef Halton JM, Atkinson SA, Fraher L, Webber C, Gill GJ, Dawson S, Barr RD (1996) Altered mineral metabolism and bone mass in children during treatment for acute lymphoblastic leukemia. J Bone Miner Res 11:1774–1783PubMedCrossRef
13.
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
14.
go back to reference Burnham JM, Shults J, Petit MA, Semeao E, Beck TJ, Zemel BS, Leonard MB (2007) Alterations in proximal femur geometry in children treated with glucocorticoids for Crohn disease or nephrotic syndrome: impact of the underlying disease. J Bone Miner Res 22:551–559PubMedCrossRef Burnham JM, Shults J, Petit MA, Semeao E, Beck TJ, Zemel BS, Leonard MB (2007) Alterations in proximal femur geometry in children treated with glucocorticoids for Crohn disease or nephrotic syndrome: impact of the underlying disease. J Bone Miner Res 22:551–559PubMedCrossRef
15.
go back to reference Wetzsteon RJ, Shults J, Zemel BS, Gupta PU, Burnham JM, Herskovitz RM, Howard KM, Leonard MB (2009) Divergent effects of glucocorticoids on cortical and trabecular compartment BMD in childhood nephrotic syndrome. J Bone Miner Res 24:503–513PubMedCrossRefPubMedCentral Wetzsteon RJ, Shults J, Zemel BS, Gupta PU, Burnham JM, Herskovitz RM, Howard KM, Leonard MB (2009) Divergent effects of glucocorticoids on cortical and trabecular compartment BMD in childhood nephrotic syndrome. J Bone Miner Res 24:503–513PubMedCrossRefPubMedCentral
16.
go back to reference Tsampalieros A, Gupta P, Denburg MR, Shults J, Zemel BS, Mostoufi-Moab S, Wetzsteon RJ, Herskovitz RM, Whitehead KM, Leonard MB (2013) Glucocorticoid effects on changes in bone mineral density and cortical structure in childhood nephrotic syndrome. J Bone Miner Res 28:480–488PubMedCrossRefPubMedCentral Tsampalieros A, Gupta P, Denburg MR, Shults J, Zemel BS, Mostoufi-Moab S, Wetzsteon RJ, Herskovitz RM, Whitehead KM, Leonard MB (2013) Glucocorticoid effects on changes in bone mineral density and cortical structure in childhood nephrotic syndrome. J Bone Miner Res 28:480–488PubMedCrossRefPubMedCentral
17.
go back to reference Krieg MA, Barkmann R, Gonnelli S, Stewart A, Bauer DC, Del Rio BL, Kaufman JJ, Lorenc R, Miller PD, Olszynski WP, Poiana C, Schott AM, Lewiecki EM, Hans D (2008) Quantitative ultrasound in the management of osteoporosis: the 2007 ISCD Official Positions. J Clin Densitom 11:163–187PubMedCrossRef Krieg MA, Barkmann R, Gonnelli S, Stewart A, Bauer DC, Del Rio BL, Kaufman JJ, Lorenc R, Miller PD, Olszynski WP, Poiana C, Schott AM, Lewiecki EM, Hans D (2008) Quantitative ultrasound in the management of osteoporosis: the 2007 ISCD Official Positions. J Clin Densitom 11:163–187PubMedCrossRef
18.
go back to reference Baroncelli GI, Federico G, Bertelloni S, Sodini F, De Terlizzi F, Cadossi R, Saggese G (2003) Assessment of bone quality by quantitative ultrasound of proximal phalangeas of the hand and fracture rate in children and adolescents with bone and mineral disorders. Pediatr Res 54:125–136PubMedCrossRef Baroncelli GI, Federico G, Bertelloni S, Sodini F, De Terlizzi F, Cadossi R, Saggese G (2003) Assessment of bone quality by quantitative ultrasound of proximal phalangeas of the hand and fracture rate in children and adolescents with bone and mineral disorders. Pediatr Res 54:125–136PubMedCrossRef
19.
go back to reference Christoforidis A, Printza N, Gkogka C, Siomou E, Challa A, Kazantzidou E, Kollios K, Papachristou F (2011) Comparative study of quantitative ultrasonography and dual-energy X-ray absorptiometry for evaluating renal osteodystrophy in children with chronic kidney disease. J Bone Miner Metab 29:321–327PubMedCrossRef Christoforidis A, Printza N, Gkogka C, Siomou E, Challa A, Kazantzidou E, Kollios K, Papachristou F (2011) Comparative study of quantitative ultrasonography and dual-energy X-ray absorptiometry for evaluating renal osteodystrophy in children with chronic kidney disease. J Bone Miner Metab 29:321–327PubMedCrossRef
20.
go back to reference Guglielmi G, de Terlizzi F, Aucella F (2004) Quantitative bone ultrasonography: state of the art and perspectives. G Ital Nefrol 21:343–354PubMed Guglielmi G, de Terlizzi F, Aucella F (2004) Quantitative bone ultrasonography: state of the art and perspectives. G Ital Nefrol 21:343–354PubMed
21.
go back to reference Di Mase R, Cerbone M, Improda N, Esposito A, Capalbo D, Mainolfi C, Santamaria F, Pignata C, Salerno M (2012) Bone health in children with long-term idiopathic subclinical hypothyroidism. Ital J Pediatr 38:56PubMedCrossRefPubMedCentral Di Mase R, Cerbone M, Improda N, Esposito A, Capalbo D, Mainolfi C, Santamaria F, Pignata C, Salerno M (2012) Bone health in children with long-term idiopathic subclinical hypothyroidism. Ital J Pediatr 38:56PubMedCrossRefPubMedCentral
22.
go back to reference International Study of Kidney Disease in Children (1981) The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. A report of the International Study of Kidney Disease in Children. J Pediatr 98:561–564 International Study of Kidney Disease in Children (1981) The primary nephrotic syndrome in children. Identification of patients with minimal change nephrotic syndrome from initial response to prednisone. A report of the International Study of Kidney Disease in Children. J Pediatr 98:561–564
23.
go back to reference Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58:259–263PubMed Schwartz GJ, Haycock GB, Edelmann CM Jr, Spitzer A (1976) A simple estimate of glomerular filtration rate in children derived from body length and plasma creatinine. Pediatrics 58:259–263PubMed
24.
go back to reference Cacciari E, Milani S, Balsamo A, Spada E, Bona G, Cavallo L, Cerutti F, Gargantini L, Greggio N, Tonini G, Cicognani A (2006) Italian cross-sectional growth charts for height, weight and BMI (2 to 20 yr). J Endocrinol Investig 29:581–593CrossRef Cacciari E, Milani S, Balsamo A, Spada E, Bona G, Cavallo L, Cerutti F, Gargantini L, Greggio N, Tonini G, Cicognani A (2006) Italian cross-sectional growth charts for height, weight and BMI (2 to 20 yr). J Endocrinol Investig 29:581–593CrossRef
25.
go back to reference Cole TJ, Bellizzi MC, Flegal KM, Dietz WH (2000) Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 320:1240–1243PubMedCrossRefPubMedCentral Cole TJ, Bellizzi MC, Flegal KM, Dietz WH (2000) Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 320:1240–1243PubMedCrossRefPubMedCentral
26.
go back to reference Tanner JM, Whitehouse RH (1976) Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch Dis Child 51:170–179PubMedCrossRefPubMedCentral Tanner JM, Whitehouse RH (1976) Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty. Arch Dis Child 51:170–179PubMedCrossRefPubMedCentral
27.
go back to reference Lombel RM, Gipson DS, Hodson EM (2013) Treatment of steroid-sensitive nephrotic syndrome: new guidelines from KDIGO. Pediatr Nephrol 28:415–426PubMedCrossRef Lombel RM, Gipson DS, Hodson EM (2013) Treatment of steroid-sensitive nephrotic syndrome: new guidelines from KDIGO. Pediatr Nephrol 28:415–426PubMedCrossRef
28.
go back to reference Baroncelli GI, Federico G, Vignolo M, Valerio G, del Puente A, Maghnie M, Baserga M, Farello G, Saggese G (2006) Phalangeal Quantitative Ultrasound Group. Cross-sectional reference data for phalangeal quantitative ultrasound from early childhood to young-adulthood according to gender, age, skeletal growth, and pubertal development. Bone 39:159–173PubMedCrossRef Baroncelli GI, Federico G, Vignolo M, Valerio G, del Puente A, Maghnie M, Baserga M, Farello G, Saggese G (2006) Phalangeal Quantitative Ultrasound Group. Cross-sectional reference data for phalangeal quantitative ultrasound from early childhood to young-adulthood according to gender, age, skeletal growth, and pubertal development. Bone 39:159–173PubMedCrossRef
29.
go back to reference Shults J, Morrow AL (2002) Use of quasi-least squares to adjust for two levels of correlation. Biometrics 58:521–530PubMedCrossRef Shults J, Morrow AL (2002) Use of quasi-least squares to adjust for two levels of correlation. Biometrics 58:521–530PubMedCrossRef
30.
go back to reference Shults J, Ratcliffe SJ, Leonard M (2007) Improved generalized estimating equation analysis via xtqls for quasi-least squares in Stata. Stata J 7:147–166 Shults J, Ratcliffe SJ, Leonard M (2007) Improved generalized estimating equation analysis via xtqls for quasi-least squares in Stata. Stata J 7:147–166
31.
go back to reference Gordon CM, Lewiecki EM, Baim S, Leonard MB, Bishop NJ, Bianchi ML, Kalkwarf HJ, Langman CB, Plotkin H, Rauch F, Zemel BS, Binkley N, Bilezikian JP, Kendler DL, Hans DB, Silverman S (2008) International Society for Clinical Densitometry Adult and Pediatric Official Positions. Bone 43:1115–1121PubMedCrossRef Gordon CM, Lewiecki EM, Baim S, Leonard MB, Bishop NJ, Bianchi ML, Kalkwarf HJ, Langman CB, Plotkin H, Rauch F, Zemel BS, Binkley N, Bilezikian JP, Kendler DL, Hans DB, Silverman S (2008) International Society for Clinical Densitometry Adult and Pediatric Official Positions. Bone 43:1115–1121PubMedCrossRef
32.
go back to reference Wüster C, Albanese C, De Aloysio D, Duboeuf F, Gambacciani M, Gonnelli S, Glüer CC, Hans D, Joly J, Reginster JY, De Terlizzi F, Cadossi R (2000) Phalangeal osteosonogrammetry study (PhOS): age related changes, diagnostic sensitivity and discrimination power. J Bone Miner Res 15:1603–1614PubMedCrossRef Wüster C, Albanese C, De Aloysio D, Duboeuf F, Gambacciani M, Gonnelli S, Glüer CC, Hans D, Joly J, Reginster JY, De Terlizzi F, Cadossi R (2000) Phalangeal osteosonogrammetry study (PhOS): age related changes, diagnostic sensitivity and discrimination power. J Bone Miner Res 15:1603–1614PubMedCrossRef
33.
34.
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
35.
go back to reference Gafni RI, Weise M, Robrecht DT, Meyers JL, Barnes KM, De-Levi S, Baron J (2001) Catch-up growth is associated with delayed senescence of the growth plate in rabbits. Pediatr Res 50:618–623PubMedCrossRef Gafni RI, Weise M, Robrecht DT, Meyers JL, Barnes KM, De-Levi S, Baron J (2001) Catch-up growth is associated with delayed senescence of the growth plate in rabbits. Pediatr Res 50:618–623PubMedCrossRef
36.
go back to reference Henderson RC, Madsen CD, Davis C, Gold SH (1998) Longitudinal evaluation of bone mineral density in children receiving chemotherapy. J Pediatr Hematol Oncol 20:322–326PubMedCrossRef Henderson RC, Madsen CD, Davis C, Gold SH (1998) Longitudinal evaluation of bone mineral density in children receiving chemotherapy. J Pediatr Hematol Oncol 20:322–326PubMedCrossRef
37.
go back to reference Skrzypczyk P, Panczyk-Tomaszewska M, Roszkowska-Blaim M, Wawer Z, Bienias B, Zajgzkowska M, Kilis-Pstrusinska K, Jakubowska A, Szczepaniak M, Pawlak-Bratkowska M, Tkaczyk M (2014) Long-term outcomes in idiopathic nephrotic syndrome: from childhood to adulthood. Clin Nephrol 81:166–173PubMedCrossRef Skrzypczyk P, Panczyk-Tomaszewska M, Roszkowska-Blaim M, Wawer Z, Bienias B, Zajgzkowska M, Kilis-Pstrusinska K, Jakubowska A, Szczepaniak M, Pawlak-Bratkowska M, Tkaczyk M (2014) Long-term outcomes in idiopathic nephrotic syndrome: from childhood to adulthood. Clin Nephrol 81:166–173PubMedCrossRef
Metadata
Title
Bone health in children and adolescents with steroid-sensitive nephrotic syndrome assessed by DXA and QUS
Authors
Gabriella Aceto
Olinda D’Addato
Giovanni Messina
Vincenza Carbone
Luciano Cavallo
Giacomina Brunetti
Maria Felicia Faienza
Publication date
01-11-2014
Publisher
Springer Berlin Heidelberg
Published in
Pediatric Nephrology / Issue 11/2014
Print ISSN: 0931-041X
Electronic ISSN: 1432-198X
DOI
https://doi.org/10.1007/s00467-014-2834-3

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