Skip to main content
Top
Published in: Osteoporosis International 2/2012

01-02-2012 | Original Article

Skeletal findings in children recently initiating glucocorticoids for the treatment of nephrotic syndrome

Authors: J. Feber, I. Gaboury, A. Ni, N. Alos, S. Arora, L. Bell, T. Blydt-Hansen, C. Clarson, G. Filler, J. Hay, D. Hebert, B. Lentle, M. Matzinger, J. Midgley, D. Moher, M. Pinsk, F. Rauch, C. Rodd, N. Shenouda, K. Siminoski, L. M. Ward, The Canadian STOPP Consortium

Published in: Osteoporosis International | Issue 2/2012

Login to get access

Abstract

Summary

Eighty children with nephrotic syndrome underwent lumbar spine densitometry and vertebral morphometry soon after glucocorticoid initiation. We found an inverse relationship between glucocorticoid exposure and spine areal bone mineral density (BMD) Z-score and a low rate of vertebral deformities (8%).

Introduction

Vertebral fractures are an under-recognized complication of childhood glucocorticoid-treated illnesses. Our goal was to study the relationships among glucocorticoid exposure, lumbar spine areal BMD (LS BMD), and vertebral shape in glucocorticoid-treated children with new-onset nephrotic syndrome.

Methods

Lateral thoracolumbar spine radiography and LS BMD were performed in 80 children with nephrotic syndrome (median age 4.4 years; 46 boys) within the first 37 days of glucocorticoid therapy. Genant semiquantitative grading was used as the primary method for vertebral morphometry; the algorithm-based qualitative (ABQ) method was used for secondary vertebral deformity analysis.

Results

Six of the 78 children with usable radiographs (8%; 95% confidence interval 4 to 16%) manifested a single Genant grade 1 deformity each. All deformities were mild anterior wedging (two at each of T6, T7, and T8). Four of the 78 children (5%; 95% confidence interval 2 to 13%) showed one ABQ sign of fracture each (loss of endplate parallelism; two children at T6 and two at T8). Two of the children with ABQ signs also had a Genant grade 1 deformity in the same vertebral body. None of the children with a Genant or ABQ deformity reported back pain. An inverse relationship was identified between LS BMD Z-score and glucocorticoid exposure.

Conclusions

Although we identified an inverse relationship between steroid exposure and LS BMD soon after glucocorticoid initiation for childhood nephrotic syndrome, there was only a low rate of vertebral deformities. The clinical significance of these findings requires further study.
Literature
1.
go back to reference Schlesinger ER, Sultz HA, Mosher WE, Feldman JG (1968) The nephrotic syndrome. Its incidence and implications for the community. Am J Dis Child 116:623–632PubMed Schlesinger ER, Sultz HA, Mosher WE, Feldman JG (1968) The nephrotic syndrome. Its incidence and implications for the community. Am J Dis Child 116:623–632PubMed
2.
go back to reference Hodson EM, Knight JF, Willis NS, Craig JC (2001) Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev 2 Hodson EM, Knight JF, Willis NS, Craig JC (2001) Corticosteroid therapy for nephrotic syndrome in children. Cochrane Database Syst Rev 2
3.
go back to reference Clark AG, Barratt TM (1999) Steroid-responsive nephrotic syndrome. In: Barratt TM, Avner ED, Harmon WE (eds) Pediatric nephrology, 4th edn. Lippincott, Hagerstown Clark AG, Barratt TM (1999) Steroid-responsive nephrotic syndrome. In: Barratt TM, Avner ED, Harmon WE (eds) Pediatric nephrology, 4th edn. Lippincott, Hagerstown
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.
go back to reference Dalle Carbonare L, Arlot ME, Chavassieux PM, Roux JP, Portero NR, Meunier PJ (2001) Comparison of trabecular bone microarchitecture and remodeling in glucocorticoid-induced and postmenopausal osteoporosis. J Bone Miner Res 16:97–103PubMedCrossRef Dalle Carbonare L, Arlot ME, Chavassieux PM, Roux JP, Portero NR, Meunier PJ (2001) Comparison of trabecular bone microarchitecture and remodeling in glucocorticoid-induced and postmenopausal osteoporosis. J Bone Miner Res 16:97–103PubMedCrossRef
6.
go back to reference Canalis E, Mazziotti G, Giustina A, Bilezikian JP (2007) Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporos Int 18:1319–1328PubMedCrossRef Canalis E, Mazziotti G, Giustina A, Bilezikian JP (2007) Glucocorticoid-induced osteoporosis: pathophysiology and therapy. Osteoporos Int 18:1319–1328PubMedCrossRef
7.
go back to reference Lukert BP (1992) Glucocorticoid-induced osteoporosis. South Med J 85(2):S48–S51 Lukert BP (1992) Glucocorticoid-induced osteoporosis. South Med J 85(2):S48–S51
8.
go back to reference Ruegsegger P, Medici TC, Anliker M (1983) Corticosteroid-induced bone loss. A longitudinal study of alternate day therapy in patients with bronchial asthma using quantitative computed tomography. Eur J Clin Pharmacol 25:615–620PubMedCrossRef Ruegsegger P, Medici TC, Anliker M (1983) Corticosteroid-induced bone loss. A longitudinal study of alternate day therapy in patients with bronchial asthma using quantitative computed tomography. Eur J Clin Pharmacol 25:615–620PubMedCrossRef
9.
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
10.
go back to reference Acott PD, Wong JA, Lang BA, Crocker JF (2005) Pamidronate treatment of pediatric fracture patients on chronic steroid therapy. Pediatr Nephrol 20:368–373PubMedCrossRef Acott PD, Wong JA, Lang BA, Crocker JF (2005) Pamidronate treatment of pediatric fracture patients on chronic steroid therapy. Pediatr Nephrol 20:368–373PubMedCrossRef
11.
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
12.
go back to reference Sbrocchi AM, Rauch F, Matzinger M, Feber J, Ward LM (2010) Vertebral fractures despite normal spine bone mineral density in a boy with nephrotic syndrome. Pediatr Nephrol 26:139–142PubMedCrossRef Sbrocchi AM, Rauch F, Matzinger M, Feber J, Ward LM (2010) Vertebral fractures despite normal spine bone mineral density in a boy with nephrotic syndrome. Pediatr Nephrol 26:139–142PubMedCrossRef
13.
go back to reference Institute of Medicine (1997) Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, fluoride. National Academy Press, Washington Institute of Medicine (1997) Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, fluoride. National Academy Press, Washington
14.
go back to reference Ogden CL, Kuczmarski RJ, Flegal KM, Mei Z, Guo S, Wei R, Grummer-Strawn LM, Curtin LR, Roche AF, Johnson CL (2002) Centers for Disease Control and Prevention 2000 growth charts for the United States: improvements to the 1977 National Center for Health Statistics version. Pediatrics 109:45–60PubMedCrossRef Ogden CL, Kuczmarski RJ, Flegal KM, Mei Z, Guo S, Wei R, Grummer-Strawn LM, Curtin LR, Roche AF, Johnson CL (2002) Centers for Disease Control and Prevention 2000 growth charts for the United States: improvements to the 1977 National Center for Health Statistics version. Pediatrics 109:45–60PubMedCrossRef
15.
go back to reference World Health Organization Multicentre Growth Reference Study Group (2006) WHO Child Growth Standards: length/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age: methods and development. World Health Organization, Geneva, pp 229–300 World Health Organization Multicentre Growth Reference Study Group (2006) WHO Child Growth Standards: length/height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age: methods and development. World Health Organization, Geneva, pp 229–300
16.
go back to reference Marshall WA, Tanner JM (1969) Variations in pattern of pubertal changes in girls. Arch Dis Child 44:291–303PubMedCrossRef Marshall WA, Tanner JM (1969) Variations in pattern of pubertal changes in girls. Arch Dis Child 44:291–303PubMedCrossRef
17.
go back to reference Marshall WA, Tanner JM (1970) Variations in the pattern of pubertal changes in boys. Arch Dis Child 45:13–23PubMedCrossRef Marshall WA, Tanner JM (1970) Variations in the pattern of pubertal changes in boys. Arch Dis Child 45:13–23PubMedCrossRef
18.
go back to reference Musgrave KO, Giambalvo L, Leclerc HL, Cook RA, Rosen CJ (1989) Validation of a quantitative food frequency questionnaire for rapid assessment of dietary calcium intake. J Am Diet Assoc 89:1484–1488PubMed Musgrave KO, Giambalvo L, Leclerc HL, Cook RA, Rosen CJ (1989) Validation of a quantitative food frequency questionnaire for rapid assessment of dietary calcium intake. J Am Diet Assoc 89:1484–1488PubMed
19.
go back to reference Halton J, Gaboury I, Grant R et al (2009) Advanced vertebral fracture among newly diagnosed children with acute lymphoblastic leukemia: results of the Canadian Steroid-Associated Osteoporosis in the Pediatric Population (STOPP) research program. J Bone Miner Res 24:1326–1334PubMedCrossRef Halton J, Gaboury I, Grant R et al (2009) Advanced vertebral fracture among newly diagnosed children with acute lymphoblastic leukemia: results of the Canadian Steroid-Associated Osteoporosis in the Pediatric Population (STOPP) research program. J Bone Miner Res 24:1326–1334PubMedCrossRef
21.
go back to reference van Staa TP, Leufkens HG, Cooper C (2002) The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int 13:777–787PubMedCrossRef van Staa TP, Leufkens HG, Cooper C (2002) The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int 13:777–787PubMedCrossRef
22.
go back to reference Curtis JR, Westfall AO, Allison J, Bijlsma JW, Freeman A, George V, Kovac SH, Spettell CM, Saag KG (2006) Population-based assessment of adverse events associated with long-term glucocorticoid use. Arthritis Rheum 55:420–426PubMedCrossRef Curtis JR, Westfall AO, Allison J, Bijlsma JW, Freeman A, George V, Kovac SH, Spettell CM, Saag KG (2006) Population-based assessment of adverse events associated with long-term glucocorticoid use. Arthritis Rheum 55:420–426PubMedCrossRef
23.
go back to reference Dubner SE, Shults J, Baldassano RN, Zemel BS, Thayu M, Burnham JM, Herskovitz RM, Howard KM, Leonard MB (2009) Longitudinal assessment of bone density and structure in an incident cohort of children with Crohn's disease. Gastroenterology 136:123–130PubMedCrossRef Dubner SE, Shults J, Baldassano RN, Zemel BS, Thayu M, Burnham JM, Herskovitz RM, Howard KM, Leonard MB (2009) Longitudinal assessment of bone density and structure in an incident cohort of children with Crohn's disease. Gastroenterology 136:123–130PubMedCrossRef
24.
go back to reference Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137–1148PubMedCrossRef Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137–1148PubMedCrossRef
25.
go back to reference Keats TE, Smith TH (1977) An atlas of normal developmental anatomy. Year book of medical publishers, 2nd Ed. Chicago Keats TE, Smith TH (1977) An atlas of normal developmental anatomy. Year book of medical publishers, 2nd Ed. Chicago
26.
go back to reference Jiang G, Eastell R, Barrington NA, Ferrar L (2004) Comparison of methods for the visual identification of prevalent vertebral fracture in osteoporosis. Osteoporos Int 15:887–896PubMedCrossRef Jiang G, Eastell R, Barrington NA, Ferrar L (2004) Comparison of methods for the visual identification of prevalent vertebral fracture in osteoporosis. Osteoporos Int 15:887–896PubMedCrossRef
27.
go back to reference Newcombe RG (1998) Two-sided confidence intervals for the single proportion: comparison of seven methods. Stat Med 17:857–872PubMedCrossRef Newcombe RG (1998) Two-sided confidence intervals for the single proportion: comparison of seven methods. Stat Med 17:857–872PubMedCrossRef
28.
go back to reference Fujita T, Satomura A, Hidaka M, Ohsawa I, Endo M, Ohi H (2000) Acute alteration in bone mineral density and biochemical markers for bone metabolism in nephrotic patients receiving high-dose glucocorticoid and one-cycle etidronate therapy. Calcif Tissue Int 66:195–199PubMedCrossRef Fujita T, Satomura A, Hidaka M, Ohsawa I, Endo M, Ohi H (2000) Acute alteration in bone mineral density and biochemical markers for bone metabolism in nephrotic patients receiving high-dose glucocorticoid and one-cycle etidronate therapy. Calcif Tissue Int 66:195–199PubMedCrossRef
29.
go back to reference Cohen A, Shane E (2003) Osteoporosis after solid organ and bone marrow transplantation. Osteoporos Int 14:617–630PubMedCrossRef Cohen A, Shane E (2003) Osteoporosis after solid organ and bone marrow transplantation. Osteoporos Int 14:617–630PubMedCrossRef
30.
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 bone mineral density in childhood nephrotic syndrome. J Bone Miner Res 24(3):503–513PubMedCrossRef 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 bone mineral density in childhood nephrotic syndrome. J Bone Miner Res 24(3):503–513PubMedCrossRef
31.
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
32.
go back to reference Dennison E, Cooper C (2000) Epidemiology of osteoporotic fractures. Horm Res 54(Suppl 1):58–63PubMed Dennison E, Cooper C (2000) Epidemiology of osteoporotic fractures. Horm Res 54(Suppl 1):58–63PubMed
33.
go back to reference Valta H, Lahdenne P, Jalanko H, Aalto K, Makitie O (2007) Bone health and growth in glucocorticoid-treated patients with juvenile idiopathic arthritis. J Rheumatol 34:831–836PubMed Valta H, Lahdenne P, Jalanko H, Aalto K, Makitie O (2007) Bone health and growth in glucocorticoid-treated patients with juvenile idiopathic arthritis. J Rheumatol 34:831–836PubMed
34.
go back to reference Gaca AM, Barnhart HX, Bisset GS 3rd (2010) Evaluation of wedging of lower thoracic and upper lumbar vertebral bodies in the pediatric population. AJR Am J Roentgenol 194:516–520PubMedCrossRef Gaca AM, Barnhart HX, Bisset GS 3rd (2010) Evaluation of wedging of lower thoracic and upper lumbar vertebral bodies in the pediatric population. AJR Am J Roentgenol 194:516–520PubMedCrossRef
35.
go back to reference Ebel KD, Blickman H, Willich E, Richter E (1999) Abnormalities in vertebral body shape and size. Differential diagnosis in pediatric radiology. Thieme Publishers, NY Ebel KD, Blickman H, Willich E, Richter E (1999) Abnormalities in vertebral body shape and size. Differential diagnosis in pediatric radiology. Thieme Publishers, NY
36.
go back to reference Rea JA, Chen MB, Li J, Blake GM, Steiger P, Genant HK, Fogelman I (2000) Morphometric X-ray absorptiometry and morphometric radiography of the spine: a comparison of prevalent vertebral deformity identification. J Bone Miner Res 15:564–574PubMedCrossRef Rea JA, Chen MB, Li J, Blake GM, Steiger P, Genant HK, Fogelman I (2000) Morphometric X-ray absorptiometry and morphometric radiography of the spine: a comparison of prevalent vertebral deformity identification. J Bone Miner Res 15:564–574PubMedCrossRef
37.
go back to reference Vallarta-Ast N, Krueger D, Wrase C, Agrawal S, Binkley N (2007) An evaluation of densitometric vertebral fracture assessment in men. Osteoporos Int 18:1405–1410PubMedCrossRef Vallarta-Ast N, Krueger D, Wrase C, Agrawal S, Binkley N (2007) An evaluation of densitometric vertebral fracture assessment in men. Osteoporos Int 18:1405–1410PubMedCrossRef
38.
go back to reference Wu C, van Kuijk C, Li J, Jiang Y, Chan M, Countryman P, Genant HK (2000) Comparison of digitized images with original radiography for semiquantitative assessment of osteoporotic fractures. Osteoporos Int 11:25–30PubMedCrossRef Wu C, van Kuijk C, Li J, Jiang Y, Chan M, Countryman P, Genant HK (2000) Comparison of digitized images with original radiography for semiquantitative assessment of osteoporotic fractures. Osteoporos Int 11:25–30PubMedCrossRef
39.
go back to reference Jackson SA, Tenenhouse A, Robertson L (2000) Vertebral fracture definition from population-based data: preliminary results from the Canadian Multicenter Osteoporosis Study (CaMos). Osteoporos Int 11:680–687PubMedCrossRef Jackson SA, Tenenhouse A, Robertson L (2000) Vertebral fracture definition from population-based data: preliminary results from the Canadian Multicenter Osteoporosis Study (CaMos). Osteoporos Int 11:680–687PubMedCrossRef
40.
go back to reference Huber A, Gaboury I, Cabral DA et al (2010) Prevalent vertebral fractures among children initiating glucocorticoid therapy for the treatment of rheumatic disorders. Arthitis Care Res (Hoboken) 62:516–526CrossRef Huber A, Gaboury I, Cabral DA et al (2010) Prevalent vertebral fractures among children initiating glucocorticoid therapy for the treatment of rheumatic disorders. Arthitis Care Res (Hoboken) 62:516–526CrossRef
41.
go back to reference Ismail AA, Cooper C, Felsenberg D, Varlow J, Kanis JA, Silman AJ, O'Neill TW (1999) Number and type of vertebral deformities: epidemiological characteristics and relation to back pain and height loss. European Vertebral Osteoporosis Study Group. Osteoporos Int 9:206–213PubMedCrossRef Ismail AA, Cooper C, Felsenberg D, Varlow J, Kanis JA, Silman AJ, O'Neill TW (1999) Number and type of vertebral deformities: epidemiological characteristics and relation to back pain and height loss. European Vertebral Osteoporosis Study Group. Osteoporos Int 9:206–213PubMedCrossRef
42.
go back to reference Delmas PD, Genant HK, Crans GG, Stock JL, Wong M, Siris E, Adachi JD (2003) Severity of prevalent vertebral fractures and the risk of subsequent vertebral and nonvertebral fractures: results from the MORE trial. Bone 33:522–532PubMedCrossRef Delmas PD, Genant HK, Crans GG, Stock JL, Wong M, Siris E, Adachi JD (2003) Severity of prevalent vertebral fractures and the risk of subsequent vertebral and nonvertebral fractures: results from the MORE trial. Bone 33:522–532PubMedCrossRef
43.
go back to reference Peel NF, Moore DJ, Barrington NA, Bax DE, Eastell R (1995) Risk of vertebral fracture and relationship to bone mineral density in steroid treated rheumatoid arthritis. Ann Rheum Dis 54:801–806PubMedCrossRef Peel NF, Moore DJ, Barrington NA, Bax DE, Eastell R (1995) Risk of vertebral fracture and relationship to bone mineral density in steroid treated rheumatoid arthritis. Ann Rheum Dis 54:801–806PubMedCrossRef
44.
go back to reference Dubner SE, Shults J, Leonard MB, Zemel BS, Sembhi H, Burnham JM (2008) Assessment of spine bone mineral density in juvenile idiopathic arthritis: impact of scan projection. J Clin Densitom 11:302–308PubMedCrossRef Dubner SE, Shults J, Leonard MB, Zemel BS, Sembhi H, Burnham JM (2008) Assessment of spine bone mineral density in juvenile idiopathic arthritis: impact of scan projection. J Clin Densitom 11:302–308PubMedCrossRef
Metadata
Title
Skeletal findings in children recently initiating glucocorticoids for the treatment of nephrotic syndrome
Authors
J. Feber
I. Gaboury
A. Ni
N. Alos
S. Arora
L. Bell
T. Blydt-Hansen
C. Clarson
G. Filler
J. Hay
D. Hebert
B. Lentle
M. Matzinger
J. Midgley
D. Moher
M. Pinsk
F. Rauch
C. Rodd
N. Shenouda
K. Siminoski
L. M. Ward
The Canadian STOPP Consortium
Publication date
01-02-2012
Publisher
Springer-Verlag
Published in
Osteoporosis International / Issue 2/2012
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-011-1621-2

Other articles of this Issue 2/2012

Osteoporosis International 2/2012 Go to the issue