Skip to main content
Top
Published in: Osteoporosis International 2/2017

01-02-2017 | Original Article

The time to and determinants of first fractures in boys with Duchenne muscular dystrophy

Authors: J. Ma, H. J. McMillan, G. Karagüzel, C. Goodin, J. Wasson, M. A. Matzinger, P. DesClouds, D. Cram, M. Page, V. N. Konji, B. Lentle, L. M. Ward

Published in: Osteoporosis International | Issue 2/2017

Login to get access

Abstract

Summary

Boys with vertebral fractures (VF) identified through routine spine radiographs had milder, less symptomatic, and fewer VF compared to those diagnosed with VF following consultation for back pain. Spontaneous (i.e., medication-unassisted) reshaping of fractured vertebral bodies was absent. Long bone fractures were present even before Duchenne muscular dystrophy (DMD) diagnosis in some boys.

Introduction

The objective of the study was to determine the time to and characteristics of first fractures in Duchenne muscular dystrophy.

Methods

This study was a retrospective longitudinal study of 30 boys with DMD <18 years. Boys were classified into four groups according to their first fracture: those with VF identified on routine lateral spine radiographs, those with VF diagnosed following consultation for back pain, those with long bone fractures, and those without fractures.

Results

Compared to boys diagnosed with VF as their initial fracture following consultation for back pain, those with VF surveillance radiographs had shorter durations of glucocorticoid (GC) therapy at the time of VF diagnosis (median 1.6 versus 5.3 years, p < 0.01), higher areal (mean ± standard deviation −1.4 ± 0.7 versus −3.1 ± 0.8, p = 0.01), and volumetric (−0.3 ± 0.5 versus −2.6 ± 0.8, p < 0.01) lumbar spine bone mineral density Z-scores, as well as fewer VF (median 1.4 versus 5.2 per person, p < 0.01) and a lower median spinal deformity index (median 1.5 versus 9.5, p < 0.01). Vertebral body reshaping following VF was not observed. Ten boys sustained a long bone fracture as their first fracture at a mean age of 8.9 ± 4.0 years; four of these boys later sustained a total of 27 incident VF.

Conclusions

Routine lateral spine radiographs led to detection of VF in their earlier stages, vertebral body reshaping following VF was absent, and VF were frequent after the first long bone fracture. These results support the inclusion of a lateral spine radiograph starting at the time of GC initiation as part of routine bone health monitoring in DMD.
Literature
1.
go back to reference Emery AE (1991) Population frequencies of inherited neuromuscular diseases—a world survey. Neuromuscul Disord 1:19–29CrossRefPubMed Emery AE (1991) Population frequencies of inherited neuromuscular diseases—a world survey. Neuromuscul Disord 1:19–29CrossRefPubMed
2.
go back to reference McDonald CM, Abresch RT, Carter GT, Fowler WM Jr, Johnson ER, Kilmer DD, Sigford BJ (1995) Profiles of neuromuscular diseases. Duchenne muscular dystrophy. Am J Phys Med Rehabil 74:S70–S92CrossRefPubMed McDonald CM, Abresch RT, Carter GT, Fowler WM Jr, Johnson ER, Kilmer DD, Sigford BJ (1995) Profiles of neuromuscular diseases. Duchenne muscular dystrophy. Am J Phys Med Rehabil 74:S70–S92CrossRefPubMed
3.
go back to reference Manzur AY, Kuntzer T, Pike M, Swan AV (2009) Glucocorticoid corticosteroids for Duchnne muscular dystrophy (Review). The Cochrane Library., pp 1–91 Manzur AY, Kuntzer T, Pike M, Swan AV (2009) Glucocorticoid corticosteroids for Duchnne muscular dystrophy (Review). The Cochrane Library., pp 1–91
4.
go back to reference McMillan HJ, Campbell C, Mah JK (2010) Duchenne muscular dystrophy: Canadian paediatric neuromuscular physicians survey. Can J Neurol Sci 37:195–205CrossRefPubMed McMillan HJ, Campbell C, Mah JK (2010) Duchenne muscular dystrophy: Canadian paediatric neuromuscular physicians survey. Can J Neurol Sci 37:195–205CrossRefPubMed
5.
go back to reference Larson CM, Henderson RC (2000) Bone mineral density and fractures in boys with Duchenne muscular dystrophy. J Pediatr Orthop 20:71–74PubMed Larson CM, Henderson RC (2000) Bone mineral density and fractures in boys with Duchenne muscular dystrophy. J Pediatr Orthop 20:71–74PubMed
6.
go back to reference McDonald DG, Kinali M, Gallagher AC, Mercuri E, Muntoni F, Roper H, Jardine P, Jones DH, Pike MG (2002) Fracture prevalence in Duchenne muscular dystrophy. Dev Med Child Neurol 44:695–698CrossRefPubMed McDonald DG, Kinali M, Gallagher AC, Mercuri E, Muntoni F, Roper H, Jardine P, Jones DH, Pike MG (2002) Fracture prevalence in Duchenne muscular dystrophy. Dev Med Child Neurol 44:695–698CrossRefPubMed
7.
go back to reference King WM, Ruttencutter R, Nagaraja HN, Matkovic V, Landoll J, Hoyle C, Mendell JR, Kissel JT (2007) Orthopedic outcomes of long-term daily corticosteroid treatment in Duchenne muscular dystrophy. Neurology 68:1607–1613CrossRefPubMed King WM, Ruttencutter R, Nagaraja HN, Matkovic V, Landoll J, Hoyle C, Mendell JR, Kissel JT (2007) Orthopedic outcomes of long-term daily corticosteroid treatment in Duchenne muscular dystrophy. Neurology 68:1607–1613CrossRefPubMed
8.
go back to reference Alos N, Grant RM, Ramsay T et al (2012) High incidence of vertebral fractures in children with acute lymphoblastic leukemia 12 months after the initiation of therapy. J Clin Oncol 30:2760–2767 Alos N, Grant RM, Ramsay T et al (2012) High incidence of vertebral fractures in children with acute lymphoblastic leukemia 12 months after the initiation of therapy. J Clin Oncol 30:2760–2767
9.
go back to reference Rodd C, Lang B, Ramsay T et al (2012) Incident vertebral fractures among children with rheumatic disorders 12 months after glucocorticoid initiation: a national observational study. Arthritis Care Res 64:122–131CrossRef Rodd C, Lang B, Ramsay T et al (2012) Incident vertebral fractures among children with rheumatic disorders 12 months after glucocorticoid initiation: a national observational study. Arthritis Care Res 64:122–131CrossRef
11.
go back to reference Greulich WW, Pyle SI (1959) Radiographic atlas of skeletal development of the hand and wrist, 2nd edn. Stanford University Press, Stanford Greulich WW, Pyle SI (1959) Radiographic atlas of skeletal development of the hand and wrist, 2nd edn. Stanford University Press, Stanford
12.
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 109:45–60CrossRefPubMed 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 109:45–60CrossRefPubMed
13.
go back to reference Institute of Medicine (2011) Dietary reference intakes for calcium and vitamin D. The National Academies Press, Washington, DC Institute of Medicine (2011) Dietary reference intakes for calcium and vitamin D. The National Academies Press, Washington, DC
14.
go back to reference Sbrocchi AM, Rauch F, Jacob P, McCormick A, McMillan HJ, Matzinger MA, Ward LM (2012) The use of intravenous bisphosphonate therapy to treat vertebral fractures due to osteoporosis among boys with Duchenne muscular dystrophy. Osteoporos Int 23:2703–2711CrossRefPubMed Sbrocchi AM, Rauch F, Jacob P, McCormick A, McMillan HJ, Matzinger MA, Ward LM (2012) The use of intravenous bisphosphonate therapy to treat vertebral fractures due to osteoporosis among boys with Duchenne muscular dystrophy. Osteoporos Int 23:2703–2711CrossRefPubMed
15.
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 66:195–199CrossRefPubMed 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 66:195–199CrossRefPubMed
16.
go back to reference Feber J, Gaboury I, Ni A et al (2012) Skeletal findings in children recently initiating glucocorticoids for the treatment of nephrotic syndrome. Osteoporos Int 23:751–760CrossRefPubMed Feber J, Gaboury I, Ni A et al (2012) Skeletal findings in children recently initiating glucocorticoids for the treatment of nephrotic syndrome. Osteoporos Int 23:751–760CrossRefPubMed
17.
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 8:1137–1148CrossRefPubMed Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137–1148CrossRefPubMed
18.
go back to reference Cummings EA, Ma J, Fernandez CV et al (2015) Incident vertebral fractures in children with leukemia during the four years following diagnosis. J Clin Endocrinol Metab 100:3408–3417CrossRefPubMedPubMedCentral Cummings EA, Ma J, Fernandez CV et al (2015) Incident vertebral fractures in children with leukemia during the four years following diagnosis. J Clin Endocrinol Metab 100:3408–3417CrossRefPubMedPubMedCentral
19.
go back to reference LeBlanc CM, Ma J, Taljaard M et al (2015) Incident vertebral fractures and risk factors in the first three years following glucocorticoid initiation among pediatric patients with rheumatic disorders. J Bone Miner Res 30:1667–1675CrossRefPubMedPubMedCentral LeBlanc CM, Ma J, Taljaard M et al (2015) Incident vertebral fractures and risk factors in the first three years following glucocorticoid initiation among pediatric patients with rheumatic disorders. J Bone Miner Res 30:1667–1675CrossRefPubMedPubMedCentral
20.
go back to reference Kerkeni S, Kolta S, Fechtenbaum J, Roux C (2009) Spinal deformity index (SDI) is a good predictor of incident vertebral fractures. Osteoporos Int 20:1547–1552CrossRefPubMed Kerkeni S, Kolta S, Fechtenbaum J, Roux C (2009) Spinal deformity index (SDI) is a good predictor of incident vertebral fractures. Osteoporos Int 20:1547–1552CrossRefPubMed
21.
go back to reference Kroger H, Kotaniemi A, Vainio P, Alhava E (1992) Bone densitometry of the spine and femur in children by dual-energy x-ray absorptiometry. Bone Miner 17:75–85CrossRefPubMed Kroger H, Kotaniemi A, Vainio P, Alhava E (1992) Bone densitometry of the spine and femur in children by dual-energy x-ray absorptiometry. Bone Miner 17:75–85CrossRefPubMed
22.
go back to reference van der Sluis IM, de Ridder MA, Boot AM, Krenning EP, de Muinck Keizer-Schrama SM (2002) Reference data for bone density and body composition measured with dual energy x ray absorptiometry in white children and young adults. Arch Dis Child 87:341–347; discussion 341–347 van der Sluis IM, de Ridder MA, Boot AM, Krenning EP, de Muinck Keizer-Schrama SM (2002) Reference data for bone density and body composition measured with dual energy x ray absorptiometry in white children and young adults. Arch Dis Child 87:341–347; discussion 341–347
23.
go back to reference James KA, Cunniff C, Apkon SD, Mathews K, Lu Z, Holtzer C, Pandya S, Ciafaloni E, Miller L (2015) Risk factors for first fractures among males with Duchenne or Becker muscular dystrophy. J Pediatr Orthop 35:640–644CrossRefPubMed James KA, Cunniff C, Apkon SD, Mathews K, Lu Z, Holtzer C, Pandya S, Ciafaloni E, Miller L (2015) Risk factors for first fractures among males with Duchenne or Becker muscular dystrophy. J Pediatr Orthop 35:640–644CrossRefPubMed
24.
go back to reference Bushby K, Finkel R, Birnkrant DJ et al (2010) Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol 9:77–93CrossRefPubMed Bushby K, Finkel R, Birnkrant DJ et al (2010) Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and pharmacological and psychosocial management. Lancet Neurol 9:77–93CrossRefPubMed
25.
go back to reference Moxley RT 3rd, Ashwal S, Pandya S, Connolly A, Florence J, Mathews K, Baumbach L, McDonald C, Sussman M, Wade C (2005) Practice parameter: corticosteroid treatment of Duchenne dystrophy: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 64:13–20CrossRefPubMed Moxley RT 3rd, Ashwal S, Pandya S, Connolly A, Florence J, Mathews K, Baumbach L, McDonald C, Sussman M, Wade C (2005) Practice parameter: corticosteroid treatment of Duchenne dystrophy: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology 64:13–20CrossRefPubMed
26.
go back to reference Nelson DA, Kleerekoper M, Peterson EL (1994) Reversal of vertebral deformities in osteoporosis: measurement error or “rebound”? J Bone Miner Res 9:977–982CrossRefPubMed Nelson DA, Kleerekoper M, Peterson EL (1994) Reversal of vertebral deformities in osteoporosis: measurement error or “rebound”? J Bone Miner Res 9:977–982CrossRefPubMed
27.
go back to reference Dal Osto LC, Konji VN, Halton J, Matzinger MA, Bassal M, Rauch F, Ward LM (2016) The spectrum of recovery from fracture-induced vertebral deformity in pediatric leukemia. Pediatr Blood Cancer 63:1107–1110CrossRefPubMed Dal Osto LC, Konji VN, Halton J, Matzinger MA, Bassal M, Rauch F, Ward LM (2016) The spectrum of recovery from fracture-induced vertebral deformity in pediatric leukemia. Pediatr Blood Cancer 63:1107–1110CrossRefPubMed
28.
go back to reference Ward LM, Glorieux FH, Rauch F, Verbruggen N, Heyden N, Lombardi A (2005) A randomized, placebo-controlled trial of oral alendronate in children and adolescents with osteogenesis imperfecta. Bone 36:0–18 Ward LM, Glorieux FH, Rauch F, Verbruggen N, Heyden N, Lombardi A (2005) A randomized, placebo-controlled trial of oral alendronate in children and adolescents with osteogenesis imperfecta. Bone 36:0–18
29.
go back to reference Rauch F, Munns CF, Land C, Cheung M, Glorieux FH (2009) Risedronate in the treatment of mild pediatric osteogenesis imperfecta: a randomized placebo-controlled study. J Bone Miner Res 24:1282–1289 Rauch F, Munns CF, Land C, Cheung M, Glorieux FH (2009) Risedronate in the treatment of mild pediatric osteogenesis imperfecta: a randomized placebo-controlled study. J Bone Miner Res 24:1282–1289
30.
go back to reference Sakkers R, Kok D, Engelbert R, van Dongen A, Jansen M, Pruijs H, Verbout A, Schweitzer D, Uiterwaal C (2004) Skeletal effects and functional outcome with olpadronate in children with osteogenesis imperfecta: a 2-year randomised placebo-controlled study. Lancet 363:1427–1431CrossRefPubMed Sakkers R, Kok D, Engelbert R, van Dongen A, Jansen M, Pruijs H, Verbout A, Schweitzer D, Uiterwaal C (2004) Skeletal effects and functional outcome with olpadronate in children with osteogenesis imperfecta: a 2-year randomised placebo-controlled study. Lancet 363:1427–1431CrossRefPubMed
31.
go back to reference Gatti D, Antoniazzi F, Prizzi R, Braga V, Rossini M, Tato L, Viapiana O, Adami S (2005) Intravenous neridronate in children with osteogenesis imperfecta: a randomized controlled study. J Bone Miner Res 20:758–763CrossRefPubMed Gatti D, Antoniazzi F, Prizzi R, Braga V, Rossini M, Tato L, Viapiana O, Adami S (2005) Intravenous neridronate in children with osteogenesis imperfecta: a randomized controlled study. J Bone Miner Res 20:758–763CrossRefPubMed
32.
go back to reference Antoniazzi F, Zamboni G, Lauriola S, Donadi L, Adami S, Tato L (2006) Early bisphosphonate treatment in infants with severe osteogenesis imperfecta. J Pediatr 149:174–179CrossRefPubMed Antoniazzi F, Zamboni G, Lauriola S, Donadi L, Adami S, Tato L (2006) Early bisphosphonate treatment in infants with severe osteogenesis imperfecta. J Pediatr 149:174–179CrossRefPubMed
33.
go back to reference Astrom E, Jorulf H, Soderhall S (2007) Intravenous pamidronate treatment of infants with severe osteogenesis imperfecta. Arch Dis Child 92:332–338CrossRefPubMed Astrom E, Jorulf H, Soderhall S (2007) Intravenous pamidronate treatment of infants with severe osteogenesis imperfecta. Arch Dis Child 92:332–338CrossRefPubMed
34.
go back to reference Palomo T, Fassier F, Ouellet J, Sato A, Montpetit K, Glorieux FH, Rauch F (2015) Intravenous bisphosphonate therapy of young children with osteogenesis imperfecta: skeletal findings during follow up throughout the growing years. J Bone Miner Res 30:2150–2157CrossRefPubMed Palomo T, Fassier F, Ouellet J, Sato A, Montpetit K, Glorieux FH, Rauch F (2015) Intravenous bisphosphonate therapy of young children with osteogenesis imperfecta: skeletal findings during follow up throughout the growing years. J Bone Miner Res 30:2150–2157CrossRefPubMed
35.
go back to reference Allington N, Vivegnis D, Gerard P (2005) Cyclic administration of pamidronate to treat osteoporosis in children with cerebral palsy or a neuromuscular disorder: a clinical study. Acta Orthop Belg 71:91–97PubMed Allington N, Vivegnis D, Gerard P (2005) Cyclic administration of pamidronate to treat osteoporosis in children with cerebral palsy or a neuromuscular disorder: a clinical study. Acta Orthop Belg 71:91–97PubMed
36.
go back to reference Soderpalm AC, Magnusson P, Ahlander AC, Karlsson J, Kroksmark AK, Tulinius M, Swolin-Eide D (2007) Low bone mineral density and decreased bone turnover in Duchenne muscular dystrophy. Neuromuscul Disord 17:919–928CrossRefPubMed Soderpalm AC, Magnusson P, Ahlander AC, Karlsson J, Kroksmark AK, Tulinius M, Swolin-Eide D (2007) Low bone mineral density and decreased bone turnover in Duchenne muscular dystrophy. Neuromuscul Disord 17:919–928CrossRefPubMed
37.
go back to reference Ma J, Siminoski K, Alos N et al (2015) The choice of normative pediatric reference database changes spine bone mineral density Z-scores but not the relationship between bone mineral density and prevalent vertebral fractures. J Clin Endocrinol Metab 100:1018–1027CrossRefPubMed Ma J, Siminoski K, Alos N et al (2015) The choice of normative pediatric reference database changes spine bone mineral density Z-scores but not the relationship between bone mineral density and prevalent vertebral fractures. J Clin Endocrinol Metab 100:1018–1027CrossRefPubMed
38.
go back to reference Bishop N, Arundel P, Clark E, Dimitri P, Farr J, Jones G, Makitie O, Munns CF, Shaw N (2014) Fracture prediction and the definition of osteoporosis in children and adolescents: the ISCD 2013 pediatric official positions. J Clin Densitom 17:275–280CrossRefPubMed Bishop N, Arundel P, Clark E, Dimitri P, Farr J, Jones G, Makitie O, Munns CF, Shaw N (2014) Fracture prediction and the definition of osteoporosis in children and adolescents: the ISCD 2013 pediatric official positions. J Clin Densitom 17:275–280CrossRefPubMed
39.
go back to reference Bachrach LK (2014) Diagnosis and treatment of pediatric osteoporosis. Curr Opin Endocrinol Diabetes Obes 21:454–460CrossRefPubMed Bachrach LK (2014) Diagnosis and treatment of pediatric osteoporosis. Curr Opin Endocrinol Diabetes Obes 21:454–460CrossRefPubMed
40.
go back to reference Makitie O (2013) Causes, mechanisms and management of paediatric osteoporosis. Nat Rev Rheumatol 9:465–475CrossRefPubMed Makitie O (2013) Causes, mechanisms and management of paediatric osteoporosis. Nat Rev Rheumatol 9:465–475CrossRefPubMed
41.
go back to reference Ward LM, Konji V, Ma J (2016) Management of osteoporosis in children. Osteoporos Int 27:2147–2179CrossRefPubMed Ward LM, Konji V, Ma J (2016) Management of osteoporosis in children. Osteoporos Int 27:2147–2179CrossRefPubMed
42.
43.
go back to reference Misof BM, Roschger P, McMillan HJ, Ma J, Klaushofer K, Rauch F, Ward LM (2016) Histomorphometry and bone matrix mineralization before and after bisphosphonate treatment in boys with Duchenne muscular dystrophy: a paired trans-iliac biopsy study. J Bone Miner Res 31:1060–1069CrossRefPubMed Misof BM, Roschger P, McMillan HJ, Ma J, Klaushofer K, Rauch F, Ward LM (2016) Histomorphometry and bone matrix mineralization before and after bisphosphonate treatment in boys with Duchenne muscular dystrophy: a paired trans-iliac biopsy study. J Bone Miner Res 31:1060–1069CrossRefPubMed
Metadata
Title
The time to and determinants of first fractures in boys with Duchenne muscular dystrophy
Authors
J. Ma
H. J. McMillan
G. Karagüzel
C. Goodin
J. Wasson
M. A. Matzinger
P. DesClouds
D. Cram
M. Page
V. N. Konji
B. Lentle
L. M. Ward
Publication date
01-02-2017
Publisher
Springer London
Published in
Osteoporosis International / Issue 2/2017
Print ISSN: 0937-941X
Electronic ISSN: 1433-2965
DOI
https://doi.org/10.1007/s00198-016-3774-5

Other articles of this Issue 2/2017

Osteoporosis International 2/2017 Go to the issue