Skip to main content

Advertisement

SpringerLink
Log in

The use of intravenous bisphosphonate therapy to treat vertebral fractures due to osteoporosis among boys with Duchenne muscular dystrophy

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Summary

The impact of intravenous bisphosphonate treatment to treat painful vertebral fractures in boys with DMD has not been documented. In this retrospective observational study of seven boys, 2 years of intravenous bisphosphonate therapy was associated with back pain improvement and stabilization or increases in the height ratios of fractured vertebrae.

Introduction

Boys with Duchenne muscular dystrophy (DMD) are at risk for vertebral fractures. We studied the impact of intravenous bisphosphonate therapy for the treatment of painful vertebral fractures in DMD.

Methods

This was a retrospective observational study in seven boys with DMD (median 11.6 years, range 8.5 to 14.3) treated with intravenous pamidronate (9 mg/kg/year) or zoledronic acid (0.1 mg/kg/year) for painful vertebral fractures.

Results

At baseline, 27 vertebral fractures were evident in the seven boys. After 2 years of bisphosphonate therapy, 17 of the fractures had an increase in the most severely affected vertebral height ratio, 10 vertebrae stabilized, and none showed a decrease in height ratio. Back pain resolved completely (N = 3) or improved (N = 4). The median change in lumbar spine volumetric bone mineral density Z-score was 0.5 standard deviations (interquartile range, −0.3 to 1.7). Two boys had three incident vertebral fractures in previously normal vertebral bodies that developed over the observation period. There was a decline in the trabecular bone formation rate on trans-iliac bone biopsy but no evidence of osteomalacia. First-dose side effects included fever and malaise (N = 4), hypocalcemia (N = 2), and vomiting (N = 1); there were no side effects with subsequent infusions.

Conclusions

Intravenous bisphosphonate therapy was associated with improvements in back pain and stabilization to improvement in vertebral height ratios of previously fractured vertebral bodies. At the same time, such therapy does not appear to completely prevent the development of new vertebral fractures in this context.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

BMD:

Bone mineral density

CTx:

C-telopeptides of type I collagen

DMD:

Duchenne muscular dystrophy

GC:

Glucocorticoid

IQR:

Interquartile range

References

  1. 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 17:919–928

    Article  PubMed  Google Scholar 

  2. Yilmaz O, Karaduman A, Topaloglu H (2004) Prednisolone therapy in Duchenne muscular dystrophy prolongs ambulation and prevents scoliosis. Eur J Neurol 11:541–544

    Article  PubMed  CAS  Google Scholar 

  3. Biggar WD, Gingras M, Fehlings DL, Harris VA, Steele CA (2001) Deflazacort treatment of Duchenne muscular dystrophy. J Pediatr 138:45–50

    Article  PubMed  CAS  Google Scholar 

  4. Bianchi ML, Mazzanti A, Galbiati E, Saraifoger S, Dubini A, Cornelio F, Morandi L (2003) Bone mineral density and bone metabolism in Duchenne muscular dystrophy. Osteoporos Int 14:761–767

    Article  PubMed  CAS  Google Scholar 

  5. Larson CM, Henderson RC (2000) Bone mineral density and fractures in boys with Duchenne muscular dystrophy. J Pediatr Orthop 20:71–74

    Article  PubMed  CAS  Google Scholar 

  6. Bothwell JE, Gordon KE, Dooley JM, MacSween J, Cummings EA, Salisbury S (2003) Vertebral fractures in boys with Duchenne muscular dystrophy. Clin Pediatr (Phila) 42:353–356

    Article  CAS  Google Scholar 

  7. 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 68:1607–1613

    Article  PubMed  CAS  Google Scholar 

  8. Houde S, Filiatrault M, Fournier A, Dube J, D'Arcy S, Berube D, Brousseau Y, Lapierre G, Vanasse M (2008) Deflazacort use in Duchenne muscular dystrophy: an 8-year follow-up. Pediatr Neurol 38:200–206

    Article  PubMed  Google Scholar 

  9. Talim B, Malaguti C, Gnudi S, Politano L, Merlini L (2002) Vertebral compression in Duchenne muscular dystrophy following deflazacort. Neuromuscul Disord: NMD 12:294–295

    Article  PubMed  CAS  Google Scholar 

  10. Hawker GA, Ridout R, Harris VA, Chase CC, Fielding LJ, Biggar WD (2005) Alendronate in the treatment of low bone mass in steroid-treated boys with Duchennes muscular dystrophy. Arch Phys Med Rehabil 86:284–288

    Article  PubMed  Google Scholar 

  11. Glorieux FH, Bishop NJ, Plotkin H, Chabot G, Lanoue G, Travers R (1998) Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. N Engl J Med 339:947–952

    Article  PubMed  CAS  Google Scholar 

  12. Sumnik Z, Land C, Rieger-Wettengl G, Korber F, Stabrey A, Schoenau E (2004) Effect of pamidronate treatment on vertebral deformity in children with primary osteoporosis. A pilot study using radiographic morphometry. Horm Res 61:137–142

    Article  PubMed  CAS  Google Scholar 

  13. Brumsen C, Hamdy NA, Papapoulos SE (1997) Long-term effects of bisphosphonates on the growing skeleton. Studies of young patients with severe osteoporosis. Med (Baltimore) 76:266–283

    Article  CAS  Google Scholar 

  14. Gafni RI, McCarthy EF, Hatcher T, Meyers JL, Inoue N, Reddy C, Weise M, Barnes KM, Abad V, Baron J (2002) Recovery from osteoporosis through skeletal growth: early bone mass acquisition has little effect on adult bone density. FASEB J 16:736–738

    PubMed  CAS  Google Scholar 

  15. 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

    Article  PubMed  CAS  Google Scholar 

  16. Bishop N, Harrison R, Ahmed F et al (2010) A randomized, controlled dose-ranging study of risedronate in children with moderate and severe osteogenesis imperfecta. J Bone Miner Res 25:32–40

    Article  PubMed  CAS  Google Scholar 

  17. Genant HK, Wu CY, van Kuijk C, Nevitt MC (1993) Vertebral fracture assessment using a semiquantitative technique. J Bone Miner Res 8:1137–1148

    Article  PubMed  CAS  Google Scholar 

  18. 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 109:45–60

    Article  PubMed  Google Scholar 

  19. Marshall WA, Tanner JM (1969) Variations in pattern of pubertal changes in girls. Arch Dis Child 44:291–303

    Article  PubMed  CAS  Google Scholar 

  20. Marshall WA, Tanner JM (1970) Variations in the pattern of pubertal changes in boys. Arch Dis Child 45:13–23

    Article  PubMed  CAS  Google Scholar 

  21. van Staa TP, Leufkens HG, Cooper C (2002) The epidemiology of corticosteroid-induced osteoporosis: a meta-analysis. Osteoporos Int 13:777–787

    Article  PubMed  Google Scholar 

  22. Institute of Medicine (1997) Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, fluoride. National Academy, Washington

    Google Scholar 

  23. Rauchenzauner M, Schmid A, Heinz-Erian P, Kapelari K, Falkensammer G, Griesmacher A, Finkenstedt G, Hogler W (2007) Sex- and age-specific reference curves for serum markers of bone turnover in healthy children from 2 months to 18 years. J Clin Endocrinol Metab 92:443–449

    Article  PubMed  CAS  Google Scholar 

  24. Greulich WW, Pyle SI (1959) Radiographic atlas of skeletal development of the hand and wrist, 2nd edn. Stanford University Press, Stanford

    Google Scholar 

  25. Spencer RP, Sagel SS, Garn SM (1968) Age changes in five parameters of metacarpal growth. Invest Radiol 3:27–34

    Article  PubMed  CAS  Google Scholar 

  26. Garn SM, Mayor GH, Shaw HA (1976) Paradoxical bilateral asymmetry in bone size and bone mass in the hand. Am J Phys Anthropol 45:209–210

    Article  PubMed  CAS  Google Scholar 

  27. Kroger H, Vainio P, Nieminen J, Kotaniemi A (1995) Comparison of different models for interpreting bone mineral density measurements using DXA and MRI technology. Bone 17:157–159

    Article  PubMed  CAS  Google Scholar 

  28. 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

    Article  PubMed  Google Scholar 

  29. Armbrecht G, Blenk T, Chesnut CH 3rd, Gardner JC, von Ingersleben G, Mahoney P, Felsenberg D (2008) Vertebral fracture diagnosis in the multinational BONE study of oral ibandronate: quality management in radiology. J Clin Densitom 11:221–231

    Article  PubMed  Google Scholar 

  30. Ravaud P, Reny JL, Giraudeau B, Porcher R, Dougados M, Roux C (1999) Individual smallest detectable difference in bone mineral density measurements. J Bone Miner Res: Off J Am Soc Bone Miner Res 14:1449–1456

    Article  CAS  Google Scholar 

  31. Bland JM, Altman DG (1999) Measuring agreement in method comparison studies. Stat Methods Med Res 8:135–160

    Article  PubMed  CAS  Google Scholar 

  32. Glorieux FH, Travers R, Taylor A, Bowen JR, Rauch F, Norman M, Parfitt AM (2000) Normative data for iliac bone histomorphometry in growing children. Bone 26:103–109

    Article  PubMed  CAS  Google Scholar 

  33. Glorieux FH, Rauch F (2006) Medical therapy of children with fibrous dysplasia. J Bone Miner Res 21(Suppl 2):P110–P113

    Article  PubMed  Google Scholar 

  34. Rauch F, Travers R, Plotkin H, Glorieux FH (2002) The effects of intravenous pamidronate on the bone tissue of children and adolescents with osteogenesis imperfecta. J Clin Invest 110:1293–1299

    PubMed  CAS  Google Scholar 

  35. Munns CF, Rauch F, Travers R, Glorieux FH (2005) Effects of intravenous pamidronate treatment in infants with osteogenesis imperfecta: clinical and histomorphometric outcome. J Bone Miner Res 20:1235–1243

    Article  PubMed  CAS  Google Scholar 

  36. Baim S, Leonard MB, Bianchi ML, Hans DB, Kalkwarf HJ, Langman CB, Rauch F (2008) Official positions of the International Society for Clinical Densitometry and executive summary of the 2007 ISCD Pediatric Position Development Conference. J Clin Densitom 11:6–21

    Article  PubMed  Google Scholar 

  37. 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 194:516–520

    Article  PubMed  Google Scholar 

  38. Weinstein RS, Jilka RL, Almeida M, Roberson PK, Manolagas SC (2010) Intermittent parathyroid hormone administration counteracts the adverse effects of glucocorticoids on osteoblast and osteocyte viability, bone formation, and strength in mice. Endocrinology 151:2641–2649

    Article  PubMed  CAS  Google Scholar 

  39. Plotkin H, Coughlin S, Kreikemeier R, Heldt K, Bruzoni M, Lerner G (2006) Low doses of pamidronate to treat osteopenia in children with severe cerebral palsy: a pilot study. Dev Med Child Neurol 48:709–712

    Article  PubMed  Google Scholar 

  40. Howe W, Davis E, Valentine J (2010) Pamidronate improves pain, wellbeing, fracture rate and bone density in 14 children and adolescents with chronic neurological conditions. Dev Neurorehabil 13:31–36

    Article  PubMed  Google Scholar 

  41. Glorieux FH, Bishop N, Bober M et al (2008) Intravenous zoledronic acid (zol) compared to IV pamidronate (PAM) in children with severe osteogenesis imperfecta (OI). Calcif Tissue Int 82(Suppl 1):S85

    Google Scholar 

  42. 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 24:1326–1334

    Article  PubMed  Google Scholar 

  43. Huber A, Gaboury I, Cabral DA et al (2010) Prevalent vertebral fractures among children initiating glucocorticoid therapy for the treatment of rheumatic disorders. Arth Care Res 62:516–526

    Article  CAS  Google Scholar 

  44. Rodd C, Lang B, Ramsay T et al (2012) Incident vertebral fractures among children with rheumatic disorders 12 months post-glucocorticoid initiation: a national observational study. Arthritis Care Res 64(1):122–131

    Article  Google Scholar 

  45. Thearle M, Horlick M, Bilezikian JP, Levy J, Gertner JM, Levine LS, Harbison M, Berdon W, Oberfield SE (2000) Osteoporosis: an unusual presentation of childhood Crohn's disease. J Clin Endocrinol Metab 85:2122–2126

    Article  PubMed  CAS  Google Scholar 

  46. Pandya NA, Meller ST, MacVicar D, Atra AA, Pinkerton CR (2001) Vertebral compression fractures in acute lymphoblastic leukaemia and remodelling after treatment. Arch Dis Child 85:492–493

    Article  PubMed  CAS  Google Scholar 

  47. Simm PJ, Johannesen J, Briody J, McQuade M, Hsu B, Bridge C, Little DG, Cowell CT, Munns CF (2011) Zoledronic acid improves bone mineral density, reduces bone turnover and improves skeletal architecture over 2 years of treatment in children with secondary osteoporosis. Bone 49:939–943

    Article  PubMed  CAS  Google Scholar 

  48. Gordon KE, Dooley JM, Sheppard KM, MacSween J, Esser MJ (2011) Impact of bisphosphonates on survival for patients with Duchenne muscular dystrophy. Pediatrics 127:e353–e358

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

Dr. Sbrocchi is supported by a NovoNordisk Canadian Pediatric Endocrine Group Clinical Research Fellowship. Dr. Ward has been supported by a CIHR New Investigator Award, a Canadian Child Health Clinician Scientist Career Enhancement Award, and a University of Ottawa Research Chair Award.

Conflicts of interest

Dr. Leanne Ward has been a consultant to Novartis Pharmaceuticals. All other authors have no conflict of interest to declare.

Author information

Authors and Affiliations

  1. Division of Endocrinology, Children’s Hospital of Eastern Ontario, 401 Smyth Rd., Ottawa, ON, Canada, K1H 8L1

    A. M. Sbrocchi & L. M. Ward

  2. Genetics Unit, Shriners Hospital for Children, Montreal, QC, Canada

    F. Rauch

  3. Division of Neurology, Children’s Hospital of Eastern Ontario, Ottawa, ON, Canada

    P. Jacob, A. McCormick & H. J. McMillan

  4. Department of Diagnostic Imaging, Children’s Hospital of Eastern Ontario, Ottawa, ON, Canada

    M. A. Matzinger

Authors
  1. A. M. Sbrocchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. F. Rauch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Jacob
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. McCormick
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H. J. McMillan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. M. A. Matzinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. L. M. Ward
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. M. Ward.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sbrocchi, A.M., Rauch, F., Jacob, P. et al. The use of intravenous bisphosphonate therapy to treat vertebral fractures due to osteoporosis among boys with Duchenne muscular dystrophy. Osteoporos Int 23, 2703–2711 (2012). https://doi.org/10.1007/s00198-012-1911-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-012-1911-3

Keywords

Search

Navigation