Zoledronic Acid in Non-Ambulatory Children and Young Adults with Fragility Fractures and Low Bone Mass Associated with Spastic Quadriplegic Cerebral Palsy and Other Neuromuscular Disorders (

Authors

  • Sasigarn A. Bowden Division of Endocrinology,Department of Pediatrics, Nationwide Children’s Hospital/The Ohio State University College of Medicine, Columbus, Ohio, USA
  • Ashley B. Jessup
  • Chiazor I. Akusoba
  • John D. Mahan Division of Nephrology, Department of Pediatrics, Nationwide Children’s Hospital/The Ohio State University College of Medicine, Columbus, Ohio, USA

DOI:

https://doi.org/10.12970/2310-9971.2015.03.02.2

Keywords:

Bisphosphonates, pamidronate, pediatric osteoporosis, osteopenia, bone density.

Abstract

 Non-ambulatory patients with neurological disorders such as spastic quadriplegic cerebral palsy often have low bone mineral density (BMD) and fragility fractures from disuse osteoporosis. Limited data exists on zoledronic acid (a third generation bisphosphonate) treatment in the pediatric population.   We report a case series of 10 patients with spastic quadriplegic cerebral palsy (n=6), spinal muscular atrophy (n=2), and myelomeningocele (n=2) treated with zoledronic acid for fragility fractures and/or low BMD associated with the underlying conditions. The clinical and BMD outcomes were retrospectively studied and compared with a historical cohort of 32 patients treated with intravenous pamidronate.   Mean lumbar BMD increased significantly (P< 0.01) by 28% at1 yearin zoledronic acid group, and by 19% in pamidronate group. Mean lumbar BMD weight-adjusted Z-scores improved from -4.31 at baseline to -2.55(P=0.003) at 1 year in zoledronic group, and from -3.66 to -2.30 in pamidronate group (P=0.001).   Total number of fractures in the zoledronic group was 18 before treatment and reduced to zero after treatment with an average follow-up of 3.9 years. All patients tolerated zoledronic acid infusion with fever in 3 patients (30%) during the initial infusion and nohypocal cemianoted during the treatment cycles.   Treatment with zoledronic acid is safe, significantly improves bone density and reduces fractures in children and young adults with fragility fractures and low bone mass secondary to neuromuscular disorders. Further follow up studies are needed to confirm safety and efficacy in long-term fracture prevention.  

References


[1] Mergler S, Evenhuis HM, Boot AM, et al. Epidemiology of low bone mineral density and fractures in children with severe cerebral palsy: a systematic review. Developmental Medicine & Child Neurology 2009; 51(10): 773-8. http://dx.doi.org/10.1111/j.1469-8749.2009.03384.x
[2] Henderson RC, Lark RK, Gurka MJ, et al. Bone density and metabolism in children and adolescents with moderate to severe cerebral palsy. Pediatrics 2002; 110(1): e5-e.
[3] King W, Levin R, Schmidt R, Oestreich A, Heubi JE. Prevalence of reduced bone mass in children and adults with spastic quadriplegia. Developmental Medicine & Child Neurology 2003; 45(1): 12-6. http://dx.doi.org/10.1111/j.1469-8749.2003.tb00853.x
[4] Henderson RC, Lark RK, Kecskemethy HH, Miller F, Harcke HT, Bachrach SJ. Bisphosphonates to treat osteopenia in children with quadriplegic cerebral palsy: a randomized, placebo-controlled clinical trial. The Journal of pediatrics 2002; 141(5): 644-51. http://dx.doi.org/10.1067/mpd.2002.128207
[5] Allington N, Vivegnis D, Gerard P. Cyclic administration of pamidronate to treat osteoporosis in children with cerebral palsy or a neuromuscular disorder: a clinical study. Acta Orthop Belg 2005; 71(1): 91-7.
[6] Plotkin H, Coughlin S, Kreikemeier R, Heldt K, Bruzoni M, Lerner G. Low doses of pamidronate to treat osteopenia in children with severe cerebral palsy: a pilot study. Developmental Medicine & Child Neurology 2006; 48(9): 709-12. http://dx.doi.org/10.1017/S0012162206001526
[7] Bachrach SJ, Kecskemethy HH, Harcke HT, Hossain J. Decreased fracture incidence after 1 year of pamidronate treatment in children with spastic quadriplegic cerebral palsy. Developmental Medicine & Child Neurology 2010; 52(9): 837-42. http://dx.doi.org/10.1111/j.1469-8749.2010.03676.x
[8] Black DM, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. New England Journal of Medicine 2007; 356(18): 1809-22. http://dx.doi.org/10.1056/NEJMoa067312
[9] Panigrahi I, Das RR, Sharda S, Marwaha RK, Khandelwal N. Response to zolendronic acid in children with type III osteogenesis imperfecta. Journal of bone and mineral metabolism 2010; 28(4): 451-5. http://dx.doi.org/10.1007/s00774-009-0149-4
[10] Vuorimies I, Toiviainen-Salo S, Hero M, Mäkitie O. Zoledronic acid treatment in children with osteogenesis imperfecta. Hormone research in paediatrics 2011; 75(5): 346-53. http://dx.doi.org/10.1159/000323368
[11] Barros ER, Saraiva GL, de Oliveira TP, Lazaretti-Castro M. Safety and efficacy of a 1-year treatment with zoledronic acid compared with pamidronate in children with osteogenesis imperfecta. Journal of Pediatric Endocrinology and Metabolism 2012; 25: 5-6. http://dx.doi.org/10.1515/jpem-2012-0016
[12] Glorieux F, Devogelaer J-P, Bishop N, et al. Intravenous zoledronic acid (ZOL) compared to iv pamidronate (PAM) in children with severe osteogenesis imperfecta (OI). Calcified tissue international 2008; 82: S85-S.
[13] Simm PJ, Johannesen J, Briody J, et al. Zoledronic acid improves bone mineral density, reduces bone turnover and improves skeletal architecture over 2 years of treatment in children with secondary osteoporosis. Bone 2011; 49(5): 939-43. http://dx.doi.org/10.1016/j.bone.2011.07.031
[14] Ooi HL, Briody J, Biggin A, Cowell C, Munns C. Intravenous Zoledronic Acid Given Every 6 Months in Childhood Osteoporosis. Hormone research in paediatrics 2013; 80(3): 179-84. http://dx.doi.org/10.1159/000354303
[15] Robinson RF, Nahata MC, Hayes JR, Batisky DL, Bates CM, Mahan JD. Effectiveness of pretreatment in decreasing adverse events associated with pamidronate in children and adolescents. Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy 2004; 24(2): 195-7. http://dx.doi.org/10.1592/phco.24.2.195.33143
[16] Southard R, Morris JD, Mahan J, et al. Bone mass in healthy children: measurement with quantitative DXA. Radiology 1991; 179(3): 735-8. http://dx.doi.org/10.1148/radiology.179.3.2027984
[17] Wildman SS, Henwood-Finley MJ. Pediatric DXA: a review of proper technique and correct interpretation. Journal of the American Osteopathic College of Radiology 2012; 1(3): 17- 26.
[18] Paksu MS, Vurucu S, Karaoglu A, et al. Osteopenia in children with cerebral palsy can be treated with oral alendronate. Child's Nervous System 2012; 28(2): 283-6. http://dx.doi.org/10.1007/s00381-011-1576-9
[19] Iwasaki T, Takei K, Nakamura S, Hosoda N, Yokota Y, Ishii M. Secondary osteoporosis in long term bedridden patients with cerebral palsy. Pediatrics International 2008; 50(3): 269- 75. http://dx.doi.org/10.1111/j.1442-200X.2008.02571.x
[20] Henderson RC, Kairalla JA, Barrington JW, Abbas A, Stevenson RD. Longitudinal changes in bone density in children and adolescents with moderate to severe cerebral palsy. The Journal of pediatrics 2005; 146(6): 769-75. http://dx.doi.org/10.1016/j.jpeds.2005.02.024
[21] Glorieux FH, Bishop NJ, Plotkin H, Chabot G, Lanoue G, Travers R. Cyclic administration of pamidronate in children with severe osteogenesis imperfecta. New England Journal of Medicine 1998; 339(14): 947-52. http://dx.doi.org/10.1056/NEJM199810013391402
[22] Lee Y-S, Low S-L, Lim L-A, Loke K-Y. Cyclic pamidronate infusion improves bone mineralisation and reduces fracture incidence in osteogenesis imperfecta. European journal of pediatrics 2001; 160(11): 641-4. http://dx.doi.org/10.1007/s004310100844
[23] Munns CF, Rajab MH, Hong J, et al. Acute phase response and mineral status following low dose intravenous zoledronic acid in children. Bone 2007; 41(3): 366-70. http://dx.doi.org/10.1016/j.bone.2007.05.002
[24] Högler W, Yap F, Little D, Ambler G, McQuade M, Cowell CT. Short-term safety assessment in the use of intravenous zoledronic acid in children. The Journal of pediatrics 2004; 145(5): 701-4. http://dx.doi.org/10.1016/j.jpeds.2004.06.066

Downloads

Published

2015-08-03

Issue

Section

Articles