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Zoledronic acid versus placebo in pediatric glucocorticoid-induced osteoporosis: A randomized double-blind phase 3 trial.

  • Ward, Leanne M1
  • Choudhury, Anup2
  • Alos, Nathalie3
  • Cabral, David A4
  • Rodd, Celia5
  • Sbrocchi, Anne Marie5
  • Taback, Shayne6
  • Padidela, Raja7
  • Shaw, Nick J8
  • Hosszu, Eva9
  • Kostik, Mikhail10
  • Alexeeva, Ekaterina11, 12
  • Thandrayen, Kebashni13
  • Shenouda, Nazih1
  • Jaremko, Jacob L14
  • Sunkara, Gangadhar15
  • Sayyed, Sarfaraz2
  • Aftring, R Paul15
  • Munns, Craig F16
  • 1 Children's Hospital of Eastern Ontario and The University of Ottawa, Ottawa, Ontario, Canada. , (Canada)
  • 2 Novartis Healthcare Pvt. Ltd., Hyderabad, India. , (India)
  • 3 Sainte Justine Hospital, Montréal, Quebec, Canada. , (Canada)
  • 4 British Columbia Children's Hospital, Vancouver, British Columbia, Canada. , (Canada)
  • 5 Montréal Children's Hospital, Montréal, Quebec, Canada. , (Canada)
  • 6 Winnipeg Children's Hospital, Winnipeg, Manitoba, Canada. , (Canada)
  • 7 Department of Pediatric Endocrinology, Royal Manchester Children's Hospital and Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK.
  • 8 Birmingham Children's Hospital, Institute of Metabolism and Systems Research, University of Birmingham Birmingham, UK.
  • 9 2nd Department of Pediatrics, Faculty of Medicine, Semmelweis University, Budapest, Hungary. , (Hungary)
  • 10 Saint- Petersburg State Pediatric Medical University of the MoH, Saint Petersburg, Russia.
  • 11 Federal State Autonomous Institution "National Medical Research Center of Children's Health" of the Ministry of Health of the Russian Federation, Moscow, Russia. , (Russia)
  • 12 Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation, Moscow Russia. , (Russia)
  • 13 Department of Pediatrics, Chris Hani Baragwanath Academic Hospital, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa. , (South Africa)
  • 14 Stollery Children's Hospital and The University of Alberta, Edmonton, Alberta, Canada. , (Canada)
  • 15 Novartis Pharmaceuticals Corporation; East Hanover, New Jersey, USA. , (Jersey)
  • 16 Children's Hospital at Westmead, Sydney, New South Wales, Australia and Discipline of Paediatrics & Child Health, University of Sydney, Sydney, Australia. , (Australia)
Published Article
The Journal of Clinical Endocrinology & Metabolism
The Endocrine Society
Publication Date
Jul 06, 2021
DOI: 10.1210/clinem/dgab458
PMID: 34228102


Glucocorticoids (GC) prescribed for chronic pediatric illnesses are associated with osteoporotic fractures. To determine the efficacy and safety of intravenous (IV) zoledronic acid (ZA) compared with placebo to treat pediatric GC-induced osteoporosis (GIO). Children 5-17 years of age with GIO were enrolled in this multi-national randomized, double-blind, placebo-controlled phase 3 trial ( NCT00799266). Eligible children were randomized 1:1 to six monthly IV ZA 0.05 mg/kg or IV placebo. The primary endpoint was the change in lumbar spine bone mineral density Z-score (LSBMDZ) from baseline to month 12. Incident fractures and safety were assessed. Thirty-four children were enrolled (mean age 12.6 ± 3.4 years [18 on ZA, 16 on placebo]), all with low-trauma vertebral fractures. LSBMDZ increased from -2.13 ± 0.79 to -1.49 ± 1.05 on ZA, compared with -2.38 ± 0.90 to -2.27 ± 1.03 on placebo (least squares means difference 0.41 [95% confidence interval 0.02, 0.81; p=0.04]); when corrected for height Z-score, the least squares means difference in LBMDZ was 0.75 [0.27, 1.22; p=0.004]. Two children on placebo had new low-trauma VF versus none on ZA. Adverse events (AEs) were reported in 15/18 children (83%) on ZA, and in 12/16 (75%) on placebo, most frequently within 10 days after the first infusion. There were no deaths, nor treatment discontinuations due to treatment-emergent AEs. LSBMDZ increased significantly on ZA compared with placebo over one year in children with GIO. Most AEs occurred after the first infusion. © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: [email protected]

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