Leanne M Ward1, Anup Choudhury2, Nathalie Alos3, David A Cabral4, Celia Rodd5, Anne Marie Sbrocchi5, Shayne Taback6, Raja Padidela7, Nick J Shaw8, Eva Hosszu9, Mikhail Kostik10, Ekaterina Alexeeva11,12, Kebashni Thandrayen13, Nazih Shenouda1, Jacob L Jaremko14, Gangadhar Sunkara15, Sarfaraz Sayyed2, R Paul Aftring15, Craig F Munns16. 1. Children's Hospital of Eastern Ontario and The University of Ottawa, Ottawa, Ontario, Canada. 2. Novartis Healthcare Pvt Ltd, Hyderabad, India. 3. Sainte Justine Hospital, Montréal, Quebec, Canada. 4. British Columbia Children's Hospital, Vancouver, British Columbia, Canada. 5. Montréal Children's Hospital, Montréal, Quebec H4A 3J1, Canada. 6. Winnipeg Children's Hospital, Winnipeg, Manitoba, 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. 10. Saint- Petersburg State Pediatric Medical University of the MoH, St 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. 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. 13. Department of Pediatrics, Chris Hani Baragwanath Academic Hospital, Faculty of Health Sciences, University of Witwatersrand, Braamfontein, Johannesburg, South Africa. 14. Stollery Children's Hospital and The University of Alberta, Edmonton, Alberta, Canada. 15. Novartis Pharmaceuticals Corp; East Hanover, New Jersey, USA. 16. Children's Hospital at Westmead, Sydney, Westmead, New South Wales 2145, Australia and Discipline of Paediatrics & Child Health, University of Sydney, Sydney, NSW, Australia.
Abstract
CONTEXT: Glucocorticoids (GCs) prescribed for chronic pediatric illnesses are associated with osteoporotic fractures. OBJECTIVE: This study aims to determine the efficacy and safety of intravenous (IV) zoledronic acid (ZA) compared with placebo to treat pediatric GC-induced osteoporosis (GIO). METHODS: Children aged 5 to 17 years with GIO were enrolled in this multinational, randomized, double-blind, placebo-controlled phase 3 trial (ClinicalTrials.gov NCT00799266). Eligible children were randomly assigned 1:1 to 6 monthly IV ZA 0.05 mg/kg or IV placebo. The primary end point was the change in lumbar spine bone mineral density z score (LSBMDZ) from baseline to month 12. Incident fractures and safety were assessed. RESULTS: Thirty-four children were enrolled (mean age 12.6 ± 3.4 years [18 on ZA, 16 on placebo]), all with low-trauma vertebral fractures (VFs). 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% CI, 0.02-0.81; P = .04]); when corrected for height z score, the least squares means difference in LBMDZ was 0.75 [95% CI, 0.27-1.22; P = .004]. Two children on placebo had new low-trauma VF vs none on ZA. Adverse events (AEs) were reported in 15 of 18 children (83%) on ZA, and in 12 of 16 (75%) on placebo, most frequently within 10 days after the first infusion. There were no deaths or treatment discontinuations due to treatment-emergent AEs. CONCLUSION: LSBMDZ increased significantly on ZA compared with placebo over 1 year in children with GIO. Most AEs occurred after the first infusion.
CONTEXT: Glucocorticoids (GCs) prescribed for chronic pediatric illnesses are associated with osteoporotic fractures. OBJECTIVE: This study aims to determine the efficacy and safety of intravenous (IV) zoledronic acid (ZA) compared with placebo to treat pediatric GC-induced osteoporosis (GIO). METHODS: Children aged 5 to 17 years with GIO were enrolled in this multinational, randomized, double-blind, placebo-controlled phase 3 trial (ClinicalTrials.gov NCT00799266). Eligible children were randomly assigned 1:1 to 6 monthly IV ZA 0.05 mg/kg or IV placebo. The primary end point was the change in lumbar spine bone mineral density z score (LSBMDZ) from baseline to month 12. Incident fractures and safety were assessed. RESULTS: Thirty-four children were enrolled (mean age 12.6 ± 3.4 years [18 on ZA, 16 on placebo]), all with low-trauma vertebral fractures (VFs). 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% CI, 0.02-0.81; P = .04]); when corrected for height z score, the least squares means difference in LBMDZ was 0.75 [95% CI, 0.27-1.22; P = .004]. Two children on placebo had new low-trauma VF vs none on ZA. Adverse events (AEs) were reported in 15 of 18 children (83%) on ZA, and in 12 of 16 (75%) on placebo, most frequently within 10 days after the first infusion. There were no deaths or treatment discontinuations due to treatment-emergent AEs. CONCLUSION: LSBMDZ increased significantly on ZA compared with placebo over 1 year in children with GIO. Most AEs occurred after the first infusion.