Zoledronic Acid vs Placebo in Pediatric Glucocorticoid-induced Osteoporosis: A Randomized, Double-blind, Phase 3 Trial

• Published in: The journal of clinical endocrinology and metabolism Vol. 106; no. 12; pp. e5222 - e5235
• Main Authors: Ward, Leanne M, Choudhury, Anup, Alos, Nathalie, Cabral, David A, Rodd, Celia, Sbrocchi, Anne Marie, Taback, Shayne, Padidela, Raja, Shaw, Nick J, Hosszu, Eva, Kostik, Mikhail, Alexeeva, Ekaterina, Thandrayen, Kebashni, Shenouda, Nazih, Jaremko, Jacob L, Sunkara, Gangadhar, Sayyed, Sarfaraz, Aftring, R Paul, Munns, Craig F
• Format: Journal Article
• Language: English
• Published: United States Oxford University Press 01-12-2021
• Subjects: Adolescent; Bone Density Conservation Agents - therapeutic use; Child; Child, Preschool; Children; Clinical trials; Corticosteroids; Diseases; Disodium pamidronate; Double-Blind Method; Female; Follow-Up Studies; Glucocorticoids - adverse effects; Humans; Male; Osteoporosis; Osteoporosis - chemically induced; Osteoporosis - drug therapy; Osteoporosis - pathology; Pediatrics; Pharmaceutical industry; Product development; Prognosis; Zoledronic acid; Zoledronic Acid - therapeutic use; Canada; United States; Russia; children; Duchenne muscular dystrophy; zoledronic acid; steroids; glucocorticoids; osteoporosis; fractures
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgab458

Glucocorticoids (GCs) prescribed for chronic pediatric illnesses are associated with osteoporotic fractures.
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).
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.
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.
LSBMDZ increased significantly on ZA compared with placebo over 1 year in children with GIO. Most AEs occurred after the first infusion.