학술논문
Zoledronic Acid vs Placebo in Pediatric Glucocorticoid-induced Osteoporosis: A Randomized, Double-blind, Phase 3 Trial
Clinical Research Article
Clinical Research Article
Document Type
Academic Journal
Author
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.
Source
Journal of Clinical Endocrinology & Metabolism. December 2021, Vol. 106 Issue 12, pe5222, 14 p.
Subject
Language
English
ISSN
0021-972X
Abstract
Glucocorticoid (GC) therapy is the cornerstone of treatment for numerous pediatric diseases, including inflammatory or autoimmune disorders, and Duchenne muscular dystrophy (DMD). However, GCs increase the risk of fragility fractures, [...]
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 NCT 00799266). 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 [+ or -] 3.4 years [18 on ZA, 16 on placebo]), all with low-trauma vertebral fractures (VFs). LSBMDZ increased from -2.13 [+ or -] 0.79 to -1.49 [+ or -] 1.05 on ZA, compared with -2.38 [+ or -] 0.90 to -2.27 [+ or -] 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. Key Words: children, fractures, osteoporosis, glucocorticoids, steroids, zoledronic acid, Duchenne muscular dystrophy
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 NCT 00799266). 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 [+ or -] 3.4 years [18 on ZA, 16 on placebo]), all with low-trauma vertebral fractures (VFs). LSBMDZ increased from -2.13 [+ or -] 0.79 to -1.49 [+ or -] 1.05 on ZA, compared with -2.38 [+ or -] 0.90 to -2.27 [+ or -] 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. Key Words: children, fractures, osteoporosis, glucocorticoids, steroids, zoledronic acid, Duchenne muscular dystrophy