Context
Glucocorticoids (GC) prescribed for chronic pediatric illnesses are associated with osteoporotic fractures.
Objective
To determine the efficacy and safety of intravenous (IV) zoledronic acid (ZA) compared with placebo to treat pediatric GC-induced osteoporosis (GIO).
Patients, Design and Setting
Children 5-17 years of age with GIO were enrolled in this multi-national randomized, double-blind, placebo-controlled phase 3 trial (ClinicaTrials.gov NCT 00799266).
Interventions and Main Outcome Measures
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.
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. 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.
Conclusions
LSBMDZ increased significantly on ZA compared with placebo over one year in children with GIO. Most AEs occurred after the first infusion.
Combined pituitary hormone deficiency is characterized by the impaired production of pituitary hormones, commonly including growth hormone. The pathomechanism of the childhood-onset form of this disorder may involve germline mutations of genes encoding pituitary transcription factors, of which PROP1 gene mutations have been studied most extensively. However, controversy exists about the significance of PROP1 gene mutations, as both low and high frequencies have been reported in these patients. Because the different results may be related to differences in patient populations and/or the variability of clinical phenotypes, we performed the present study to examine the prevalence and spectrum of PROP1 gene mutations in 35 patients with non-acquired childhood-onset growth hormone deficiency combined with at least one other anterior pituitary hormone deficiency. Genetic testing indicated the presence of disease-causing mutations in exons 2 and 3 of the PROP1 gene in 15 patients (43% of all patients; homozygous mutations in 10 patients and compound heterozygous mutations in 5 patients). Comparison of clinical data of patients with and without PROP1 gene mutations failed to show significant differences, except an earlier growth retardation detected in patients with PROP1 gene mutations. In one patient with PROP1 gene mutation, radiologic imaging showed an enlargement of the anterior lobe of the pituitary, whereas the other patients had hypoplastic or normal pituitary gland. All patients with PROP1 gene mutations had normal posterior pituitary lobe by radiologic imaging. These results indicate that using our inclusion criteria for genetic testing, PROP1 gene mutations can be detected in a high proportion of Hungarian patients with non-acquired childhood-onset growth hormone deficiency combined with at least one other anterior pituitary hormone defect.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.