Bone Mineral Density to Assess Pediatric Bone Health in Drug Development

Brian M Maas; Jian Wang; Freda Cooner; Dionna Green; Ye Yuan; Lynne Yao; Gilbert J Burckart

doi:10.1177/2168479017709047

Bone Mineral Density to Assess Pediatric Bone Health in Drug Development

Ther Innov Regul Sci. 2017 Nov;51(6):756-760. doi: 10.1177/2168479017709047. Epub 2017 May 11.

Authors

Brian M Maas¹, Jian Wang², Freda Cooner³, Dionna Green⁴, Ye Yuan⁵, Lynne Yao², Gilbert J Burckart⁴

Affiliations

¹ 1 University of North Carolina Eshelman School of Pharmacy, Chapel Hill, NC, USA.
² 2 Office of New Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
³ 3 Office of Biostatistics, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, MD, USA.
⁴ 4 Office of Clinical Pharmacology, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, USA.
⁵ 5 University of Florida, Gainesville, FL, USA.

PMID: 30227097
DOI: 10.1177/2168479017709047

Abstract

Background: Pediatric bone health is an important part of the safety assessment of inhaled corticosteroids and certain other drugs. Current regulatory guidance for assessment of bone health for intranasal and inhaled corticosteroid drugs is a single 1-year study of linear growth.

Objective: The objective of this study was to assess whether a significant change in bone mineral density (BMD) could be observed during a 12-month period in pediatric patients being treated for asthma with an inhaled corticosteroid using a previously conducted study.

Methods: The publicly available information from the Childhood Asthma Management Program (CAMP) study was used to assess whether a statistically significant difference in BMD could be detected over a 1-year period. Patients who were at Tanner stage ≥2 were excluded from analysis as is stated in the present FDA Guidance on growth studies with inhaled corticosteroids, and children with any use of oral corticosteroids were also excluded. A comparison in BMD change over time (bone mineral accretion [BMA]) between baseline and 12 months of follow-up was made for the placebo and inhaled budesonide groups using multiple regression analysis to account for age, race, and gender as covariates.

Results: From the original 1041 patients in the CAMP study, 74 patients met the criteria for evaluation, with 42 patients receiving budesonide and 32 placebo patients. Children randomized to budesonide had a lower mean BMA than those receiving placebo (0.021 ± 0.023 [SD] g/cm²/y vs 0.036 ± 0.025 [SD] g/cm²/y).

Conclusion: In a select pediatric patient population, a significant change in BMA can be observed over 12 months on an inhaled corticosteroid. Based on this post hoc analysis, measurement of BMA as an assessment of pediatric bone health may be considered for certain drugs, especially when there is a potential signal of bone toxicity from animal or human data. The clinical relevance of this finding is presently unknown, and more data on the relationship between changes in BMA and clinical pediatric bone health outcomes are needed.

Keywords: bone mineral density; drug development; inhaled corticosteroids; pediatric growth.