Advances in Pediatric Endocrinology

Growth hormone is important during childhood and puberty to maximize bone mass and to form normal bone architecture. The variability in presentation and limited tools available for the diagnosis of growth hormone deficiency (GHD) have contributed to ongoing challenges with understanding and managing this condition. Some of the gaps in the collective knowledge about the pathophysiology of GHD are related to the effects of hormone deficiency on bone geometry, architecture, and strength. Traditional techniques such as dual X-ray absorptiometry (DXA) have been limited in this application by inconsistencies in size corrections and inadequate resolution to completely outline the microarchitectural characteristics that drive bone strength.

Pediatric endocrinologists at NewYork-Presbyterian Morgan Stanley Children’s Hospital and Columbia University Irving Medical Center conducted research to elucidate the pathophysiology and clinical effects of GHD on bone mineral density and bone microarchitecture in pre-pubertal boys. The research was led by Tamar G. Baer, MD, principal investigator and a pediatric endocrinology fellow at the time, in collaboration with Patricia Vuguin, MD, MSc, Director of the Pediatric Thyroid Center and Director of the Pediatric Endocrine Fellowship Program at Columbia. Key to the study was the use of high-resolution peripheral quantitative computed tomography (HR-pQCT) to perform high fidelity comparisons of bone mineral density, geometry, and strength. This noninvasive imaging modality assesses volumetric bone mineral density and microarchitecture.

Dr. Tamar Baer

Dr. Patricia Vuguin

Their study involved 30 boys 5 to 11 years old – 15 had a diagnosis of GHD and no prior exposure to growth hormone treatment and the other 15 served as controls. The boys with GHD were found to have a significantly smaller cortical perimeter of the distal radius. This difference persisted even after adjusting for height, age, lean mass, and vitamin D levels. Other metrics evaluated, including estimated strength, body composition, bone turnover markers, and microarchitecture, were similar across both groups.

The research team focused on pre-pubertal boys to eliminate any effect of sex hormones and did not take into consideration the influence of maturation/puberty and other biological determinants of bone strength. Additionally, they note, “including girls in a future study may help evaluate the effect of other factors such as sex on pre-pubertal bone health.”

According to the authors, these findings have significant implications for the management of pre-pubertal boys with growth hormone deficiency, and provide a foundation for future research in GHD that would address timing of earlier growth hormone replacement to facilitate the development of normal peak bone mass during adulthood.

Dr. Sharon Oberfield

“This study provides novel insights into the structural characteristics of cortical and trabecular bone architecture in pre-pubertal boys with GHD,” says Sharon E. Oberfield, MD, Director, Division of Pediatric Endocrinology, Diabetes, and Metabolism at NewYork-Presbyterian Morgan Stanley Children’s Hospital and Columbia University Irving Medical Center, and a co-author on the study. “As DXA underestimates bone mineral density when evaluating smaller bones, using HR-pQCT measurements allows for a more accurate assessment of true volumetric bone mineral density in these children. By incorporating state-of-the-art technology, we were able to demonstrate that bones of young boys with GHD were more narrow compared to controls, suggesting that CT imaging in this population could improve their future quality of life.”