Researchers Uncover Genetic Factors Affecting Pediatric Bone Density

Researchers at the Children’s Hospital of Philadelphia (CHOP) have identified significant genetic factors that influence bone density in children and adolescents. This discovery is set to improve early interventions aimed at enhancing bone health, potentially reducing the risk of fractures later in life. The findings highlight the complex interplay between genetics and environmental factors that affect pediatric bone health.

Understanding bone density in pediatric patients is crucial because while many children recover quickly from fractures due to accidents, some may face prolonged issues related to weak bones. Factors such as chronic health conditions, dietary restrictions, and steroid use can compromise bone mineral metabolism. Until now, the role of genetics in childhood bone density has been less explored compared to adult studies, which often focus on more severe consequences of fractures.

Two pivotal studies conducted by researchers at CHOP have advanced the understanding of genetic influences on bone development in children. The first study, published in March 2025 in the journal Genome Biology, examined genetic signals linked to bone mineral density identified through prior genome-wide association studies (GWAS) involving both adults and children. Notably, previous research had struggled to pinpoint a causal gene associated with these signals.

This study revealed that the relationship between osteoblasts—cells responsible for forming new bone tissue—and osteoclasts—cells that break down old bone tissue—is essential for understanding bone growth in children. The researchers employed a technique known as CRISPR interference (CRISPRi) to silence gene expression without altering the DNA sequence. They identified four specific genes: ARID5B, CC2D1B, EIF4G2, and NCOA3, which are linked to osteoblast maturation. Additionally, they observed that many genetic signals associated with bone density might also indicate other health issues, suggesting a broader implication for pediatric health.

In the second study, published in the Journal of Bone and Mineral Research, researchers utilized a polygenic risk score known as genetic quantitative ultrasound speed of sound (gSOS). This score had previously been employed to assess fracture risk in adults. By analyzing data from two observational studies, including the Bone Mineral Density in Childhood Study (BMDCS) and CHOP’s Center for Applied Genomics, the researchers aimed to determine the correlation between gSOS and bone health in children.

The results were promising. A higher gSOS score correlated with increased bone mineral density at multiple skeletal sites and lower fracture risk across both studies. These findings are particularly noteworthy given that they account for various factors such as sex, puberty stage, dietary calcium intake, height, weight, and body mass index (BMI), as well as the likelihood of accidents that could lead to fractures.

Dr. Babette S. Zemel, a senior author of the study and Professor of Pediatrics at CHOP, remarked, “Our study found that genetics represent a powerful component of bone density across the entire lifespan.” She expressed surprise at how accurately the polygenic risk score could predict fracture risk, even when considering typical childhood activities.

Both studies underscore the potential for early identification of children at risk for fractures, allowing for targeted interventions to enhance bone health. While maintaining a balanced diet and engaging in regular weight-bearing activities—such as volleyball and basketball—are vital for bone strength, these measures remain beneficial even for children with a high genetic risk of fractures.

The findings from these studies hold promise for advancing pediatric care and informing strategies to optimize bone health from an early age. Continued research in this area could lead to more personalized approaches to managing bone health in children, potentially reducing the burden of fractures in adulthood.