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 could enable healthcare providers to identify young patients at risk of developing weak bones, allowing for early interventions to improve their long-term bone health and reduce fracture risks in adulthood.

Many children sustain fractures from accidents, typically recovering quickly; however, some face underlying issues that weaken their bones. Factors such as chronic health conditions, dietary restrictions, and steroid usage can adversely affect bone mineral metabolism. While the genetic component has been less understood, particularly in pediatric populations, recent studies aim to bridge this knowledge gap.

Genetic Insights into Bone Health

Two pivotal studies conducted by CHOP researchers explore the intersection of genetics and pediatric bone development. The first study, published in March 2025 in the journal Genome Biology, examined genetic signals associated with bone mineral density identified through genome-wide association studies (GWAS) involving both adults and children. Previous studies failed to pinpoint a causal gene related to these signals, which are crucial for understanding the dynamic interplay between osteoblasts—cells responsible for forming new bone tissue—and osteoclasts, which break down old bone.

Utilizing a technique known as CRISPR interference (CRISPRi), which silences gene expression without altering the DNA, researchers identified four genes—ARID5B, CC2D1B, EIF4G2, and NCOA3—that are linked to osteoblast maturation. Their findings also suggested that many genetic signals correlated with bone density might reflect health issues in other tissues, indicating a broader significance to bone health.

“Our hope is to further study these signals specifically in pediatrics and help identify which children are more likely to experience fractures, optimizing their bone health for life,” stated Struan F.A. Grant, Ph.D., Director of the Center for Spatial and Functional Genomics at CHOP.

Linking Genetics to Fracture Risk

The second study, published in the Journal of Bone and Mineral Research, employed a polygenic risk score called genetic quantitative ultrasound speed of sound (gSOS), previously used to assess fracture risk in adults. Researchers aimed to determine its applicability for children, utilizing data from two observational studies: the Bone Mineral Density in Childhood Study (BMDCS) and CHOP’s Center for Applied Genomics, covering over two decades.

The findings revealed that a higher gSOS score correlated with increased bone mineral density across multiple skeletal sites and a reduced likelihood of fractures. This is particularly noteworthy, as the study accounted for various factors, including sex, puberty stage, dietary calcium levels, height, weight, and body mass index (BMI), alongside potential fracture-causing accidents.

“Our study found that genetics represent a powerful component of bone density across the entire lifespan,” remarked Babette S. Zemel, Ph.D., Professor of Pediatrics at CHOP. “We were surprised to see that the polygenic risk score could accurately predict which patients were more likely to experience a fracture, even after considering normal childhood activities that often lead to broken bones.”

The implications of these studies suggest that early identification of genetic factors can significantly enhance bone health strategies in children. While maintaining a balanced diet and engaging in regular weight-bearing physical activities—such as sports like volleyball and basketball—are critical for bone health, these measures are especially beneficial even for those with a high genetic risk of fracture.

As researchers continue to delve into the genetic underpinnings of bone density, the hope is that this knowledge will lead to improved preventive measures and treatment options for young patients, ultimately supporting their long-term health and wellness.