Research into the mechanisms underlying bone growth rate change in young mice is providing critical information on factors that affect bone growth and mineral accrual in children, including the profound effects of corticosteroid use on bone aging and fracture risk in children and young adults.1
“Adolescence is a critical period for optimizing bone growth and mineral accrual,” says Mei Wan, PhD, professor of Orthopaedic Surgery at Johns Hopkins University School of Medicine, Baltimore, Maryland. “During childhood, those with genetic bone disorders or chronic diseases have bone growth and mineral accrual that are often compromised and lead to bone loss, osteoporosis, and a high rate of bone fracturing.”
One such factor contributing to this loss of bone, osteoporosis, and bone fracturing in children is the use of glucocorticoids to treat chronic inflammatory childhood illnesses such as rheumatoid arthritis, Crohn disease, nephrotic syndrome, acute lymphoblastic leukemia, and rarer conditions such as muscular dystrophy.
Glucocorticoid use is the most common cause of secondary osteoporosis in children, and Wan highlights that 6% to 10% of children and adolescents started on high-dose, long-term corticosteroid therapy will develop osteoarthritis, and between 29% to 45% of children already on glucocorticoid therapy already have it.2
In addition, she points out that epidemiologic data show that long-term glucocorticoid therapy is associated with a 34% prevalence of fracture in children and young adults.
“Even though it is known that glucocorticoids adversely affect the skeleton, I think sometimes pediatricians neglect focusing on the bones in children until there is a bone fracture,” says Wan. “For children who use long-term glucocorticoids, especially at high doses, they need guidance on bone health to offset the adverse effects of glucocorticoids.”
As the lead investigator of the study that looked at the mechanisms underlying bone growth and aging in young mice, Wan emphasizes that what she and her colleagues found sheds light on potential new therapies to treat secondary pediatric osteoporosis, for whom current therapies with frontline bisphosphonates are limited at best.
Mechanisms of bone growth change
Because of the importance of bone growth in adolescence on bone mass and strength, Wan and her colleagues at Johns Hopkins Medicine wanted to better understand the mechanisms underlying how bone cells change during adolescence and the regulatory mechanisms underlying these changes.
To do this, they focused on a region in long bones (legs and arms) that sits underneath the growth plate on either end of the long bone. Called the primary spongiosa, this region of rich bone precursor cells supports bone growth by containing the blood vessels and mesenchymal stem cells (MSCs) that mature into bone-forming osteoblasts.2
Building on what is already known about bone growth in adolescence—that is, long bones rapidly elongate during adolescence and taper off in later puberty primarily driven by the division of (or lack of) cartilage cells in the growth plate—they questioned whether the primary spongiosa contributed to changes in the growth rate of bones and mineral accrual.