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Innovations for Children with Steroid-Induced Osteoporosis

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As a pediatric endocrinologist in the Department of Orthopaedic Surgery, Janet Crane is well-equipped to deal with complex cases. “I often work with patients whose conditions are initially a giant question mark,” says Crane. “Primarily, I see kids with chronic illnesses who have secondary forms of osteoporosis. This may be a complication of an underlying disease or a medication-related complication.”

Many of Crane’s patients have steroid-induced osteoporosis, and approximately 1 in 6 have Duchenne muscular dystrophy. Although steroids can prolong life expectancy for patients with this disorder, they can also lead to bone loss, osteoporosis and fractures. Crane works with families to make the best treatment decisions for their children, weighing the benefits of steroid treatment against the adverse effects.

In addition to her clinical work, Crane conducts research using young mice with steroid-induced osteoporosis to learn how to maximize the benefit of steroids while minimizing damage to growing bone. “Mouse models usually focus on the adult skeleton, so there is a huge gap in knowledge about the effects of different steroid doses on a growing child’s skeleton,” Crane explains. To create a model for studying pediatric bone health, Crane and her team inject glucocorticoids daily into young mice of different ages and adjust the dosage based on their growth.

“To extrapolate mouse findings to humans, we have to ensure our mouse models mimic the complications seen clinically. We started working on the model four to five years ago,” Crane says. Basing the glucocorticoid dose on body size rather than weight has resulted in a model that demonstrates both growth impairment and osteoporosis. Her team has published a paper based on the model, and additional studies are ongoing. “The main questions we are now exploring are: What are the signaling molecules that are disrupted in the bone by the glucocorticoids, and how can we manipulate them with other medications? Should we continue to use the osteoporosis medications currently on the market, or do we shift our focus to new drugs being developed?”

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Crane is uniquely positioned to understand the needs of her patients. “As a pediatrician, I understand that this dose may need to be adjusted for disease control,” she says. “As an endocrinologist, I can interpret this dose relative to what the body should normally be making and I understand how a high dose of steroids can cause complications particularly on the skeleton.”

With NIH funding, Crane collects patient specimens to study bone cells and gene expression in children for whom chronic steroid treatment leads to osteoporosis versus healthy children or those for whom the same treatment does not lead to fractures. “We are looking for a biomarker in the blood to predict risk of fracture in children taking steroids so we can use it as a way to make the diagnosis of osteoporosis earlier, prior to a fracture and to monitor response to treatment,” she explains.

Crane’s research is an example of how Johns Hopkins researchers target gaps in medical knowledge while addressing the needs of individual patients. “This is what Hopkins is,” says Crane. “Our specialized knowledge lets us develop the most personalized plan that makes the most scientific sense.”

Learn more about research in the Department of Orthopaedic Surgery in the Orthopaedic Surgery Archives.


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