Study explores musculoskeletal effects of GLP-1s in adolescent females

It’s estimated that for every 100 pounds lost while taking a GLP-1 receptor agonist, 30 of those pounds are lean mass. For females—more prone to degenerative musculoskeletal conditions as they age—this poses a potential risk of complications, including osteoporosis and fracture, later in life.

“There is a critical need to determine, for this population in particular, the degree to which lean mass loss is occurring—whether it’s muscle loss, bone loss or both—and to quantify it to fully understand the issues facing these patients,” said Dr. DeBosch, co-division chief of pediatric gastroenterology (GI) at Riley Children’s. “We hope our findings will help develop next-generation weight-loss medications that don’t initiate lean mass loss, or that we can use this knowledge to direct the proper use of these drugs to ensure this generation of adolescent females receives optimal care to protect their future health.”

A National Institutes of Health-funded physician-scientist known for his research on metabolic dysfunction-associated steatotic liver disease (MASLD) and intermittent fasting, Dr. DeBosch is collaborating on the study with Rachel Surowiec, PhD, assistant professor of biomedical engineering in the Purdue University College of Engineering. Specifically, the project focuses on identifying imaging biomarkers of musculoskeletal risk and resilience through AI-driven radiomics in adolescent females undergoing semaglutide drug treatment for obesity. The research team is using machine learning to assess short-term musculoskeletal changes and identify features associated with risk or resilience in baseline bone density and structure scans of patients to provide key insight into the musculoskeletal consequences of rapid weight loss.

Internally funded through a joint program between Indiana University School of Medicine and the Purdue College of Engineering, the study highlights the strengths of the research environment at Riley Children’s and IU School of Medicine.

“The key to successfully conducting cutting-edge research is the soil in which we sit,” said Dr. DeBosch, an American Society for Clinical Investigation member who was recently elected a fellow in basic and clinical research of the American Gastroenterological Association. "The collaborative environment and robust support for Riley and the Wells center (Herman B Wells Center for Pediatric Research) from Indiana’s health and life sciences community has been instrumental, not just to my own research program, but for many others walking the halls here."

In addition to research collaborations with Purdue and industry partners that include Eli Lilly and Company, Dr. DeBosch said that Riley GI researchers benefit from a wealth of university-based and local resources. For example, his colleague Steven Steiner, MD, a national leader in treating children with inflammatory bowel disease, is collaborating with Jiang Bian, an IU School of Medicine partner also affiliated with the Regenstrief Institute on AI-driven modeling of serum metabolomics to predict patient response to standard-of-care IBD drugs.

Since joining Riley Children’s and relocating his research lab to IU School of Medicine in July 2024, Dr. DeBosch has focused on expanding the pediatric GI division’s basic and translational science portfolio. Transplant hepatologist and researcher Abigail Russi, MD, PhD, who studies immune regulation in inflammatory GI and liver disease, joined the division in 2025.

Most recently, Dr. DeBosch has focused on circadian metabolic control related to the linkage between obesity and metabolic disorders, including Type 2 diabetes, MASLD and cardiovascular disease. In research studying the metabolic effects of time-restricted feeding (TNF), closely associated with the circadian clock function in the liver, Dr. DeBosch and his team demonstrated that Period 1 (Per1), a circadian gene, mediates appropriate fuel selection during acute fasting in males and females. Hypothesizing that Per1 in liver cells contributes to long-term adaptations to repeated time-restricted feeding (TRF), the team also investigated how Per1 in the liver interacts with time-restricted feeding to protect against diet-induced obesity in males and females.

“GLP-1s are good drugs, and really good if you have fatty liver disease, but not everyone loses weight in response to these drugs,” said Dr. DeBosch. “Our research intends to inform future therapy, toward precision medicine, which would fill the gap for people who have circadian metabolic dysregulation, by answering questions about how we select and use the right fuel at the right time during fasting.”

Learn more

Check out the Gastroenterology section of the latest Riley Children’s Health annual report for more information about treatment, programs, novel procedures and research.