VCU-led study suggests fatty liver disease may increase bone fracture risk
Researchers offer a target for more study: that bone formation might be compromised by a protein made by the liver.
October 07, 2026
According to the study, those diagnosed with metabolic dysfunction-associated steatotic liver disease (MASLD) had a 23% higher risk of bone fractures. (Getty Images)
By A.J. Hostetler
People with metabolic dysfunction-associated steatotic liver disease, commonly called fatty liver disease or MASLD, may face a higher risk of bone fractures, independent of obesity and other metabolic diseases, according to a Virginia Commonwealth University-led study.
MASLD is often linked to obesity, diabetes, high blood pressure and abnormal cholesterol levels. In some people, it worsens into metabolic dysfunction-associated steatohepatitis, or MASH, which causes liver inflammation and scarring.
“Understanding the connection between the liver and bone could help identify patients who need earlier assessment of bone strength,” said Arun Sanyal, M.D., a study co-author and director of VCU’s Stravitz-Sanyal Institute for Liver Disease and Metabolic Health. “It may also guide the development of safer treatments for MASLD and MASH.”
People with fatty liver disease are often older, which already raises fracture risk. Some current and experimental MASH treatments may also cause loss of muscle and other lean body mass, increasing the risk of falls.
Published in Nature’s Communications Biology journal, the study examined medical records from more than 3.8 million people with metabolic conditions. Researchers compared people with MASLD with people who had similar metabolic conditions, but no recorded MASLD.
People with MASLD had a 23% higher risk of fractures. The increase was greatest among adults older than 40. After age 50, people with MASLD also had a higher risk of fractures caused by weakened bones.
“Our findings show that liver disease, in humans, may affect bone health beyond the effects of diabetes, obesity and other metabolic conditions. Using animal models, we found this was mostly driven by slowing the formation of new bone,” said the study’s lead author, Galen M. Goldscheitter, an M.D./Ph.D. student at VCU’s School of Medicine and the College of Engineering’s Department of Biomedical Engineering.
Goldscheitter completed his Ph.D. thesis on skeletal fragility and MASLD at VCU in May under the supervision of Henry J. Donahue, Ph.D., the study’s senior author and a VCU biomedical engineering professor. Sanyal was among his doctoral advisors.
Studying the liver-bone connection
The researchers also studied male mice that developed MASH after eating a high-fat, high-sugar diet. The mice developed thinner, weaker outer bones, which help give the skeleton strength. Their inner, spongy bones showed no major changes. They also had fewer osteoblasts, the cells that build new bone. Cells that break down bone were slightly more active.
The diseased mice also had lower levels of liver-produced substances that support bone growth, including an enzyme related to vitamin D, and higher levels of other substances that may interfere with bone formation.
One of these substances was FGF21, a protein made by the liver that helps control how the body uses sugar and fat. The researchers believe high FGF21 levels may slow the growth of new bone and weaken bones, but more research is needed to confirm how the protein affects bone health.
“This study highlights the need for additional studies to better understand how liver disease affects bone health. This will be critical for the development of therapies for those most at risk of fractures,” Sanyal said.
Implications for patient care
The findings could help doctors better understand bone risks in people with liver disease and raise questions about whether MASLD treatments may affect fracture risk.
However, researchers said further studies are needed to confirm the human findings and determine whether fracture risk changes with disease severity. Future research should examine the roles of physical activity, vitamin D, calcium intake, medications and hormone levels, they said.
The study had several limitations. The human analysis relied on past medical records that did not capture every factor affecting bone health. The animal study included only male mice because previous research found that female mice do not develop bone disease alongside MASLD. Yet women with MASLD have a higher fracture risk than women without the disease, highlighting an important area for future research.
Other VCU researchers involved in the study included gastroenterology fellow Vinay Jahagirdar, M.D.; Mulugeta Seneshaw and Faridoddin Mirshahi of the Stravitz-Sanyal Institute; and Evan Buettmann, Ph.D., of the Department of Biomedical Engineering. Researchers from Georgia Tech, the University of Virginia, Yale University and the University of California at Davis also contributed.
VCU places the ethical treatment of animals as a primary responsibility and the founding principal of its Animal Care and Use Program. Overseeing this program campuswide, ACUP ensures humane and appropriate animal care and use by providing for the animals' husbandry and veterinary care, and monitoring their use by all VCU animal users. The policy is available here.
