New research from the Ludwig Boltzmann Institute for Osteology is challenging conventional understanding of heart failure, revealing a surprising link between bone metabolism and cardiovascular health. A study published this week in *npj Metabolic Health and Disease* identifies Fibroblast Growth Factor-23 (FGF23), a hormone traditionally associated with phosphate regulation [[1]], as a key regulator of energy use in stressed hearts. The findings suggest a novel therapeutic target for a condition affecting millions worldwide and may clarify how existing drugs like SGLT2 inhibitors exert their protective effects.
A hormone originating in bone has been discovered to regulate energy metabolism in a stressed heart, according to a new study from the Ludwig Boltzmann Institute (LBI) for Osteology.
The research, published in npj Metabolic Health and Disease, reveals previously unknown connections between bone, kidney, and heart function, potentially opening avenues for new heart failure therapies. Understanding the complex interplay between these systems is crucial for improving cardiovascular health.
Led by Reinhold Erben at the LBI for Osteology, the study identified Fibroblast Growth Factor-23 (FGF23) as a key regulator of energy use within the heart. The research, which began approximately seven years ago at the University of Veterinary Medicine Vienna and continued at the LBI for Osteology, demonstrates that FGF23 acts as a central metabolic regulator in a hypertrophic heart – a heart that has enlarged due to being forced to work harder than normal. The findings may explain why elevated FGF23 levels, particularly in patients with kidney disease, are linked to a significantly increased risk of heart failure and mortality.
Shifting Energy Sources in a Stressed Heart
Researchers investigated the role of FGF23 in hypertrophic hearts by selectively suppressing its activity, essentially “switching off” the hormone. The results showed that without FGF23, the heart experienced less damage despite being under stress. Scarring was reduced, blood pressure lowered, and the heart muscle altered its primary energy source. Instead of relying mainly on glucose (sugar), the heart increased its use of fat for fuel. This suggests that the hormone, originally produced in bone, functions as a metabolic switch in the overloaded heart. These fundamental changes in energy metabolism were further confirmed in a related study published in Kidney International.
The LBI for Osteology’s findings offer promising new therapeutic possibilities. The observed shift in the heart’s energy metabolism mirrors the mechanism of action of SGLT2 inhibitors, a class of drugs known to protect the heart in both heart failure and diabetes. While these medications effectively reduce the risk of severe heart complications, the reason for their beneficial effects has remained largely unclear. This new research could contribute to a better understanding of how SGLT2 inhibitors work.
“Our data shows for the first time that FGF23 controls energy metabolism in the hypertrophic heart,” said Reinhold Erben, research group leader at the LBI for Osteology. “If we can successfully block this signaling pathway, we may be able to prevent the heart from changing and losing strength due to chronic overload.”
Future Research: Decoding the Signal Pathway
Researchers now plan to further unravel the molecular signaling pathway of FGF23 in the heart to develop new therapies for heart failure and hypertrophic cardiomyopathy. The project highlights the importance of basic, hypothesis-driven research. “Unexpected discoveries like this can be the starting point for urgently needed medical innovations,” Erben concluded.
About Reinhold Erben
Reinhold G. Erben studied veterinary and human medicine at the University of Munich. From 2006 to 2009, he served as President of the International Society of Bone Morphometry and was a member of the Board of Trustees of the Austrian Science Fund (FWF) between 2005 and 2014. He is an inventor of several patents and has published more than 160 scientific publications. His research focuses on the hormonal regulation of mineral and bone metabolism and the molecular mechanisms of bone remodeling.
Publication:
Deletion of cardiacfibroblast growthfactor-23 beneficially impacts myocardialenergy metabolism in left ventricularhypertrophy. npj Metabolic Health and Disease 3, 42 (2025).
https://doi.org/10.1038/s44324-025-00087-w
More information about the LBI for Osteology: https://osteologie.lbg.ac.at/
