Osteoporosis is one of the most common age-related bone diseases, affecting millions of people worldwide and increasing the risk of fractures, disability, and reduced quality of life. Although current treatments can slow bone loss or stimulate new bone formation, many anabolic therapies rely on biologic drugs that are costly and require regular injections. Finding more accessible treatments that encourage the body to build new bone remains a major challenge.

A new study published online on July 6, 2026, in Volume 14 of the journal Bone Research suggests that blocking the Axl - a receptor tyrosine kinase involved in cell signaling - may offer a new way to promote bone formation. The study was conducted by researchers led by Dr. Mubashir Ahmad, who initiated the project with Prof. Dr. Jan Tuckermann from the Institute of Molecular Endocrinology and Physiology, Ulm University, Germany. After completing his graduation, Dr. Ahmad continued the work as a postdoctoral researcher with Prof. Dr. Anita Ignatius at the Institute of Orthopedic Research and Biomechanics, Ulm University Hospital, Germany, in strong cooperation with the Tuckermann Lab. . The researchers found that inhibiting Axl enhances the activity of bone-forming cells (osteoblasts) and increases bone mass in mice. These findings highlight Axl as a promising therapeutic target for the treatment of osteoporosis and other bone-related disorders.

"Our findings identify Axl as a promising therapeutic target for osteoporosis and other bone-related disorders," says Dr. Ahmad. "By targeting this receptor, we were able to stimulate bone formation in preclinical models, providing a foundation for developing new anabolic therapies."

To uncover new regulators of bone formation, the researchers first performed a kinome-wide RNA interference (RNAi) screen, a technique that systematically switches off genes to identify their functions. Screening hundreds of protein kinases, they identified Axl as a previously unrecognized regulator of osteoblasts, the cells responsible for building new bone. The team then confirmed these findings by reducing Axl activity using both genetic approaches and a small-molecule inhibitor called BGB324, before evaluating its effects in bone-forming cells grown in the laboratory and in mice.

The results consistently showed that blocking Axl promoted the maturation of osteoblasts and increased their ability to produce mineralized bone tissue. Mice treated with BGB324 developed greater bone mass in the long bones and vertebrae because of increased bone formation. The treatment also increased the number of osteocytes, suggesting that Axl inhibition supports normal bone development. Importantly, the treatment was well tolerated in mice, with no evidence of significant toxicity during the study period.

To understand how Axl influences bone formation, the researchers examined the underlying molecular pathways. They found that blocking Axl increased the activity of interferon-stimulating gene 15, a protein that helped activate signals needed for osteoblast maturation. "In simple terms, inhibiting Axl removed a molecular signal that normally restrains bone-forming cells, allowing them to mature and build bone more effectively. This newly identified pathway provides fresh insight into how bone formation is regulated," says Prof. Dr. Tuckermann.

Interestingly, BGB324 has already been investigated in clinical trials as a treatment for certain cancers because Axl plays important roles in tumor growth and immune regulation. Although the current findings are based on in vitro and in vivo studies, the availability of an existing Axl inhibitor could help support future research into treatments for osteoporosis.

"Our study provides new insight into the molecular mechanisms that regulate osteoblast differentiation and bone formation," says Prof Dr. Ignatius. "Further studies are needed to determine whether targeting Axl can be translated into a safe and effective treatment for osteoporosis and other bone disorders."

Together, these findings identify Axl as a previously unrecognized regulator of bone formation and suggest that blocking its activity could represent a new strategy for treating osteoporosis. Further clinical research will be needed to determine whether this approach can safely improve bone health in people.

Source:

Journal reference:

Ahmad, M., et al. (2026). Inhibition of AXL receptor tyrosine kinase increases osteoblast function and bone mass. Bone Research. DOI: 10.1038/s41413-026-00554-0. https://www.nature.com/articles/s41413-026-00554-0