Bones respond positively to external forces

The way for developing new therapies that may one day benefit patients suffering from bone fractures.

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When bones heal after a fracture, they don’t just grow randomly. Bone cells respond to external forces, and targeted mechanical loading during healing can make bones larger, denser, and more stable. Professor Ralph Müller’s team showed this in mice by using special plates to press healing bone parts together in a form of vibration therapy.

Scientists, including researcher Neashan Mathavan, emphasize that understanding how mechanical forces affect bones is crucial for developing new therapies. This research aims to heal fractures and prevent them, especially in older people with lower bone density. New treatments are needed to slow down bone deterioration in old age.

Mathavan, Müller, and their team studied which genes are active in healing bones. They used mice with broken thigh bones and supported the healing with vibration therapy, mapping gene activity with high spatial resolution. They combined this 3D gene activity atlas with data on mechanical forces using computer simulations, providing a detailed understanding of bone healing at a genetic level.

healed fracture point
Cross section of the healed fracture point of a mouse’s thigh bone. The researchers determined the gene activity in cells throughout the bone in high resolution. Each of the circles represents a specific gene, and the colour represents that gene’s activity. (Figure: Mathavan et al., Science Advances 2025)

ETH professor Müller said, “For each point in the bone, we now know what mechanical conditions exist there, where the bone is being formed and where the bone is being broken down.”

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The researchers found that specific genes are active in areas of bone under strong mechanical stress, helping to form the collagen matrix and promote bone mineralization. In contrast, genes that inhibit bone formation are inactive in these stressed areas.

The team plans to use these findings to develop new therapies to improve fracture healing and maintain bone strength, especially in older people. Their future research will focus on bone aging in mice. They noted that it may be possible to use drugs to target the desired genes, but vibration therapy might offer advantages with fewer side effects.

Journal Reference:

  1. Mathavan N, Singh A, Correia Marques F, Günther D, Kuhn GA, Wehrle E, Müller R: Spatial transcriptomics in bone mechanomics: Exploring the mechanoregulation of fracture healing in the era of spatial omics. Science Advances, 1 January 2025: doi: 10.1126/sciadv.adp8496
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