June 16, 2014

Factor impacts bone toughness

The factor ATF4 has a role in the toughness of bone and its resistance to fracture, suggesting new therapeutic targets.


The increased risk of bone fractures with aging is not solely related to loss in bone mineral density (bone strength). Bones also lose toughness and the capacity to resist crack growth with age.

The transcription factor ATF4 is important to the maturation of bone-building osteoblast cells and may have a role in bone toughness. Jeffry Nyman, Ph.D., and colleagues compared bones from young and mature mice with and without ATF4. Femurs from mice missing ATF4 were brittle with reduced fracture toughness compared to control mice, but there were no differences in bone material strength, tissue hardness and mineral density. Tests using Raman spectroscopy suggested that bone matrix organization in bones missing ATF4 may contribute to the brittleness.

The findings, reported in the May issue of the journal Bone, suggest that loss of ATF4 lowers resistance to fracture through changes in the bone matrix, not deficits in strength/mineral density, and may suggest new therapeutic targets to generate tough bone tissue with high resistance to fracture.

This research was supported by the Department of Veterans Affairs through the Office of Research and Development.

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