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Fatigue as the missing link between bone fragility and fracture

Abstract

The prevention of fragility fractures in bone—pathologic fractures resulting from daily activity and mostly occurring in the elderly population—has been a long-term clinical quest. Recent research indicating that falls in the elderly might be the consequence of fracture rather than its cause has raised fundamental questions about the origin of fragility fractures. Is day-to-day cyclic loading, instead of a single-load event such as a fall, the main cause of progressively growing fractures? Are fragility fractures predominantly affected by bone quality rather than bone mass, which is the clinical indicator of fracture risk? Do osteocytes actively participate in the bone repair process? In this Perspective, we discuss the central role of cyclic fatigue in bone fragility fracture.

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Fig. 1: Non-enzymatic crosslinking stiffens collagen fibrils.
Fig. 2: Repair or acceleration of the formation of fatigue cracks.

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Acknowledgements

We acknowledge financial support from the Swiss National Science Foundation grants PBELP2_141095 and P300P2_167583 (C.A.), from NIH-NIDCR R01 DE019284 (T.A.) and from DOD PRORP OR130191 (T.A.). R.O.R. was supported through the Mechanical Behavior of Materials Program (KC13) at the Lawrence Berkeley National Laboratory by the US Department of Energy, Office of Science, Office of Basic Energy Sciences, Materials Sciences and Engineering Division, under contract no. DE-AC02-05CH11231.

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C.A., T.A. and R.O.R. conceived the project, and wrote and edited the manuscript. C.A. prepared the figures. V.A.S. and D.P.P. edited and advised on the manuscript.

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Correspondence to Claire Acevedo.

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Acevedo, C., Stadelmann, V.A., Pioletti, D.P. et al. Fatigue as the missing link between bone fragility and fracture. Nat Biomed Eng 2, 62–71 (2018). https://doi.org/10.1038/s41551-017-0183-9

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