ORIGINAL RESEARCH article
Front. Physiol.
Sec. Exercise Physiology
Volume 16 - 2025 | doi: 10.3389/fphys.2025.1587766
Load-bearing aerobic exercise prior to injury moderates systemic immunosuppression response to fracture
Provisionally accepted
- University of Oregon, Eugene, United States
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Bone fracture non-unions are common and often lead to costly revision surgeries, long-term patient pain and loss of function. Identifying fractures at-risk for non-union remains challenging due to an incomplete understanding of underlying mechanisms. Preclinical and clinical studies have shown that dysregulated immune responses are linked to impaired healing. These studies have also identified fracture characteristics, biologic factors, and lifestyle habits associated with a higher risk of poor healing. However, the impact of exercise history on the immune response to fracture remains underexplored. Load-bearing aerobic exercise is known to modulate properties of bone and systemic inflammation, suggesting that exercise history could influence post-fracture immune responses and healing outcomes. This preclinical study sought to determine if regular exercise pre-fracture affects the systemic immune response and healing outcomes. We hypothesized that pre-fracture treadmill running would attenuate immunosuppressive mediators—shown previously to correlate with poor healing—and improve bone regeneration compared to sedentary controls. Subjects that exercised before fracture had decreased post-fracture circulating immunosuppressive myeloid-derived suppressor cells and pain sensitivity, however there was no significant effect of prehabilitation on bone repair volume, defect bridging rate, or biomechanical properties.
Keywords: Prehabilitation, Exercise immunology, osteoimmunology, Bone Regeneration, preclinical
Received: 04 Mar 2025; Accepted: 13 Aug 2025.
Copyright: © 2025 Strait, Dewan, Williams, Guyer, Willett and Gulberg. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Robert E Gulberg, University of Oregon, Eugene, United States
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