Background:​ Running is a popular form of exercise that more than 55 million Americans actively participate. Endurance running like marathon and half-marathon is getting increasingly popular among active runners. Although the effect of running is considered beneficial to bone health, the direct relationship between strains and strain gradients occurred during long distance running and bone changes is still not clear. Especially, given a high rate of injury associated with the first-time marathon, understanding the direct effect of strain stimuli on bone health is an important issue. Based on the previous studies, we hypothesized that the higher values of strain will induce bone adaptation more effectively and will lead to higher bone osteogenic changes. Since osteocytes sense shear stress caused by the interstitial fluid flow, which is created by the deformations, and regulate activities of osteoblasts and osteoclast that govern bone adaptation, we also hypothesized that the local strain gradient will create pressure differences within the interstitial fluid network and will increase fluid flow. Furthermore, due to that increased fluid flow, the regions with the higher strain gradient will experience a higher amount of bone adaptation. Thus, in this study, our purpose was to define the effect of the strains and strain gradients on bone changes within distal tibia, which is the most prone anatomical site to low risk stress fracture, during training for first-time marathon.

Methods:​ High-resolution and low-resolution computed tomographic (CT) images of the distal tibia were obtained before and after a self-selected training from runners who were actively training to participate in their first- time marathon in the next calendar year. The low resolution scan covered a 69.864 mm length of the distal end of the tibia while the high resolution CT scan covered a 9.02 mm region of the distal tibia. Using low resolution CT image based subject specific finite element (FE) models, the strains and strain gradients of the distal tibia at the instance of the peak ground reaction force (GRF) were calculated. The baseline and follow-up high resolution CT scans were used in high resolution peripheral quantitative CT (HRpQCT) analysis and the estimation of bone changes over the training period. Finally, the effect of strains and strain 8 | Pagegradients on the distal tibia bone changes was estimated based on the FE model driven strain values and HRpQCT analysis driven bone changes. We used a linear mixed model to define the relationship between strain values and bone changes in the distal tibia.

Results:​ The strain values that occurred during marathon training had significant effects on bone changes in the distal tibia. Particularly, the strain gradients showed a higher effect than the strains. In the cortical compartment, the strain gradients, which were calculated as a strain difference of a node from the surrounding nodes (Strain Gradient-1), affected the bone mineral density (BMD) negatively, and per 1000 με increase resulted in 2.123% decrease in the cortical BMD. The strain gradients, which were calculated as a strain difference of a node from the surrounding nodes normalized to distance to surrounding nodes (Strain Gradient-2), presented a positive effect on the cortical bone volume with a slope of 4.335% / 1000 με. In the trabecular compartment, the strain gradient-1 showed negative effects on the percent change in BMD and bone mineral density (BMC), whereas the strain gradient-2 showed positive effects on the percent change in BMD and BMC.

Conclusion:​ The linear mixed model analysis revealed a statistically significant (p < 0.05) relationship between strain gradients that occurred during running and distal tibia bone changes. The strains, biometrics, and initial parameters of bone did not show any significant effect on the bone changes. The connection between local strain environment and bone changes in the distal tibia investigated in this study is an important step to understand the mechanism of mechanically induced bone adaptation.