Abstract
It is well-established that cyclic, but not static, mechanical loading has anabolic effects on bone. However, the function describing the relationship between the loading frequency and the amount of bone adaptation remains unclear. Using a combined experimental and computational approach, this study aimed to investigate whether trabecular bone mechano-regulation is controlled by mechanical signals in the local in vivo environment and dependent on loading frequency. Specifically, by combining in vivo micro-computed tomography (micro-CT) imaging with micro-finite element (micro-FE) analysis, we monitored the changes in microstructural as well as the mechanical in vivo environment [strain energy density (SED) and SED gradient] of mouse caudal vertebrae over 4 weeks of either cyclic loading at varying frequencies of 2, 5, or 10 Hz, respectively, or static loading. Higher values of SED and SED gradient on the local tissue level led to an increased probability of trabecular bone formation and a decreased probability of trabecular bone resorption. In all loading groups, the SED gradient was superior in the determination of local bone formation and resorption events as compared to SED. Cyclic loading induced positive net (re)modeling rates when compared to sham and static loading, mainly due to an increase in mineralizing surface and a decrease in eroded surface. Consequently, bone volume fraction increased over time in 2, 5, and 10 Hz (+15%, +21% and +24%, p ≤ 0.0001), while static loading led to a decrease in bone volume fraction (−9%, p ≤ 0.001). Furthermore, regression analysis revealed a logarithmic relationship between loading frequency and the net change in bone volume fraction over the 4 week observation period (R2 = 0.74). In conclusion, these results suggest that trabecular bone adaptation is regulated by mechanical signals in the local in vivo environment and furthermore, that mechano-regulation is logarithmically dependent on loading frequency with frequencies below a certain threshold having catabolic effects, and those above anabolic effects. This study thereby provides valuable insights toward a better understanding of the mechanical signals influencing trabecular bone formation and resorption in the local in vivo environment.
Highlights
It is well-established that cyclic, but not static loading has anabolic effects on bone (Hert et al, 1971; Lanyon and Rubin, 1984; Turner et al, 1995; Robling et al, 2001)
In order to investigate the effects of varying loading frequencies on bone adaptation, we used an in vivo micro-CT approach (Lambers et al, 2011) to monitor bone adaptation of the sixth caudal vertebrae of C57BL/6J mice subjected to a 4week loading regime of either sham (0 N), 8 N static or 8 N cyclic loading with frequencies of 2, 5, or 10 Hz, respectively
In line with previous studies using the tail loading model (Lambers et al, 2011, 2015), cyclic loading over 4 weeks led to an increase in BV/TV, which was driven by the thickening of individual trabeculae rather than a prevention of loss in trabecular number
Summary
It is well-established that cyclic, but not static loading has anabolic effects on bone (Hert et al, 1971; Lanyon and Rubin, 1984; Turner et al, 1995; Robling et al, 2001). The exact relationship between loading frequency and bone (re)modeling and bone adaptation remains unclear While both experimental (Rubin and Mcleod, 1994; Turner et al, 1994; Hsieh and Turner, 2001) and theoretical studies (Turner, 1998; You et al, 2001) have suggested a dose-response relationship such that bone formation increases with higher loading frequencies, Warden and Turner have shown this relationship to be non-linear (Warden and Turner, 2004) using an axial loading model of mouse ulnae. As frequency effects have been shown to vary depending on the anatomical region investigated (Zhang et al, 2007), the optimal frequency must be identified for every specific loading model
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
