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.

中文翻译：

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小梁骨适应的机械调节由局部体内环境控制，并且与加载频率呈对数关系


众所周知，循环机械负荷（而非静态机械负荷）对骨骼具有合成代谢作用。然而，描述加载频率和骨适应量之间关系的函数仍不清楚。本研究采用实验和计算相结合的方法，旨在研究小梁骨机械调节是否受局部体内环境中的机械信号控制并依赖于加载频率。具体来说，通过将活体微计算机断层扫描（micro-CT）成像与微有限元（micro-FE）分析相结合，我们监测了微结构以及体内机械环境[应变能量密度（SED）和小鼠尾椎在 4 周内分别以 2、5 或 10 Hz 的不同频率进行循环加载或静态加载的 SED 梯度]。局部组织水平上较高的 SED 值和 SED 梯度导致小梁骨形成的可能性增加，而小梁骨吸收的可能性降低。在所有负荷组中，与 SED 相比，SED 梯度在确定局部骨形成和骨吸收事件方面均优于 SED。与假加载和静态加载相比，循环加载诱导了正的净（重新）建模率，这主要是由于矿化表面的增加和侵蚀表面的减少。因此，骨体积分数在 2、5 和 10 Hz 下随时间增加（+15%、+21% 和 +24%，p ≤ 0.0001），而静态载荷导致骨体积分数下降（-9%， p ≤ 0.001）。此外，回归分析揭示了 4 周观察期内负荷频率与骨体积分数净变化之间的对数关系（R2 = 0.74）。 总之，这些结果表明，骨小梁适应受到局部体内环境中的机械信号的调节，此外，机械调节对数依赖于负载频率，低于某个阈值的频率具有分解代谢效应，而高于某个阈值的频率则具有合成代谢效应。因此，这项研究为更好地理解影响局部体内环境中小梁骨形成和吸收的机械信号提供了宝贵的见解。