Preclinical mouse models for assessing axial compression of long bones during exercise.

The aim of this laboratory method is to describe two approaches for the investigation of bone responses to mechanical loading in mice in vivo. The first is running exercise, because it is easily translatable clinically, and the second is axial compression of the tibia, because it is precisely controllable. The effects of running exercise, and in general physical activity, on bone tissue have been shown to be both direct through mechanical loading (ground impact and muscle tension) and indirect through metabolic changes. Therefore, running exercise has been considered the most convenient preclinical model for demonstrating the general idea that exercise is good for bone health, either early in age for increasing peak bone mass or later in age by slowing down bone loss. However, numerous combinations of protocols have been reported, which makes it difficult to formulate a simple take-home message. This laboratory method also provides a detailed description of in vivo direct mechanical axial compression of the mouse tibia. The effects of mechanical loading depend on the force (strain), frequency, waveform and duration of application, and they range from bone anabolism with low bone remodeling, inducing lamellar bone accumulation, to bone catabolism with high bone remodeling, leading to microdamage, woven bone formation and bone loss. Direct in vivo loading models are extensively used to study mechanotransduction pathways, and contribute by this way to the development of new bone anabolism treatments. Although it is particularly difficult to assemble an internationally adopted protocol description, which would give reproducible bone responses, here we have attempted to provide a comprehensive guide for best practice in performing running exercise and direct in vivo mechanical loading in the laboratory.