The Role of the Loading Condition in Predictions of Bone Adaptation in a Mouse Tibial Loading Model

Abstract

The in vivo mouse tibial loading model is used to evaluate the effectiveness of mechanical loading treatment against skeletal diseases. Although studies have correlated bone adaptation with the induced mechanical stimulus, predictions of bone remodeling remained poor, and the interaction between external and physiological loading in engendering bone changes have not been determined. The aim of this study was to determine the effect of passive mechanical loading on the strain distribution in the mouse tibia and its predictions of bone adaptation. Longitudinal micro-computed tomography (micro-CT) imaging was performed over 2 weeks of cyclic loading from weeks 18 to 22 of age, to quantify the shape change, remodeling, and changes in densitometric properties. Micro-CT based finite element analysis coupled with an optimization algorithm for bone remodeling was used to predict bone adaptation under physiological loads, nominal 12N axial load and combined nominal 12N axial load superimposed to the physiological load. The results showed that despite large differences in the strain energy density magnitudes and distributions across the tibial length, the overall accuracy of the model and the spatial match were similar for all evaluated loading conditions. Predictions of densitometric properties were most similar to the experimental data for combined loading, followed closely by physiological loading conditions, despite no significant difference between these two predicted groups. However, all predicted densitometric properties were significantly different for the 12N and the combined loading conditions. The results suggest that computational modeling of bone’s adaptive response to passive mechanical loading should include the contribution of daily physiological load.

Therapeutic Efficacy and Safety of Osteoinductive Factors and Cellular Therapies for Long Bone Fractures and Non-Unions: A Meta-Analysis and Systematic Review

“…Recent findings have also detected links between induction of endosteal progenitors and mechanical loading-induced growth factors released from osteoblastic cells [80]. As tibial bones receive increased axial loading [81], we can assume that these benefit the most from application of osteogenic factors after fracture.…”

“…Mechanical loading is a significant factor of bone remodelling and the absence of mechanical signals was accompanied by increased bone resorption and reduced bone formation [77][78][79][80]. Furthermore, mechanical strain increased the secretion of chemokines and the recruitment of MSCs to bone surface, promoting bone formation [81]. Recent findings have also detected links between induction of endosteal progenitors and mechanical loading-induced growth factors released from osteoblastic cells [80].…”

Combining PTH(1-34) and mechanical loading has increased benefit to tibia bone mechanics in ovariectomised mice

“…This approach, applied within a longitudinal study design 41 , has contributed to a substantial reduction in the number of animals used herein than is typically used in the preclinical assessment of antiosteoporotic treatment strategies, a fundamental step towards the 3Rs (replacement, re nement and reduction of the usage of animals in research) 12 . Moreover, the longitudinal data has been essential to inform mechanistic models of bone remodeling e.g., references 34,42,43 .…”

Using Finite Element Modeling in Bone Mechanoadaptation

“…FE models allow estimation of the mechanical environment within a region of interest [ 33 , 42 ] that can be correlated to areas of bone adaptation [ 31 , 38 , 41 ]. Recently, mechanical environments have been compared between males and females [ 51 ], after ovariectomy [ 52 , 53 ], after pharmaceutical treatment [ 54 ], and with genetic modifications [ 55 , 56 •].…”

“…change in structure or modulus). Typically remodeling algorithms use a mechanoadaptive theory [ 57 , 66 , 67 ]: when the mechanical signal of interest is above/below a certain threshold, bone formation/resorption is implemented according to the proposed algorithm [ 53 , 68 ••, 69 ]. Studies have also implemented a lazy zone in which no formation or resorption occurs [ 63 , 70 •, 71 , 72 •].…”