Trabecular bone recovers from mechanical unloading primarily by restoring its mechanical function rather than its morphology

Abstract

Upon returning to normal ambulatory activities, the recovery of trabecular bone lost during unloading is limited. Here, using a mouse population that displayed a large range of skeletal susceptibility to unloading and reambulation, we tested the impact of changes in trabecular bone morphology during unloading and reambulation on its simulated mechanical properties. Female adult mice from a double cross of BALB/cByJ and C3H/HeJ strains (n = 352) underwent 3 wk of hindlimb unloading followed by 3 wk of reambulation. Normally ambulating mice served as controls (n = 30). As quantified longitudinally by in vivo μCT, unloading led to an average loss of 43% of trabecular bone volume fraction (BV/TV) in the distal femur. Finite element models of the μCT tomographies showed that deterioration of the trabecular structure raised trabecular peak Von-Mises (PVM) stresses on average by 27%, indicating a significant increase in the risk of mechanical failure compared to baseline. Further, skewness of the Von-Mises stress distributions (SVM) increased by 104% with unloading, indicating that the trabecular structure became inefficient in resisting the applied load. During reambulation, bone of experimental mice recovered on average only 10% of its lost BV/TV. Even though the addition of trabecular tissue was small during reambulation, PVM and SVM as indicators of risk of mechanical failure decreased by 56% and 57%, respectively. Large individual differences in the response of trabecular bone, together with a large sample size, facilitated stratification of experimental mice based on the level of recovery. As a fraction of all mice, 66% of the population showed some degree of recovery in BV/TV while in 89% and 87% of all mice, PVM and SVM decreased during reambulation, respectively. At the end of the reambulation phase, only 8% of the population recovered half of the unloading induced losses in BV/TV while 50% and 49% of the population recovered half of the unloading induced deterioration in PVM and SVM, respectively. The association between morphological and mechanical variables was strong at baseline but progressively decreased during the unloading and reambulation cycles. The preferential recovery of trabecular micromechanical properties over bone volume fraction emphasizes that mechanical demand during reambulation does not, at least initially, seek to restore bone's morphology but its mechanical integrity. © 2014 Elsevier Inc. All rights reserved. IntroductionLoss of weight-bearing in skeletal extremities reduces tissue mass as mechanical loads provide critical anabolic and anti-catabolic signals [1][2][3]. The accompanying deterioration of bone's estimated [4] and actual [5] mechanical properties, combined with decreases in muscle strength [6,7] and postural stability [8] increase the risk of traumatic and non-traumatic fractures, particularly upon returning to regular weight bearing activities [9][10][11]. Daily bouts of exercise [12] or highfrequency motions [13][14][15] can partially alleviate the reduction in bone quant...

Quantitative trait loci that modulate trabecular bone's risk of failure during unloading and reloading

“…It is therefore not surprising that QTLs identified for stiffness and peak stress values at baseline overlapped with QTLs previously identified for trabecular morphology, in particular trabecular bone volume fraction [29]. Upon removal of habitual weight bearing activities, associations between morphology and mechanical properties become significantly weaker as shown in our companion article [65]. That risk of mechanical failure, the most important clinical outcome variable, is more directly associated with bone stiffness and the heterogeneity of mechanical stress distributions [28,46], rather than morphology, emphasizes the importance of identifying the underlying genetic regulators.…”

“…With mice under isoflurane, the left and right metaphyses of the distal femur were μCT scanned (vivaCT 40, Scanco Medical, Switzerland) at a voxel size of 17.5 μm as described in more detail in the companion article [65]. The selected voxel size was small enough to exceed the minimal recommended voxel size for assessing bone's microstructure in rodents with μCT [32].…”

“…The finite element (FE) model that evaluated mechanical parameters of trabecular bone is discussed in our companion article [65]. Briefly, μCT voxels used to describe the morphologic variables [29] were directly converted into 17.5 μm mechanical elements in the FE model.…”

“…Trabecular bone's simulated mechanical properties, and changes in them during altered levels of weightbearing, are presented in detail in our companion article [65]. Here, we sought to identify QTLs for outcome variables that determine bone's mechanical integrity prior to and during unloading and reambulation.…”

Disorder of Iron Metabolism Inhibits the Recovery of Unloading-Induced Bone Loss in Hypomagnetic Field

“…In the distal tibia of 13 cosmonauts, cortical size and density eventually recovered completely, whereas cortical porosity and trabecular bone was only partially restored after returning to Earth . An animal experiment also showed that in female adult mice subjected to HLU for 3 weeks, and then reloaded for 3 weeks, 66% of mice showed partial of recovery in bone volume/total volume (BV/TV) . At present, most people believe that the recovery of bone mass after returning to the ground is due to the astronauts re‐adapting to Earth's gravity.…”