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Distal radius microstructure and finite element bone strain are related to site-specific mechanical loading and areal bone mineral density in premenopausal women.

ABSTRACT: While weight-bearing and resistive exercise modestly increases aBMD, the precise relationship between physical activity and bone microstructure, and strain in humans is not known. Previously, we established a voluntary upper-extremity loading model that assigns a person's target force based on their subject-specific, continuum FE-estimated radius bone strain. Here, our purpose was to quantify the inter-individual variability in radius microstructure and FE-estimated strain explained by site-specific mechanical loading history, and to determine whether variability in strain is captured by aBMD, a clinically relevant measure of bone density and fracture risk. Seventy-two women aged 21-40 were included in this cross-sectional analysis. High resolution peripheral quantitative computed tomography (HRpQCT) was used to measure macro- and micro-structure in the distal radius. Mean energy equivalent strain in the distal radius was calculated from continuum finite element models generated from clinical resolution CT images of the forearm. Areal BMD was used in a nonlinear regression model to predict FE strain. Hierarchical linear regression models were used to assess the predictive capability of intrinsic (age, height) and modifiable (body mass, grip strength, physical activity) predictors. Fifty-one percent of the variability in FE bone strain was explained by its relationship with aBMD, with higher density predicting lower strains. Age and height explained up to 31.6% of the variance in microstructural parameters. Body mass explained 9.1% and 10.0% of the variance in aBMD and bone strain, respectively, with higher body mass indicative of greater density. Overall, results suggest that meaningful differences in bone structure and strain can be predicted by subject characteristics.

SUBMITTER: Mancuso ME

PROVIDER: S-EPMC6021193 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Isolating the role(s) of microstructural pathological features in affecting diastolic filling is important in developing targeted treatments for heart diseases. We developed a microstructure-based constitutive model of the myocardium and implemented it in an efficient open-source finite element modeling framework to simulate passive inflation of the left ventricle (LV) in a representative 3D geometry based on experimentally measured muscle fiber architecture. The constitutive model was calibrated using previous tissue-level biaxial mechanical test data derived from the canine heart and validated with independent sets of measurements made at both the isolated constituent and organ level. Using the validated model, we investigated the load taken up by each tissue constituent and their effects on LV passive inflation. The model predicts that the LV compliance is sensitive to the collagen ultrastructure, specifically, the collagen fiber azimuthal angle with respect to the local muscle fiber direction and its waviness. The model also predicts that most of the load in the sub-epicardial and sub-endocardial regions is taken up, respectively, by the muscle fibers and collagen fiber network. This result suggests that normalizing LV passive stiffness by altering the collagen fiber network and myocyte stiffness is most effective when applied to the sub-endocardial and sub-epicardial regions, respectively. This finding may have implication for the development of new pharmaceutical treatments targeting individual cardiac tissue constituents to normalize LV filling function in heart diseases. STATEMENT OF SIGNIFICANCE: Current constitutive models describing the tissue mechanical behavior of the myocardium are largely phenomenological. While able to represent the bulk tissue mechanical behavior, these models cannot distinguish the contribution of the tissue constituents and their ultrastructure to heart function. Although microstructure-based constitutive models can be used to isolate the role of tissue ultrastructure, they have not been implemented in a computational framework that can accommodate realistic 3D organ geometry. The present study addresses these issues by developing and validating a microstructure-based computational modeling framework, which is used to investigate the role of tissue constituents and their ultrastructure in affecting heart function.

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Distal radius microstructure and finite element bone strain are related to site-specific mechanical loading and areal bone mineral density in premenopausal women.

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