Age-related changes in human trabecular bone: Relationship between microstructural stress and strain and damage morphology

Abstract

Accumulation of microdamage in aging and disease can cause skeletal fragility and is one of several factors contributing to osteoporotic fractures. To better understand the role of microdamage in fragility fracture, the mechanisms of bone failure must be elucidated on a tissue-level scale where interactions between bone matrix properties, the local biomechanical environment, and bone architecture are concurrently examined for their contributions to microdamage formation. A technique combining histological damage assessment of individual trabeculae with linear finite element solutions of trabecular von Mises and principal stress and strain was used to compare the damage initiation threshold between pre-menopausal (32-37 years, n=3 donors) and post-menopausal (71-80 years, n=3 donors) femoral cadaveric bone. Strong associations between damage morphology and stress and strain parameters were observed in both groups, and an age-related decrease in undamaged trabecular von Mises stress was detected. In trabeculae from younger donors, the 95% CI for von Mises stress on undamaged regions ranged from 50.7-67.9MPa, whereas in trabeculae from older donors, stresses were significantly lower (38.7-50.2, p<0.01). Local microarchitectural analysis indicated that thinner, rod-like trabeculae oriented along the loading axis are more susceptible to severe microdamage formation in older individuals, while only rod-like architecture was associated with severe damage in younger individuals. This study therefore provides insight into how damage initiation and morphology relate to local trabecular microstructure and the associated stresses and strains under loading. Furthermore, by comparison of samples from pre- and post-menopausal women, the results suggest that trabeculae from younger individuals can sustain higher stresses prior to microdamage initiation.

Figure 1

Damage was separated into three categories based on morphology. Bullet points indicate metrics used to categorize individual trabeculae.

Figure 2

Representative microdamaged trabeculae extracted from histology sections and homogeneous finite element models (von Mises effective stress shown) for young and old donors.

Figure 3

Representative undamaged trabeculae extracted from histology sections and homogeneous finite element models (von Mises effective stress shown) for young and old donors.

Figure 4

The 95% confidence intervals for a. von Mises and b. principal compressive stress initiation ranges calculated by damage category are shown. A significantly greater stress range is demonstrated in young, undamaged trabeculae compared with old, undamaged trabeculae. Significant increases are also seen in the stress state of severely damaged trabeculae compared to linear and undamaged trabeculae in both age groups. Bars represent significant differences (p<0.01).

Figure 5

The 95% confidence intervals for a. von Mises and b. principal compressive strain initiation ranges calculated by damage category are shown. Significant increases were seen in the strain state of severely damaged trabeculae compared to linear and undamaged trabeculae in both age groups. Bars represent significant differences (p≤0.01).

Figure 6

Trabecular bone microarchitecture and mineralization for young (32–37 year old) and old (71–80 year old) age groups. a. Trabecular thickness is plotted, indicating that severely damaged trabeculae are thinner than undamaged in the older age group, and thinner than linearly damaged trabeculae in the younger age group (p<0.01). b. Trabecular orientation relative to the loading axis is plotted, indicating that in the older age group, trabeculae aligned more acutely with the loading axis is more likely to sustain severe damaged compared to undamaged trabeculae. c. SMI is plotted, showing more rod-like trabecular architecture in severely damaged trabeculae compared to undamaged trabeculae in both groups (p<0.01). d. In severely damaged, diffusely damaged, and undamaged trabeculae, the trabecular mineralization was significantly increased in the post-menopausal group (p<0.01).