Heterogenous Aging of Local Tissues Is a Major Contributor to the Age-Related Decline in Glycosaminoglycans and Fracture Toughness of Cortical Bone
Abstract
Bone fragility fractures increase with age as bone toughness declines, potentially in part due to the loss of glycosaminoglycans (GAGs). However, the mechanisms linking GAG depletion to bone quality remain unclear, partly due to the dynamic and heterogeneous nature of bone remodeling during aging. During bone remodeling, newly formed secondary osteons and older interstitial tissue are randomly distributed throughout the bone, each with distinct material properties. This microstructural heterogeneity adds complexity to studying age-related changes in bone quality that cannot be explained by donor age alone. This study hypothesized that the age-related decline in bulk bone fracture toughness originates from changes in local tissue GAGs with tissue aging and is amplified by an increasing proportion of old tissue relative to new tissue with advancing donor age. To test this, local tissues in human cortical bone samples across different ages and sexes were analyzed using Raman spectroscopy, DMMB, Alcian blue, histomorphometry, microcompression, and fracture toughness testing. The results showed that compositional and mechanical properties of local tissues changed significantly with tissue age, but not with donor age or sex. The volume fraction of old tissue as well as GAG heterogeneity (FWHM) increased significantly with donor age. Furthermore, age-related changes in bulk bone GAG content were strongly correlated with bone fracture toughness. These findings suggest that age-related loss of bone quality arises from the combined effects of tissue age-dependent deterioration in local properties and donor age–dependent accumulation of older tissue.
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BibTeX
@misc{heath2026heterogenous,
title = {{Heterogenous Aging of Local Tissues Is a Major Contributor to the Age-Related Decline in Glycosaminoglycans and Fracture Toughness of Cortical Bone}},
author = {Savannah Heath and Ashley Ridoutt and Michael Reyes and Keying Ye and Jean X. Jiang and Xiaodu Wang},
howpublished = {Research Square},
year = {2026},
month = oct,
doi = {10.21203/rs.3.rs-11379365/v1},
url = {https://doi.org/10.21203/rs.3.rs-11379365/v1},
note = {CC BY 4.0},
}
RIS
TY - UNPB
TI - Heterogenous Aging of Local Tissues Is a Major Contributor to the Age-Related Decline in Glycosaminoglycans and Fracture Toughness of Cortical Bone
AU - Savannah Heath
AU - Ashley Ridoutt
AU - Michael Reyes
AU - Keying Ye
AU - Jean X. Jiang
AU - Xiaodu Wang
PY - 2026
DA - 2026/10/30
PB - Research Square
DO - 10.21203/rs.3.rs-11379365/v1
UR - https://doi.org/10.21203/rs.3.rs-11379365/v1
AB - Bone fragility fractures increase with age as bone toughness declines, potentially in part due to the loss of glycosaminoglycans (GAGs). However, the mechanisms linking GAG depletion to bone quality remain unclear, partly due to the dynamic and heterogeneous nature of bone remodeling during aging. During bone remodeling, newly formed secondary osteons and older interstitial tissue are randomly distributed throughout the bone, each with distinct material properties. This microstructural heterogeneity adds complexity to studying age-related changes in bone quality that cannot be explained by donor age alone. This study hypothesized that the age-related decline in bulk bone fracture toughness originates from changes in local tissue GAGs with tissue aging and is amplified by an increasing proportion of old tissue relative to new tissue with advancing donor age. To test this, local tissues in human cortical bone samples across different ages and sexes were analyzed using Raman spectroscopy, DMMB, Alcian blue, histomorphometry, microcompression, and fracture toughness testing. The results showed that compositional and mechanical properties of local tissues changed significantly with tissue age, but not with donor age or sex. The volume fraction of old tissue as well as GAG heterogeneity (FWHM) increased significantly with donor age. Furthermore, age-related changes in bulk bone GAG content were strongly correlated with bone fracture toughness. These findings suggest that age-related loss of bone quality arises from the combined effects of tissue age-dependent deterioration in local properties and donor age–dependent accumulation of older tissue.
SN - 2693-5015
ER -