The age-related decrease in material properties of BALB/c mouse long bones involves alterations to the extracellular matrix

•Toughness and fracture toughness of cortical bone decrease with advanced age in female and male BALB/c mice.•Accompanying the loss in material properties are several age-related changes in the extracellular matrix such as lower bound water fraction.•With aging, female mice had thicker cortices and...

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Published in:Bone (New York, N.Y.) N.Y.), 2020-01, Vol.130, p.115126-115126, Article 115126
Main Authors: Creecy, Amy, Uppuganti, Sasidhar, Girard, Madeline R., Schlunk, Siegfried G., Amah, Chidi, Granke, Mathilde, Unal, Mustafa, Does, Mark D., Nyman, Jeffry S.
Format: Article
Language:English
Subjects:
Advanced glycation end-products
Animals
Bone and Bones - diagnostic imaging
Bone Density
Bone quality
Bound water
Collagen
Extracellular Matrix
Female
Femur - diagnostic imaging
Male
Mice
Mice, Inbred BALB C
Raman spectroscopy
Toughness
X-Ray Microtomography
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Summary:•Toughness and fracture toughness of cortical bone decrease with advanced age in female and male BALB/c mice.•Accompanying the loss in material properties are several age-related changes in the extracellular matrix such as lower bound water fraction.•With aging, female mice had thicker cortices and stronger long bones in bending, while males had thinner cortices and no strength difference. One possibility for the disproportionate increase in fracture risk with aging relative to the decrease in bone mass is an accumulation of changes to the bone matrix which deleteriously affect fracture resistance. In order to effectively develop new targets for osteoporosis, a preclinical model of the age-related loss in fracture resistance needs to be established beyond known age-related decreases in bone mineral density and bone volume fraction. To that end, we examined long bones of male and female BALB/c mice at 6-mo. and 20-mo. of age and assessed whether material and matrix properties of cortical bone significantly differed between the age groups. The second moment of area of the diaphysis (minimum and maximum principals for femur and radius, respectively) as measured by ex vivo micro-computed tomography (μCT) was higher at 20-mo. than at 6-mo. for both males and females, but ultimate moment as measured by three-point bending tests did not decrease with age. Cortical thickness was lower with age for males, but higher for old females. Partially accounting for differences in structure, material estimates of yield, ultimate stress, and toughness (left femur) were 12.6%, 11.1%, and 40.9% lower, respectively, with age for both sexes. The ability of the cortical bone to resist crack growth (right femur) was also 18.1% less for the old than for the young adult mice. These decreases in material properties were not due to changes in intracortical porosity as pore number decreased with age. Rather, age-related alterations in the matrix were observed for both sexes: enzymatic and non-enzymatic crosslinks by high performance liquid chromatography increased (femur), volume fraction of bound water by 1H-nuclear magnetic resonance relaxometry decreased (femur), cortical tissue mineral density by μCT increased (femur and radius), and an Amide I sub-peak ratio I1670/I1640 by Raman spectroscopy increased (tibia). Overall, there are multiple matrix changes to potentially target that could prevent the age-related decrease in fracture resistance observed in BALB/c mouse.
ISSN:8756-3282
1873-2763
DOI:10.1016/j.bone.2019.115126