title: Age-related changes in the fracture resistance of male Fischer F344 rat bone.
abstract: In addition to the loss in bone volume that occurs with age, there is a decline in material properties. To test new therapies or diagnostic tools that target such properties as material strength and toughness, a pre-clinical model of aging would be useful in which changes in bone are similar to those that occur with aging in humans. Toward that end, we hypothesized that similar to human bone, the estimated toughness and material strength of cortical bone at the apparent-level decreases with age in the male Fischer F344 rat. In addition, we tested whether the known decline in trabecular architecture in rats translated to an age-related decrease in vertebra (VB) strength and whether non-X-ray techniques could quantify tissue changes at micron and sub-micron length scales. Bones were harvested from 6-, 12-, and 24-month (mo.) old rats (n=12 per age). Despite a loss in trabecular bone with age, VB compressive strength was similar among the age groups. Similarly, whole-bone strength (peak force) in bending was maintained (femur) or increased (radius) with aging. There was though an age-related decrease in post-yield toughness (radius) and bending strength (femur). The ability to resist crack initiation was actually higher for the 12-mo. and 24-mo. than for 6-mo. rats (notch femur), but the estimated work to propagate the crack was less for the aged bone. For the femur diaphysis region, porosity increased while bound water decreased with age. For the radius diaphysis, there was an age-related increase in non-enzymatic and mature enzymatic collagen crosslinks. Raman spectroscopy analysis of embedded cross-sections of the tibia mid-shaft detected an increase in carbonate subsitution with advanced aging for both inner and outer tissue.
authors.affiliation: Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37212, United States; Department of Orthopaedic Surgery & Rehabilitation, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN 37232, United States.
authors.forename: Sasidhar
authors.initials: S
authors.lastname: Uppuganti
authors.affiliation: Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37212, United States; Department of Orthopaedic Surgery & Rehabilitation, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN 37232, United States.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Granke
authors.affiliation: Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37212, United States; Department of Orthopaedic Surgery & Rehabilitation, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37232, United States.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Makowski
authors.affiliation: Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37232, United States; Institute of Imaging Science, Vanderbilt University, Nashville, TN 37232, United States; Department of Radiology and Radiological Sciences, Vanderbilt University, Nashville, TN 37232, United States.
authors.forename: Mark D
authors.initials: MD
authors.lastname: Does
authors.affiliation: Department of Veterans Affairs, Tennessee Valley Healthcare System, Nashville, TN 37212, United States; Department of Orthopaedic Surgery & Rehabilitation, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN 37232, United States; Department of Biomedical Engineering, Vanderbilt University, Nashville, TN 37232, United States. Electronic address: jeffry.s.nyman@vanderbilt.edu.
authors.forename: Jeffry S
authors.initials: JS
authors.lastname: Nyman
mesh_terms: D000375:Aging / Q000473:pathology*; D000818:Animals; D001696:Biomechanical Phenomena; D001835:Body Weight; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology; D005269:Femur / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D020342:Finite Element Analysis; D050723:Fractures, Bone / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D008297:Male; D016062:Porosity; D011884:Radius / Q000000981:diagnostic imaging / Q000473:pathology / Q000503:physiopathology; D011916:Rats, Inbred F344; D013059:Spectrum Analysis, Raman; D055114:X-Ray Microtomography
keywords: Advanced glycation end-products; Bound water; Fracture toughness; Porosity; Raman spectroscopy