The BALB/c mouse as a preclinical model of the age-related deterioration in the lumbar vertebra

Harris, Dominique; Garrett, Kate; Uppuganti, Sasidhar; Creecy, Amy; Nyman, Jeffry S.

Affiliations

¹Meharry Medical College, 1005 Dr. DB Todd Jr. Blvd., Nashville, TN 37208, USA

²Department of Orthopaedic Surgery, Vanderbilt University Medical Center, 1215 21st Ave. S., Suite 4200, Nashville, TN 37232, USA

³Center for Bone Biology, Vanderbilt University Medical Center, Nashville, TN 37232, USA

⁴Department of Biomedical Engineering, Vanderbilt University, 5824 Stevenson Center, Nashville, TN 37232, USA

⁵Department of Veterans Affairs, Tennessee Valley Healthcare System, 1310 24th Ave. S., Nashville, TN 37212, USA

Abstract and keywords

The likelihood of experiencing an osteoporotic fracture of one or more vertebral bodies increases with age, and this increase is not solely due to sex steroid deficiency. For the purpose of assessing the effectiveness of novel therapeutic strategies in the prevention of vertebral fractures among the elderly, we hypothesized that the BALB/c mouse model of aging phenocopies the age-related decrease in human VB strength. To test this hypothesis, we assessed the age-related changes in trabecular architecture of the L6 VB, with respect to those in the distal femur metaphysis, between 6-mo. (young adulthood, n = 20/sex) and 20-mo. of age (old age, n = 18/sex) and then determined how well the architectural characteristics, volumetric bone mineral density (vBMD), and predicted failure force from μCT-derived finite element analysis (μFEA) with linear elastic failure criteria explained the age-related variance in VB strength, which was the ultimate force during quasi-static loading of the VB in compression. While there was a pronounced age-related deterioration in trabecular architecture in the distal femur metaphysis of female and male BALB/c mice, the decrease in trabecular bone volume fraction and trabecular number between 6-mo. and 20-mo. of age occurred in male mice, but not in female mice. As such, the VB strength was lower with age in males only. Nonetheless, BV/TV and volumetric bone mineral density (vBMD) positively correlated with the ultimate compressive force of the L6 VB for both females and males. Whether using a fixed homogeneous distribution of tissue modulus (E_t = 18 GPa) or a heterogeneous distribution of E_t based on a positive relationship with TMD, the predicted failure force of the VB was not independent of age, thereby suggesting linear μFEA may not be a suitable replacement for mechanical-based measurements of strength with respect to age-related changes. Overall, the BALB/c mouse model of aging mimics the age-related in decline in human VB strength when comparing 6-mo. and 20-mo. old male mice. The decrease in VB strength in female mice may occur over a different age range.

Keywords: Osteoporosis; Aging; Vertebral body strength; Preclinical model; Trabecular architecture; Finite element analysis

Links

DOI: 10.1016/j.bone.2020.115438

PubMed: 32480022

WoS: 000547005800043

History

Received: 2020-04-3

Revised: 2020-05-15

Accepted: 2020-05-15

Online: 2020-05-29

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