Age-related changes in bone structure and strength in female and male BALB/c mice

Mice may be useful for studies of skeletal aging, but there are limited data on changes in bone structure and strength over their life span. We obtained bones from female and male BALB/c mice at ages 2, 4, 7, 12, and 20 months and evaluated their structural, densitometric, and mechanical properties. MicroCT of the mid-diaphysis of the femur and radius indicated that during skeletal growth (2-7 months) bone cross-sectional size (area, moment of inertia) increased rapidly; during aging (7-20 months) cortical area was maintained, while moment of inertia continued to increase. Bones from females were smaller than those from males at young ages but not at later ages. Changes in whole-bone stiffness and strength reflected the changes in bone size, with a rapid increase from 2 to 7 months, followed by little or no change. In contrast, energy-to-fracture declined with aging. Cortical tissue mineral density increased during growth and was maintained with aging. MicroCT of trabecular bone revealed age-related changes that were site-dependent. The proximal tibia showed a clear pattern of age-related decline in trabecular BV/TV, with progressive decreases after 4 months in both sexes; lumbar vertebra L5 had more modest age-related declines; in contrast, caudal vertebra Ca7 had increasing BV/TV with aging. Overall, we found no evidence that females had more pronounced age-related deterioration than males. We conclude that bones from aging female and male BALB/c mice exhibit many of the changes seen in humans and are therefore a clinically relevant model for studies of skeletal aging.