Prolonging disuse in aged mice amplifies cortical but not trabecular bones' response to mechanical loading

Area of Science:

• Bone biology
• Skeletal mechanobiology
• Aging research

Background:

• Aging impairs the skeleton's ability to respond to mechanical loading.
• Short-term disuse has previously restored load responses in aged mice.
• The impact of prolonged disuse on aged bone mechanoadaptation is not fully understood.

Purpose of the Study:

• To investigate if extending short-term neurectomy-induced disuse (SN) further enhances cortical and trabecular bone responses to loading in aged mice.
• To determine the effects of prolonged disuse on bone mechanoadaptation across different age groups.

Main Methods:

• Tibiae from female C57BL/J6 mice of various ages (8 weeks to 18 months) were subjected to loading after SN.
• Long-term SN (5 or 100 days) effects were examined in 18-month-old mice with or without subsequent loading.
• Cortical and trabecular bone changes were assessed using histomorphometry and micro-computed tomography.

Main Results:

• Loading increased cortical bone formation in younger mice but not in aged mice.
• Short-term SN restored load responses in aged mice, increasing bone accrual at specific tibial locations.
• Prolonged SN significantly heightened and expanded cortical bone responses to loading across all measured tibial lengths.
• Trabecular bone mass and architecture were not affected by loading or SN duration.

Conclusions:

• Mechanoadaptation to mechanical loading becomes deficient with aging.
• Prolonging disuse amplifies the impaired mechanoadaptive response in cortical bone of aged mice.
• Trabecular bone does not exhibit similar amplification of disuse effects.