Hindlimb unloading results in accelerated bone loss compared to aging in select bone compartments of female murine femurs.

Abstract

Disuse- and age-induced bone loss both increase skeletal fragility and therefore are important to public health. There is a strong research foundation in each type of bone loss individually, but no study has directly compared the two in a controlled setting in female mice. In this study, we compare skeletally mature 6-month-old female mice subjected to hindlimb unloading for three weeks (HLU), to aged 22-month-old female mice to identify similarities and differences. Bone microarchitecture results indicated that there are compartmental differences that change in response to HLU and aging, but HLU demonstrates an intermediate phenotype between control groups of age-matched controls and aged mice. Similar results were observed biomechanically after three-point bending, with HLU demonstrating an intermediate phenotype in bone strength compared to aging. On histological examination, there was a significantly higher level of bone marrow adiposity after HLU greater than aging. There was a higher amount of DNA damage markers such as yH2Ax when comparing aged to young samples, but this was not seen with HLU. These findings indicate that disuse- and aging in bone show some phenotypic similarities but proceed along different timelines.