Publication
Age Dependence of Systemic Bone Loss and Recovery Following Femur Fracture in
Mice.
Authors Emami AJ, Toupadakis CA, Telek SM, Fyhrie DP, Yellowley CE, Christiansen BA
Submitted By Submitted Externally on 9/27/2018
Status Published
Journal Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
Year 2018
Date Published 9/1/2018
Volume : Pages Not Specified : Not Specified
PubMed Reference 30189111
Abstract The most reliable predictor of future fracture risk is a previous fracture of
any kind. The etiology of this increased fracture risk is not fully known, but
it is possible that fracture initiates systemic bone loss, leading to greater
fracture risk at all skeletal sites. In this study, we investigated systemic
bone loss and recovery after femoral fracture in young (3-month-old) and
middle-aged (12-month-old) mice. Transverse femur fractures were created using a
controlled impact, and whole-body bone mineral density (BMD), trabecular and
cortical microstructure, bone mechanical properties, bone formation and
resorption rates, mouse voluntary movement, and systemic inflammation were
quantified at multiple time points post-fracture. We found that fracture led to
decreased whole-body BMD in both young and middle-aged mice 2 weeks
post-fracture; this bone loss was recovered by 6 weeks in young but not
middle-aged mice. Similarly, trabecular bone volume fraction (BV/TV) of the L5
vertebral body was significantly reduced in fractured mice relative to control
mice 2 weeks post-fracture (-11% for young mice, -18% for middle-aged mice); no
significant differences were observed 6 weeks post-fracture. At 3 days
post-fracture, we observed significant increases in serum levels of
interleukin-6 and significant decreases in voluntary movement in fractured mice
compared with control mice, with considerably greater changes in middle-aged
mice than in young mice. At this time point, we also observed increased
osteoclast number on L5 vertebral body trabecular bone of fractured mice
compared with control mice. These data show that systemic bone loss occurs after
fracture in both young and middle-aged mice, and recovery from this bone loss
may vary with age. This systemic response could contribute to increased future
fracture risk after fracture; these data may inform clinical treatment of
fractures with respect to improving long-term skeletal health. © 2018 American
Society for Bone and Mineral Research.