Age Dependence of Systemic Bone Loss and Recovery Following Femur Fracture in Mice.

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.