The most reliable predictor of a future bone fracture is a previous fracture at any skeletal site. The etiology of this increased fracture risk is not fully understood, but one possibility is that fracture initiates a systemic loss of bone in order to utilize mineral for the formation of a fracture callus, with this systemic resorption of bone leading to a greater fracture risk at all skeletal sites. Age at the time of the first fracture is also predictive of the increased risk of future fractures, with older individuals having long-lasting effects of fracture risk compared to younger individuals. In this body of work, we sought to determine the mechanisms and age-related differences of systemic bone loss after an initial fracture. We used a mouse femur fracture model to investigate this systemic bone loss phenomenon and elucidate the underlying mechanisms that may contribute to an increased fracture risk. Measured outcomes included whole-body bone mineral density, trabecular and cortical microstructure, bone mechanical properties, bone formation and resorption rates, lacunar-canalicular morphology, mouse voluntary movement, bone biomarkers, and systemic inflammation. We showed that systemic bone loss occurs within two weeks after femoral fracture in both young (3-month-old) and middle-aged (12-month-old) mice. This bone loss was fully recovered in young mice by 6 weeks post-fracture, whereas middle-aged mice did not fully recover from the acute bone loss by 6 weeks. Moreover, at day 3 post-fracture, systemic markers of inflammation and osteoclast activity are elevated, while voluntary activity is lower. We also showed that changes in canalicular widths is greater at weeks 2 and 4. Altogether, these data provide fundamental insights that may lead to further research of therapeutic targets for reducing future fracture risk following an initial fracture.
|Commitee:||Genetos, Damian, Stover, Susan, Yellowley, Clare|
|School:||University of California, Davis|
|School Location:||United States -- California|
|Source:||DAI-B 81/8(E), Dissertation Abstracts International|
|Subjects:||Biomedical engineering, Bioengineering|
|Keywords:||Bone, Fracture risk, Osteoporosis, Perilacunar remodeling, Systemic bone loss|
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