Grant: Project Grant

Forces applied to the skeleton during daily ambulation and physical activity can cause the formation of small cracks in the bone called microdamage. If this microdamage is not repaired through bone remodeling, it may accumulate and grow, resulting in a full fracture. Fractures that occur in this manner are referred to as stress fractures in young healthy individuals and insufficiency fractures in older adults. It has long been hypothesized that bone remodeling is not a purely random process, but that it purposefully targets microdamage in an effort to keep bones healthy and strong; however, bone remodeling also makes the bone more porous because it transiently removes local bone tissue and leaves behind a vascular canal. In previous work from our lab, we significantly reduced bone remodeling in an animal model using osteoporosis drugs. Vascular porosity in the bone significantly reduced and this led to functionally meaningful increases in bone strength. In this regard, it remains unclear if bone remodeling targets microdamage in an effort to maintain bone strength. This study will quantify the relationship between bone remodeling, microdamage, and bone strength in unique animal model that is directly translatable to humans. Our approach takes advantage of state-of-the-art mechanical testing, advanced imaging, and cell quantification techniques, and our team's unique expertise and innovative biomedical engineering approach is well suited to address this question, which has burdened the field for decades. Although our research is basic in nature, it has important clinical implications, as bone remodeling and microdamage are believed to play critical roles in bone fracture and metabolic bone disease.