Systemic Bone Loss after Fracture
The most common predictor of future fracture risk is a previous fracture of any kind. Armaun studies the systemic skeletal response to an initial fracture to understand the effects that may lead to future fracture risk. He uses an established mouse femur fracture model and measures both mechanical and biological responses that occur systemically after fracture (Fig. 1). He also is understanding the age-related effects of this increased fracture risk phenomenon.
Figure 1. Mouse femur fracture model. Radiographs, and micro-CT generated 3D renditions. Figure from Toupadakis et al., J Orthop Res, 2012.
Post-Traumatic Osteoarthritis (PTOA)
PTOA is a degenerative joint disease that affects approximately 5.6 million people in the United States, and up to 90% of ACL injury patients. Despite the prevalence of PTOA, current treatments only mitigate symptoms, without correcting the tissue-level changes, such as articular cartilage degeneration and osteophyte formation, that occur during the disease. We seek to increase understanding of the biomechanical factors that contribute to these tissue changes, as well as the role bone plays in disease progression, to aid in the development of new treatments for PTOA.
We use a novel mouse model of PTOA that consistently produces anterior cruciate ligament (ACL) rupture (Fig. 2). Animal models are essential to evaluate PTOA development on a compressed time scale, but most models employ invasive injury methods that may confound disease progression at early time points. Our model is noninvasive and ruptures the ACL with a single mechanical load, making it highly clinically relevant. Importantly, this model allows us to examine early time points after injury, which is useful to study and identify potential therapeutic targets for PTOA treatment. We have previously used the model to examine the effect of alendronate, as well as the role of osteophytes, in joint changes during PTOA.
Current and future projects continue examining bone changes during PTOA, with a focus on osteophytes. We aim to understand the biomechanical factors that lead to osteophyte formation, as well as how osteophytes influence disease progression.
Figure 2. Our noninvasive mouse model of PTOA produces ACL rupture via a single tibial compressive overload. The overload can be adjusted for force and speed, and causes subluxation of the knee joint to consistently tear the ACL. Figure from Christiansen et al., Osteoarthritis Cartilage, 2012.