Project Summary Osteopenic fragility fractures are a devastating result of poor bone quality secondary to high mortality and long- term patient disability. Currently there is limited understanding on the mechanistic level reflected in the relatively few available treatment and diagnostic options. Dual-energy x-ray absorptiometry (DEXA) is utilized in combination with established patient standards for diagnosis and management of osteoporosis, however its use is limited in patients. There is a clear need to improve technologies that enable bone quality measurements, especially to avoid refracture. In the proposed work we will develop technology that enables chronic insight into bone health for rodent animal models to enable real-time high-fidelity readout enabling advanced insight for the study of mechanisms and to evaluate the efficacy of new treatments. Specifically, we will build on our recently introduced device class, osseosurface electronics, which are battery free and fully implantable bone strain monitors. In aim 1 we will evaluate permanent interfacing and sensing capabilities of the platform that is grown to the bone via calcium phosphate ceramic particles on month long timescales. Data captured from daily exercise on a treadmill will enable insight in sensing fidelity and will be compared against gait parameters automatically captured by deep neural net image analysis. In aim 2 we will develop a new sensing modality, thermal conductivity measurements, that will be validated by the attachment of the biointerface to the bone, a mechanism we already characterized with strain sensors. This platform will then be used to compare the sensitivity of serial DEXA, µCT, in vivo strain and thermal conductivity measurement in detecting bone changes following administration of an anabolic medication used to treat osteoporosis in aim 3. Ovariectomy animal models with and without treatment will be evaluated by osseosurface electronics against DEXA and µCT. Successful expansion of our osseosurface electronic platform will enable new real time and high-fidelity measurement of bone health in freely moving small animal models. This capability is instrumental to explore mechanisms of chronic and acute changes attributed to fracture or disease in models that have the full genetic toolset and enable rapid test of hypothesis with little cost. The experiments will also inform the utility of the devices towards the use in patients for chronic treatment of osteoporosis.