Bone is an inherently dynamic tissue which is uniquely capable of recognizing and adapting to mechanical forces to meet its functional demands. While skeletal loading stimulates bone remodeling, which serves to adjust bone architecture and to repair microdamage in the bone matrix, excessive bone forces can be pathologic and initiate bone and joint degeneration and skeletal fractures. Numerous methods can evaluate long-term impacts of bone adaptation through structure and mineral density; however the acute response of bone to loading remains poorly understood. Imaging assessment of these acute changes in bone remodeling remains a major challenge. The scientific premise of this proposal is the development of a new method to measure the acute metabolic response of bone to external forces. This proposal aims to develop and validate a novel methodology to use 18F-NaF PET kinetic uptake to study the acute vascular and metabolic response of bone to mechanical loads.
Our specific aims are to (1) develop a signal recovery model to isolate 18F-NaF uptake from multiple injections, (2) create a muscle stimulation model for localized generation and simplified measurement of bone forces and (3) evaluate the relationship between measured acute bone forces and altered 18F-NaF kinetics. The innovation of this project is a novel method to induce localized joint forces, expanded pharmacokinetic models of 18F-NaF uptake to account for multiple tracer injections and a framework to study the relationship between mechanical forces and acute bone changes in vivo. The significance of this is a novel method to assess the acute vascular and metabolic bone response to mechanical forces. Successful integration of this technology will provide a breakthrough in how we assess bone metabolism in response to mechanical stimuli to tackle key questions in musculoskeletal physiology and pathophysiology.
Mechanical loading of bone not only stimulates new bone formation but is also a key element in joint disease and osteoporosis. While current methods can assess long-term bone adaptation through structure and mineral density, functional imaging of bone remains challenging. This work aims to develop multi-injection 18F-Sodium fluoride (18F-NaF) PET to acutely assess the in vivo metabolic response of bone from a novel method to induce a localized and measurable mechanical load.