ObjectiveThis mini review delves into the mechanisms of [18F]Sodium Fluoride positron emission tomography ([18F]NaF PET), which, by interrogating areas of newly mineralizing bone, provides a valuable tool to study the joint response to loading and areas of altered whole-joint function in osteoarthritis (OA). DesignThe review consolidates and discusses findings from both preclinical and clinical studies that utilize [18F]NaF PET to evaluate the bone response to various loading paradigms. It also briefly reviews technical considerations for PET imaging and discusses its strong potential as a tool in the quest to understand bone metabolism in the context of loading and osteoarthritis. ResultsWhile considering previous studies, technical considerations and potential new applications of this methodology are also discussed. [18F]NaF PET/MRI reveals localized, load-related bone responses after exercise, providing insights into early OA progression. In human studies, significant increases in tracer uptake are observed in areas affected by OA pathology, driven by bone perfusion and blood volume. Future work to examine the relationship between metabolic bone response to exercise and the bone loading environment is needed. ConclusionsIntegrating [18F]NaF PET/MRI with advanced biomechanical modeling holds promise for guiding clinical management of OA, primarily by examining the relationship between bone, soft tissues of the joint, and loading forces.