Project Summary/Abstract Temporomandibular disorders (TMDs) are prevalent, with estimates of 5% to 10%, with two-fold higher prevalence for females than males (NASEM, 2020), and projected annual costs of $4 billion (Stowell et al. 2007). TMD represents a group of conditions with and without pain, such as temporomandibular joint (TMJ) disc displacement and degenerative disease. Osseous changes are late-stage, degenerative characteristics (Farina et al. 2009; Luder 2002; Wiese et al. 2008) that tend to occur >10 years earlier in the TMJ than in other human joints. The long-term goals are to elucidate the variables responsible for precocious TMJ tissue failure and the predilection for females compared to males. TMJ tissue fatigue depends on applied mechanics and behavior; that is, magnitudes and frequencies of energy input to tissues. Published and preliminary data show that magnitudes and frequencies of energy input to TMJ tissues, quantified by Mechanobehavior Score (MBS, mJ∙%/mm3), predict longitudinal changes in TMJ structures. It was found that in 35 subjects over ≥5.3 years, TMJs where intracapsular diagnoses worsened had average MBS 8-times and 3-times greater than TMJs where diagnoses improved and remained stable, respectively. However, there are anatomical and psychophysiological variables that are more easily measured and clinically translatable. The Anatomic- Psychophysiologic Score (APS), the arithmetic product of these measures, correlated well with MBS. Therefore, the overall objective is to use an existing landmark data set from the TMJ Impact Project (Schiffman et al. 2017) to evaluate these markers (APS) to predict longitudinal changes in TMJ structures and intracapsular diagnoses over 8 years in 401 subjects (789 TMJs). The specific aims are to: (1) Determine if easily measured anatomical and psychophysiological variables predict conversion rate and direction of changes to TMJ structures associated with changes in intracapsular diagnoses, and if there are sex differences. (2) Test for sex differences in longitudinal changes in mandibular condyle volume within and between diagnostic groups. The outcomes of these specific aims will help to address the current needs identified by the National Academies of Sciences, Engineering, and Medicine 2020 consensus report for "new tools, metrics, and biomarkers to diagnose TMD and forecast their trajectory.”