Knee osteoarthritis (OA) is a leading cause of chronic disability in the elderly. The natural rate of progression or worsening of knee OA varies; the reasons for this are poorly understood. The influence of impairments in the local, joint-organ-level environment on OA progression rate or on patient-centered physical functioning has received little attention in epidemiologic study. Whether such impairments develop before or after OA onset, they may contribute to subsequent OA progression and/or functional decline. Meniscal tears and malalignment are local impairments which are present in a subset of patients with mild-moderate OA and adversely affect load distribution. Another key element of the local environment is the functional capacity of the cartilage itself, i.e. its ability to withstand and transmit load. Our primary goal is to examine the relationship of meniscal tears and malalignment with compartment-specific tibiofemoral progression and with functional status decline in a cohort of 300 patients with knee OA. Secondarily, we will examine the impact of malalignment, laxity, muscle weakness and proprioception impairment on long-term (0-7 year) outcome. We also propose to measure cartilage deformation after exercise (which may be an in vivo measure of the functional capacity of cartilage) in a pilot study involving a subset of the cohort. A longitudinal, natural history study of knee OA with radiographic and functional outcomes is ongoing, Mechanical Factors in Arthritis of the Knee (MAK), in which time 0, 1.5 (completed) and 3 year (ongoing) evaluations of alignment, laxity, proprioception and strength in 300 subjects are funded. The project proposed here builds upon the infrastructure and results of this study. Support to evaluate the MAK cohort at 5 and 7 years (on the MAK timeline) is sought. The proposed study will provide much needed information regarding local determinants of the natural outcome of knee OA and will help to identify the joint-organ-level factors which should ultimately become the target of intervention, based upon their link to disease progression and/or their link to declining functional status.