Based on the premise that bone mass and bone geometry are related to load history and that subchondral bone may play a role in osteoarthritis (OA), we sought to determine if static and dynamic markers of knee joint loads explain variance in the medial-to-lateral ratio of proximal tibial bone mineral density (BMD) in subjects with mild and moderate medial knee OA. We utilized two surrogate markers of dynamic load, the peak knee adduction moment and the knee adduction angular momentum, the latter being the time integral of the frontal plane knee joint moment. BMD for medial and lateral regions of the proximal tibial plateau and one distal region in the tibial shaft was measured in 84 symptomatic subjects with Kellgren and Lawrence radiographic OA grades of 2 or 3. Utilizing gait analysis, the peak knee adduction moment (the external adduction moment of greatest magnitude) and the time integral of the frontal plane knee joint moment (the angular momentum) over the entire stance phase as well as for each of the four subdivisions of stance were calculated. The BMD ratio was not significantly different in grade 2 (1.32 +/- 0.27) and grade 3 knees (1.47 +/- 0.40) (P = 0.215). BMD of the tibial shaft was not correlated with any loading parameter or static alignment. Of all the surrogate gait markers of dynamic load, the knee adduction angular momentum in terminal stance explained the most variance (20%) in the medial-to-lateral BMD ratio (adjusted r(2) = 0.196, P < 0.001). The knee adduction angular momentum for the entire stance phase explained 18% of the variance in the BMD ratio (adjusted r(2) 0.178, P < 0.001), 10% more variance than explained by the overall peak knee adduction moment (adjusted r(2) = 0.081, P < 0.001). 18% of the variance in the BMD ratio was also explained by the knee alignment angle (adjusted r(2) = 0.183, P < 0.001), and the total explanatory power was increased to 22% when the knee adduction angular momentum in terminal stance was added (change in r(2) = 0.041, P < 0.05, total adjusted r(2) = 0.215, P < 0.001). The BMD ratio and its relationship to dynamic and static markers of loading were independent of height, weight, and the body mass index, demonstrating that both dynamic markers of knee loading as well as knee alignment explained variance in the tibial BMD ratio independent of body size. (c) 2006 Elsevier Inc. All rights reserved.