Lower limb alignment, tibiofemoral (TF) subluxation, and bone density changes around the knee are significant factors related to the development of knee osteoarthritis (OA) and have great impact on its severity. The relation of each factor to knee OA was evaluated separately in previous studies; however, few studies have attempted to integrate their respective effects. The purpose of this study was to determine if an identifiable interaction exists between coronal limb alignment, TF subluxation, and bone density in the development of knee OA. A total of 120 patients with symptomatic, varus knee OA, with preoperative standing anteroposterior (AP) hip-to-ankle radiographs and a computed tomographic scan of the knee, were included in this study. Overall mechanical lower extremity alignment, and TF subluxation were measured on the AP radiographs, while trabecular bone density (TBD) was measured in four regions of interest for both the tibial plateau and distal femur in all patients. The patients were stratified into the following four cohorts: (A) high subluxation, high angulation; (B) high subluxation, low angulation; (C) low subluxation, high angulation; and (D) low subluxation, low angulation. The mean TBD in group B was significantly higher than in groups C and D (p = 0.003 and 0.03, respectively). In addition, the mean TBD in group A was significantly higher than in group C. This study highlights the relationship between limb alignment, knee subluxation, and bone density in the osteoarthritic knee. These preliminary results present a proof-of-principle, that bone mineral density affects the degree of coronal alignment and TF subluxation in OA.