ABSTRACT: OBJECTIVE:Static alignment influences knee loading and predicts osteoarthritis (OA) progression. Periarticular bone is important in dispersing forces across the knee, and there is substantial evidence for molecular crosstalk between cartilage and subchondral bone. The aim of this study was to evaluate the relationship between periarticular trabecular bone morphology and bone mineral density (BMD) and knee alignment in OA. METHODS:This was a cross-sectional analysis of participants in the Osteoarthritis Initiative Bone Ancillary Study. Dual x-ray absorptiometry (DXA) was performed to measure tibial periarticular bone mineral density (paBMD). Magnetic resonance imaging of knee trabecular bone was performed to calculate the apparent bone volume fraction (aBVF), apparent trabecular number (aTbN), apparent trabecular spacing (aTbSp), and apparent trabecular thickness (aTbTh). Static alignment was assessed by measuring the hip-knee-ankle (HKA) angle on long-limb films. RESULTS:The study group comprised 436 participants (mean ± SD age 65.4 ± 9.2 years, 46% female, mean ± SD body mass index 29.6 ± 4.6 kg/m2 ), 71% of whom had OA. Correlations between the HKA angle and medial:lateral paBMD, medial paBMD, aBVF, aTbN, aTbTh, and aTbSp were -0.63, -0.34, -0.29, -0.32, -0.22, and 0.30, respectively. More varus alignment was associated with higher medial:lateral paBMD, medial paBMD, aBVF, aTbN, aTbTh, and lower aTbSp. In OA knees, the results were more pronounced. In non-OA knees, the most consistent association was with medial:lateral paBMD. CONCLUSION:Static alignment was associated with medial:lateral paBMD in all knees and with medial paBMD and trabecular morphometry in OA knees only. Aberrant knee loading may lead to increased relative subchondral bone density, which is partly related to a higher aBVF and a greater number of thicker trabeculae with smaller intertrabecular spacing. Knee DXA may be a useful early biomarker of knee OA.