Severity‐dependent shift in knee osteoarthritis toward a dominant varus–flexion alignment phenotype on weight‐bearing 3D imaging

Abstract Purpose To determine whether weight‐bearing three‐dimensional (3D) spatial hip–knee–ankle (HKA) alignment exhibits severity‐dependent changes across knee osteoarthritis (KOA) stages, whether it is more strongly associated with joint structure and symptoms than conventional two‐dimensional (2D) HKA alignment, and whether these 3D alignment patterns correspond to distinct cartilage stress distributions. Methods This prospective study enroled 151 patients (296 knees) with radiographic KOA (Kellgren–Lawrence KL Grades 1–4). Spatial HKA angles, defined as 3D mechanical alignment angles without projection onto any anatomical plane, were measured using weight‐bearing cone‐beam computed tomography (CBCT) and compared with conventional 2D radiographic HKA angles. Knees were classified into 3D alignment phenotypes based on their alignment orientation: valgus–extension, valgus–flexion, varus–extension and varus–flexion. Joint space narrowing and Western Ontario and McMaster Universities osteoarthritis index (WOMAC) scores were assessed. For each KL grade, the average spatial HKA orientation was incorporated into finite element models to estimate cartilage stress distributions. Results Spatial HKA angles showed stronger correlations with joint space narrowing ( r = 0.52–0.61) and WOMAC scores ( r = 0.45–0.56) than single‐plane alignment measures. Spatial HKA angles increased progressively across KL grades. Knees with mild osteoarthritis clustered near neutral, whereas knees with KL Grades 3 and 4 predominantly shifted toward a varus–flexion pattern. The prevalence of varus–flexion alignment increased markedly with severity, reaching 67.2% and 89.1% in KL Grades 3 and 4, respectively. Medial and posterior cartilage stress increased with severe varus–flexion alignment. Conclusion The spatial HKA angle derived from weight‐bearing CBCT captured severity‐dependent multiplanar malalignment and demonstrated stronger structural and symptomatic associations than 2D measures. Advanced KOA was characterized by a dominant varus–flexion alignment phenotype, associated with increased medial and posterior cartilage stress. Level of Evidence Level IV.