Functional knee phenotyping: A paradigm for patient-specific alignment in total knee arthroplasty

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Total knee arthroplasty has historically relied on mechanical alignment (MA); however, a systematic neutral target cannot accommodate the biological diversity of the knee. Based on functional knee phenotype analysis, large imaging series have demonstrated broad coronal variability even in young, non-osteoarthritic knees, with constructs corresponding to classic neutral alignment in only 4–6% of limbs. These data indicate that MA as a universal goal is insufficient and the data support a paradigm shift toward patient-specific alignment (PSA). The study institution practices a tibia-first, gap-balanced, phenotype-based PSA within defined safe zones to respect joint line obliquity and soft tissue balance while avoiding outlier alignment. Targets are defined with reproducible metrics, namely hip–knee–ankle angle, femoral mechanical angle, tibial mechanical angle, and joint line convergence angle (JLCA). Current evidence shows high target attainment and reliable intra-operative balance, with balanced gaps in >90% of PSA and JLCA improving from 1.8 to 4.3° pre-operatively to 0.6–1.2° post-operatively ( p ​< ​0.001). Moreover, results from related strategies (inverse kinematic alignment and functional alignment) consistently report outcomes at least equivalent, and in selected domains superior, to MA while requiring fewer soft tissue releases. The next step for PSA is scalability: multicenter datasets, registry linkage, and long-term follow-up are needed to determine durability, to refine phenotype-specific safe zones, and to validate this strategy across implants and patient populations. • TKA alignment should respect functional knee phenotypes, not a single neutral target. • Hirschmann's phenotype-based patient-specific alignment (PSA): tibia-first, gap-balanced procedure within safe zones. • PSA cohort: >90% balanced gaps; JLCA improved from 1.8–4.3° to 0.6–1.2°. • RCTs/series: iKA/FA match or exceed MA with fewer releases and better KOOS.

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