BMI and Varus Malalignment Compound to Define a High-Risk Phenotype for Compartment-Specific Knee Osteoarthritis Progression

作者：McKenzie S. White, Feliks Kogan, Scott L. Delp, Constance R. Chu, Seth L. Sherman, Anoosha Pai S, Garry E. Gold, Akshay Chaudhari, Anthony A. Gatti · 发表于：medRxiv · 年份：2026 · DOI：10.64898/2026.04.15.26350819 · 研究领域：Osteoarthritis Treatment and Mechanisms、Total Knee Arthroplasty Outcomes、Lower Extremity Biomechanics and Pathologies

Objectives: Knee osteoarthritis (KOA) is a leading cause of disability, yet which patients will experience structural decline remains unclear. Body mass index (BMI) and lower limb alignment are established risk factors for KOA, but their independent and interactive effects on compartment-specific cartilage loss and total knee replacement (TKR) have not been characterized at scale. Methods: We analyzed 5,832 limbs from 3,016 participants in the Osteoarthritis Initiative followed over 7 years. Cartilage thickness in the weight-bearing medial and lateral femur and tibia was quantified, and lower limb alignment was measured using hip-knee-ankle (HKA) angle obtained from full-limb radiographs. Linear mixed-effects models estimated the independent and interactive effects of BMI and lower limb alignment on longitudinal cartilage thinning, and mixed-effects logistic regression modeled TKR risk. Results: BMI and +10° varus, the rate of medial femur cartilage thinning was 243.5% faster than the reference rate. In the lateral compartment, BMI and valgus alignment were independently associated with faster cartilage thinning, with no significant interaction. TKR risk increased exponentially with HKA deviation (odds ratio [OR] = 1.38 per 1°; ~five-fold at 5° malalignment) but was not associated with BMI. Conclusion: BMI and lower limb alignment influence structural KOA progression through compartment-specific pathways. The multiplicative interaction in the medial compartment identifies hig...