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

Area of Science:

• Orthopedics
• Radiology
• Biostatistics

Background:

• Knee osteoarthritis (KOA) is a major cause of disability, but predicting structural decline is challenging.
• Body mass index (BMI) and lower limb alignment are known risk factors, but their combined impact on cartilage loss and total knee replacement (TKR) is not well understood.

Purpose of the Study:

• To investigate the independent and interactive effects of BMI and lower limb alignment on compartment-specific cartilage loss.
• To analyze the association between these factors and the risk of total knee replacement (TKR).

Main Methods:

• Analysis of 5,832 limbs from 3,016 participants in the Osteoarthritis Initiative over 7 years.
• Quantification of cartilage thickness and measurement of hip-knee-ankle (HKA) angle from full-limb radiographs.
• Use of linear mixed-effects models and mixed-effects logistic regression to assess effects on cartilage thinning and TKR risk.

Main Results:

• A multiplicative interaction between BMI and varus alignment was observed in the medial compartment, significantly accelerating cartilage thinning.
• In the lateral compartment, BMI and valgus alignment were independently associated with faster cartilage thinning.
• TKR risk increased exponentially with hip-knee-ankle (HKA) deviation, but was not associated with BMI.

Conclusions:

• BMI and lower limb alignment impact KOA progression via distinct, compartment-specific mechanisms.
• The combination of high BMI and varus malalignment defines a high-risk phenotype for medial compartment knee osteoarthritis.
• Findings have implications for clinical risk stratification and the design of disease-modifying interventions for KOA.