Axial alignment is a critical regulator of knee osteoarthritis

Taking a load off
Osteoarthritis (OA) is characterized by subchondral bone thickening in addition to cartilage degeneration. Here, Oláh et al. studied the role of joint alignment in OA development. Unloading the knee joint of a patient with OA with varus malalignment by high tibial osteotomy, which corrected axial malalignment, improved pain and cartilage microstructure and reduced subchondral bone thickness. Similarly, joint overload in OA induced by varus malalignment and partial medial meniscectomy in sheep led to cartilage degeneration and bone plate thickening, which could be corrected by unloading the joint. Results detail the structural and biochemical changes to the knee during osteoarthritis and support the therapeutic potential of unloading via correction of joint malalignment.

Although osteoarthritis (OA), a leading cause of disability, has been associated with joint malalignment, scientific translational evidence for this link is lacking. In a clinical case study, we provide evidence of osteochondral recovery upon unloading symptomatic isolated medial tibiofemoral knee OA associated with varus malalignment. By mapping response correlations at high resolution, we identify spatially complex degenerative changes in cartilage after overloading in a clinically relevant ovine model. We further report that unloading diminishes OA cartilage degeneration and alterations of critical parameters of the subchondral bone plate in a similar topographic fashion.

Last, therapeutic unloading shifted the articular cartilage and subchondral bone phenotype to normal and restored several physiological correlations disturbed in neutral and varus OA, suggesting a protective effect on the integrity of the entire osteochondral unit. Collectively, these findings identify modifiable trajectories with considerable translational potential to reduce the burden of human OA.