Biomechanics and Obesity in Osteoarthritis: From Mechanism to Precision Medicine.

Osteoarthritis (OA) is a degenerative joint disease driven by complex biomechanical and inflammatory mechanisms, particularly in weight-bearing joints such as the knee. This review explores the pivotal role of biomechanics in OA pathogenesis, focusing on abnormal joint loading, malalignment, and instability as key contributors to cartilage degeneration and subchondral bone remodeling. Special attention is given to the interplay between obesity and OA, highlighting how mechanical overload and adipokine-mediated inflammation synergistically accelerate disease progression. Emerging interventions-including physical therapy, gait retraining, orthotics, high tibial osteotomy (HTO), and total knee arthroplasty (TKA)-are analyzed for their biomechanical impact. Novel technologies such as wearable sensors, finite element analysis (FEA), and digital twin models are discussed as tools for real-time assessment, predictive modeling, and personalized treatment planning. The review emphasizes the need for integrated, multiscale research strategies that account for individual biomechanical profiles and systemic factors like obesity. Advancing biomechanical precision in OA management holds promise for improving early diagnosis, optimizing interventions, and informing regenerative therapies aimed at restoring joint function and delaying disease progression.