A novel hypothesis on the pathogenesis of knee osteoarthritis: the muscle weakness-joint instability and stress overload – uneven bone settlement cascade

• Proposes muscle weakness as the initiating factor in the KOA cascade, contrasting with traditional cartilage degeneration theories. • Integrates theories of uneven bone settlement, joint instability, and stress overload into a unified biomechanical model. • Provides a mechanistic explanation for the efficacy of Proximal Fibular Osteotomy (PFO), highlighting the key role of bone-soft tissue rebalancing. • Predicts that muscle strengthening can halt early KOA progression, guiding optimization of non-surgical treatment. The pathogenesis of knee osteoarthritis (KOA) remains incompletely elucidated. Traditional perspectives emphasize the roles of articular cartilage degeneration and soft tissue laxity. This article synthesizes recent research to propose an integrated musculoskeletal biomechanical hypothesis: weakness of the periarticular knee musculature is the initiating factor in KOA development, leading to diminished dynamic joint stability. This instability triggers abnormal distribution of contact stresses and excessive loading within the joint. Coupled with the unique anatomical features of the tibia and fibula (such as fibular support and the abundance of trabecular bone in the medial tibia) and underlying osteoporosis, this culminates in the characteristic “uneven bone settlement” of the tibial plateau. This settlement further exacerbates varus deformity, joint space narrowing, soft tissue imbalance, and pain, establishing a vicious cycle of KOA progression. The clinical efficacy of the currently employed Proximal Fibular Osteotomy (PFO) provides robust support for this theory. This hypothesis underscores the central importance of muscle strengthening to restore joint stability and early intervention in bone metabolism for the prevention and management of KOA.