A Systems View of Risk Factors for Knee Osteoarthritis Reveals Insights into the Pathogenesis of the Disease

Abstract

Early detection of osteoarthritis (OA) remains a critical yet unsolved multifaceted problem. To address the multifaceted nature of OA a systems model was developed to consolidate a number of observations on the biological, mechanical and structural components of OA and identify features common to the primary risk factors for OA (aging, obesity and joint trauma) that are present prior to the development of clinical OA. This analysis supports a unified view of the pathogenesis of OA such that the risk for developing OA emerges when one of the components of the disease (e.g. mechanical) becomes abnormal, and it is the interaction with the other components (e.g. biological and/or structural) that influences the ultimate convergence to cartilage breakdown and progression to clinical OA. The model, applied in a stimulus-response format, demonstrated that a mechanical stimulus at baseline can enhance the sensitivity of a biomarker to predict cartilage thinning in a five year follow-up in patients with knee OA. The systems approach provides new insight into the pathogenesis of the disease and offers the basis for developing multidisciplinary studies to address early detection and treatment at a stage in the disease where disease modification has the greatest potential for a successful outcome.

Cartilage Strain Distributions Are Different Under the Same Load in the Central and Peripheral Tibial Plateau Regions

“…Therefore, the differences in strain between the regions are likely due to differences in the collagen network structure. These regional differences in internal mechanical environment under the same applied load and nominal strain suggest a sensitivity of cartilage to shifts in the location of applied joint load and support the hypothesis that altered gait kinematics may be a mechanism to cartilage degeneration [13].…”

“…This suggests a potential pathway to degeneration following altered knee kinematics [13], which likely shift the regions of high load from the central region to the peripheral region [11,14,44]. Previous studies have demonstrated differences in biomechanical properties between regions [8,17,45], but did not analyze the internal strain fields in isolated regions of cartilage.…”

“…The regional conditioning of cartilage to its local mechanical loading has been suggested [12] as a potential explanation for the increased risk of developing knee OA following kinematic changes at the knee, which are common to some of the primary risk factors for OA [13]. The clinical evidence for this sensitivity is most clearly apparent with the incidence of premature knee OA developed following joint destabilizing events, such as ACL and meniscus injury [12,14].…”

Early Changes in Knee Center of Rotation During Walking After Anterior Cruciate Ligament Reconstruction Correlate With Later Changes in Patient-Reported Outcomes

“…15,23,24 It has been suggested that these kinematic changes shift the location of repetitive joint contact loads during walking to regions of cartilage not conditioned for these loads because of regional variations in both cartilage structure and biology. 3,8,9 If the new region of cartilage cannot adapt to the change in repetitive loading during ambulation, a degenerative pathway ensues. 4,5,10,23,27 …”

Systems approaches in osteoarthritis: Identifying routes to novel diagnostic and therapeutic strategies

“…While insidious degeneration results in a common end‐point, a non‐functional articulation, the initiating causes or mechanisms are often unclear. For the homeostasis or health of the joint stability of the system arises as a function of the integrated behavior of the biological, mechanical, and structural elements of the system 20. In Chu et al,21 an apt analogy is made between the probability of developing OA and the alignment of biological, mechanical, and structural factors as a slot/fruit machine.…”