The in vivo pathomechanics of osteoarthritis (OA) at the knee is described in a framework that is based on an analysis of studies describing assays of biomarkers, cartilage morphology, and human function (gait analysis). The framework is divided into an Initiation Phase and a Progression Phase. The Initiation Phase is associated with kinematic changes that shift load bearing to infrequently loaded regions of the cartilage that cannot accommodate the loads. The Progression Phase is defined following cartilage breakdown. During the Progression Phase, the disease progresses more rapidly with increased load. While this framework was developed from an analysis of in vivo pathomechanics, it also explains how the convergence of biological, morphological, and neuromuscular changes to the musculoskeletal system during aging or during menopause lead to the increased rate of idiopathic OA with aging. Understanding the in vivo response of articular cartilage to its physical environment requires an integrated view of the problem that considers functional, anatomical, and biological interactions. The integrated in vivo framework presented here will be helpful for the interpretation of laboratory experiments as well as for the development of new methods for the evaluation of OA at the knee.

The response of healthy and diseased cartilage of the knee to the mechanics of walking is examined, with the goal of providing insight into the relationship between the kinematics and kinetics of the knee during walking and the maintenance of cartilage health. The combination of information from three-dimensional thickness models of cartilage derived from magnetic resonance imaging and the analysis of the interaction between load at the knee and kinematic changes during walking associated with loss of the anterior cruciate ligament demonstrated the importance of considering walking mechanics as an important factor in the initiation and progression of osteoarthritis. In particular, this material suggests that knee cartilage becomes conditioned to loading and to the large number of repetitive cycles of loading that occur during walking and that healthy cartilage homeostasis is maintained as long as there are no changes to the normal patterns of locomotion, the structure of the knee joint, or cartilage biology. Thus, there is the potential for a degenerative pathway to be initiated when a condition such as anterior cruciate ligament injury causes the repetitive loading during walking to shift to a new location. The sensitivity of cartilage to the kinematic changes is illustrated with the anterior cruciate ligament-deficient knee and the regional variations in cartilage morphology. The material presented here supports the conclusion that individual variations in the range of loading and kinematics at the knee during walking can have a profound influence on the initiation and progression of osteoarthritis of the knee.

This review examines a mechanism for the initiation of osteoarthritis after anterior cruciate ligament (ACL) injury by considering the relationship between reported ambulatory changes after ACL injury, cartilage adaptation to load, and the association between cartilage loads during walking and regional variations in cartilage structure and biology. Taken together, these observations suggest that cartilage degeneration after ACL injury could be caused by a kinematic gait change that shifts ambulatory loading applied to cartilage. Such a shift may cause regions of cartilage to become newly loaded, be subjected to altered levels of compression and tension, or become unloaded. The metabolic sensitivity of chondrocytes to such changes in their mechanical environment, combined with the low adaptation potential of mature cartilage, could lead to cartilage degeneration and premature osteoarthritis after ACL injury. This proposed mechanism demonstrates the value of using the ACL injury model to understand the relationship between mechanics and biology, as well as helping to explain the importance of restoring normal ambulatory kinematics after ACL injury to avoid premature osteoarthritis.

We examined the relationship between specific gait changes after anterior cruciate ligament injury and the progression of osteoarthritis at the knee. The study was done using a finite-element model derived from subject specific three-dimensional cartilage volumes created from magnetic resonance images. Cartilage thinning was predicted using an iterative algorithm based on the octahedral shear stress. Simulations were done for a knee with normal alignment and for a knee with an internal tibial rotation offset, as associated with anterior cruciate ligament deficiency. For the healthy knee, the model predicted patterns of cartilage thinning consistent with a previous clinical report of idiopathic osteoarthritis. For the ACL-deficient scenario the model predicted a more rapid rate of cartilage thinning throughout the knee, especially in the medial compartment. The results suggest that the progression of osteoarthritis after anterior cruciate ligament injury is associated with a shift in the normal load bearing regions of the knee joint during normal function due to kinematic changes, and highlight the importance of restoring proper gait during anterior cruciate ligament reconstruction.

A rule-based approach can substantially increase inter-observer reproducibility when measuring cartilage thickness from multiple observers. This improvement in inter-observer reproducibility could be an important consideration for longitudinal studies of disease progression. In quantifying cartilage thickness, central and weight bearing regions on each condyle can provide more accurate measurement than boundary and non-weight bearing regions with average accuracy of +/-0.2-0.3 mm. An important finding of this study was that the weight bearing regions, which are usually of the greatest clinical interest, were measured most accurately by sagittal plane imaging.