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.

Objective. This study tested the hypothesis that gait changes related to knee osteoarthritis (OA) of varied severity are associated with increased loads at the ankle, knee, and hip.Methods. Forty-two patients with bilateral medial compartment knee OA and 42 control subjects matched for sex, age, height, and mass were studied. Nineteen patients had Kellgren/Lawrence (K/L) radiographic severity grades of 1 or 2, and 23 patients had K/L grades of 3 or 4. Three-dimensional kinematics and kinetics were measured in the hip, knee, and ankle while the subjects walked at a self-selected speed.Results. Patients with more severe knee OA had greater first peak knee adduction moments than their matched control subjects (P ‫؍‬ 0.039) and than patients with less severe knee OA (P < 0.001). All patients with knee OA made initial contact with the ground with the knee in a more extended position than that exhibited by control subjects. An increased axial loading rate was present in all joints of the lower extremity. Patients with more severe knee OA had lower hip adduction moments compared with their matched control subjects.Conclusion. The secondary gait changes observed among patients with knee OA reflect a potential strategy to shift the body's weight more rapidly from the contralateral limb to the support limb, which appears to be successful in reducing the load at the knee in only patients with less severe knee OA. The increased loading rate in the lower extremity joints may lead to a faster progression of existing OA and to the onset of OA at joints adjacent to the knee. Interventions for knee OA should therefore be assessed for their effects on the mechanics of all joints of the lower extremity.Osteoarthritis (OA) is a degenerative joint disease that affects an increasing proportion of the population (1-3). Although most joints of the lower extremity, including the ankle and hip, may be involved, the knee is the most common site for OA (4). Changes related to OA are more frequently observed in the medial compartment than in the lateral compartment of the knee (5). Moreover, loads transferred through the medial compartment during walking are substantially higher than loads transferred through the lateral compartment (6). The distribution of loads transferred through the medial and lateral compartments during walking can be estimated by the external knee adduction moment (6); a higher external knee adduction moment indicates greater loads in the medial than in the lateral compartment. The first peak knee adduction moment during walking has been shown to be a strong predictor of the presence (7-9), severity (10,11), and rate (12) of progression of medial compartment knee OA. However, little attention has been paid to the changes in the mechanical environment of other joints of the affected limb, which presumably occur concomitantly with changes in knee-joint mechanics.Most studies investigating the gait of patients with knee OA have concentrated on kinematics and kinetics at the knee (7,8,(13)(14)(15)(16), ground reaction for...

The initiation of osteoarthritis occurs when healthy cartilage experiences some condition (traumatic or chronic) that causes kinematic changes during ambulation at the knee to shift the load-bearing contact location of the joint to a region not conditioned to the new loading. The rate of progression of osteoarthritis is associated with increased load during ambulation.

Objective. To determine whether reducing walking speed is a strategy used by patients with knee osteoarthritis (OA) of varying disease severity to reduce the maximum knee adduction moment.Methods. Self-selected walking speeds and maximum knee adduction moments of 44 patients with medial tibiofemoral OA of varying disease severity, as assessed by using the Kellgren/Lawrence grade, were compared with those of 44 asymptomatic control subjects matched for sex, age, height, and weight.Results. Differences in self-selected normal walking speed explained only 8.9% of the variation in maximum knee adduction moment for the group of patients with knee OA. The severity of the disease influenced the adduction moment-walking speed relationship; the individual slopes of this relationship were significantly greater in patients with less severe OA than in asymptomatic matched control subjects. Self-selected walking speed did not differ between patients with knee OA, regardless of the severity, and asymptomatic control subjects. However, knees with more-severe OA had significantly greater adduction moments (mean ؎ SD 3.80 ؎ 0.89% body weight ؋ height) and were in more varus alignment (6.0 ؎ 4.5°) than knees with less-severe OA (2.94 ؎ 0.70% body weight ؋ height; and 0.0 ؎ 2.9°, respectively).Conclusion. Patients with less-severe OA adapt a walking style that differs from that of patients with more-severe OA and controls. This walking style is associated with the potential to reduce the adduction moment when walking at slower speeds and could be linked to decreased disease severity.Mechanical loads placed upon the joint during walking have been related to the progression of knee osteoarthritis (OA) (1,2). Theoretical estimations show that loads transferred through the medial compartment of the knee are ϳ2.5 times greater than loads transferred through the lateral compartment of the knee (3), and the majority of symptomatic OA knees are radiographically diagnosed with degenerative changes in the medial compartment of the joint (4). Moreover, increased mechanical load on the medial compartment of the knee has been associated with knee varus alignment, typically measured statically as mechanical axis alignment (5) or dynamically as external knee adduction moment (3), and a positive correlation between mechanical axis alignment and maximum external knee adduction moment has been reported (6,7).The relevance of the maximum knee adduction moment for the course of the disease has been emphasized by results of recent studies (1,2) that showed that high maximum adduction moments at the knee at a controlled walking speed are related to OA disease severity and to a higher rate of progression of knee OA. Nevertheless, it is still unclear whether the maximum knee adduction moment in patients with OA is higher than that of healthy control subjects when walking at

Even a moderate walking activity can significantly influence serum COMP concentration. The immediate response points to a diffusion time of COMP fragments from cartilage to the blood of 30 min or less. The response at 5.5h indicates a metabolic delay for COMP in the range of 5h to 6h.