Objective To test the hypothesis that knee cartilage changes over five years are associated with baseline peak knee adduction moment (KAM) and peak knee flexion moment (KFM) during early stance. Design Baseline KAM and KFM were measured in sixteen subjects with medial knee OA. Regional changes in cartilage thickness and changes in medial-to-lateral thickness ratio were quantified using magnetic resonance imaging at baseline and again after five years. Multiple regression was used to determine whether baseline measures of KAM and KFM were associated with cartilage changes over five years. Associations with baseline pain score, Kellgren-Lawrence grade, walking speed, age, gender, and body mass index were tested one-by-one in the presence of KAM and KFM. Results Changes over five years in femoral medial-to-lateral thickness ratio were associated with baseline KAM, KFM, and pain score (R2=0.60, p=0.010), and most significantly with KAM (R2=0.33, p=0.019). Changes in tibial medial-to-lateral thickness ratio were associated with baseline KAM, KFM, and walking speed (R2=0.49, p=0.039), with KFM driving this association (R2=0.40, p=0.009). Changes in medial tibial thickness were associated with baseline KAM, KFM, and walking speed (R2=0.49, p=0.041); KFM also drove this association (R2=0.42, p=0.006). Conclusions The findings that the KAM has a greater influence on femoral cartilage change and the KFM has a greater influence on tibial cartilage change provide new insight into the tibiofemoral variations in cartilage changes associated with walking kinetics. These results suggest that both KAM and KFM should be considered when designing disease interventions as well as when assessing the risk for OA progression.

The results of this study support the hypothesis that a change in COMP concentration induced by a mechanical stimulus is associated with cartilage thinning at 5 years. Mechanically-induced changes in mechano-sensitive biomarkers should be further explored in the context of stimulus-response models to improve the ability to assess OA progression.

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.

Objective. To compare age-related patterns of gait with patterns associated with knee osteoarthritis (OA), the following hypotheses were tested: H1) The sagittal-plane knee function during walking is different between younger and older asymptomatic subjects; H2) The age-related differences in H1 are increased in patients with knee OA. Design. Walking trials were collected for 110 participants (1.70 ± 0.09 m, 80 ± 14 kg). There were 29 younger asymptomatic subjects (29 ± 4 years) and 81 older participants (59 ± 9 years), that included 27 asymptomatic subjects and 28 and 26 patients with moderate and severe medial knee OA. Discrete variables characterizing sagittal-plane knee function were compared among the four groups using ANOVAs. Results. During the heel-strike portion of the gait the cycle at preferred walking speed, the knee was less extended and the shank less inclined in the three older groups compared to the younger asymptomatic group. There were similar differences between the severe OA group and the older asymptomatic and moderate OA groups. Both OA groups also had the femur less posterior relative to the tibia and smaller extension moment than the younger group. During terminal stance, the severe OA group had the knee less extended and smaller knee extension moment than the younger asymptomatic and older moderate OA groups. Conclusions. The differences in knee function, particularly those during heel-strike which were associated with both age and disease severity, could form a basis for looking at mechanical risk factors for initiation and progression of knee OA on a prospective basis.

No abstract

This study investigated the load-modifying and clinical efficacy of variable-stiffness shoes after 12 months in subjects with medial compartment knee osteoarthritis. Subjects who completed a prior 6-month study were asked to wear their assigned constantstiffness control or variable-stiffness intervention shoes during the remainder of the study. Changes in peak knee adduction moment, total Western Ontario and McMaster Universities (WOMAC), and WOMAC pain scores were assessed. Seventy-nine subjects were enrolled, and 55 completed the trial. Using an intention-to-treat analysis, the variable-stiffness shoes reduced the within-day peak knee adduction moment (À5.5%, p < 0.001) in the intervention subjects, while the constant-stiffness shoes increased the peak knee adduction moment in the control subjects (þ3.1%, p ¼ 0.015) at the 12-month visit. WOMAC pain and total scores for the intervention group were significantly reduced from baseline to 12 months (À32%, p ¼ 0.002 and À35%, p ¼ 0.007, respectively). The control group had a reduction of 27% in WOMAC pain score (p ¼ 0.04) and no significant reduction in total WOMAC score. Reductions in WOMAC pain and total scores were similar between groups (p ¼ 0.8 and p ¼ 0.47, respectively). In the intervention group, reductions in adduction moment were related to improvements in pain and function (R 2 ¼ 0.11, p ¼ 0.04). Analysis by disease severity revealed greater efficacy in adduction moment reduction in the less severe intervention group. While the long-term effects of the intervention shoes on pain and function did not differ from control, the data suggest wearing the intervention shoe reduces the within-day adduction moment after long-term wear, and thus should reduce loading on the affected medial compartment of the knee. ß

Articular cartilage is sensitive to mechanical loading, so increased risk of osteoarthritis in older or obese individuals may be linked to changes in the relationship between cartilage properties and extrinsic joint loads. A positive relationship has been reported between ambulatory loads and cartilage thickness in young individuals, but whether this relationship exists in individuals who are older or obese is unknown. This study examined the relationship between femoral cartilage thickness and load, measured by weight  height and the peak adduction moment, in young normal-weight (28 subjects, age: 28.0 AE 3.8 years, BMI: 21.9 AE 1.9 kg/m 2 ), middle-aged normal-weight (27 subjects, 47.0 AE 6.5 years, 22.7 AE 1.7 kg/m 2 ), young overweight/obese (27 subjects, 28.4 AE 3.6 years, 33.3 AE 4.6 kg/m 2 ), and middle-aged overweight/obese (27 subjects, 45.8 AE 7.2 years, 31.9 AE 4.4 kg/m 2 ) individuals. On the lateral condyle, cartilage thickness was positively correlated with weight  height for all groups (R 2 ¼ 0.26-0.20) except the middle-aged overweight/ obese. On the medial condyle, weight  height was significantly correlated only in young normal-weight subjects (R 2 ¼ 0.19), as was the case for the correlation between adduction moment and medial-lateral thickness ratio (R 2 ¼ 0.20). These results suggest that aging and obesity are both associated with a loss of the positive relationship between cartilage thickness and ambulatory loads, and that the relationship is dependent on the compartment and whether the load is generated by body size or subject-specific gait mechanics. ß

Measures of mean cartilage thickness over predefined regions in the femoral plate using magnetic resonance imaging have provided important insights into the characteristics of knee osteoarthritis (OA), however, this quantification method suffers from the limited ability to detect OA-related differences between knees and loses potentially important information regarding spatial variations in cartilage thickness. The objectives of this study were to develop a new method for analyzing patterns of femoral cartilage thickness and to test the following hypotheses: (1) asymptomatic knees have similar thickness patterns, (2) thickness patterns differ with knee OA, and (3) thickness patterns are more sensitive than mean thicknesses to differences between OA conditions. Bi-orthogonal thickness patterns were extracted from thickness maps of segmented magnetic resonance images in the medial, lateral, and trochlea compartments. Fifty asymptomatic knees were used to develop the method and establish reference asymptomatic patterns. Another subgroup of 20 asymptomatic knees and three subgroups of 20 OA knees each with a Kellgren/Lawrence grade (KLG) of 1, 2, and 3, respectively, were selected for hypotheses testing. The thickness patterns were similar between asymptomatic knees (coefficient of multiple determination between 0.8 and 0.9). The thickness pattern alterations, i.e., the differences between the thickness patterns of an individual knee and reference asymptomatic thickness patterns, increased with increasing OA severity (Kendall correlation between 0.23 and 0.47) and KLG 2 and 3 knees had significantly larger thickness pattern alterations than asymptomatic knees in the three compartments. On average, the number of significant differences detected between the four subgroups was 4.5 times greater with thickness pattern alterations than mean thicknesses. The increase was particularly marked in the medial compartment, where the number of significant differences between subgroups was 10 times greater with thickness pattern alterations than mean thickness measurements. Asymptomatic knees had characteristic regional thickness patterns and these patterns were different in medial OA knees. Assessing the thickness patterns, which account for the spatial variations in cartilage thickness and capture both cartilage thinning and swelling, could enhance the capacity to detect OA-related differences between knees.