The article by Felson and colleagues (1) in this issue of Arthritis & Rheumatism reports that valgus malalignment increases the risk of radiographic progression of knee osteoarthritis (OA) as well as the incidence of lateral cartilage damage. Furthermore, the article suggests that even a relatively slight valgus alignment may cause lateral compartment OA, in part by increasing the risk of meniscal damage. Given that the major percentage of the ambulatory load during walking is transferred to the medial compartment of the knee even for knees with slight valgus alignment, this study raises some important questions regarding the role of static frontal plane alignment and, more specifically, of ambulatory forces in the natural course of knee OA. Does this study present a possible biomechanical paradox, or do these results point to the need for a deeper understanding of the role of ambulatory load in the pathomechanics of knee OA? This editorial will address this potential paradox by examining the role of mechanical factors in OA across scales ranging from full-body ambulation to cell biology.
The biomechanical paradox
The mechanics of walking produces forces that tend to move the knee toward varus alignment (adduction moment). The adduction moment drives the major portion of the load at the knee to pass through the medial compartment. Thus, the finding that a slight valgus alignment will increase the risk of lateral compartment knee OA seems to be in conflict with the presence of the adduction moment even in knees with a moderate valgus alignment (1). The knee adduction moment has been frequently used as a surrogate measure for the medial-to-lateral distribution of force across the knee, and there is substantial evidence that the adduction moment during normal walking is associated with the progression of medial compartment knee OA (2). However, the fact that a slight valgus alignment is associated with an increased incidence of lateral compartment disease raises questions regarding the meaning of the adduction moment in the broader context of the other factors that influence this measure in the analysis of knee OA.
Why has the adduction moment been found to be such a consistent marker of medial compartment disease?
Addressing this question provides insight into a meaningful interpretation of the adduction moment in the context of knee OA. Given that multiple factors can influence the load on the medial compartment, the observation that cartilage adapts to a chronic pattern of loading over time suggests that the key to the cartilage response to the adduction moment is the maintenance of a consistent pattern of locomotion over time. However, conditions such as soft tissue damage and loss of joint stability can alter normal patterns of locomotion and, in some cases, can actually lower the adduction moment while increasing the risk of medial compartment knee OA.
What does the adduction moment mean and not mean for knee OA?
It is useful to explore what the adduction moment represents and, more importantly, what is not represented by the adduction moment. Individuals with healthy cartilage who walk with a higher adduction moment have thicker cartilage in the medial compartment relative to the lateral compartment, whereas the reverse is true in patients with knee OA (3), where patients with a high adduction moment have a lower ratio of medial-to-lateral cartilage thickness. The substantial differences in the responses of healthy and OA cartilage to load suggest that load is not an initial cause of OA but rather a factor in the rate of progression (3). The responses of both healthy and OA cartilage are associated with the adduction moment under certain conditions. Probably the most critical condition is that the adduction moment represents a consistent pattern of locomotion, since the relationship between thickness and load results suggests that cartilage adapts to a consistent cyclic loading over time. Also, the finding that the load-bearing cartilage during walking was the most sensitive to the adduction moment (3) suggests that it is the cyclic loading during walking that drives the regional variations in cartilage thickness. While severe changes that induce loads of sufficient levels to produce local damage can initiate a pathway to OA (4), in the absence of these severe conditions, the chronic pattern of loading over time appears to be the dominant mechanical factor.
It is important to note that the adduction moment does not represent the actual force on the medial compartment but rather the relative medial-to-lateral distribution of force across the joint (5). The total force across the joint represents the summation of dynamic forces, body weight, and muscle forces, where the muscle force produces the major portion of the force across the joint. As such, an increase in the adduction moment does not always mean a higher medial compartment load or a lower lateral compartment load. Two subjects walking with the same peak adduction moment can have different forces on the medial compartment (as well as on the lateral compartment) if there are different patterns of muscle contraction. Understanding the physical meaning of the adduction moment is critical to the interpretation of this metric in the context of knee OA.
What about muscle contraction force to compensate for joint instability?
Returning to the issue of lateral compartment disease, the loss of joint stability due to meniscal damage and perhaps increasing valgus alignment can stimulate increased muscle cocontraction to compensate for a loss of passive stability in the lateral compartment. The increase in muscle cocontraction will increase the total force on the joint. If valgus alignment is added to the analysis, then the increase in force will be greater on the lateral compartment. Thus, a potential explanation for the increased incidence and progression of lateral compartment OA (1) is that the valgus alignment and related lateral meniscus degeneration are associated with a loss of passive knee stability, and patients compensate for this loss with increased muscle cocontraction. However, an increase in muscle cocontraction will also increase the load on the medial compartment, yet the disease primarily advances in the lateral compartment. Thus, it seems that increased joint force due to muscle contraction alone may not explain the increased incidence of lateral compartment OA. Bringing the analysis down to the scale of the articular surface geometry provides additional insight into a potential explanation for the lateral compartment disease.
Are articular surface geometry differences important?
Differences in the shape of the articular contact will have a profound influence on cartilage tissue stresses, and there are important differences in geometry between the medial and lateral compartments of the knee (6). The medial compartment is more conforming than the lateral compartment, and thus the same force will produce lower contact stress on the medial compartment. The importance of the articular contacting geometry was illustrated in a study (6) that showed thicker lateral compartment cartilage and suggested that the local thickness was influenced by the local contact stress. The thicker cartilage in the lateral compartment points to the fact that the cartilage adapts to its local mechanical environment, and the regional adaptations represent an important consideration in attempting to interpret the incidence of lateral compartment disease (1). In addition, the lower conformity in the lateral compartment will make this compartment more vulnerable to meniscal damage, as there is a high incidence of degenerative changes following partial lateral meniscectomy (7). The lower conformity in the lateral compartment combined with a damaged lateral meniscus can also lead to kinematic changes in a manner similar to the rotational changes reported following medial meniscectomy (8). Can kinematic changes following damage to the lateral meniscus help explain the increase in lateral compartment OA?
Is the lateral cartilage sensitive to kinematic changes?
It has been suggested that the regional morphologic cartilage variations make cartilage vulnerable to kinematic changes during walking (3). It has been observed that the kinematic changes reported in anterior cruciate ligament (ACL)–deficient knees shift the location of the repetitive contact during walking to regions of the cartilage not conditioned over time to altered loading and thus initiate a degenerative pathway. The lateral compartment has thicker cartilage and a more focal region of maximum thickness (6) than the medial compartment (Figure 1). Therefore, a very slight shift toward a valgus alignment as well as changes in kinematic patterns during walking can shift contact to regions not conditioned to sustain the repetitive loads during walking and thus initiate a degenerative pathway in a manner similar to that reported in patients with ACL injury (3). A more focal thickness distribution in the lateral compartment makes this compartment vulnerable to kinematic changes that can result from meniscal damage.
Is biology a factor?
While there are consistent biomechanical conditions that converge to place the lateral compartment at risk, there are also biologic changes associated with a degrading lateral meniscus that can increase the risk of lateral compartment OA. Increased catabolic activity in damaged meniscal tissue may elevate the risk of progression of OA (9). In addition, the catabolic changes combined with increased mechanical stress in the lateral compartment can interact to accelerate the breakdown of the cartilage (10). Thus, the interaction between biologic and mechanical factors should be considered in the analysis of OA.
In conclusion, the analysis of the potential biomechanical paradox raised in the study by Felson et al (1) can provide new insights into the complexity of OA. The paradox can be explained when the disease is addressed from an integrated point of view that considers how mechanical, structural, and biologic factors converge across scales at an in vivo systems level.
At a full-body scale, walking mechanics must be considered in the pathomechanics of the disease. While the adduction moment is an extrinsic metric, it has been shown to be a robust marker of medial compartment knee OA; it must be evaluated in the context of a repeatable pattern of locomotion, as the evidence suggests that cartilage responds to a cyclic pattern of loading during walking. Therefore, care must be taken when evaluating conditions that change the pattern of locomotion, since the pattern must be sustained over a substantial period of time to influence structural changes. More importantly, any change in the pattern of locomotion should be evaluated for an unanticipated response to other factors that influence joint loading components, such as muscle cocontraction. The above observations may explain why some interventions that produce large reductions in the adduction moment have not been effective in altering the course of the disease (11) or in lowering the medial compartment load (12), since a change in the magnitude of the adduction moment alone may not reflect the change in the medial compartment load if other conditions are changed.
At the scale of the joint, the transfer of the extrinsic load during ambulation to intrinsic stress sustained by the cartilage is dependent on the shape of the articulating surface in the region of contact. The differences in the contact geometry produce a higher contact stress on the lateral compartment than on the medial compartment (13), and the local contact stress likely explains the thicker cartilage in the lateral compartment. The thicker and more focal region of thick cartilage in the lateral compartment is evidence that the chondrocyte responds to the local mechanical environment in the tissue, and there appears to be a unique regional conditioning of the structural, mechanical, and biologic properties of articular cartilage that is reflected by the variations in cartilage thickness (Figure 1). The regional variations in cartilage thickness reflect a unique “fingerprint” of cartilage properties with important information about the health of cartilage. The regional variations in cartilage also increase the potential sensitivity of cartilage to destabilizing conditions that change movement at the articular surface.
Finally, there is a need for prospective studies to assess if these observations can be extrapolated to a more general understanding of OA. For example, the increased rates of knee OA with aging, the fact that OA often remains symptomatically silent until an advanced stage, and the physiologic changes that occur with aging raise the question of potential interactions between ambulatory function and biologic changes that occur with aging prior to the initiation of OA. Ultimately, a comprehensive approach is needed to understand knee OA as a system that encompasses ambulatory mechanics, joint structure, and biologic factors to address the complexity of the disease (14).
Dr. Andriacchi drafted the article, revised it critically for important intellectual content, and approved the final version to be published.