How Obesity and Aging Interact to Create Increased Risk of Osteoarthritis and Disability

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URL: http://purl.stanford.edu/pf376fx1793

Abstract

Obesity, a condition characterized by excess adipose tissue, is becoming an important public health problem. Not only has the prevalence rate in adults risen steadily since the 1980’s, obesity is a strong risk factor for the development of a number of medical conditions, including cardiovascular disease, diabetes, and musculoskeletal disease. This dissertation focused on two musculoskeletal disorders: knee osteoarthritis (OA), which is a degenerative disease of the knee joint, and general mobility disability, which is an inability to carry out activities of daily living. While aging is the largest risk factor for developing both conditions, obesity further increases the risk and causes earlier onset of symptoms. There are currently no disease-modifying treatments for osteoarthritis, so it is important to develop preventive strategies. Similarly, mobility disability is much easier to prevent than to subsequently treat. In order to develop rational prevention programs, however, we must first understand the mechanism of increased risk in the obese population. Knee cartilage and other joint structures respond both to mechanical loads applied to the joint during activities of daily living (primarily walking) and the biological environment within the joint. Obesity is linked to changes in both: an increase in the levels of pro-inflammatory cytokines which affect cartilage, and alterations in the pattern of ambulation. The pathway to osteoarthritis in the obese therefore likely involves both changes in joint biology and joint loads.

The primary goal of this dissertation was to test the hypothesis that aging and obesity are linked to changes in gait mechanics and changes in the relationship between cartilage morphology and joint loads, and that these changes are consistent with increased knee OA risk. We also analyzed whether these changes are also observed in individuals with early asymptomatic knee joint degeneration. Finally, we tested the hypothesis that stair climbing, a more demanding activity of daily living, requires adaptive changes that reflect a reduction in muscle strength in the aging obese population and indicate increased mobility disability risk.

The first analysis in this dissertation focused on medial compartment loads in the knee, since the medial compartment is the knee region most frequently affected by osteoarthritis. The results indicate that in obese, but not normal-weight individuals, age was associated with an increased adduction moment, which reflects increased loads on the medial compartment of the knee. This increase was due to a change in walking strategy, likely adopted in an effort to improve medial-lateral stability.

Prior studies report that cartilage thickness in young healthy normal-weight individuals is positively correlated with ambulatory loads, but it is unknown if this association persists in older and obese individuals. The second analysis in this dissertation therefore focused on the relationships between height, weight, adduction moment, and cartilage thickness and weight-bearing area. The results show that the positive relationships between cartilage thickness and ambulatory load observed in young subjects were weaker in middle-aged normal-weight individuals and disappeared in the middle-aged obese subjects. This indicates that there is an increase in the variability of this relationship in obese and especially middle-aged obese individuals, suggesting that some individuals in this group are farther along the pathway to OA development. Given the increase in medial compartment load reported in the first analysis, the increased OA risk in older obese individuals is likely due to both an increase in ambulatory loads, and a change in the relationship between those ambulatory loads and cartilage properties due to the elevated pro-inflammatory cytokine levels characteristic of obesity.

The next study explored stair climbing as an activity that sheds light on why obesity is associated with mobility disability. Stair climbing requires more muscle strength than walking, and therefore it can illuminate potential areas where obese individuals lack sufficient strength in order to carry out activities of daily living. The adaptive changes during stair climbing reported in this study suggest that middleaged obese individuals had lower quadriceps strength not only due to the gradual loss of muscle strength due to aging, but also relative to their weight. This group adopted altered kinematic patterns of movement in order to complete stair ascent, chiefly by increasing anterior pelvic tilt. While this adaptation allowed the middle-aged obese individuals to complete the stair climbing task, this may lead to muscle atrophy due to disuse, increasing the disability risk.

Finally, the last analysis examined the gait characteristics of normal-weight and obese individuals with early knee joint degeneration who were not included in the previous three analyses, in order to understand whether the healthy subjects who were included represented a population at risk for OA development. The results show that the gait and stair climbing mechanics of individuals with early OA were not different from their age- and BMI-matched healthy counterparts. This indicates that the gait alterations seen in healthy middle-aged obese individuals are the same as those in obese individuals who have already developed the disease, and are likely risk factors or early functional markers of OA. Specifically, the adduction moment was the same in middle-aged obese individuals with and without OA, but was higher than in younger obese individuals, supporting the theory that the mechanism of OA initiation in obese individuals may be a combination of an increase in medial compartment loads over time coupled with an altered relationship between cartilage thickness and knee joint loads. Furthermore, decreases in the knee flexion moment during stair climbing suggest that obese individuals with early OA have reduced quadriceps strength compared to their age-matched normal-weight healthy counterparts. This puts them at even greater risk of mobility disability and because weaker quadriceps function is associated with worse outcomes of symptomatic OA, this may put them at greater risk of increasing OA severity.

This dissertation proposes a pathway to OA in obese and aging individuals based on an increase in medial compartment loads due to an altered walking pattern, coupled with a change in the relationship between cartilage thickness and ambulatory loads. This suggests that gait retraining or a shoe intervention to reduce the medial compartment load may reduce OA risk in this population. Furthermore, the quadriceps weakness mechanism indicates that a program of muscle strengthening may reduce the rate of disability in older obese individuals, improving the quality of life in this increasingly numerous population.

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