Age and osteoarthritis: are AGEs the link?

Osteoarthritis is a common joint disease in the elderly. By far the most important risk factor for osteoarthritis is aging. Age-related changes in the articular cartilage may be responsible for age-related increase in the number of people with osteoarthritis. One of the most striking changes in cartilage is the accumulation of non-enzymatic glycation (NEG) products in cartilage. NEG is the spontaneous reaction of proteins with sugars. Earlier in vitro experiments showed that NEG negatively affects the cartilage. The cartilage is stiffer and more fragile being more susceptible to damage. In addition, there is less capacity to repair the cartilage because NEGs interfere with chondrocyte activity. This combination can lead to initiation and progression of damage of the cartilage as can be seen in osteoarthritis. In this thesis the role of NEG on specificallythe occurrence of osteoarthritis is examined. In animal experiments we have shown that artificial increased NEG in the cartilage of the knee joints of dogs plays a role at the progression of osteoarthritis. We were not able to demonstrate the effect of NEG on the development of osteoarthritis. In a cohort of individuals with early signs of osteoarthritis the NEG content (measure in skin as surrogate for cartilage NEG) was higher in participants with some osteoarthritis on their X-ray than with participants without any signs of radiographic osteoarthritis. The NEG content measured at baseline was not able to predict the limited radiographic progression of osteoarthritis over 5 years follow-up. At end stage osteoarthritis, the amount of NEG in the cartilage tissue appeared inversely related to the degree of osteoarthritis in the cartilage. This was considered due to the formation of new cartilage, not yet being glycated, in an attempt to repair. Conclusion: The influence of NEG on the occurrence of osteoarthritis is not undisputedly demonstrated. We still expect that AGEs do play a role in OA, however, regarding development of OA it is hard to proof, and the causality is definitely not a strong one.