Sex differences in the association of skin advanced glycation endproducts with knee osteoarthritis progression

Background: The accumulation of advanced glycation endproducts in articular cartilage has been suggested as an etiologic factor in the development and progression of knee osteoarthritis (KOA). Methods: We conducted a prospective cohort study of skin advanced glycation endproducts (sAGEs) measured non-invasively by skin intrinsic fluorescence and the relationship between sAGE KOA progression in 160 men and 287 women in a sub-cohort of the Osteoarthritis Initiative at a single site. KOA progression was measured by yearly changes in Osteoarthritis Research Society International (OARSI)-defined joint space narrowing (JSN) and by yearly changes in joint space width (JSW) from baseline to 48 months. Sex-stratified repeated measures, mixed models to account for correlation between the knees within persons and adjusted for age, body mass index (BMI), Kellgren-Lawrence (KL) grade, beam angle and rim-to-rim distance were utilized. Results: Increasing tertiles of sAGE measured at 36 months were associated with greater JSN over 4 years in men but not in women. The percentage of knees with JSN at 48 months, by tertiles of sAGE, were 7.0%, 16.0% and 17. 7% in men (rho for linear trend = 0.03) and 11.4%, 14.4% and 8.4% in women (rho for linear trend = 0.33). Using change in JSW as the outcome, a similar trend was found in men but it was not statistically significant in fully adjusted models and no association was found in women. Conclusion: This study provides preliminary evidence that sAGEs independent of age and BMI, are associated with knee JSN in men but not in women.