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

Charles B Eaton,John D Maynard,Maria Sayeed,Timothy E Mcalindon,Mary B Roberts,Jeffrey B Driban,Syeda Ameernaz

doi:10.1186/s13075-017-1226-z

Abstract

BackgroundThe accumulation of advanced glycation endproducts in articular cartilage has been suggested as an etiologic factor in the development and progression of knee osteoarthritis (KOA).MethodsWe 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.ResultsIncreasing 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 (p for linear trend = 0.03) and 11.4%, 14.4% and 8.4% in women (p 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.ConclusionThis study provides preliminary evidence that sAGEs independent of age and BMI, are associated with knee JSN in men but not in women.

Highlights

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)
We evaluated crude models and models adjusted for age, body mass index (BMI), and baseline K/L grade to evaluate the effect of increasing tertiles of skin AGE (sAGE) on joint space narrowing (JSN) and joint space width (JSW) over the 4-year period from baseline to year 4
In this study of progression of knee OA, using semiquantitative measurements we found that higher levels of skin advanced glycation endproducts (AGEs) were associated with progression of medial-tibial knee OA in men but not in women, and identified a trend using serial measurements of loss of JSW

Summary

Introduction

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). Osteoarthritis (OA) is characterized by the progressive destruction of articular cartilage and is strongly and positively associated with chronological age, but the mechanism by which aging contributes to this increased susceptibility is largely unknown. The hypothesis has been promulgated that accumulation of advanced glycation endproducts (AGEs) that are associated with cumulative glycemic exposure, oxidative stress and aging might explain some or most of this association [1]. Pentosidine, a fluorescent AGE formed by lysine and arginine residues, is a highly sensitive marker of AGE and is often used to characterize the whole family of AGEs in human tissues. Pentosidine has been shown to accumulate in the collagen matrix of skin, lens, and articular cartilage [1]

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