Background/Purpose:

Hand Osteoarthritis (HOA) is characterized by the progressive destruction of articular cartilage and bony changes and is strongly and positively associated with age but the mechanism by which aging contributes to this increased susceptibility is largely unknown. Recently the hypothesis that accumulation of advanced glycation endproducts (AGEs) that are associated with oxidative stress and aging might explain some or most of this association has been suggested. We compared skin autofluorescence as a measure of dermal AGEs and its association with the prevalence of HOA, symptomatic HOA, and the number of finger joints with osteophytes and joint space narrowing (JSN)  as a measure of severity.

Methods:

We performed a cross-sectional analysis of a purposeful sample of the Osteoarthritis Initiative (OAI) from a single site who had dermal AGEs measured by skin autofluoresence using  SCOUT DS machine (Vera light Inc., Albuquerque, New Mexico) at the 36 month visit. We used an excitation wavelength of 375nm and emission wavelengths of 435-660nm. This wavelength is correlated with cross-links of collagen, FAD, and NADH. A mathematical algorithm is applied to spectrum results to adjust for age, hemoglobin, skin pigmentation and light scattering. Hand x-rays from the dominant hand were read for definite osteophytes with JSN at 48 months. We classified a person as having radiographic HOA if their hand x-ray had two or more finger joints (DIP, PIP, MCP) affected on different fingers.  Symptomatic HOA was defined as having radiographic HOA and presence of hand/finger pain, aching or stiffness for more than half the days in past 30 days. Simple T tests or Pearson correlation coefficients were used  to evaluate the  the mean number of finger joints involved by tertiles of dermal AGE levels. Then Analysis of Covariance was performed to adjust for age and gender.  T-tests comparing levels of dermal AGEs between those with and without HOA and with and without symptomatic HOA were performed.

Results:

In a sub-sample from the OAI (n=200)with equal proportions of participants with and without abdominal adiposity had hand x-rays read. Of this sample, 171 had dermal AGEs measured and analyses performed. Mean levels of AGEs were greater both for those with radiographic HOA (n=114) [29.3(4.8) vs. 27.1(5.0), p = 0.005], and symptomatic HOA(n=35) [30.5(5.2) vs. 28.1(4.8), p=0.01] compared to those without HOA or symptomatic HOA. Furthermore level of AGEs correlated significantly with the number of joints affected per hand (r= 0.25, p<0.001) and exhibited a dose-response relationship in categorical analysis(with 2.34, 2.70 and 3.59 joints involved by increasing tertiles of dermal AGE levels after adjustment for age and gender (p trend <0.001).

 Conclusion:

Non-enzymatic glycation of dermal tissues as a proxy for the accumulation of AGEs in articular cartilage is associated with HOA, symptomatic HOA and the severity of HOA as measured by the number of finger joints affected in this cross-sectional study. Replication of these findings in prospective cohort studies and understanding of metabolic pathways that may modify or mediate the relationship of AGEs with HOA are indicated.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/relationship-of-dermal-advanced-glycation-end-products-and-hand-oa/