Background/Purpose: Hand OA (HOA) is a painful, destructive and deforming polyarticular disorder that impairs an individual’s ability to perform manipulative activities of daily life and has a strong association with increasing age. Telomeres are specialized chromatin structures at the end of linear eukaryotic chromosomes that perform a capping function, protecting chromosomes from degradation, recombination, and fusion between chromosomes. After each round of DNA replication there is a progressive loss of terminal telomere sequences, so telomeres progressively shorten with ageing in replicating somatic cells. There is also evidence that telomeric structure may be damaged as a result of oxidative stress. Ultimately, the telomeric sequence array may become critically shortened and trigger replicative senescence or apoptosis, contributing to processes related to aging. Peripheral blood leukocyte (PBL) telomere length is a biomarker for biological age and longevity. Data from cross-sectional studies are conflicting on whether telomere length is shorter in subjects with OA.

Methods: This used a convenience sample of Caucasian participants in the Osteoarthritis Initiative who had right hand x-rays at 0 and month 48; and PBL telomere length measured at baseline using real-time quantitative PCR. We defined interphalangeal OA (IPOA) as KL ≥2 in a finger or thumb joint (excluding thumb-base); and incidence if KL score increased from ≤1 to ≥2. We defined symptomatic IPOA as KL≥2 in ≥1 joint on 2 different fingers and report of hand pain (“During the past 30 days, pain, aching or stiffness on most days”) after baseline. We analyzed the standardized log of telomere length as a predictor for OA incidence at a joint level and across all joints using generalized linear mixed models to control for confounders and account for within-person correlation among joints.

Results: 275 participants were eligible for the analysis (mean baseline age 59.1y [s.d.8.7], 56.7% female, BMI 27.4 Kgm^-2[4.4], 39 [14.2%] physician-diagnosed hand OA). 494 joints had OA at baseline and 47 developed incident IPOA. Prevalent IPOA at baseline was cross-sectionally associated with older age (OR=2.2; 95% CI 1.8, 2.6) and shorter telomere length (OR=1.3; 1.1, 1.6) but not with gender or BMI (all mutually adjusted). In prospective analyses with adjustment for age, BMI and gender, shorter telomere length predicted IPOA incidence in a joint (OR=1.5, 1.07, 2.1 -i.e. for every s.d. decrease in log of telomere length there is 50% increase in the likelihood of OA incidence); and the increase in number of affected joints (β=0.06, p=0.02), as well as incidence of symptomatic IPOA (OR=1.7, 1.1, 2.7). This association was consistent in the smaller subset without HOA at baseline (OR=1.7, 0.99, 2.8).

Conclusion: Shorter PBL telomere length is strongly and independently associated with prevalent and incident OA in finger joints and development of symptomatic IPOA. This may indicate an accelerated ageing phenotype associated with impaired chondrocyte function and capacity of cartilage and joint structures to maintain health and respond to biomechanical and inflammatory/metabolic stressors, leading to OA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/incident-hand-oa-is-strongly-associated-with-reduced-peripheral-blood-leukocyte-telomere-length/