Knee osteoarthritis and the risk of premature mortality in the community: An international individual patient level meta-analysis in 9889 subjects

Abstract

sensitization/pain sensitivity; at a site of disease (e.g., knee), it indicates peripheral sensitization, and at a site without disease (e.g., wrist), it indicates central sensitization. The Intermittent and Constant OA Pain (ICOAP) instrument assesses presence and severity of intermittent and constant pain, and for intermittent pain, its frequency. Using the knee-specific ICOAP, pain patterns were defined as: 1) no intermittent or constant pain; 2) intermittent pain only (of at least mild severity occurring at least sometimes); and 3) constant pain (of at least mild severity) with or without intermittent pain. Among subjects with either no pain or intermittent pain only at baseline, we evaluated the relation of baseline PPT to incidence of constant pain using logistic regression. We evaluated baseline PPT as a continuous measure, and also evaluated PPT as tertiles to evaluate for a dose-response and threshold effect. All analyses were adjusted for age, sex, BMI, depressive symptoms, catastrophizing, widespread pain, and clinic site. Results: There were 1951 subjects included (mean age 68, 60% female, mean BMI 31), of whom~8% developed constant pain over two years. A higher level of sensitization, as reflected by lower PPT, was associated with higher risk of developing incident constant pain [knee PPT: OR 1.14 (95% CI 1.01e1.27, p ¼ 0.03); wrist PPT: OR 1.12 (95% CI 0.97e1.33, p ¼ 0.1)]. Figure 1 illustrates the adjusted ORs for risk of incident constant pain by PPT tertiles for the knee (p ¼ 0.05) and the wrist (p ¼ 0.02). Because there appeared to be a threshold effect for the wrist PPT, we evaluated the lowest PPT tertile with the higher two tertiles. The lowest knee PPT tertile, reflecting greater peripheral sensitization, was associated with a higher risk of developing incident constant pain compared with the two higher PPT tertiles (less sensitization) [OR: 1.57 (95% CI 1.00e2.48, p ¼ 0.05)]. Similarly, a higher level of central sensitization as measured by the lowest wrist PPT tertile was also associated with a higher risk of incident constant pain [OR: 2.01 (95% CI 1.15e3.51, p ¼ 0.01)]. Conclusions: Higher levels of peripheral and central sensitization were associated with greater risk of evolution or progression of the pain pattern from no or intermittent pain to constant pain over time. These findings support the hypothesis that sensitization plays an important role in changing a patient's pattern and severity of OA-related pain. These findings have implications for understanding the transition from acute to chronic pain.

Is osteoarthritis a deadly disease?

“…Veronese et al [8][9][10] performed a meta-analysis of the literature and found that hip or knee OA was associated with increased mortality (HR 1.18[95% CI 1.08-1.28]). 8 This study also found that hip or knee OA was associated with a 21% increase in cardiovascular mortality.…”