: Background: There have been few studies reporting the association between health-related quality of life (HRQoL) and osteoarthritis (OA) in female subjects performing aerobic exercise or not. The aim of this study is to compare HRQoL between OA patients and non-OA subjects in middle aged Korean women (40–59 y) with/without aerobic physical activity, and also to identify an association between EQ-5D instrument based HRQoL and OA controlling for aerobic exercise. Methods: This study used the cross-sectional data, the Korea National Health and Nutrition Examination Survey (KNANES) from 2016 to 2017. We only selected those who had completed the evaluations of aerobic physical activity and osteoarthritis diagnosis. In total, 2445 middle aged women were finally selected for this study. The European quality of life-5 dimensions (EQ-5D) was used for the evaluation of HRQoL as a dependent variable. In socio-demographic factors, age, sex, income level, education level, marital status, economic activity, type of insurance and private insurance and behaviour-related factors were included. One-way analysis of variance was conducted to compare the EQ-5D index and multiple linear regression analysis was employed to identify associated factors with the EQ-5D index. Results: In total, 2445 middle aged women were included in this study, in which 2209 participants were normal (90.0%) with aerobic physical activity (no: 55.0%, yes: 45.0%) and 246 participants were diagnosed with osteoarthritis (10.0%) with aerobic physical activity (no: 56.1%, yes: 43.9%). In group 2-2 (OA with aerobic), the moderate level of muscle exercise (less than 5 days per week) showed the highest HRQoL (p < 0.05) and high level exercise showed the lowest HRQoL (p < 0.05). In menopause status, the participants under menopause status showed lower HRQoL (p < 0.05) than those not under menopause status in group 2-2 (OA with aerobic) only. Conclusion: The HRQoL of OA patients was significantly lower than that of normal participants in middle aged Korean women (40–59 y). Especially, OA patients with maintained aerobic physical activity showed significantly higher HRQoL than those without that under controlling covariates such as age, income level, education level, marital status, economic activity, type of insurance, etc.
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