Individuals with osteoarthritis (OA) often experience significant changes in their metabolic status and have a higher risk of mortality compared to the general population. However, no study has quantified the metabolic status of OA patients. Moreover, the association between metabolic status and risk of mortality among OA patients remains unclear. The analysis included baseline populations with OA from the UK Biobank (UKBB) study and the National Health and Nutrition Examination Survey (NHANES) 1999–2018. Metabolic status was assessed using composite scores based on body mass index, waist-hip ratio, blood pressure, fasting plasma glucose, hemoglobin A1c, C-reactive protein, triacylglycerols, and lipoproteins. Restricted cubic splines were used to define healthy ranges for each indicator regarding mortality risk. Factors received 1 if within a healthy range, else 0. Total scores ranged from 0 to 7, with 3+ indicating good metabolic health. The traditional metabolic syndrome criteria (ATP III) and the Strict definition were used for comparison. Associations between metabolic unhealth and mortality were examined using Cox proportional hazards models. Integrated Discrimination Improvement (IDI) evaluated discriminatory capacity, and Net Reclassification Improvement (NRI) assessed reclassification performance in predicting ten-year mortality. Among 44,302 UKBB OA participants, 36.0 % were metabolically unhealthy (scores: 0–2), while in 5233 NHANES OA participants, 39.1 % were metabolically unhealthy based on our newly-established definition. After adjustment for covariates, metabolically unhealthy individuals had significantly higher all-cause mortality risk (HR: 1.36; 95 % CI: 1.26–1.47 in UKBB; HR: 1.16; 95 % CI: 1.03–1.30 in NHANES) compared to metabolically healthy individuals. In UKBB, compared to ATP III definition, the changes in IDI and NRI for our newly-established definition were 0.10 % (0.01 %, 0.20 %) and 10.60 % (1.8 %, 13.60 %), respectively. When the comparison was made with the Strict definition, the newly-established definition showed changes in IDI and NRI of 0.18 % (0.10 %, 0.20 %) and 12.10 % (10.30 %, 13.80 %), respectively. results. A new definition for quantifying metabolic unhealth in OA was proposed. It identified a significant mortality risk with poorer metabolic status and outperformed general definitions in predictive accuracy. conclusion. OA is the leading joint disease worldwide, carrying a heavy health burden. Our newly established definition, evaluating metabolic health through waist-to-hip ratio, BMI, blood pressure, glucose, lipids, and C-reactive protein, identified 36.0 % OA patients in UK Biobank and 39.1 % OA patients in NHANES as having poor metabolic status, which is applicable in clinical and research settings. This study also showed that poor metabolic status, as classified by these criteria, is significantly correlated with an elevated risk of all-cause mortality in OA patients. It further highlights the importance of maintaining a holistic approach to care for OA patients, emphasizing the need to address both joint and metabolic health.

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OBJECTIVE: To investigate the association of both individual and combined healthy lifestyle factors with the risk of all-cause mortality among patients with osteoarthritis (OA). DESIGN: Prospective population-based cohort study. SETTING: UK biobank and US National Health and Nutrition Examination Survey (US NHANES, 2007-2018) PARTICIPANTS: 104, 142 UK participants with OA aged 39-72 years and 3, 472 US participants with OA aged 20-80 years. EXPOSURES: Individual healthy lifestyle factors and a combined healthy lifestyle score were constructed from body mass index (BMI) and self-reported information on diet, sleep duration, physical activity, sedentary time, social connection, smoking and alcohol drinking. MAIN OUTCOME MEASURES: All-cause mortality was the primary outcome in both studies. Secondary outcomes included cause-specific mortalities (cardiovascular, cancer, digestive and respiratory). Hazard ratios were adjusted for age, sex, economic situation, race, education and employment (UK biobank only). RESULTS: UK Biobank documented 9,914 deaths during a median follow-up of 12.7 years, and US NHANES documented 463 deaths during a mean follow-up of 6.01 years. For all-cause mortality using restricted cubic spline graph (RCS) models, sleep duration had a U-shaped (with a nadir at 7 hours/day), moderate physical activity (MPA) had an L-shaped (with a turning point at 550 minutes/week), while BMI, vigorous physical activity (VPA) and sedentary time had J-shaped (with turning points at 28 kg/m ² , 240 minutes/week and 5 hours/day, respectively) associations in the UK biobank. Similar results were observed in US NHANES. In multivariable Cox models, each healthy lifestyle factor was significantly associated with all-cause mortality (hazard ratio [HRs] range 0.49 to 0.84 for UK biobank, and 0.26 to 0.73 for US NHANES), and HRs (95% CI) for associations with combined healthy lifestyle score (scoring 6-8 vs. 0-2) were 0.38 (0.35, 0.41) in UK biobank and healthy lifestyle score (scoring 5-7 vs. 0-1) were 0.20 (0.13, 0.31) in US NHANES for all-cause mortality. The results for cause-specific mortality were largely similar and consistent across two cohorts. CONCLUSIONS: The nonlinear relationships suggested patients with OA had the lowest risk of all-cause mortality when BMI was 28 kg/m ² , sleep was 7 hours/day, VPA was 240 minutes/week, sedentary time was less than 5 hours/day, MPA was more than 550 minutes/week. The newly constructed healthy lifestyle score for OA population was associated with a significantly lower risk of all-cause mortality. WHAT IS ALREADY KNOWN ON THIS TOPIC: Healthy lifestyles are thought to reduce the risk of multiple causes of mortality in the general population. People with osteoarthritis (OA) are at higher risk of mortality than the general population. However, evidence of associations between combined healthy lifestyle and risks of all-cause and cause-specific mortality among OA patients are lacking. Whether and what kind of healthy lifestyles in patients with OA could offset the risk of mortality are unknown. WHAT THIS STUDY ADDS: By using two nationwide cohort studies in UK and US, a comprehensive healthy lifestyle pattern that integrates 8 or 7 lifestyle factors was established among OA individuals for the first time. People who had the highest combined healthy lifestyle score were significantly associated with 62% to 80% lower risk of all-cause mortality compared with those who had the lowest score in both the UK and US OA populations.