Metabolic Syndrome-Associated Osteoarthritis: Global Burden and Associations of the C-Reactive Protein-Triglyceride Glucose Index and Platelet-to-HDL-C Ratio in CHARLS and NHANES.

BACKGROUND: Osteoarthritis (OA) represents a significant global health concern, and metabolic factors may contribute to its development. We assessed the global burden of OA and metabolic-attributable disability and examined associations of two biomarkers-the C-reactive protein-Triglyceride Glucose Index (CTI) and Platelet-- to-High-Density Lipoprotein Cholesterol Ratio (PHR)-with Metabolic Syndrome-associated Osteoarthritis (MetS-OA). METHODS: Three datasets were used in this study: the Global Burden of Disease (GBD) 2021, the China Health and Retirement Longitudinal Study (CHARLS; baseline data from 2011), and the National Health and Nutrition Examination Survey (NHANES; data from 2003 to 2010). GBD data were used to quantify OA burden, metabolic attribution, and projected trends. CHARLS and NHANES were analysed using multivariable logistic regression, subgroup analyses, Restricted Cubic Spline (RCS) modelling, and threshold- effect analysis. Discrimination was assessed using Receiver Operating Characteristic (ROC) curves. RESULTS: From 1990 to 2021, annual incident OA cases increased from 20.9 to 46.63 million, with an estimated global prevalence exceeding 600 million. The proportion of OA DALYs attributable to metabolic factors rose from 16% to 21%, and the age-standardised DALY rate is projected to reach 258.24 per 100,000 by 2035. We included 9,183 CHARLS and 3,842 NHANES participants. In fully adjusted models, CTI and PHR were associated with higher odds of MetS-OA (per 1-unit increase: CTI OR = 2.03 and 1.67 in CHARLS and NHANES, respectively; PHR OR = 1.11 and 1.12, respectively). CTI showed non-linearity in CHARLS (threshold 9.20) but not in NHANES (P for non-linearity = 0.136), whereas PHR showed non-linearity in both datasets (thresholds 8.02 and 8.43). Discrimination was moderate for CTI (AUC 0.74/0.66) and modest for PHR (AUC 0.63/0.59). DISCUSSION: These findings place metabolic factors in a broader context as an increasingly important contributor to the global OA burden. CTI and PHR were positively associated with MetS-OA in two independent cross-sectional datasets. These markers showed limited-to-moderate discriminatory ability, but their clinical utility and predictive value require longitudinal and external validation. CONCLUSION: This study highlights the potential role of metabolic factors in osteoarthritis and links CTI and PHR with MetS-OA in adults 45 years or older. However, longitudinal studies are needed to confirm these associations and assess predictive value.