Abstract
BACKGROUND: Osteoarthritis (OA) and sarcopenia are common musculoskeletal disorders in the aged population, and a growing body of evidence indicated that they mutually influence one another. Nevertheless, there was still substantial controversy and uncertainty about the causal relationship between sarcopenia and OA. We explored the complex association between sarcopenia-related traits and OA using cross-sectional analysis and Mendelian randomization (MR). METHODS: The cross-sectional study used the data from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Weighted multivariable-adjusted logistic regression and subgroup analyses were used to evaluate the correlation between sarcopenia, grip, appendicular lean mass (ALM) and the risk of OA. Then, we further performed MR analysis to examine the causal effect of sarcopenia-related traits (grip strength, ALM) on OA. Instrumental variables for grip strength and ALM were from the UK Biobank, and the summary-level data for OA was derived from the Genetics of Osteoarthritis (GO) Consortium GWAS (n = 826,690). RESULTS: In this cross-sectional analysis, we observed that sarcopenia, grip were significantly linked with the risk of OA (OR 1.607, 95% CI 1.233-2.094, P < 0.001), (OR 0.972, 95% CI 0.964-0.979, P < 0.001). According to subgroup analyses stratified by gender, body mass index (BMI), and age, the significant positive relationship between sarcopenia and OA remained in males, females, the age (46-59 years) group, and the BMI (18.5-24.9 kg/m(2)) group (P < 0.05). Furthermore, MR analysis and sensitivity analyses showed causal associations between right grip, left grip and KOA (OR 0.668; 95% CI 0.509 to 0.877; P = 0.004), (OR 0.786; 95% CI 0.608 to 0.915; P = 0.042). Consistent directional effects for all analyses were observed in both the MR-Egger and weighted median methods. Subsequently, sensitivity analyses revealed no heterogeneity, directional pleiotropy or outliers for the causal effect of grip strength on KOA (P > 0.05). CONCLUSIONS: Our research provided evidence that sarcopenia is correlated with an increased risk of OA, and there was a protective impact of genetically predicted grip strength on OA. These findings needed to be verified in further prospective cohort studies with a large sample size.