Neuro-axonal injury biomarker serum neurofilament light chain is associated with osteoarthritis: a dual-cohort study from NHANES and UK Biobank

Background Osteoarthritis (OA) affects over half a billion people globally, representing a major public health burden. Serum neurofilament light chain (sNFL) has recently been implicated in systemic inflammation and metabolic disorders.Research design and methods This dual-cohort study analyzed data from the National Health and Nutrition Examination Survey (NHANES) and the UK Biobank. In NHANES, sNFL was measured via a high-sensitivity immunoassay, while in UKB, NfL was quantified using the Olink Explore 3072 proteomics platform. OA was defined by self-report in NHANES, and a combination of self-report and ICD-10 hospital records in UKB. The associations were evaluated using multivariate logistic regression and RCS.Results Higher sNFL levels were significantly associated with increased OA odds in both cohorts. In fully adjusted models, each 1-unit increase in log-transformed sNFL corresponded to 85% higher odds in NHANES [OR = 1.85, 95% CI: (1.51, 2.23)] and 28% higher odds in UKB [OR = 1.28, 95% CI: (1.21, 1.36)]. Comparing the highest to lowest quartiles, ORs were 4.41 (95% CI: 2.71, 7.13) and 1.46 (95% CI: 1.34, 1.59), respectively (both P for trend < 0.01).Conclusions Elevated sNFL levels are independently and consistently associated with a higher prevalence of OA across two distinct national cohorts.