Abstract
<title>Abstract</title> <p>Objective The neutrophil-to-lymphocyte ratio (NLR) is a cost-effective indicator of systemic inflammation. This study aimed to systematically evaluate the dynamics and translational relevance of NLR in osteoarthritis (OA), determining its utility and constraints as a biomarker for monitoring disease progression. Design: NLR dynamics were assessed in both bone marrow and peripheral blood using destabilization of the medial meniscus (DMM) surgery and natural aging mouse models. Translational relevance was validated by analyzing large-scale clinical datasets from healthy donors (n = 3482) and patients with knee or hip OA, examining associations between NLR, age, body mass index (BMI), and radiographic severity. Results In DMM and aged mice, peripheral blood NLR was significantly elevated and more sensitive than bone marrow NLR in reflecting OA progression. In human cohorts, peripheral NLR increased significantly with age in both sexes and was higher in OA patients compared to healthy controls. However, NLR did not correlate with BMI nor distinguish between moderate (grade 3) and severe (grade 4) radiographic OA. Human bone marrow NLR exhibited a baseline value of approximately 6, markedly higher than peripheral levels. Conclusion Peripheral blood NLR serves as a context-dependent biomarker for OA, effectively capturing age-associated systemic inflammation and discriminating OA patients from healthy individuals. However, it fails to reflect mechanical overload-driven disease or radiographic severity, highlighting distinct inflammatory endotypes in OA pathogenesis. The established human bone marrow NLR reference range provides a foundation for future investigations into hematopoietic contributions to OA.</p>