OBJECTIVES: This study aimed to investigate the associations between radiographic damage, serum biomarkers, and clinical assessments in Czech patients with hand osteoarthritis (HOA) over a five-year follow-up period. METHODS: The study cohort comprised 129 patients diagnosed with HOA, including 72 patients with an erosive subtype and 57 patients with a non-erosive subtype. Radiographs were evaluated using the Kallman scoring system by two independent readers. Blood samples were analysed for markers of dyslipidaemia, bone metabolism, and inflammation. Clinical assessments focused on symptom severity and functional impairment. We employed generalised additive modelling (GAM) to analyse the associations between the Kallman score, serum biomarkers and clinical outcomes. RESULTS: The Kallman score was consistently higher in the erosive subtype compared to the non-erosive subtype across all time points and demonstrated a positive correlation with age in both groups. We demonstrated significant positive associations between radiographic progression and erythrocyte sedimentation rate across both HOA subtypes. Additionally, positive associations with the number of swollen joints and health assessment questionnaire scores were observed in all HOA patients, particularly in those with non-erosive subtypes. In contrast, markers of dyslipidaemia (e.g. LDL‑c or atherogenic index) were negatively associated with radiographic progression. No biomarker reliably differentiated between the erosive and non-erosive subtypes. CONCLUSIONS: Our longitudinal study revealed a significant association between systemic/local inflammation, dyslipidaemia, functional impairment and structural progression in HOA. However, these findings warrant further validation through additional studies to confirm these associations.