Objective: Genetic factors play an important role in the pathogenesis of knee osteoarthritis (OA), but which knee structural changes mediate this is unclear. This study aimed to describe the differences in knee structural changes over 8-10 years between offspring having at least one parent with total knee replacement (TKR) for severe primary knee OA and controls with no family history of knee OA. Design: 115 offspring (mean age 45 years) with a family history of TKR for severe knee OA were compared with 104 (mean age 46 years) controls. T1 or T2-weighted fat saturated magnetic resonance imaging (MRI) was performed respectively to evaluate knee cartilage defects, bone marrow lesions (BMLs), meniscal extrusion and tears at baseline and 10 years. Multivariate logistic regression model was used to adjust for potential confounders. Results: Offspring had a greater increase in cartilage defect score (1.03 vs 0.52, P=0.007) and meniscal extrusion score (0.28 vs 0.10, P=0.027) over 10 years, and a greater increase in meniscal tear score (0.40 vs 0.10, P=0.012) over 8 years in the medial but not the lateral tibiofemoral compartment. Changes in BMLs over 8-years were not different between the two groups. These associations were independent of potential confounders, and strengthened after further adjustment for each other. Conclusion: With the exception of BMLs, offspring with a family history of knee OA have a greater risk of increases in multiple knee structural abnormalities in the medial tibiofemoral compartment suggesting pleiotropic familial effects.