Objective:To delineate the histomorphological disparities of subchondral bone between hemophilic arthritis (HA) and osteoarthritis (OA) and to explore the mechanisms underpinning aberrant bone remodeling in HA.Methods:Fifteen male HA patients, aged 32.60±7.58 years (range 22-45), who underwent total knee arthroplasty at the Second Affiliated Hospital of Anhui Medical University from January 2021 to June 2023, were included. All patients had hemophilia A and tested negative for coagulation factor VIII antibodies. Simultaneously, fifteen male OA patients, aged 75.67±5.09 years (range 71-87), also underwent arthroplasty. Tibial plateau bones were extracted for micro-CT, which assessed morphological parameters. Histological changes in the subchondral bone plate (SBP) and trabecular bone were evaluated with HE and Safranin O-Fast Green staining. TRAP staining determined osteoclast differentiation levels, and VEGF-A and Osterix immunohistochemistry gauged angiogenesis and osteoblast differentiation.Results:Micro-CT revealed that HA patients had a BV/TV of 25.14%±0.70% (medial) and 22.31%±0.53% (lateral), Conn.D. of 4.20±0.10 1/mm 3 (medial) and 3.27±0.08 1/mm 3 (lateral), BMD of 0.288±0.006 g/cm 3 (medial) and 0.285±0.004 g/cm 3 (lateral), Tb.Th of 0.257±0.008 mm (medial) and 0.206±0.008 mm (lateral), Tb.N of 0.984±0.043 1/mm (medial) and 0.908±0.026 1/mm (lateral), and Tb.Sp of 0.683±0.008 mm (medial) and 0.808±0.010 mm (lateral). These parameters were significantly lower than those in the OA group except for Tb.Sp, which was higher ( P<0.001). Histological staining indicated that the HA group's SBP thickness was 177.43±6.42 μm (medial) and 117.96±5.08 μm (lateral) with significant differences observed ( P<0.001). TRAP staining showed that TRAP + osteoclasts accounted for 33.4%±3.1% (medial) and 25.1%±2.3% (lateral) in HA subchondral bone, again significantly different ( P<0.001). Immunohistochemical staining revealed VEGFA + cells at 34.1%±5.9% (medial) and 25.9%±3.7% (lateral), and Osterix + cells at 14.6%±1.4% (medial) and 5.8%±1.1% (lateral) in HA patients, differing significantly from the OA group ( P<0.001). Conclusion:The HA group exhibited more extensive subchondral bone destruction, thinner trabeculae, a nearly absent tidemark, higher osteoclast differentiation, increased angiogenesis, and reduced osteoblast differentiation, indicating severe osteoporosis, despite thicker SBP. These findings suggest that targeting abnormal bone remodeling and angiogenesis in HA could retard its progression and provide therapeutic benefits.