Background: Spontaneous joint bleeding is common in people with hemophilia (PWH) leading to reduced physical activity and weakening of the musculature. Common sequelae of this are synovitis and cartilage damage. Following, secondary osteoarthritis, so-called hemophilic arthropathy, occurs with changes and progressive destruction of joint structures (Lafeber et al., 2008). Hemophilic arthropathy can lead to severe movement restrictions and significant limitations in health-related quality of life (HRQoL) (Varaklioti et al., 2018). To prevent advanced stages of arthropathy not only regular assessment of musculoskeletal status and early detection of symptoms, but also daily rehabilitation exercises at home, and implementation of appropriate physiotherapy and medical training are important (Bossard et al., 2008). Home exercises and manual therapy can be used without causing bleeding or pain to improve pain, HRQoL and functionality (Tat et al., 2021). The primary aim of the Physio-FUN study was to assess subjective (HEP-Test-Q]) and objective physical functioning (HJHS]) during the course of 1-year applied physiotherapy comparing PWH with arthropathy and patients with osteoarthritis (PWO). Methods: In this prospective, controlled monocentric cohort study it was planned to enroll 20 adult PWH A or B compared to 20 matched adult PWO without a bleeding disorder. Patients with a blood pressure ≥ 180/110 mmHg were excluded. A positive ethical approval for the study was obtained by the Ethics Committee North Rhine, Germany. After informed consent had been obtained, the study participants underwent examinations and completed questionnaires for Clinical Outcome Assessments (COAs) (see table 1); clinical, anthropometric and socio-demographic data were collected. All patients took part in regular physiotherapy (once a week) at the ARZD as prescribed by a physician. During the study, PWH continued to receive their usual hemophilia treatment regimen without study-related changes. Over a period of 12 months, Clinical Outcome Assessment (COAs) were collected repeatedly on a quarterly basis. Each patient was supposed to participate in 5 measure points (baseline, every 12 weeks over a one-year period). Ultrasound examinations were performed at baseline and at the conclusion at MZP5 in all patients. Results: At baseline 17 PWH (mean age 43.29±13.1 years) and 12 PWO (mean age 61.42±8.5 years) were enrolled; most PWH had HA (88.2%), were severely affected (58.8%), had a target joint (52.6%) and 6/17 had a knee endoprosthesis. 88.2% of PWH had a disabled card (most with a disability degree of ≥ 80) compared to 45.5% of PWO (most with a disability degree of 50). PWH had a significant worse orthopaedic joint status ( p<.003) and subjective physical functioning ( p<.001) compared to PWO; PWH had a mean HJHS of 26.76±18.0 vs. 11.0±5.7 and a mean HEP-Test-Q of 48.12±16.4 vs. 67.08±9.1. PWO reported highest impairments in the HEP-Test-Q domain ‘mobility’, while PWH suffered mainly under reduced ‘endurance’. The NNM showed a significant impairment in the mobility of the left ( p<.001) and right ( p<.013) ankle, 58.3% PWO had no impairments compared to 58.9-76.5% of PWH with moderate-severe impairments. This was confirmed by the ultrasound showing a worse progression of their disease ( p<.001) compared to PWO (mean HEAD-US 11.41±6.5 vs. 3.75±3.3). PWH had a worse HRQoL ( p<.001) (mean PCS of 37.51±8.3 vs. 49.45±7.2) and reported a significant higher ( p<.001) emotional distress due to pain (mean SES affective 30.0±12.8, SES sensory 20.94±6.2 vs. SES affective 16.75±2.6, SES sensory 12.08±2.5). Compared to PWO, PWH had a significant lower PAL-value ( p<.045) describing the level of physical activity over the period of 24 hours, most had a sedentary job (87.5% vs. 50%). Most of the PWH were below the predicted lower limit of the 6MWD compared to the PWO who all were above the lower limit. No difference was found between the groups regarding FMS and RPE before and after 6MWT and in the MCS. Conclusions: Although PWH were significantly younger than PWO, they had a significantly worse subjective and objective physical functioning; in addition they had a worse HRQoL, HEAD-US, NNM, PAL and a higher pain experience. Our study took place during the Corona pandemic and was quite time consuming for the participants, resulting in a failure to reach the desired number of cases and led to a high drop-out rate over the duration of the project.