Background: Spontaneous joint bleeding is common in people with hemophilia (PWH). These bleeds lead to reduced physical activity and thus to a weakening of the musculature. Common sequelae of this are synovitis and cartilage damage. In the long term, secondary osteoarthritis, so-called hemophilic arthropathy, occurs with changes and progressive destruction of joint structures (Lafeber et al., 2008). Hemophilic arthropathy is age-independent and can lead to severe movement restrictions and significant limitations in health-related quality of life (HRQoL) of affected PWH (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 the subjective (Hemophilia Exercise Project Test-Questionnaire [HEP-Test-Q]) and objective physical functioning (Hemophilia Joint Health Score [HJHS]) during the course of 1-year applied physiotherapy comparing PWH with arthropathy and patients with osteoarthritis (PWO). Methods: In this prospevtive, controlled monocentric cohort study it was planned to enroll 20 adult PWH A or B compared to 20 gender-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 based on clinician-reported outcomes (ClinRO) and performance outcomes (PerfO) and completed different patient-reported outcomes (PROs). ClinROs included ultrasound, functional movement screen (FMS) and the collection of anthropometric and clinical data; PerfOs included cardiopulmonary performance, 6-minute walk test (6MWT), blood pressure measurement before and after 6MWT, joint mobility (neutral-zero method) and Functional Movement Screen (FMS) to evaluate movement pattern quality; PROs included the assessment of sociodemographic data, HRQoL (SF-12), Physical Activity Questions (EPIC - Simple Index), pain sensation scale (SES) and Borg Rating of Perceived Exertion (RPE) measuring physical activity intensity level. 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, ClinROs, PerfOs and PROs 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%) 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<.002) 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 domain ‘mobility’, while PWH suffered mainly under reduced ‘endurance’. With respect to their age, height and weight most of the PWH were below the predicted lower limit of the 6MWD compared to the PWO who all were above the lower limit of the 6MWD. No difference was found between the groups regarding FMS (11.34±3.8) and RPE before (11.5±3.3) after 6MWT (11.5±3.3). Conclusions: 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 lead to a high drop-out rate over the duration of the project. Although PWH were significantly younger than PWO, they had a significantly worse subjective (HEP-Test-Q) and objective physical functioning (HJHS).