{
  "abstract": "Background: Hemophilic arthropathy (HA) is a major cause of disability in patients with severe hemophilia A. However, long-term data describing progression to advanced radiographic HA across major joint sites remain limited. We investigated risk factors for progression to advanced HA over extended follow-up.\n\nMethods: We conducted a retrospective cohort study of inhibitor-negative patients with severe hemophilia A followed at our institute between 1984 and 2020. Bilateral elbows, knees, and ankles were evaluated (six joints per patient). HA progression was defined as reaching Arnold–Hilgartner stage ≥ IV. Time to progression was analyzed using Cox proportional hazards models with cluster-robust standard errors, with participant as the clustering variable, to account for within-participant correlation across joints. Covariates included joint site, Arnold–Hilgartner stage at initiation of regular prophylaxis, age at first visit to our institute, prophylaxis status at the first visit, and laterality.\n\nResults: The cohort included 109 patients (mean age at first visit to our institute, 14.3 years). At the first visit, Arnold–Hilgartner stage ≥ I changes were present in 15% of elbows (29/200), 8% of knees (16/200), and 27% of ankles (51/186). Across 583 joints and 8,634 joint-years of follow-up, 94 joints progressed to stage ≥ IV (10.9 per 1,000 joint-years of follow-up). In multivariable analysis, baseline radiographic status at the start of regular prophylaxis was strongly associated with progression (vs stage 0: stage I HR 14.95; stage II HR 11.84; stage III HR 34.47). Patients already receiving regular prophylaxis at the first visit had a lower risk of progression (HR 0.54). After adjustment, joint-site differences were not evident, and the independent association of age at first visit to our institute with progression was not estimated with sufficient precision.\n\nConclusions: Baseline radiographic status at initiation of regular prophylaxis was strongly associated with long-term progression to advanced radiographic HA. These findings support initiating regular prophylaxis before radiographic joint changes become established.\n\nSupplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12891-026-10343-9.",
  "abstract_shown": true,
  "affiliations": [
    "Department of Orthopedics, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi, Kitakyushu, 8078555 Japan",
    "Department of Environmental Epidemiology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi, Kitakyushu, 8078555 Japan",
    "Department of Pediatrics, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi, Kitakyushu, 8078555 Japan"
  ],
  "article_type": "research article",
  "arxiv": null,
  "author_total": 10,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Hitoshi Suzuki",
      "orcid": "0000-0001-6936-3019"
    },
    {
      "affs": [
        1
      ],
      "name": "Yoshihisa Fujino"
    },
    {
      "affs": [
        2
      ],
      "name": "Rie Shirayama"
    },
    {
      "affs": [
        0
      ],
      "name": "Takafumi Tajima"
    },
    {
      "affs": [
        0
      ],
      "name": "Yoshiaki Yamanaka"
    },
    {
      "affs": [
        0
      ],
      "name": "Kotaro Tokuda"
    },
    {
      "affs": [
        0
      ],
      "name": "Manabu Tsukamoto"
    },
    {
      "affs": [
        0
      ],
      "name": "Tomoya Arashi"
    },
    {
      "affs": [
        2
      ],
      "name": "Reiji Fukano"
    },
    {
      "affs": [
        0
      ],
      "name": "Akinori Sakai"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/4r4mdd2e8c42j.bib",
  "cited_by": 0,
  "doi": "10.1186/s12891-026-10343-9",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13737607/",
  "id": "4r4mdd2e8c42j",
  "issns": [
    "1471-2474"
  ],
  "landing_url": "https://doi.org/10.1186/s12891-026-10343-9",
  "language": "en",
  "licence": "CC-BY-NC-ND-4.0",
  "licence_label": "CC BY-NC-ND 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Research"
    ],
    [
      "openalex",
      "2720|Hemophilia Treatment and Research"
    ]
  ],
  "openalex": "W7201968535",
  "pdf_url": null,
  "pmcid": "PMC13737607",
  "pmid": "42983703",
  "published": "2026-08-08",
  "publisher": "BMC",
  "ris": "https://research.draconitic.com/paper/4r4mdd2e8c42j.ris",
  "sources": [
    {
      "first_seen": "2026-11-09T12:22:45Z",
      "native_id": "PMC13737607",
      "source": "pmc",
      "url": "https://doi.org/10.1186/s12891-026-10343-9"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2720|Hemophilia Treatment and Research",
      "subfield": "general"
    }
  ],
  "title": "Long-term risk factors for hemophilic arthropathy in patients with severe hemophilia A: a 36-year retrospective cohort study",
  "title_text": "Long-term risk factors for hemophilic arthropathy in patients with severe hemophilia A: a 36-year retrospective cohort study",
  "type": "peer-reviewed",
  "updated_at": "2026-11-09T12:22:45Z",
  "url": "https://research.draconitic.com/paper/4r4mdd2e8c42j",
  "venue": "BMC Musculoskeletal Disorders",
  "versions": []
}