{
  "abstract": "ObjectivesObservational studies report large, conflicting associations between common drugs and hip or knee replacement. We tested them in the serious adverse event (SAE) tables of randomized trials on ClinicalTrials.gov.\n\nMethodsWe included randomized drug trials with [≥]500 participants. A language model classified arms from summaries without outcome counts (masked by instruction only). We pooled osteoarthritis-related SAEs by drug class as Mantel-Haenszel risk ratios (RRs). Because the plan followed a preliminary analysis of 72 trials, we report estimates rather than tests, checked by positive and negative controls and calibration.\n\nResultsThe 881 placebo- or usual-care-controlled trials included 1.75 million participants and 9,408 osteoarthritis-related SAEs. The tables reproduced CANTOSs own canakinumab effect (RR 0.57, 95% CI 0.39 to 0.82), the anti-nerve growth factor excess (2.31, 1.82 to 2.92) and two of three modest effects specified before extraction: gallbladder disease with glucagon-like peptide-1 receptor agonists (GLP-1RAs; 1.36, 1.22 to 1.51) and ketoacidosis with sodium- glucose cotransporter-2 (SGLT2) inhibitors (1.96, 1.48 to 2.60). In the same trials, osteoarthritis-related SAEs did not differ detectably with GLP-1RAs (0.97, 0.86 to 1.10; calibrated 0.87, 0.54 to 1.41) or SGLT2 inhibitors (0.96, 0.82 to 1.12; calibrated 0.86, 0.53 to 1.40). Other proposed drugs gave imprecise estimates. Post hoc, 8 of 21 published observational estimates differed from randomized ones, in both directions (3 to 6 after calibration).\n\nConclusionsOver about two years, GLP-1RAs and SGLT2 inhibitors had no detectable effect on osteoarthritis-related SAEs in trials that detected their known effects. Slow or modest structural effects remain possible.\n\nKey messagesWhat is already known on this topic O_LIObservational studies associate glucose-lowering drugs, bisphosphonates and warfarin with large and conflicting changes in the risk of hip or knee replacement; randomized evidence is limited to a few exploratory analyses of single trials. C_LI\n\nWhat this study adds O_LIGLP-1 receptor agonists and SGLT2 inhibitors had no detectable effect on serious osteoarthritis events over about two years, in randomized trials whose adverse-event tables detected these drugs known effects. C_LI\n\nHow this study might affect research, practice or policy O_LITrial registries can test osteoarthritis repurposing signals for large, short-term effects before dedicated trials are funded; slow structural effects still need such trials. C_LI",
  "abstract_shown": true,
  "affiliations": [
    "Hubei University of Medicine"
  ],
  "article_type": "PUBLISHAHEADOFPRINT",
  "arxiv": null,
  "author_total": 7,
  "authors": [
    {
      "name": "Z. Xu"
    },
    {
      "name": "M. Pan"
    },
    {
      "name": "J. Cheng"
    },
    {
      "name": "X. Chen"
    },
    {
      "name": "J. Luo"
    },
    {
      "affs": [
        0
      ],
      "name": "X. Guo"
    },
    {
      "name": "X. Zhu"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/d0xtnd8yhnecd.bib",
  "cited_by": 0,
  "doi": "10.64898/2026.10.13.26365377",
  "fulltext_url": "https://www.medrxiv.org/content/10.64898/2026.10.13.26365377v1.full",
  "id": "d0xtnd8yhnecd",
  "issns": [],
  "landing_url": "https://www.medrxiv.org/content/10.64898/2026.10.13.26365377v1",
  "language": null,
  "licence": "CC-BY-NC-ND",
  "licence_label": "CC BY-NC-ND",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by-nc-nd/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "medrxiv",
      "rheumatology"
    ],
    [
      "openalex",
      "3005|Pharmacovigilance and Adverse Drug Reactions"
    ]
  ],
  "openalex": "W7221749008",
  "pdf_url": "https://www.medrxiv.org/content/10.64898/2026.10.13.26365377v1.full.pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-13",
  "publisher": null,
  "ris": "https://research.draconitic.com/paper/d0xtnd8yhnecd.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:52Z",
      "native_id": "10.64898/2026.10.13.26365377",
      "source": "medrxiv",
      "url": "https://www.medrxiv.org/content/10.64898/2026.10.13.26365377v1"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:3005|Pharmacovigilance and Adverse Drug Reactions",
      "subfield": "pharmacology-toxicology"
    }
  ],
  "title": "Do drugs proposed to protect or harm joints change serious osteoarthritis events? A meta-analysis of adverse event tables from 881 randomized trials",
  "title_text": "Do drugs proposed to protect or harm joints change serious osteoarthritis events? A meta-analysis of adverse event tables from 881 randomized trials",
  "type": "preprint",
  "updated_at": "2026-10-30T12:20:52Z",
  "url": "https://research.draconitic.com/paper/d0xtnd8yhnecd",
  "venue": "medRxiv",
  "versions": []
}