{
  "abstract": "Background: Whether localized joint failure in knee osteoarthritis (KOA) interacts with systemic pathways, including psychological distress and neuro-endocrine stress response, to precipitate systemic bone fragility remains an unresolved question. Capitalizing on the large-scale prospective design of the UK Biobank and translational clinical biomarker profiling, this investigation aims to clarify this association and delineate the long-term risk profile linking joint failure to systemic skeletal degradation.\n\nMethods: This prospective analysis tracked 406,810 participants who were free of metabolic bone disease or confounding joint pathologies at baseline. Participants were stratified by ICD-10 defined KOA status, with incident OP serving as the primary longitudinal endpoint over a median 10-year follow-up. Survival profiles were contrasted via log-rank tests, and multivariable Cox proportional hazards formulations were constructed to yield rigorously adjusted hazard ratios (HR) controlling for socioeconomic deprivation, lifestyle habits, multi-systemic comorbidities, and history of malignancies. To validate these epidemiological findings in human biology, circulating bone resorption biomarkers (β-CTX and TRACP-5b) were further evaluated in an independent clinical validation cohort of 35 KOA patients and 30 matched controls.\n\nResults: Long-term follow-up unveiled a clear divergence in bone health trajectories, with the KOA cohort experiencing a significantly elevated cumulative OP incidence of 5.2 vs. 3.9% in the unexposed reference group (log-rank p < 0.001). Fully adjusted multivariable modeling confirmed KOA as a robust, standalone predictor of systemic skeletal deterioration, conferring a 22% independent risk premium (HR = 1.22, 95% CI: 1.16–1.29). While vulnerability was compounded by current smoking, physical inactivity, high Townsend deprivation, and cardiometabolic clusters, enhanced physical and structural reserves (greater grip strength and higher BMI) exerted pronounced protective effects. In parallel, clinical serum profiling validated an upregulation of bone resorption activity in KOA patients, evidenced by elevated circulating levels of β-CTX and TRACP-5b compared with non-OA controls.\n\nConclusion: These findings provide prospective population-level evidence and biochemical validation that knee osteoarthritis is independently associated with an increased risk of osteoporosis. While pain-related physical unloading, low-grade systemic inflammation, and hypothesized neuro-endocrine pathways may underlie this systemic vulnerability, our results highlight the clinical need for comprehensive musculoskeletal monitoring and proactive bone health management in patients with knee osteoarthritis.",
  "abstract_shown": true,
  "affiliations": [
    "Jinshazhou Hospital of Guangzhou University of Chinese Medicine",
    "Dayan Technology (Tongxiang) Co., Ltd",
    "Shenzhen Bao'an Chinese Medicine Hospital, The Seventh Clinical Medical School of Guangzhou University of Chinese Medicine",
    "Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences",
    "SciBio Innovation Technology Limited"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 6,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Weizheng Sun"
    },
    {
      "affs": [
        0
      ],
      "name": "Jianrong Ma"
    },
    {
      "affs": [
        0
      ],
      "name": "Juqin He"
    },
    {
      "affs": [
        1
      ],
      "name": "Yanxin Liu"
    },
    {
      "affs": [
        2,
        3,
        4
      ],
      "name": "Wei Zhang"
    },
    {
      "affs": [
        2
      ],
      "name": "Liang Zhang"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/dsp8ede34n794.bib",
  "cited_by": 0,
  "doi": "10.3389/fpubh.2026.1964979",
  "fulltext_url": null,
  "id": "dsp8ede34n794",
  "issns": [
    "2296-2565"
  ],
  "landing_url": "https://www.frontiersin.org/articles/10.3389/fpubh.2026.1964979/full",
  "language": null,
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "openalex",
      "2732|Bone health and osteoporosis research"
    ]
  ],
  "openalex": "W7223172804",
  "pdf_url": "https://www.frontiersin.org/journals/public-health/articles/10.3389/fpubh.2026.1964979/pdf",
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-22",
  "publisher": "Frontiers Media SA",
  "ris": "https://research.draconitic.com/paper/dsp8ede34n794.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T12:20:24Z",
      "native_id": "10.3389/fpubh.2026.1964979",
      "source": "crossref",
      "url": "https://www.frontiersin.org/articles/10.3389/fpubh.2026.1964979/full"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "openalex:2732|Bone health and osteoporosis research",
      "subfield": "surgery"
    }
  ],
  "title": "Bridging joint degeneration and systemic skeletal fragility: knee osteoarthritis as an independent risk factor for osteoporosis",
  "title_text": "Bridging joint degeneration and systemic skeletal fragility: knee osteoarthritis as an independent risk factor for osteoporosis",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T12:20:24Z",
  "url": "https://research.draconitic.com/paper/dsp8ede34n794",
  "venue": "Frontiers in Public Health",
  "versions": []
}