{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T04:59:15Z","timestamp":1780462755126,"version":"3.54.1"},"reference-count":18,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T00:00:00Z","timestamp":1759363200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Osteoporosis (OP) is a growing global public health challenge, often underdiagnosed and underestimated due to limitations in current diagnostic tools such as DXA-based bone mineral density (BMD) assessment and FRAX score. These methods do not fully capture fracture risk nor account for gender-specific and metabolic differences. A novel patented diagnostic method, based on the <jats:italic>in vitro<\/jats:italic> behavior of peripheral mononuclear cells (PBMCs) may offer a more accessible, dynamic, and biologically representative approach to OP diagnosis and stratification.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods and analysis<\/jats:title><jats:p>This multicenter, double-blind, cross-sectional clinical trial protocol aims to evaluate the diagnostic potential of the PBMC-based test using blood samples (2\u20135 mL) from 120 participants stratified by BMD (healthy, osteopenic, osteoporotic fractured and non-fractured). PBMCs are isolated and cultured <jats:italic>in vitro<\/jats:italic> to assess viability, number, size, and spontaneous osteoclast differentiation over time. Additionally, blood samples are analyzed for T lymphocyte subpopulations, pro- and anti-inflammatory cytokines, platelet-related parameters, and markers of bone turnover. All outcomes are analyzed considering gender differences. Correlation and accuracy analyses will determine the relationship between cellular and biochemical markers and OP status.<\/jats:p><\/jats:sec><jats:sec><jats:title>Ethics and dissemination<\/jats:title><jats:p>The study protocol has been approved by Emilia Romagna\u2019s Ethics Committee (CE-AVEC), Bologna, Italy. Written informed consent is obtained from all participants. Findings of this study will be disseminated through peer-reviewed publications and conference presentations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical Trial Registration<\/jats:title><jats:p><jats:uri>https:\/\/clinicaltrials.gov\/<\/jats:uri>, identifier NCT06551155.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1647800","type":"journal-article","created":{"date-parts":[[2025,10,2]],"date-time":"2025-10-02T04:21:08Z","timestamp":1759378868000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Sustainable innovation with a method based on peripheral mononuclear cells to screen, monitor and stratify the population at risk of osteoporosis and fractures \u2013 a multicenter cross-sectional trial 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