{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T06:05:04Z","timestamp":1784613904507,"version":"3.55.0"},"reference-count":144,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018694","name":"HORIZON EUROPE Marie Sklodowska-Curie Actions","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100018694","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Bioeng. Biotechnol."],"abstract":"<jats:p>The skeletal consequences of COVID-19 have emerged as an important but still underrecognized component of post-viral systemic disease. Increasing clinical, experimental, and imaging-based evidence indicates that SARS-CoV-2 infection may impair bone health through multiscale mechanisms involving bone remodeling, osteoimmune signaling, vascular regulation, and mechanical adaptation. In this review, we summarize current evidence linking COVID-19 to skeletal deterioration, ranging from changes in bone mineral density, trabecular microarchitecture, and mechanical competence to osteocyte lacunar remodeling and altered bone-cell activity. We discuss both potential direct and indirect mechanisms by which SARS-CoV-2 may affect the skeletal system. Direct effects may involve viral infection-associated inflammatory and oxidative responses that promote osteoclastogenesis and bone resorption. Indirectly, SARS-CoV-2 may disturb bone homeostasis through ACE2 downregulation and renin\u2013angiotensin system imbalance, systemic inflammation, endothelial dysfunction, glucocorticoid exposure, avascular necrosis, prolonged bed rest and mechanical unloading, vitamin D deficiency, and mineral dysregulation. Based on well-characterized mechanisms from other osteotropic viral diseases, we propose possible modes by which SARS-CoV-2 may affect the skeletal system. This review emphasizes key knowledge gaps, including the limited availability of longitudinal human data, the need for advanced imaging and multiscale mechanical modeling, and the potential role of host genetic susceptibility. Overall, COVID-19-related skeletal impairment should be considered a multifactorial and multiscale process. Integrated clinical, molecular, imaging, genetic, and biomechanical approaches will be essential to identify vulnerable individuals, monitor long-term skeletal outcomes, and develop targeted strategies to preserve bone health in COVID-19 survivors.<\/jats:p>","DOI":"10.3389\/fbioe.2026.1812439","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T05:35:12Z","timestamp":1784612112000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Multiscale bone remodeling in COVID-19: from osteoimmune signaling to structural and mechanical impairment"],"prefix":"10.3389","volume":"14","author":[{"given":"G.","family":"Jiang","sequence":"first","affiliation":[{"name":"Department of Mechanical Engineering (DMEC), Politecnico di Milano","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Buccino","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering (DMEC), Politecnico di Milano","place":["Milan, Italy"]},{"name":"IRCCS Galeazzi-Sant\u2019Ambrogio","place":["Milan, Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L. 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