{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T00:45:10Z","timestamp":1792889110340,"version":"4.5.0"},"reference-count":109,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2020,3,19]],"date-time":"2020-03-19T00:00:00Z","timestamp":1584576000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medicina"],"abstract":"<jats:p>Alarmins are endogenous mediators released by cells following insults or cell death to alert the host\u2019s innate immune system of a situation of danger or harm. Many of these, such as high-mobility group box-1 and 2 (HMGB1, HMGB2) and S100 (calgranulin proteins), act through RAGE (receptor for advanced glycation end products), whereas the IL-1 and IL-33 cytokines bind the IL-1 receptors type I and II, and the cellular receptor ST2, respectively. The alarmin family and their signal pathways share many similarities of cellular and tissue localization, functions, and involvement in various physiological processes and inflammatory diseases including osteoporosis. The aim of the review was to evaluate the role of alarmins in osteoporosis. A bibliographic search of the published scientific literature regarding the role of alarmins in osteoporosis was organized independently by two researchers in the following scientific databases: Pubmed, Scopus, and Web of Science. The keywords used were combined as follows: \u201calarmins and osteoporosis\u201d, \u201cRAGE and osteoporosis\u201d, \u201cHMGB1 and osteoporosis\u201d, \u201cIL-1 and osteoporosis\u201d, \u201cIL 33 and osteopororsis\u201d, \u201cS100s protein and osteoporosis\u201d. The information was summarized and organized in the present review. We highlight the emerging roles of alarmins in various bone remodeling processes involved in the onset and development of osteoporosis, as well as their potential role as biomarkers of osteoporosis severity and progression. Findings of the research suggest a potential use of alarmins as pharmacological targets in future therapeutic strategies aimed at preventing bone loss and fragility fractures induced by aging and inflammatory diseases.<\/jats:p>","DOI":"10.3390\/medicina56030138","type":"journal-article","created":{"date-parts":[[2020,3,20]],"date-time":"2020-03-20T07:29:07Z","timestamp":1584689347000},"page":"138","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":43,"title":["Alarmins in Osteoporosis, RAGE, IL-1, and IL-33 Pathways: A Literature Review"],"prefix":"10.3390","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4253-1312","authenticated-orcid":false,"given":"Massimo","family":"De Martinis","sequence":"first","affiliation":[{"name":"Department of Life, Health, &amp; Environmental Sciences, University of L\u2019Aquila, 6700 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lia","family":"Ginaldi","sequence":"additional","affiliation":[{"name":"Department of Life, Health, &amp; Environmental Sciences, University of L\u2019Aquila, 6700 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1006-7121","authenticated-orcid":false,"given":"Maria Maddalena","family":"Sirufo","sequence":"additional","affiliation":[{"name":"Department of Life, Health, &amp; Environmental Sciences, University of L\u2019Aquila, 6700 L\u2019Aquila, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Pioggia","sequence":"additional","affiliation":[{"name":"National Research Council of Italy (CNR)-Institute for Biomedical Research and Innovation (IRIB), 98164 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gioacchino","family":"Calapai","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastiano","family":"Gangemi","sequence":"additional","affiliation":[{"name":"School and Division of Allergy and Clinical Immunology, Department of Experimental Medicine, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1292-6284","authenticated-orcid":false,"given":"Carmen","family":"Mannucci","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Dental Sciences and Morphofunctional Imaging, University of Messina, 98125 Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,3,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Genazzani, A.R., and Brincat, M. 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