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This study aimed to assess bone status in SSc using dual X-ray absorptiometry (DXA) complemented by peripheral quantitative computed tomography (pQCT), and to evaluate their associations with a targeted osteoimmunological biomarker panel and clinical risk scores. This prospective cross-sectional study included 40 women with SSc (disease duration\u2009\u2264\u20097 years from diagnosis) and 45 non-immune female controls, frequency-matched by age. Bone status was assessed by DXA (lumbar spine, femoral neck) and distal radius pQCT. Serum levels of routine bone and mineral metabolism markers, alongside a targeted panel of osteoimmunological mediators (OPG, OPN, PDGF-BB, ACP5, RANKL, TNF-\u03b1, IL-6, IL-1\u03b2, DKK-1) using multiplex immunoassay were measured. FRAX scores were calculated to contextualize clinical fracture risk. With broadly comparable DXA-defined bone status, pQCT revealed significantly lower trabecular volumetric bone mineral density (vBMD) in SSc, while total and cortical+subcortical vBMD were comparable. Routine biochemical markers showed substantial overlap between groups, whereas SSc patients exhibited a distinct osteoimmune profile with significantly elevated OPG, ACP5, RANKL, PDGF-BB, IL-6, IL-1\u03b2, DKK-1, and RANKL\/OPG after FDR correction. Exploratory biomarker\u2013bone associations did not remain significant after correction for multiple testing. In women with relatively early SSc, pQCT identified compartment-specific differences, particularly within the trabecular compartment, despite comparable DXA-defined bone status. A distinct osteoimmunological biomarker profile was also observed in SSc, providing complementary information on disease-related skeletal alterations, while specific biomarker\u2013bone associations require further confirmation.<\/jats:p>","DOI":"10.1007\/s00223-026-01624-5","type":"journal-article","created":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T11:52:10Z","timestamp":1792669930000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Compartment-specific skeletal involvement in systemic sclerosis characterized by peripheral QCT and serum osteoimmune mediators: a case-control study"],"prefix":"10.1007","volume":"117","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-5082-3944","authenticated-orcid":false,"given":"D\u00f3ra","family":"Csige","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c1gnes","family":"Horv\u00e1th","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Bodoki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Istv\u00e1n","family":"Rebenku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e1ra","family":"Lipt\u00e1k-Luk\u00e1csik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilla Ram\u00f3na","family":"Pom\u00e1zi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zs\u00f3fia","family":"Peth\u0151","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e1ndor","family":"Mogyor\u00f3ssy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"Hamar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N\u00f3ra","family":"Bodn\u00e1r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebeka","family":"Falcsik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katalin","family":"Hodosi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gy\u00f6rgy","family":"Panyi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szilvia","family":"Szamosi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zolt\u00e1n","family":"Szekanecz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Sz\u0171cs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edit","family":"V\u00e9gh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Levente","family":"Bodoki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,10,22]]},"reference":[{"key":"1624_CR1","doi-asserted-by":"publisher","first-page":"2783","DOI":"10.1093\/rheumatology\/keae543","volume":"64","author":"K Lillpers","year":"2025","unstructured":"Lillpers K, McGuigan F, Andr\u00e9asson K, Hesselstrand R, Kapetanovic MC, \u00c5kesson KE (2025) Increased prevalence of osteopenia and osteoporosis in systemic sclerosis patients, including in men and young women-a case\u2013control study. 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